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IMAI district clinician manual: hospital care adolescents and adults : guidelines for the management of illnessess with limited-resources

11 décembre 2012 Organisation mondiale de la santé

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Texte intégral

VOLUME 2

IMAI District Clinician Manual: Hospital Care for Adolescents and Adults

G U ID ELIN ES FO R TH E M A N A G EM EN T O F C O M M O N I LLN ES S ES W ITH LI M I TED R ES O U R C ES I ntegrated M anagement of A dolescent and A dult I llness (IMAI)

WHO Library Cataloguing-in-Publication Data IMAI district clinician manual: hospital care for adolescents and adults: guidelines for the management of illnesses with limited-resources. 2 v. 1.Community health services - standards. 2.Hospitals. 3.Delivery of health care - standards. 4.Clinical competence. 5.Disease management. 6.Adolescent. 7.Adult. 8.Manuals. 9.Developing countries. I.World Health Organization. ISBN 978 92 4 154831 1 (package) ISBN 978 92 4 154828 1 (vol. 1) ISBN 978 92 4 154829 0 (vol. 2) (NLM classiﬁcation: WA 546)

© World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@ who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http:// www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of speciﬁc companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. Cover images: © Bahizi Jovan (left), Petra Rohr-Rouendaal (right). Production coordination: L’IV Com Sàrl, Villars-sous-Yens, Switzerland. Printed in Switzerland.

VO L U ME 2

IMAI District Clinician Manual: Hospital Care for Adolescents and Adults GUIDEL INES F O R T H E MAN A G E M E N T O F CO MMO N IL LN E S S E S W ITH L IMIT ED RE SO U R C E S I ntegrated M anagement of A dolescent and A dult I llness (IMAI)

Table of contents Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

xiii

9. HIV diagnosis . 9.1 9.2

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1 3 7 9 11 13 14

9.3

Provider-initiated HIV testing and counselling at the district hospital and the role of the district clinician. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Re-testing and repeat testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.1 Re-testing for HIV-negative individuals in the context of a generalized epidemic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.2 Re-testing for HIV-negative individuals in low level or concentrated epidemics . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.3 Explain to patients the meaning of discordant or HIV-negative test results . CD4 testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10. Acute and subacute by symptom 10.1

10.2

10.3

10.4

10.5

Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1.2 Consider likely differential diagnosis using the DDx tables . . . . . . . . 10.1.3 Initiate treatment(s), monitor response, and reconsider diagnosis . . . 10.1.4 Management of severely ill patient with fever . . . . . . . . . . . . . . . 10.1.5 Management of fever as an outpatient (not severely ill) . . . . . . . . . Skin disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.2 Skin and soft tissue infections . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.3 Papular lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.4 Vesicular or bullous lesions . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.5 Nodular lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.6 Maculopapular rash . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.7 Plaques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.8 Pruritus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.9 Urticaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.10 Skin ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Weight loss and malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3.2 Consider the likely cause of loss of weight . . . . . . . . . . . . . . . . . 10.3.3 Treat weight loss and malnutrition and its underlying causes . . . . . . 10.3.4 Prevent malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Swelling of the limbs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.2 Differential diagnosis of oedema . . . . . . . . . . . . . . . . . . . . . . . 10.4.3 Treatment of limb swelling . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.4 Symptom management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.5 Manage lymphoedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lymphadenopathy and lumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5.2 Classify the lymphadenopathy and consider the differential diagnosis 10.5.3 Approach to lymphadenopathy in PLHIV. . . . . . . . . . . . . . . . . . . 10.5.4 Symptom management of lymphadenopathy . . . . . . . . . . . . . . . .

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15 19 19 22 27 28 29 30 31 34 38 48 49 52 53 57 60 61 69 70 75 78 81 84 85 86 88 89 89 90 90 92 95 96

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10.6

Chest symptoms: cough and shortness of breath . . . . . . . . . . . . . . . . . . . 10.6.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6.2 Differential diagnosis of chest complaints . . . . . . . . . . . . . . . . . 10.6.3 Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6.4 Asthma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6.5 Chronic obstructive pulmonary disease (COPD) . . . . . . . . . . . . . . 10.7 Abdominal complaints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a Abdominal pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a.2 Differential diagnosis of abdominal pain and management of speciﬁc conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a.3 Approach to abdominal pain in PLHIV . . . . . . . . . . . . . . . . . . . . 10.7b Painful or difﬁculty swallowing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7b.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7b.2 Differential diagnosis and treatment of painful or difﬁcult swallowing . 10.7b.3 Approach to oesophagitis in PLHIV . . . . . . . . . . . . . . . . . . . . . . 10.7c Nausea and vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7c.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7c.2 Differential diagnosis and treatment of nausea or vomiting . . . . . . . 10.7c.3 Symptom management for nausea or vomiting . . . . . . . . . . . . . . . 10.7d Diarrhoea (and constipation). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7d.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7d.2 Classify and manage diarrhoea . . . . . . . . . . . . . . . . . . . . . . . . 10.7d.3 Approach to persistent or chronic diarrhoea in PLHIV . . . . . . . . . . 10.7d.4 Constipation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.8 Jaundice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.8.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.9 Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.9.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.9.2 Classify ascites and consider the likely differential diagnosis . . . . . . 10.9.3 Manage ascites according to cause . . . . . . . . . . . . . . . . . . . . . 10.10 Neurological problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a Neurological deﬁcit (without meningeal signs) . . . . . . . . . . . . . . . . . . . . . 10.10a.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.2 Classify the neurological deﬁcit and consider the likely differential diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.3 Stroke-like syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.4 Spinal cord problem (myelopathy) . . . . . . . . . . . . . . . . . . . . . . 10.10a.5 Peripheral motor or sensory nervous system problem . . . . . . . . . . 10.10a.6 Peripheral neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.7 Common cranial nerve palsies and their differentials . . . . . . . . . . 10.10b Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10b.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10b.2 Consider the likely differential diagnosis . . . . . . . . . . . . . . . . . . 10.10b.3 Treatment of speciﬁc conditions . . . . . . . . . . . . . . . . . . . . . . . 10.10b.4 Symptom management of headache . . . . . . . . . . . . . . . . . . . . 10.10c Neurological problems: seizures (without meningism or fever) . . . . . . . . . . . 10.10c.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10c.2 Consider the likely differential diagnosis . . . . . . . . . . . . . . . . . . 10.11 Approach to patients with mental health problems . . . . . . . . . . . . . . . . . . 10.11.1 Clinical approach to mental health problems . . . . . . . . . . . . . . . . 10.11.2 Suicide and deliberate self-harm assessment and management . . . . 10.11.3 Abnormal behaviour or thinking . . . . . . . . . . . . . . . . . . . . . . . . 10.11.4 Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.11.5 Bipolar disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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97 97 102 111 115 118 123 123 123 126 134 136 136 137 138 140 140 141 145 146 146 148 156 158 159 160 166 166 169 171 174 175 175 177 178 181 182 185 187 188 189 193 199 202 203 203 204 209 210 215 219 227 231

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iii

10.12

10.13

10.14

10.15

10.16

10.17

10.18

10.11.6 Sad or low mood including depression . . . . . . . . . . . . . . . . 10.11.7 Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Eye problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.2 Approach to red eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.3 Acute visual loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.4 Progressive visual loss . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.5 Geographically conﬁned eye diseases – onchocerciasis and trachoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.6 Eye problems in patients with HIV infection . . . . . . . . . . . . . . 10.12.7 Neuro-ophthalmic involvement from mass lesions, TB, or cryptococcal meningitis . . . . . . . . . . . . . . . . . . . . . . . Painful joints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.13.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.13.2 Diagnosis of single and multiple painful joints . . . . . . . . . . . . 10.13.3 Symptom management . . . . . . . . . . . . . . . . . . . . . . . . . . Female and male anorectal problems and genital ulcers . . . . . . . . . . . 10.14.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.14.2 Anorectal problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.14.3 Genital ulcer disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.14.4 Special considerations in patients with HIV. . . . . . . . . . . . . . 10.14.5 Symptom management: rectal tenderness . . . . . . . . . . . . . . Female genitourinary complaints . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.2 Abnormal vaginal bleeding or amenorrhoea, or lower abdominal or pelvic pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.3 Pelvic mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.4 Abnormal vaginal discharge not responding to syndromic management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.5 Pelvic inﬂammatory disease . . . . . . . . . . . . . . . . . . . . . . . 10.15.6 Septic abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.7 Approach to urinary incontinence . . . . . . . . . . . . . . . . . . . 10.15.8 Cervical cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.9 Schistosomiasis of the female genitourinary tract . . . . . . . . . . Male genitourinary complaints . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.2 Genital growths in men . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.3 Dysuria and penile discharge . . . . . . . . . . . . . . . . . . . . . . 10.16.4 Testicular and scrotal problems . . . . . . . . . . . . . . . . . . . . . 10.16.5 Foreskin problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.6 Prostate problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.7 Schistosomiasis of the male genitourinary tract . . . . . . . . . . . Disorders of the mouth and throat . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.2 HIV and the mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.3 Soft tissue lesions of the mouth . . . . . . . . . . . . . . . . . . . . . 10.17.4 Oral cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.5 Conditions related to the hard tissue of the mouth . . . . . . . . . . 10.17.6 Gum disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.7 Noma disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.8 Dry mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.9 Pharyngitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pallor and anaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.18.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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235 244 254 254 259 265 266 268 269 271 272 272 274 280 281 281 282 285 289 290 291 292 295 302 305 309 312 313 317 321 322 323 325 325 327 328 330 332 333 334 336 336 343 343 345 346 346 347 350 350

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10.19

10.20

10.18.2 Classiﬁcation of anaemia . . . . . . . . . . . . . . . . . . . . . . . 10.18.3 Management of anaemia . . . . . . . . . . . . . . . . . . . . . . . Abnormal bleeding and bruising . . . . . . . . . . . . . . . . . . . . . . . . 10.19.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.19.2 Diagnostic approach to active bleeding . . . . . . . . . . . . . . 10.19.3 Diagnostic approach to low platelets with no active bleeding . 10.19.4 Speciﬁc bleeding conditions in detail . . . . . . . . . . . . . . . Splenomegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.20 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.21 Use the DDx table to establish a likely differential diagnosis . 10.22 Management of splenomegaly . . . . . . . . . . . . . . . . . . .

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354 356 361 361 366 368 370 374 374 374 376

11. Multisystem communicable diseases, renal and HIV-related cancers (in alphabetical order) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9 11.10 11.11 11.12 11.13 11.14 11.15 11.16 11.17 11.18 11.19 11.20 11.21 11.22 11.23 11.24 11.25 11.26 11.27 11.28 11.29 11.30 11.31 11.32 11.33 11.34 11.35 11.36 11.37 11.38 Amoebiasis . . . . . . . . . . . . . Bartonellosis . . . . . . . . . . . . Brucellosis. . . . . . . . . . . . . . Candida . . . . . . . . . . . . . . . . Cryptococcosis . . . . . . . . . . . Cryptosporidiosis . . . . . . . . . . Cysticercosis . . . . . . . . . . . . Cytomegalovirus . . . . . . . . . . Dengue fever . . . . . . . . . . . . Endocarditis . . . . . . . . . . . . . Fascioliasis . . . . . . . . . . . . . Filariasis, lymphatic . . . . . . . . Gonorrhoea . . . . . . . . . . . . . Hepatitis – viral . . . . . . . . . . . Herpes simplex virus . . . . . . . Histoplasmosis . . . . . . . . . . . Inﬂuenza . . . . . . . . . . . . . . . Isosporiasis . . . . . . . . . . . . . Kaposi sarcoma . . . . . . . . . . . Leishmaniasis . . . . . . . . . . . . Leprosy . . . . . . . . . . . . . . . . Leptospirosis . . . . . . . . . . . . Liver abscess . . . . . . . . . . . . Loaisis . . . . . . . . . . . . . . . . Malaria . . . . . . . . . . . . . . . . Microsporidiosis . . . . . . . . . . Mycobacterium avium complex . Onchocerciasis . . . . . . . . . . . Penicilliosis . . . . . . . . . . . . . Rabies and animal bites . . . . . . Renal problems . . . . . . . . . . . Rheumatic fever. . . . . . . . . . . Rickettsial diseases . . . . . . . . Schistosomiasis . . . . . . . . . . Sinusitis . . . . . . . . . . . . . . . Strongyloidiasis. . . . . . . . . . . Syphilis . . . . . . . . . . . . . . . . Taeniasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

381 383 385 387 389 393 394 396 399 403 406 409 413 414 418 419 420 424 425 427 433 437 438 439 441 455 455 456 458 458 462 477 478 479 481 483 484 487

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11.39 11.40 11.41 11.42 11.43 11.44 11.45 11.46 11.47

Tetanus . . . . . . . . . . . . . . . . Toxoplasmosis . . . . . . . . . . . Trypanosomiasis, human African Trypanosomiasis, American . . . Typhoid fever . . . . . . . . . . . . Urinary tract infection . . . . . . . Varicella/zoster . . . . . . . . . . . Viral haemorrhagic fever . . . . . Yellow fever . . . . . . . . . . . . .

. . . . . . . . .

488 489 491 494 498 499 501 503 504

Chronic and long-term care

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

507 509

12. General principles of good chronic care .

Your role as health-care providers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509 For the patient in chronic or long-term care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510

13. Chronic HIV care, antiretroviral therapy (ART), and prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sequence of care after positive HIV test . . . . . . . . . . . . . . . . . . 13.1 Clinical approach when the district clinician is consulted on a HIV patient in chronic HIV care . . . . . . . . . . . . . . . . . 13.2 Determine HIV clinical stage . . . . . . . . . . . . . . . . . . . . . 13.3 Prophylaxis for PLHIV . . . . . . . . . . . . . . . . . . . . . . . . . . Cotrimoxazole prophylaxis . . . . . . . . . . . . . . . . . . . . . Isoniazid preventive therapy . . . . . . . . . . . . . . . . . . . . 13.4 Initiate and manage patients on ART . . . . . . . . . . . . . . . . . Determine ART eligibility . . . . . . . . . . . . . . . . . . . . . . Determine appropriate ARV regimen . . . . . . . . . . . . . . . Preferred ﬁrst-line ARV regimens for treatment-naive adults and adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . Drug interactions with ﬁrst-line ARV regimens . . . . . . . . . 13.5 ART monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitoring for new clinical events. . . . . . . . . . . . . . . . . Monitor and support adherence . . . . . . . . . . . . . . . . . . Monitoring response to ART . . . . . . . . . . . . . . . . . . . . Laboratory monitoring . . . . . . . . . . . . . . . . . . . . . . . . 13.6 ART initiation in complicated patients . . . . . . . . . . . . . . . . 13.7 Second-line ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Deﬁning ART failure . . . . . . . . . . . . . . . . . . . . . . . . . Second-line ARV regimens . . . . . . . . . . . . . . . . . . . . . Monitoring second-line regimens . . . . . . . . . . . . . . . . . 13.8 ART toxicity and management . . . . . . . . . . . . . . . . . . . . . Short- and long-term toxicities on ART . . . . . . . . . . . . . . Clinical and laboratory monitoring for ART toxicity . . . . . . . Side-effects of ﬁrst-line ARVs . . . . . . . . . . . . . . . . . . . Management of ART toxicity . . . . . . . . . . . . . . . . . . . . 13.9 Management of speciﬁc ART toxicities . . . . . . . . . . . . . . . Haematological toxicity . . . . . . . . . . . . . . . . . . . . . . . Hepatotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rash and hypersensitivity . . . . . . . . . . . . . . . . . . . . . . Dyslipidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hyperlactataemia and lactic acidosis . . . . . . . . . . . . . . . Peripheral neuropathy . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 511 . . . . . . . . . . . . . 512 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

514 517 523 523 526 529 529 529 531 532 532 532 533 533 533 535 542 542 543 543 544 544 545 545 546 546 546 548 549 552 552 554

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13.10

13.11 13.12

13.13

13.14

Lipodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abdominal pain and symptoms . . . . . . . . . . . . . . . . . . . Clinical toxicities grading and management . . . . . . . . . . . ARVs and other HIV-related medications associated with selected toxicities . . . . . . . . . . . . . . . . . . . . . . . . . IRIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HIV/TB co-management . . . . . . . . . . . . . . . . . . . . . . . . . Cotrimoxazole prophylaxis . . . . . . . . . . . . . . . . . . . . . When to start ART in patients with TB . . . . . . . . . . . . . . Recommended ART for patients with TB . . . . . . . . . . . . . Women of childbearing potential (ore pregnant women) with TB and eligible for ART . . . . . . . . . . . . . . . . . . . Summary of ﬁrst-line ART for TB patients . . . . . . . . . . . . TB immune reconstitution inﬂammatory syndrome (TB-IRIS) . New TB in patients already receiving ART . . . . . . . . . . . . ART recommendations for patients who develop TB within 6 months of starting a ﬁrst-line or second-line ART regimen Second-line ART regimens for patients with TB . . . . . . . . . Adherence preparation, monitoring, and support. . . . . . . . . . Barriers to adherence and suggestions for addressing them . Positive health, dignity, and prevention for PLHIV . . . . . . . . . Preventing sexual transmission of HIV . . . . . . . . . . . . . . Preventing non-sexual transmission of HIV . . . . . . . . . . . Reproductive choice and family planning . . . . . . . . . . . . Positive living for PLHIV . . . . . . . . . . . . . . . . . . . . . . . . . Counsel PLHIV on how to prevent other infections . . . . . . . Encourage physical activity as appropriate . . . . . . . . . . . Support adequate and balanced nutrition . . . . . . . . . . . . Assess alcohol use . . . . . . . . . . . . . . . . . . . . . . . . . . Brief interventions for patients with hazardous or harmful alcohol use . . . . . . . . . . . . . . . . . . . . . . . . Special considerations for adolescents in chronic HIV care . . Psychosocial support . . . . . . . . . . . . . . . . . . . . . . . . Differences among adolescents . . . . . . . . . . . . . . . . . . What to do and what to avoid when communicating with adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . ART in adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . Tanner stage for female and male adolescents . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

554 554 555 556 559 560 560 560 560 560 561 561 562 562 563 563 564 566 566 567 567 568 568 569 569 569 570 570 570 570 572 573 573

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14. PMTCT, HIV prevention, care, and treatment during pregnancy, and family planning . . . . . . . . .

14.1 HIV prevention, care, and treatment during pregnancy . . . . . . . . . . . . . . . 14.1.1 Recommend HIV testing and counselling, and optimize care for HIV-positive pregnant women and their infants . . . . . . . . . . . Optimization of care for HIV-positive women and their infants . . . . 14.1.2 Identify and treat opportunistic infections (OIs) . . . . . . . . . . . . . . 14.1.3 Offer ART or ARV prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . Eligibility criteria for ART or ARV prophylaxis in HIV-positive pregnant women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Considerations for choice of ART regimen . . . . . . . . . . . . . . . . Considerations for the choice of ﬁrst-line ART for pregnant women in need of treatment for their own health . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . 577 . . . . 579 . . . . . . . . . . . . . . . .

579 580 581 582 583 583 585

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14.2

14.3 14.4 14.5

Immune reconstitution inﬂammatory syndrome (IRIS) . . . . . . . Women who become pregnant while taking ART . . . . . . . . . . . Monitoring antiretroviral response in pregnant women. . . . . . . . Use of second-line ART in pregnancy . . . . . . . . . . . . . . . . . . ARV prophylaxis for infants of HIV-positive women taking ART . . . ARV prophylaxis to prevent MTCT of HIV . . . . . . . . . . . . . . . . Maternal ARV prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . Recommended ARV-prophylaxis for pregnant women not yet eligible for ART and their infants . . . . . . . . . . . . . . Infant ARV prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of infant ARV prophylaxis regimens . . . . . . . . . . . . Infant ARV prophylaxis dosing recommendations . . . . . . . . . . 14.1.9 Safety of antiretroviral and other medicines in pregnancy . . . . . . Safety monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Anaemia in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . NVP rash and hepatitis in pregnancy . . . . . . . . . . . . . . . . . Management of NVP-associated rash and liver toxicity . . . . . . EFV use in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . Lactic acidosis in pregnancy . . . . . . . . . . . . . . . . . . . . . . Rash and hypersensitivity due to abacavir (ABC) . . . . . . . . . . Safety of medicines in pregnancy . . . . . . . . . . . . . . . . . . . 14.1.10 Antiretroviral drug resistance . . . . . . . . . . . . . . . . . . . . . . . Choice of ART regimen for HIV-positive women with prior exposure to ARV prophylaxis for PMTCT . . . . . . . . . . . . . . 14.1.11 Improved care and support for HIV-positive pregnant women . . . Nausea and vomiting in pregnancy . . . . . . . . . . . . . . . . . . Antiemetic medication in pregnancy. . . . . . . . . . . . . . . . . . Intrapartum care for HIV-positive women . . . . . . . . . . . . . . . . . . . . . Summary of ARV regimens during pregnancy, intrapartum, postpartum, and breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Safer intrapartum practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . Caesarean delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Breast care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Infant feeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replacement feeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Postpartum care for HIV-positive women . . . . . . . . . . . . . . . . . . . . . Care for HIV-exposed infants . . . . . . . . . . . . . . . . . . . . . . . . . . . Reproductive choice and family planning . . . . . . . . . . . . . . . . . . . . . 14.5.1 Dual protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5.2 Guidance on the use of contraceptive methods . . . . . . . . . . . . Drug-drug interactions . . . . . . . . . . . . . . . . . . . . . . . . . . Medical eligibility criteria for contraceptive use: conditions relevant to HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5.3 Contraceptive method mix . . . . . . . . . . . . . . . . . . . . . . . . . Emergency contraception . . . . . . . . . . . . . . . . . . . . . . . . Indications for pregnancy testing . . . . . . . . . . . . . . . . . . . Special considerations when pregnancy is desired by a discordant couple . . . . . . . . . . . . . . . . . . . . . . . . . . 14.1.4 14.1.5 14.1.6 14.1.7 14.1.8

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

586 586 586 586 587 587 587 588 589 589 589 589 589 590 590 591 591 591 592 592 592 593 593 593 594 594 594 595 595 595 596 596 597 599 600 601 601 602 602 603 603 604 605 605

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15. Tuberculosis .

15.1 Suspect TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Extrapulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2 Diagnose TB (with DDx table) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Case deﬁnitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laboratory and radiology in TB diagnosis . . . . . . . . . . . . . . . . . . . . Extrapulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Case deﬁnitions for the diagnosis of TB . . . . . . . . . . . . . . . . . . . . . Algorithm for the diagnosis of AFB smear-negative PTB in HIV-negative patients where Xpert MTB/RIF test is not available . . . . . . . . . . . . . Algorithm for the management of ambulatory HIV-positive patients with presumptive TB where Xpert MTB/RIF test is available . . . . . . . . Algorithm for the diagnosis of TB in ambulatory patients in HIV-prevalent settings where Xpert MTB/RIF test is not available . . . . . . . . . . . . . . Summary of signs and symptoms of EPTB . . . . . . . . . . . . . . . . . . . . Diagnosis of TB in the seriously ill patient with danger signs . . . . . . . . . Algorithm for the diagnosis of TB in seriously ill patients in HIV-prevalent settings where Xpert MTB/RIF test is possible . . . . . . . . . . . . . . . . Algorithm for the diagnosis of TB in seriously ill patients in HIV-prevalent settings at ﬁrst-level facilities where Xpert MTB/RIF test is not available Differential diagnosis of PTB in PLHIV . . . . . . . . . . . . . . . . . . . . . . DDx: PTB in PLHIV by stage of immunosuppression . . . . . . . . . . . . . . TB in pregnant and postpartum women. . . . . . . . . . . . . . . . . . . . . . 15.3 Treatment of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Standardized TB treatment regimens . . . . . . . . . . . . . . . . . . . . . . . Standard code for TB treatment regimens . . . . . . . . . . . . . . . . . . . . First-line anti-tuberculosis drugs. . . . . . . . . . . . . . . . . . . . . . . . . . Standard anti-TB regimen and dosing frequency in new TB cases . . . . . Dose of ﬁrst-line anti-tuberculosis drugs for adults . . . . . . . . . . . . . . Registration group by outcome of most recent TB treatment . . . . . . . . . TB treatment in special situations . . . . . . . . . . . . . . . . . . . . . . . . . Anti-TB treatment regimens in special situations . . . . . . . . . . . . . . . . Empirical treatment in EPTB . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adjuvant corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.4 Monitor TB treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitor response to TB treatment . . . . . . . . . . . . . . . . . . . . . . . . . Manage drug side-effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Symptom-based approach to managing side-effects of anti-TB drugs . . . Determine TB treatment outcomes . . . . . . . . . . . . . . . . . . . . . . . . Standard deﬁnitions of TB treatment outcomes . . . . . . . . . . . . . . . . . 15.5 Drug-resistant TB (with DDx table) . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of recommended TB treatment regimens . . . . . . . . . . . . . . MDR-TB treatment regimen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MDR-TB and HIV infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Manage common problems in patients with MDR-TB . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .

607 . . . . . . . .

609 609 610 610 610 610 613 613 615

. . . . .

. . . . . 616 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

617 618 619 620 621 622 623 623 624 624 624 624 625 625 626 626 627 627 627 628 628 628 629 630 630 630 631 631 632 632

Vol. 2 • Table of contents

16. Assessment and therapy for alcohol use disorders

16.1 Deﬁnitions of hazardous and harmful alcohol use and alcohol dependence . . . . 16.2 Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alcohol Use Disorders Identiﬁcation Test (AUDIT) . . . . . . . . . . . . . . . . . . Brief assessment using AUDIT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laboratory ﬁndings suggestive of harmful alcohol use or alcohol dependence . 16.3 Classify, then advise and treat the patient . . . . . . . . . . . . . . . . . . . . . . . . If the AUDIT score is 8–19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . If the AUDIT score is ≥20 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Special advice for pregnant patients . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of interventions by classiﬁcation of alcohol use disorder . . . . . . . . 16.4 Brief interventions for those with hazardous or harmful drinking . . . . . . . . . . . FLAGS approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.5 Treatment and care for those with alcohol dependence . . . . . . . . . . . . . . . . Withdrawal management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Relapse prevention after withdrawal from alcohol . . . . . . . . . . . . . . . . . . Psychosocial support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . .

635 . . . . . . . . . . . . . . . . .

637 638 639 639 641 642 643 643 643 643 644 644 645 646 647 647 648

17. Substance use

17.1 General approach to substance use . . . . . . . . . . . . . . . . . . . . . . . . Patterns of substance use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Deﬁnitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmacological classes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Routes of administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effects of drug use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.2 Assessing drug use and dependence . . . . . . . . . . . . . . . . . . . . . . . . General principles of engaging and assessing the patient . . . . . . . . . Identify the drugs used. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Screening for substance use disorders using the ASSIST questionnaire. 17.3 General approach to managing drug use disorders . . . . . . . . . . . . . . . A pragmatic, client-centred approach . . . . . . . . . . . . . . . . . . . . . Other sources of medical care and psychosocial support. . . . . . . . . . Link with health and social welfare agencies . . . . . . . . . . . . . . . . . 17.4 Management of opioid dependence with opioid substitution treatment . . . What is opioid substitution treatment? . . . . . . . . . . . . . . . . . . . . . Overview of OST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to initiate OST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OST side-effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Psychosocial support during OST . . . . . . . . . . . . . . . . . . . . . . . . Cessation of OST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OST dose reduction and cessation . . . . . . . . . . . . . . . . . . . . . . . 17.5 Harm reduction approaches for injecting drug users . . . . . . . . . . . . . . 17.6 Antiretroviral therapy and substance use . . . . . . . . . . . . . . . . . . . . . Initiation of antiretroviral therapy (ART) . . . . . . . . . . . . . . . . . . . . ARV-methadone interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . Interactions of OST and rifampicin . . . . . . . . . . . . . . . . . . . . . . . 17.7 Pain control in people with drug use disorders. . . . . . . . . . . . . . . . . . Management of acute pain in patients with a drug use disorder . . . . . Management of acute pain in patients receiving opioid OST . . . . . . . . Management of chronic pain in patients with drug use disorders . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

649 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

651 651 651 651 652 652 654 654 654 655 655 655 656 656 657 657 658 660 661 661 661 662 663 664 664 664 665 665 666 667 667

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17.8 Management of complications from injecting drug use . . . . . Complications of injection-related infections . . . . . . . . . 17.9 Involving the family . . . . . . . . . . . . . . . . . . . . . . . . . . Social support for the family . . . . . . . . . . . . . . . . . . . 17.10 Integrating alcohol and drug use management with HIV care .

. . . . .

667 669 671 672 672

18. General principles of geriatric care .

18.1 Helpful considerations while caring for older adults Frailty . . . . . . . . . . . . . . . . . . . . . . . . . . . Symptoms and signs of frailty. . . . . . . . . . . . . 18.2 Assessment of the older adult . . . . . . . . . . . . . . 18.3 Nutrition and hydration in older adults . . . . . . . . . 18.4 Medicines in older adults . . . . . . . . . . . . . . . . . 18.5 Older adults need ongoing vaccination . . . . . . . . 18.6 Family caregivers for older adults . . . . . . . . . . . . 18.7 Decision-making capacity and legal issues of care . 18.8 End-of-life care . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . .

675 . . . . . . . . . .

677 677 677 678 678 679 679 679 680 680

19. Prevention services for adolescents, adults and health workers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

19.1 Prevention services for adolescents and adults . . . . . . . . . . . . . . . . . . . . All acute and chronic patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Special prevention for adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . 19.2 Discordant couples counselling and services . . . . . . . . . . . . . . . . . . . . . 19.3 Special considerations for MSM and transgender persons . . . . . . . . . . . . . MSM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Transgender persons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Societal responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.4 Provide prevention, care and treatment services to health workers and other staff in health facilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.4.1 Manage workplace exposure to HIV . . . . . . . . . . . . . . . . . . . . . . 19.4.2 Facilitate and promote HIV testing, counselling, care and ART for staff . 19.4.3 Address workplace stigma about HIV through education and advocacy 19.4.4 Provide TB prevention and care services for health service workers . . 19.4.5 Prevention of hepatitis B in health workers . . . . . . . . . . . . . . . . . . 19.5 Urgent response to workplace HIV exposure . . . . . . . . . . . . . . . . . . . . . . First aid in the event of possible workplace HIV exposure . . . . . . . . . . . . How to determine if the exposure warrants PEP . . . . . . . . . . . . . . . . . . 19.6 Prevent, recognize and manage stress and burnout in staff . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . .

681 . . . . . . . . . . . . . . . . . .

683 683 685 686 687 687 690 690 691 691 692 692 692 693 694 694 695 696

20. Palliative care: symptom management and end-of-life care . . . . . . . . . . . . . . . . . . . . . . . . . . . .

20.1 Assess pain (acute or chronic pain) . . . . . . . . . . . . . . . . . . . . . . . . . . . . Assess the patient for pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Assessment tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.2 Manage chronic pain in lifethreatening diseases including cancer and HIV/AIDS Manage chronic pain with analgesics, other medications for special pain, and non-medical treatments . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

697 . . . .

700 700 700 701 701

. .

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20.3

20.4 20.5 20.6 20.7 20.8 20.9

20.10 20.11 20.12 20.13

Speciﬁc considerations regarding the use of oral morphine in chronic pain. . . Teaching the health worker and the patient about the use of pain medications . Reduction or cessation of opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . Non-pharmacological interventions for chronic pain . . . . . . . . . . . . . . . . Medications to control special pain problems . . . . . . . . . . . . . . . . . . . . . . The use of adjuvant analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Examples of the use of adjuvant analgesics . . . . . . . . . . . . . . . . . . . . . . Nerve blocks for speciﬁc severe pains . . . . . . . . . . . . . . . . . . . . . . . . . Manage acute pain in emergency or acute conditions . . . . . . . . . . . . . . . . . Manage acute severe pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Morphine IV infusion for refractory severe acute pain . . . . . . . . . . . . . . . . Symptom management: cough or difﬁculty breathing . . . . . . . . . . . . . . . . . . Symptom management: hiccups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Symptom management: trouble sleeping. . . . . . . . . . . . . . . . . . . . . . . . . . Manage other symptoms using other Sections of this manual . . . . . . . . . . . . . Preventive interventions for all patients . . . . . . . . . . . . . . . . . . . . . . . . . . Oral care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preventing bedsores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preventing pain, stiffness, and contractures in muscles, and moving the bedridden patient . . . . . . . . . . . . . . . . . . . . . . . . . . . Special considerations in palliative care for PLHIV . . . . . . . . . . . . . . . . . . . Special consideration in palliative care for TB patients . . . . . . . . . . . . . . . . Special considerations in palliative care for cancer . . . . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bereavement care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . .

705 706 706 707 708 708 709 710 711 711 711 712 713 714 714 715 715 715 715 716 716 717 718 718

21. Patient monitoring and reporting including reporting outbreaks and pharmacovigilance . . . . . . . . . . . . . . . . . . . . . 21.1 Longitudinal monitoring of patients in chronic or long-term care . 21.2 Monitoring inpatient care . . . . . . . . . . . . . . . . . . . . . . . . . Problem list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Regular monitoring and the monitoring chart . . . . . . . . . . . 21.3 Identifying and reporting notiﬁable diseases . . . . . . . . . . . . . Priority diseases, conditions and events for integrated disease surveillance and response . . . . . . . . . . . . . . . . . . . . . 21.4 Pharmacovigilance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spontaneous reporting. . . . . . . . . . . . . . . . . . . . . . . . . Cohort event monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . .

721 . . . . . . . . .

723 725 725 725 726 726 727 727 727

Index .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

729 742 747

Abbreviations and acronyms

Writers and reviewers, and process of development

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Vol. 2 • Table of contents

Foreword IMAI District Clinician Manual: Hospital Care for Adolescents and Adults The manual is written for clinicians working at the district hospital (ﬁrst-level referral care) who diagnose and manage sick adolescents and adults in resourceconstrained settings. It aims to support clinical reasoning, and to provide an effective clinical approach and protocols for the management of common and serious or potentially life-threatening conditions at district hospitals. The target audience thus includes doctors, clinical ofﬁcers, health ofﬁcers, and senior nurse practitioners. It has been designed to be applicable in both high and low HIV prevalence settings. The manual is divided into two volumes. The ﬁrst covers emergency triage assessment and treatment, and acute care for a severely ill or acutely injured patient for approximately the ﬁrst 24 hours of care. The ﬁrst volume also describes the clinical procedures commonly used in emergency and acute care, and gives a summary of the drugs used and the steps necessary for infection control. This second volume provides a symptoms-based approach to clinical care for acute and subacute conditions (including mental health). It provides short summaries of the management of diseases that affect multiple systems of the body, focusing on communicable diseases. It also includes the chronic or longterm management of HIV, TB, and alcohol and substance use disorders. Future editions may incorporate the chronic management of non-communicable diseases. The manual was developed to support clinicians in diagnosing and managing adolescent and adult patients at district hospitals with limited essential drugs, laboratory tests, and equipment. It is one component of a broader WHO secondlevel learning programme. It has been developed through a large collaboration of WHO Departments and their experts from many countries and regions across the world working in expert subgroups. Recommendations in the manual are predominately based on recent WHO evidence-based normative guidelines developed by several Departments and disease control programmes, including WHO HIV/AIDS, Stop TB, Global Malaria Programme, Neglected Tropical Diseases (NTD), Mental Health Gap (mhGAP), the Reproductive Health and Research (RHR) STI and cervical cancer and family planning guidelines, Integrated Management of Emergency and Essential Surgical Care (IMEESC), Integrated Management of Pregnancy and Childbirth (IMPAC) , Global Inﬂuenza Programme (GIP), Global Alert Response (GAR), and others. To put these normative guidelines into operation within an integrated clinical manual supports the implementation of multiple disease-control strategies. Good clinical care is a component of most effective public health approaches. Simpliﬁcation and standardization of case detection and ﬁrst-line treatments support decentralization and expand access to care. Within a district network, the district clinician receives patients in referral who have not responded to ﬁrst-line treatment or who require hospitalization for severe illness. The ability to provide effective emergency care for severely ill patients, to establish a likely differential diagnosis, to provide appropriate management and then monitor the patient’s response to treatment can contribute substantially to the health of the community. Where current WHO guidelines do not exist, selected national guidelines and evidence-based medicine sources, existing systematic reviews of evidence, and randomised clinical trials were reviewed. These evidence checks and updated sections of the manual can be accessed on the IMAI second-level EZcollab site.

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xiii

The relevant WHO normative guidelines are listed in footnotes in each Section, including an indication of when these will be revised (when available). The manual will be updated as other WHO guidelines are updated or new WHO guidelines are developed. Within three months of the revision and release of a relevant WHO normative guideline, an updated Section will be posted on the IMAI second-level EZcollab website. Each volume will be reprinted yearly. To request access to this website, or to provide comments or further queries, please send an email to imaimail@who.int. As updates to the manual sections are frequent, readers of the manual are advised to ensure that they are using a current version of the manual. This manual is for country adaptation, to match the national essential medicine list, availability of laboratory tests, and local disease epidemiology. An evolving country Adaptation Guide will be available from the same website. We thank the large number of people who have given valuable input, comments and feedback on this manual to date. Drs Sandy Gove, Kirsty McHarry and Eyerusalem Negussie for the IMAI team.

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Vol. 2 • Foreword

9. HIV diagnosis Table of contents 9.1 9.2 Provider-initiated HIV testing and counselling at the district hospital and the role of the district clinician. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Re-testing and repeat testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.1 Re-testing for HIV-negative individuals in the context of a generalized epidemic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.2 Re-testing for HIV-negative individuals in low level or concentrated epidemics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.3 Explain to patients the meaning of discordant or HIV-negative test results . CD4 testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .

3 7 9 11 13 14

9.3

9. HIV diagnosis 9.1 Provider-initiated HIV testing and counselling at the district hospital and the role of the district clinician1 In provider-initiated testing and counselling (PITC), health care workers recommend HIV testing and counselling to individuals attending health care facilities as a standard part of medical care. PITC enables clinical decisions to be made and services offered that would not have been possible without knowledge of a person’s HIV status. District clinicians are directly responsible for provision of PITC for patients attending hospital facilities (outpatients and inpatients) and also need to supervise implementation of PITC in ﬁrst-level facilities. Much of this entails supporting counsellors and other cadres of health workers to provide PITC for large numbers of patients, to encourage and offer referral for testing and counselling of partners and children, and to provide prevention services, especially for discordant couples. Discordant couples counselling and prevention services are key for preventing further HIV transmission (see Section 19 Prevention). In PITC (in generalized epidemics) HIV testing is recommended to patients who present for medical care regardless of their initial reason for seeking care. It is especially important to highlight that HIV testing and counselling is recommended for all patients whose clinical presentation might result from underlying HIV infection, for all HIV-exposed children, for children presenting with suboptimal growth or malnutrition or who are malnourished and not responding to appropriate nutritional therapy, and for all patients prior to HIV post-exposure prophylaxis. Throughout this manual, whenever a diagnosis makes HIV infection likely, it is marked in the differential diagnosis tables with a red ribbon. In generalized epidemics PITC includes testing and counselling for adults, adolescents, children, and infants. Health workers should encourage and offer testing for family members and partners of HIV-positive people. HIV testing and counselling as early as possible during pregnancy enables pregnant women to beneﬁt from prevention, treatment, and care and to access interventions for reducing HIV transmission to their infants. Health workers should not recommend HIV testing and counselling to all people attending all health facilities in settings with low-level or concentrated epidemics, since most people will have a low risk of exposure to HIV. In such settings the priority should be to ensure that HIV testing and counselling is recommended to all adults, adolescents, and children who present to health facilities with signs and symptoms suggestive of underlying HIV infection, including tuberculosis, and to children known to have been perinatally exposed to HIV.

1 Guidance on provider-initiated HIV testing and counselling in health facilities. WHO, 2007. Available at http:// www.who.int/hiv/pub/vct/pitc/en/index.html

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PITC

When to recommend HIV testing Low-level epidemics: • all adults and adolescents who present with signs or symptoms that could indicate HIV infection • HIV-exposed children or children born to HIV-positive women • men seeking circumcision as an HIV prevention intervention • consider for patients of: ° STI services ° services for most-at-risk populations ° antenatal, childbirth, and postpartum services ° TB settings. Concentrated epidemics: • all adults and adolescents who present with signs or symptoms that could indicate HIV infection • HIV-exposed children or children born to HIV-positive women • men seeking circumcision as an HIV prevention intervention • consider for patients of: ° STI services ° services for most-at-risk populations ° antenatal, childbirth, and postpartum services ° TB settings. Generalized epidemics: In generalized epidemics HIV testing and counselling should be recommended for all adults, adolescents, and children seen in all health facilities. This should include mobile or outreach medical services for targeted populations. In the case of phased implementation of PITC, the priorities for implementation, depending on local conditions, are: • medical inpatient and outpatient facilities, including TB clinics • antenatal, childbirth, and postpartum health facilities • STI services • health services for most-at-risk populations • services for children less than 10 years of age • services for adolescents • men seeking circumcision as an HIV prevention intervention • medical inpatient and outpatient facilities • surgical services • reproductive health services, including family planning.

Provider-initiated HIV testing and counselling is based on the three Cs 1. Counselling 2. Consent 3. Conﬁdentiality

Counselling: pre-test Patients require pre-test information, either individually or through group pre-test information sessions. The following information should be provided: • Reasons that HIV testing is being recommended. For example, say to the patient, “In order to understand your health problem, it is important to know if it is related to your having HIV” or “HIV is common in this community. Therefore, in order to provide the best health care possible, it is recommended that you receive a HIV test today’’. • Clinical and preventive beneﬁts and risks of HIV testing. These could be described in this way: “There are many things we can do if we ﬁnd out you have HIV, including providing (or referring for) medicines that keep patients healthy for a long time” or “If you know you that have HIV, you can protect

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•

• •

•

yourself from other diseases and keep your partner and baby (if the woman is pregnant), safe”. Services that are available depending on whether the test result is negative or positive, including, in the latter case, ART. For example, say to patients, “We will offer drugs that ﬁght HIV if you have the virus” or “If you are negative, we will treat your health problems, and we have counsellors who can help you to stay negative and to protect yourself”. If the health facility cannot offer some of the required services, the patient will be referred for appropriate services. In that case you can say, ‘’We will refer you to another health facility for any of the other services that you need and that we do not have at our health facility”. The right to decline HIV testing and that the test will be performed unless they object. Say, “As part of your visit today, we will be testing you for HIV unless you tell me that you do not want the test. Do you have any questions? If you do not want the test, please tell me” or “This test will help ensure that you receive good health care, and, unless you do not want to be tested for HIV today, I’m going to perform the test. Do you have any questions?” Declining HIV testing will not limit access to services. For example, say “If you refuse this test, we will still take care of you”. The importance of disclosure to former partners if the test is positive. Say, “If your test result is positive, it will be very important to let your former partners know that they may have been exposed to HIV. We will help you with that if you like”. For women of reproductive age, and especially if pregnant, include: ° The risk of transmitting HIV to the infant. Explain that HIV can be passed from a mother to her baby. For example, say, “When a woman has HIV, the virus can be passed to her baby’’. ° PMTCT interventions that are available. For example, say, “The risk to the baby is greatly reduced if a woman ﬁnds out her HIV status early in her pregnancy and receives treatment” or “There are very good medicines that can protect a baby and help the mother, but we must know a mother’s HIV status to start these”. Beneﬁts to the infant of early diagnosis of HIV. Say to patients, “If we ﬁnd out a baby has HIV early, we can take measures to keep the baby healthy” or “There are important things that can help a baby whose mother has HIV, but we must know early in order to help”.

PITC requires informed consent, with the patient given sufﬁcient information to make a rational decision and given the opportunity to decline testing. This opportunity should be given in private, in the presence of a health worker. Conﬁdentiality should be guaranteed, and health workers should explain to patients the procedures in place to safeguard conﬁdentiality. If a patient declines HIV testing, the health worker may wish to identify barriers and devise a strategy to overcome these barriers. Note also that some patient groups may be more susceptible to coercion to be tested or to adverse outcomes of disclosure of HIV status (e.g. violence, abandonment, incarceration). In these cases providing additional information beyond the minimum requirements may be appropriate to ensure that consent is voluntary and informed.

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PITC

Counselling: post-test Post-test counselling should be tailored to the test result and, in the case of a positive result, should be more extensive. As with all HIV testing, conﬁdentiality should be guaranteed.

Post-test counselling if the test result is negative • An explanation of the test result • Basic advice on methods to prevent HIV transmission ° Say, “Having one partner who you know is HIV-negative and who does not have other sexual partners will prevent you from getting HIV from your partner” or “If you aren’t with only one partner, or if you aren’t sure about your partner’s practices or HIV status, using a latex condom every time you have sex can prevent you from getting HIV from your partner”. • Include some information about the window period for appearance of antibodies and possible need for re-testing (refer to the tables below). ° Say: “This test is negative. HIV antibodies weren’t found. This test will not reﬂect any contacts you have had in the last 3 months. Can we talk about that?” or “If you have had unprotected sex in the past 3 months, we will need to schedule another test in 6 weeks to be sure you didn’t get HIV from that partner”. • Provision of male and female condoms and guidance for their usage ° Say, “Here are some latex condoms. Tell me what you have heard about how to use them.” or “This is a female condom. You can decide when to use one; it will be your decision. Let me show you how it works” or “Since you may become pregnant, and that could mean a risk that your baby would have HIV, I’d like to schedule an appointment for you to talk to our family planning nurse about contraception. For now, it might be a good idea for you to use a condom every time you have sex”.

Post-test counselling if the test result is positive • Inform the patient of the result and give time to consider. ° Say, “The test is positive. This means we found HIV in your body” or “The results indicate that you are infected with HIV”. • Ensure that the patient understands. ° Say, “What does what I just said mean to you?” or “If you were going to explain to someone what I just told you, what would you say?” • Allow the patient to ask questions. ° Say, “What would you like to ask me now?” or “Is there information I can offer that will be helpful to you?” • Help patient cope with emotions. ° Say, “This is really hard news to hear. Tell me about how you are feeling” or “How are you feeling now that you’ve heard this result?” It may be helpful to include a message about positive living—that many people are living with HIV and living productive lives. • Discuss immediate concerns and immediate sources of support. ° Say, “What do you plan do to in the next 24 hours?” or, “Let’s talk about who could support you in this difﬁcult time. Who do you think you can tell about this news?”

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• Discuss available follow-up services. ° Say, “We have staff here providing medical treatment and support groups. I think both of these could help you” or “There is a doctor who provides specialized HIV care, and I want you to consult with him the next time he is in the village”. • Provide information on preventing transmission. ° Say, “Remember how HIV is transmitted. It will be important now for you not to get your blood (or semen or vaginal secretions) in someone else’s body, or to share needles or injection equipment” or “Abstaining from sex or using condoms every time you have sex are ways to protect yourself and other people”. (If there is anyone who may inject drugs, vitamins, or traditional medicines in your target audience, risk-reduction messages about injection should be included, too.) • Provide information on relevant preventive health measures. ° Say, “There are many things you can do to take care of yourself, which may have a big effect on your future health. Can we talk about how healthy people stay healthy?” or “Eating right, exercising, and taking medications are 3 important ways that people with HIV keep themselves healthy”. • Assess the risk of violence. ° Say, “What do you think people will say when you tell them your status?” or “If you have a partner, how do you think your partner will respond if you tell him (or her) that you are HIV-positive?” • Arrange appointments for follow-up services (e.g. counselling, family planning, STI treatment). ° Say, “I’d like to schedule an appointment for you to come back and see the nurse this week. She will do some tests and decide the best things we can do now to keep you well” or “Since you may become pregnant, and that could mean a risk that your baby would have HIV, I’d like to schedule an appointment for you to talk to our family planning nurse about contraception. For now, it is a good idea for you to ﬁnd a protection method to use every time you have sex such as condoms”. • Encourage referral for testing of children and partners ° Say, “Because HIV can be passed from a mother with HIV to her children during pregnancy or breastfeeding, we recommend testing your children as soon as possible. I’d like us to make a plan to test them.” or “It is very important that your partner be tested. Your partner may be infected and will need care, or, if negative, we can help your partner stay that way”.

9.2 Re-testing and repeat testing2 Re-testing Re-testing refers to a situation where additional testing is performed for an individual for speciﬁc reasons after a deﬁned period of time. Reasons include a speciﬁc incident of possible HIV exposure within the past 3 months or ongoing risk of HIV exposure, such as sharing injecting equipment. Re-testing is always performed on a new specimen and may or may not use the same assays (tests) as at the initial test visit.

2 Delivering HIV test results and messages for re-testing and counselling in adults. WHO, 2010. Available at http:// www.who.int/hiv/pub/vct/hiv_re_testing/en/index.html

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Re-testing and repeat testing

Early detection of HIV enhances referral to care, treatment, and prevention for people newly identiﬁed as HIV-positive. The meaning of repeat testing and of the test results needs to be carefully explained to patients (see box below). At the time of the initial test encounter, most individuals will not receive a recommendation to validate an HIV-negative result. The majority of people who test HIV-negative on their ﬁrst test are truly negative, and do not require another test. Avoid unnecessary re-testing for patients who have been previously tested and have learned their results. This wastes resources, causes confusion about the accuracy of HIV antibody tests, and takes time away from provision of focused post-test HIV prevention counselling that discusses risk-reduction strategies for an individual (or couple).

Repeat testing Repeat testing refers to a situation where additional testing is performed for an individual immediately following a ﬁrst test, during the same testing visit. This can be due to inconclusive or discordant test results. The same assays are used and, where possible, the same specimen. Re-testing is not recommended for people who test HIV-negative and who: • do not have a known ongoing risk for HIV infection, i.e. they are not current injecting drug users (IDU), sex workers, or men who have sex with men (MSM); • are not at high risk or do not have a known HIV-positive partner; • do not have clinical indications for testing, such as a new STI; • cannot identify any speciﬁc incident of HIV exposure in the last 3 months prior to HIV testing (i.e. no occupational exposure, no unprotected sex with a known HIV-positive person, or no sharing of injecting equipment with a known HIV-positive person). Re-testing is recommended for: • A person who has discordant test results (when one HIV test result in an individual is reactive and another test result using a different HIV assay in the same individual is non-reactive).2 • People who have tested HIV-negative but may be in the early stages of HIV infection. On average, HIV antibody tests are not able to identify people who have acquired HIV in the past 4 weeks, as the person may still have insufﬁcient antibodies (window period). Therefore, a person may be recently infected with HIV, known as acute HIV infection, and receive a false negative test result, Often, however, errors by the tester are often the cause of a false negative or a discordant test result. • Pregnant women in generalized epidemics who test HIV-negative in the 1st or 2nd trimester. To prevent motherto-child HIV transmission, pregnant women should be tested as early as possible in pregnancy and again later in pregnancy. If a woman does not return for re-testing in her 3rd trimester, testing is recommended during labour, or, if that is not possible, immediately after delivery. • People who have ongoing risks of acquiring HIV, including current IDU, MSM, sex workers and their clients, persons with a known HIV-positive partner, and people with a partner of unknown HIV status. These individuals should be tested for HIV and provided with population-appropriate risk reduction counselling at least annually. • Patients seen for STIs or outpatients with clinical conditions suggestive of HIV infection who test HIVnegative within the context of a generalized epidemic. These individuals should receive a repeat test after 4 weeks. STI patients can also beneﬁt from future testing with each new STI diagnosis. • Individuals with speciﬁc incidents of HIV exposure within the last 3 months (i.e. occupational exposure, sex with a known HIV-positive person, rape, sharing of injection equipment with a known HIV-positive person), When individuals test HIV-negative at the initial HIV test, a repeat HIV test in 6 weeks Is warranted to ensure they are truly HIV-negative.

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9.2.1 Re-testing for HIV-negative individuals in the context of a generalized epidemic In generalized epidemics it is essential to bring people back for re-testing after an initial negative test. Explain this during post-test counselling and arrange a speciﬁc date for the patient to come back. The table below shows which people should return, and when, for re-testing to conﬁrm their HIV-negative status in different settings. Often, return rates for individuals who need a re-test are low, and active follow-up is needed. Table: Re-testing for HIV-negative individuals in the context of a generalized epidemic (HIV prevalence >1%) Setting Antenatal clinic Re-testing recommended? Yes When to re-test? 3rd trimester, preferably between 28 and 36 weeks of pregnancy _ Future re-testing recommended? Yes – with each new pregnancy No, unless new potential exposure or if individual is in a high-risk category* Yes – with each new STI or if individual is in a high-risk category* No – unless new potential exposure or individual is in a high-risk category* No – unless new potential exposure or individual is in a high-risk category* If still discordant, retest in 2 weeks. If still discordant, the patient should be referred, or a specimen sent, to a higher level facility. Annually – if sexual relationship is ongoing

TB clinic

STI clinic

Yes

4 weeks

Inpatient ward

Outpatient clinic

With clinical indication of HIV infection†

4 weeks

HIV test results are discordant, leading to an indeterminate HIV status

Yes

Repeat the test immediately, using the same specimen and testing algorithm.

Partner status unknown

Yes (new individuals only)

4 weeks if initial test result is discordant 6 weeks if initial test result is negative 4 weeks if initial test result is discordant 6 weeks if initial test result is negative 4 weeks if initial test result is discordant 6 weeks if initial test result is negative

Known HIV-positive partner

Yes (new individuals only)

Annually – if sexual relationship is ongoing

Sex worker, male or female*

Yes (new individuals only)

At least annually

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Re-testing and repeat testing

Setting Current injecting drug user*

Re-testing recommended? Yes (new individuals only)

Future re-testing recommended? At least annually

Men who have sex with men*

Yes (new individuals only)

At least annually

Post-rape

Yes, if baseline HIV test was negative or if ﬁrst HIV test following the encounter was negative or status was indeterminate; see WHO/ ILO PEP guidelines1 Yes, if baseline HIV test was negative or if ﬁrst HIV test following the encounter was negative or status was indeterminate; see WHO/ ILO PEP guidelines3 No No

Occupational injury

4 and 12 weeks

Negative HIV test in past 3 months No possible HIV exposure in past 3 months

_ _

No No

* Denotes high-risk category (i.e. current injecting drug users, sex workers and clients of sex workers, men who have sex with men) † Depends on HIV prevalence in the clinic setting, individual’s presenting complaint, and individual’s risk factors; to be determined by country HTC policies or programme manager

3 Post-exposure prophylaxis to prevent HIV infection: joint WHO/ILO guidelines on post-exposure prophylaxis (PEP) to prevent HIV infection. WHO, 2007. Available at http://www.who.int/hiv/pub/guidelines/PEP/ en/

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9.2.2 Re-testing for HIV-negative individuals in low-level or concentrated epidemics In the context of a low-level epidemic (prevalence <1%), patients will not require re-testing if their risk of exposure has been low, whereas for higher risk exposures, re-testing will be required. Details are presented in the table below. Table: Re-testing for HIV-negative patients in low-level or concentrated epidemics (HIV prevalence rates <1%) Setting Antenatal clinic Re-testing recommended? No When to re-test? – Future re-testing recommended? Yes – with each new pregnancy or if individual is in a high-risk category* No – unless new potential exposure or individual is in a high-risk category* Yes – with each new STI or if individual is in a high-risk category* No – unless new potential exposure or individual is in a high-risk category* No – unless individual is in a high-risk category* If still discordant, re-test in 2 weeks.

TB clinic

–

STI clinic

Yes

–

Inpatient ward

–

Outpatient clinic HIV test results are discordant, leading to an indeterminate HIV status Partner status unknown; low-risk partner Partner status unknown; high-risk partner*

No Yes

– Repeat the test immediately using the same specimen and testing algorithm. – 4 weeks if initial test result is discordant 6 weeks if initial test result is negative 4 weeks if initial test result is discordant 6 weeks if initial test result is negative

No Yes (new patients only)

No Annually – if sexual relationship is ongoing

Known HIV-positive partner*

Yes (new patients only)

Annually – if sexual relationship is ongoing

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Re-testing and repeat testing

Setting Sex worker, male or female*

Re-testing recommended? Yes (new patients only)

When to re-test? 4 weeks if initial test result is discordant 6 weeks if initial test result is negative 4 weeks if initial test result is discordant 6 weeks if initial test result is negative 4 weeks if initial test result is discordant 6 weeks if initial test result is negative 4 and 12 weeks 4 and 12 weeks – –

Future re-testing recommended? At least annually

Current injecting drug user*

Yes (new patients only)

At least annually

Men who have sex with men*

Yes (new patients only)

At least annually

Post-sexual violence or rape Occupational injury Negative HIV test in past 3 months No possible HIV exposure in past 3 months * Denotes high-risk category.

No No No No

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9.2.3 Explain to patients the meaning of discordant or HIV-negative test results Post-test services include appropriate prevention messages and supportive counselling and referrals to prevention, care, treatment, and support services. People with acute HIV infection should be counselled especially carefully, as HIV is transmitted much more efﬁciently during the acute HIV stage than during later stages of HIV infection. Setting A person with NO speciﬁc incident of HIV exposure in the last 3 months, and no ongoing HIV risk behaviours An individual with discordant HIV rapid test results Re-testing recommended? Your HIV test result is negative. This means that you do not have HIV infection.

Upon the ﬁrst discordant results: Your test results are discordant. This means that one test had a positive result and another test had a negative result. This is rare, but it does happen sometimes. I would like to repeat these same tests again right now to clarify the results. If the results are still discordant after immediate repeat testing: Your test results are still discordant. Therefore, I cannot determine your HIV status at this time. Sometimes people with very recent HIV infections have uncertain test results like these. I would like for you to come back in 4 weeks so that you can be tested again. If you are in the early stages of HIV infection, you could infect other people very easily. Therefore, please take extra precautions during these 4 weeks—do not have sex or, if you do, use condoms every time; do not share needles.

A pregnant woman in 1st or 2nd trimester of pregnancy in a generalized epidemic

Your HIV test result is negative. This means that you do not have HIV infection. I would like you to bring your partner in for HIV testing so that we can be sure you and your baby are not at risk of HIV infection before delivery. If you do become infected while you are pregnant, there is a chance that your baby could also have HIV. However, if you test positive before your 36th week of pregnancy, there may still be time to give you medication to reduce the risk of HIV transmission to your baby before you give birth. Therefore, I would like you to come back for another HIV test between your 28th and 36th weeks of pregnancy. If you are not able to come back then, we can test you at the time of labour. If you test positive at that time, there are some measures that can be taken to reduce transmission to your baby during delivery. Your HIV test result is negative. This means that you do not have HIV infection. I would like you to bring your partner in for HIV testing so that we can be sure you are not at risk of HIV infection. Also, it sounds like you have been engaging in behaviour that could put you at risk for becoming infected with HIV in the future. [Name the behaviour(s).]. If you continue with this behaviour, I recommend that you get a HIV test at least once each year. This will give you the opportunity to learn your HIV status and, if the test result remains negative, to discuss strategies to help you stay HIV-negative. Your HIV test result is negative. This means that you do not have HIV infection. However, these HIV tests are not able to detect a HIV infection that happened very recently. Based on your speciﬁc incident of HIV exposure, it is recommended that you come back in 6 weeks for another test to conﬁrm your HIV status. If you are in the early stages of HIV infection, you could infect other people very easily. Therefore, take extra precautions during these 6 weeks—do not have sex or, if you do, use condoms every time; do not share needles.

An individual with continuous or ongoing risk behaviours

An individual with a speciﬁc incident of HIV exposure in the last 3 months (i.e. rape, occupational exposure)

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CD4 testing

9.3 CD4 testing Patients with a positive HIV test require a CD4 cell count and clinical staging (see Section 13 Chronic HIV care, ART and prevention). Table: CD4 cell counts and correlated infections and non-infectious complications, with reference to Sections of this manual for differential diagnosis and clinical management4 CD4 cell count* >500/mm 3

Infectious complications Acute retroviral syndrome – see Section 10.1 Candida vaginitis – see sections 10.15 and 11

Non-infectious† complications Persistent generalized lymphadenopathy – see Section 10.4 Guillain-Barré syndrome – see Section 10.10a Myopathy Aseptic meningitis – see Section 10.10b Cervical and anal dysplasia – see Section 10.15 Cervical and anal cancer – see Section 10.15 B-cell lymphoma Anaemia – see Section 10.18 Mononeuronal multiplex – see Section 10.10a Idiopathic thrombocytopenic purpura – see Section 10.19 Hodgkin’s lymphoma Lymphocytic interstitial pneumonitis – see Section 10.6 Wasting – see Section 10.3 Peripheral neuropathy – see Section 10.10a HIV-associated dementia − see Section 3.4 Cardiomyopathy Vacuolar myelopathy Progressive polyradiculopathy – see Section 10.10a Non-Hodgkin’s lymphoma

200–500/mm3

Pneumococcal and other bacterial pneumonia Pulmonary tuberculosis – see Section 15 Herpes zoster – see Sections 10.2 and 11.25 Oropharyngeal candidiasis (thrush) Cryptosporidiosis, self-limited Kaposi sarcoma – see Section 11.19 Oral hairy leukoplakia – see Section 10.17

<200/mm3

P. jiroveci pneumonia (pneumocystis pneumonia‡) – see Section 10.6 Disseminated histoplasmosis and coccidioidomycosis Miliary or extrapulmonary TB – see Section 15 Progressive multifocal leukoencephalopathy (PML) Disseminated herpes simplex – see Section 10.2 Toxoplasmosis – see Section 10.10 Cryptosporidiosis, chronic Microsporidiosis Candida oesophagitis – see Section 11.4 Disseminated cytomegalovirus (CMV) − see Section 11.8 Disseminated Mycobacterium avium complex − see Section 11.27

<100/mm3

<50/mm3

Primary central nervous system lymphoma

- Most complications occur with increasing frequency at lower CD4 cell counts. † Some conditions listed as non-infectious are associated with transmissible microbes. Examples include lymphoma (Epstein-Barr virus [EBV]) and anal and cervical cancers (human papillomavirus [HPV]). ‡ The preferred name is now P. jiroveci pneumonia; PCP is the accepted abbreviation.

4 Table modiﬁed from John Bartlett, who derived it from Arch Intern Med 1995; 55:1537; permission obtained.

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10. Acute and subacute by symptom Table of contents 10.1 Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1.2 Consider likely differential diagnosis using the DDx tables . . . . . . . . 10.1.3 Initiate treatment(s), monitor response, and reconsider diagnosis . . . 10.1.4 Management of severely ill patient with fever . . . . . . . . . . . . . . . 10.1.5 Management of fever as an outpatient (not severely ill) . . . . . . . . . Skin disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.2 Skin and soft tissue infections . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.3 Papular lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.4 Vesicular or bullous lesions . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.5 Nodular lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.6 Maculopapular rash . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.7 Plaques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.8 Pruritus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.9 Urticaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.10 Skin ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Weight loss and malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3.2 Consider the likely cause of loss of weight . . . . . . . . . . . . . . . . . 10.3.3 Treat weight loss and malnutrition and its underlying causes . . . . . . 10.3.4 Prevent malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Swelling of the limbs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.2 Differential diagnosis of oedema . . . . . . . . . . . . . . . . . . . . . . . 10.4.3 Treatment of limb swelling . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.4 Symptom management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4.5 Manage lymphoedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lymphadenopathy and lumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5.2 Classify the lymphadenopathy and consider the differential diagnosis 10.5.3 Approach to lymphadenopathy in PLHIV. . . . . . . . . . . . . . . . . . . 10.5.4 Symptom management of lymphadenopathy . . . . . . . . . . . . . . . . Chest symptoms: cough and shortness of breath . . . . . . . . . . . . . . . . . . . 10.6.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6.2 Differential diagnosis of chest complaints . . . . . . . . . . . . . . . . . 10.6.3 Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6.4 Asthma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6.5 Chronic obstructive pulmonary disease (COPD) . . . . . . . . . . . . . . Abdominal complaints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abdominal pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a.2 Differential diagnosis of abdominal pain and management of speciﬁc conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7a.3 Approach to abdominal pain in PLHIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10.2

10.3

10.4

10.5

10.6

10.7 10.7a

19 19 22 27 28 29 30 31 34 38 48 49 52 53 57 60 61 69 70 75 78 81 84 85 86 88 89 89 90 90 92 95 96 97 97 102 111 115 118 123 123 123 126 134

. . . .

10.7b

Painful or difﬁculty swallowing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7b.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7b.2 Differential diagnosis and treatment of painful or difﬁcult swallowing . 10.7b.3 Approach to oesophagitis in PLHIV . . . . . . . . . . . . . . . . . . . . . . 10.7c Nausea and vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7c.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7c.2 Differential diagnosis and treatment of nausea or vomiting . . . . . . . 10.7c.3 Symptom management for nausea or vomiting . . . . . . . . . . . . . . . 10.7d Diarrhoea (and constipation). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7d.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7d.2 Classify and manage diarrhoea . . . . . . . . . . . . . . . . . . . . . . . . 10.7d.3 Approach to persistent or chronic diarrhoea in PLHIV . . . . . . . . . . 10.7d.4 Constipation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.8 Jaundice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.8.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.9 Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.9.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.9.2 Classify ascites and consider the likely differential diagnosis . . . . . . 10.9.3 Manage ascites according to cause . . . . . . . . . . . . . . . . . . . . . 10.10 Neurological problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a Neurological deﬁcit (without meningeal signs) . . . . . . . . . . . . . . . . . . . . . 10.10a.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.2 Classify the neurological deﬁcit and consider the likely differential diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.3 Stroke-like syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.4 Spinal cord problem (myelopathy) . . . . . . . . . . . . . . . . . . . . . . 10.10a.5 Peripheral motor or sensory nervous system problem . . . . . . . . . . 10.10a.6 Peripheral neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10a.7 Common cranial nerve palsies and their differentials . . . . . . . . . . 10.10b Headaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10b.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10b.2 Consider the likely differential diagnosis . . . . . . . . . . . . . . . . . . 10.10b.3 Treatment of speciﬁc conditions . . . . . . . . . . . . . . . . . . . . . . . 10.10b.4 Symptom management of headache . . . . . . . . . . . . . . . . . . . . . 10.10c Neurological problems: seizures (without meningism or fever) . . . . . . . . . . . 10.10c.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10c.2 Consider the likely differential diagnosis . . . . . . . . . . . . . . . . . . 10.11 Approach to patients with mental health problems . . . . . . . . . . . . . . . . . . 10.11.1 Clinical approach to mental health problems . . . . . . . . . . . . . . . . 10.11.2 Suicide and deliberate self-harm assessment and management . . . . 10.11.3 Abnormal behaviour or thinking . . . . . . . . . . . . . . . . . . . . . . . . 10.11.4 Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.11.5 Bipolar disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.11.6 Sad or low mood including depression . . . . . . . . . . . . . . . . . . . 10.11.7 Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12 Eye problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.2 Approach to red eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.3 Acute visual loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.4 Progressive visual loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.5 Geographically conﬁned eye diseases – onchocerciasis and trachoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12.6 Eye problems in patients with HIV infection . . . . . . . . . . . . . . . . . 10.12.7 Neuro-ophthalmic involvement from mass lesions, TB, or cryptococcal meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

136 136 137 138 140 140 141 145 146 146 148 156 158 159 160 166 166 169 171 174 175 175 177 178 181 182 185 187 188 189 193 199 202 203 203 204 209 210 215 219 227 231 235 244 254 254 259 265 266 268 269 271

. . . . . .

10.13

10.14

10.15

10.16

10.17

10.18

10.19

10.20

Painful joints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.13.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.13.2 Diagnosis of single and multiple painful joints . . . . . . . . . . . . 10.13.3 Symptom management . . . . . . . . . . . . . . . . . . . . . . . . . . Female and male anorectal problems and genital ulcers . . . . . . . . . . . 10.14.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.14.2 Anorectal problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.14.3 Genital ulcer disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.14.4 Special considerations in patients with HIV. . . . . . . . . . . . . . 10.14.5 Symptom management: rectal tenderness . . . . . . . . . . . . . . Female genitourinary complaints . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.2 Abnormal vaginal bleeding or amenorrhoea, or lower abdominal or pelvic pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.3 Pelvic mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.4 Abnormal vaginal discharge not responding to syndromic management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.5 Pelvic inﬂammatory disease . . . . . . . . . . . . . . . . . . . . . . . 10.15.6 Septic abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.7 Approach to urinary incontinence . . . . . . . . . . . . . . . . . . . 10.15.8 Cervical cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.15.9 Schistosomiasis of the female genitourinary tract . . . . . . . . . . Male genitourinary complaints . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.2 Genital growths in men . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.3 Dysuria and penile discharge . . . . . . . . . . . . . . . . . . . . . . 10.16.4 Testicular and scrotal problems . . . . . . . . . . . . . . . . . . . . . 10.16.5 Foreskin problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.6 Prostate problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.16.7 Schistosomiasis of the male genitourinary tract . . . . . . . . . . . Disorders of the mouth and throat . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.2 HIV and the mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.3 Soft tissue lesions of the mouth . . . . . . . . . . . . . . . . . . . . . 10.17.4 Oral cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.5 Conditions related to the hard tissue of the mouth . . . . . . . . . . 10.17.6 Gum disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.7 Noma disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.8 Dry mouth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.17.9 Pharyngitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pallor and anaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.18.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.18.2 Classiﬁcation of anaemia . . . . . . . . . . . . . . . . . . . . . . . . . 10.18.3 Management of anaemia . . . . . . . . . . . . . . . . . . . . . . . . . Abnormal bleeding and bruising . . . . . . . . . . . . . . . . . . . . . . . . . . 10.19.1 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.19.2 Diagnostic approach to active bleeding . . . . . . . . . . . . . . . . 10.19.3 Diagnostic approach to low platelets with no active bleeding . . . 10.19.4 Speciﬁc bleeding conditions in detail . . . . . . . . . . . . . . . . . Splenomegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.20 Clinical approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.21 Use the DDx table to establish a likely differential diagnosis . . . 10.22 Management of splenomegaly . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .

272 272 274 280 281 281 282 285 289 290 291 292 295 302 305 309 312 313 317 321 322 323 325 325 327 328 330 332 333 334 336 336 343 343 345 346 346 347 350 350 354 356 361 361 366 368 370 374 374 374 376

10. Acute and subacute by symptom 10.1 Fever In this section: 10.1.1 Clinical approach to a patient with fever 10.1.2 Consider likely differential diagnosis using the DDx tables • DDx: Fever 7 days or less without clinically obvious focus or site • DDx: Fever more than 7 days without clinically obvious focus or site 10.1.3 Initiate treatment(s), monitor response, and reconsider diagnosis • Systematic approach to reassessment and empirical treatment if unclear diagnosis 10.1.4 Management of severely ill patient with fever • Management of hyperthermia • Symptomatic management of fever in hospitalized patients 10.1.5 Management of fever as an outpatient (not severely ill)

Fever refers to a recent history of fever or an elevated body temperature of more than 38oC if measured centrally (ear, rectal, or oral) or 37.5oC axillary. The most common cause is an infection which may be localized or systemic; other causes include malignancy, allergic reaction, and inﬂammatory disorders. This section deals with fever without focal signs. For fever with focal signs, please see the appropriate section.

10.1.1 Clinical approach to a patient with fever Step 1: Perform Quick Check ° Use the Quick Check and ensure that there are no serious or life-threatening conditions. Be aware that patients with severe febrile illness may require active ﬂuid management and require empirical antibiotics for possible life-threatening sepsis and antimalarials for possible severe malaria (in malaria endemic areas). Step 2: Take a history and examine the patient. Look for signs and symptoms that may point to a focus of infection, e.g. cough, painful ear, pain on urination. Consult the speciﬁc Section. Step 3: Assess HIV status Step 4: Consider likely differential diagnosis using the DDx table(s). • If there is no obvious focus of infection, classify the fever: ° fever 7 days or less ° fever more than 7 days. • If hyperthermia (temperature >40.5oC), see DDx and treat. • If speciﬁc focus of infection, see appropriate Section. Step 5: Perform investigations. Step 6: Initiate treatment, monitor the response, and reconsider the diagnosis. • If the cause of the fever is found, go to the relevant Sections for management. • If the diagnosis is still unclear, follow a systematic approach to reassessment and empirical treatment.

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Fever

History Ask the patient for symptoms of infection, and then use the relevant Sections of this manual to further manage the patient, e.g.: • headache, neck stiffness, photophobia (Section 10.10b Headache) • cough, shortness of breath, chest pain (Section 10.6 Cough) • skin lesion (Section 10.2 Skin disorders) • abdominal pain (Section 10.7a Abdominal pain) Important features of the history include: • duration of fever (less than or more than 7 days) • exposure to locally endemic diseases ° consider the local geographical distribution of diseases ° consider outbreaks of speciﬁc infections ° consider seasonal variation of diseases • recent exposure history ° ask about recent travel – consider diseases that are common in the area that was visited ° contact with animals and birds ° known TB contact ° recent unprotected sex ° intravenous drug use • co-morbidities ° consider infections that a patient may be predisposed to as a result of comorbidities such as diabetes, HIV, sickle-cell anaemia; ° medical history of recent illness and the possibility of incompletely treated disease or drug resistance, e.g. malaria, typhoid, TB; ° current medications; ° consider drug reactions if the patient has recently initiated a new medication known to commonly cause drug reactions, e.g. cotrimoxazole, ART (especially nevirapine or abacavir), TB medication.

Examination Examine the patient thoroughly paying attention to sites of possible infection: • general examination ° monitor temperature (might be normal at that particular moment) ° assess for confusion or decreased level of consciousness ° assess hydration, count heart rate and respiratory rate ° look for pallor, jaundice, lymphadenopathy, nail abnormalities (splinter haemorrhages) ° skin lesions, including rash ° insect or animal bites ° nutritional status (wasting) • head and neck ° neck pain or stiffness ° throat, tonsils, ears for inﬂammation and discharge ° sinus tenderness ° mouth (Koplik’s spots, ulcers or lesions)

Fever

Vol. 2 • 10. Acute and subacute by symptom: July 2011

• chest ° difﬁcult breathing, fast breathing ° crackles, bronchial breathing, absent breath sounds ° new heart murmur, change in old murmur • abdominal or genitourinary: ° enlarged liver or spleen ° abdominal tenderness or mass ° pain over kidneys (ﬂank pain) ° pelvic tenderness or mass ° rectal and vaginal examination for pain, discharge, ulcers, mass • muscles and joints ° red, hot, swollen, painful joint(s) with reduced mobility ° swollen, painful limb (deep venous thrombosis, cellulitis).

If evidence of focal infection, use the appropriate Section of the manual. If no evidence of focal infection is found, use this Section to assess the patient. Perform investigations In all patients consider: • malaria test (RDT or microscopy), if living in1 or travelled to an endemic area • urine dipstick. Additional tests, as indicated (see DDx tables in next Section): • full blood count with differential white cell count • blood smear for louse-borne relapsing fever (Borrellia recurrentis), in endemic areas • liver function tests • chest X-ray • sputum for microscopy, acid fast bacilli, and sometimes culture • other urine tests – if positive ﬁndings on dipstick: microscopy, culture • lumbar puncture • bone marrow, lymph node, or splenic aspirate for microscopy • serum or whole blood for rapid test • stool microscopy and culture • ultrasound • blood cultures.

1 In low malaria endemic areas, follow the national guidelines and test only patients fulﬁlling the deﬁnition of a suspected malaria case (e.g. fever plus no other obvious cause of fever).

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Fever

10.1.2 Consider likely differential diagnosis using the DDx tables Classify the fever according to its duration and symptoms or signs found on examination and laboratory investigations: • fever with obvious focus of infection – see relevant Sections in the manual • fever 7 days or less without clinically obvious focus (use the ﬁrst DDx table below) • fever more than 7 days (use the second DDx table below) • hyperthermia – temperature >40.5°C (also use third DDx table below) For the severely ill patient – see Section 3 Approach to the severely ill patient.

DDx: Fever 7 days or less without clinically obvious focus or site Condition Bacteraemic sepsis see Section 3.1.5 In favour Seriously ill with no obvious apparent cause Hypotension Full blood count (FBC) – leucocytosis, leucopoenia, or thrombocytopaenia Risk factors – HIV , injecting drug use, immunocompromised Blood cultures – positive Any sign of organ dysfunction – confusion, low urine output, respiratory depression Chemistries if available – acidosis, elevated creatinine Maculopapular haemorrhagic petechial rash Shock, hypotension Living in, or travelled to an endemic area Positive malaria test (RDT or microscopy) Absence of other obvious cause of fever Headache Constipation or diarrhoea Abdominal pain and tenesmus Hepato or splenomegaly “Rose spots” pink macules on abdomen Headache, stupor (or other central neurological sign) Eschar Rash (sometimes petechial) Exposure to ticks, known area of endemicity History of travel to endemic area or local outbreak Positive dengue RDT for NS1 or IgM Headache, pain behind the eyes Backache, arthralgia, myalgia Fine macular rash, petechiae FBC – leukopenia, thrombocytopenia In severe cases: • signs of plasma leakage, shock • severe bleeding, e.g. from GI or oriﬁces, dark urine • organ failure

Meningococcal septicaemia see Section 3.1.5 Malaria see Section 11.25 Typhoid see Section 11.43

Rickettsial disease see Section 11.33

Dengue fever see Section 11.9

Fever

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Chikungunya

Resembles non-severe dengue fever Severe joint pains with fever and rash No simple test available to conﬁrm the diagnosis Sudden onset of fever and cough Sometimes rhinitis or sore throat Frequent systemic symptoms (headache, arthralgia, or myalgia) Local epidemics, or history of travel to epidemic areas Close contact with a person with a similar illness, or contact with person from epidemic area with inﬂuenza History of travel to endemic area or local outbreak Sudden onset of acute fever and rigors Headache, backache, bone pains Followed by jaundice within 2 weeks Lymphadenopathy Rash, pharyngitis History of unprotected sexual contact or unsafe injecting drug use in the last 3 months ART usually initiated 2–12 weeks previously Worsening of present condition or development of new signs and symptoms More likely if baseline CD4 <50 cells/mm3 New drug initiated days or weeks prior Associated rash Patient on drugs – ART (NVP, ABC, EFV) , cotrimoxazole, dapsone, B-lactams, INH, anticonvulsants Tachycardia Arthritis, rash – erythema marginatum Recent sore throat Transient dermatitis Cough, wheezing (pulmonary stage) Nausea, vomiting, diarrhoea, constipation Eosinophilia Septic shock, acute respiratory distress syndrome Small-bowel obstruction Conjunctivitis, coryza, and cough Koplik’s spots on buccal mucosa (“grains of salt on a red background”) Maculopapular, blanching rash Lymphadenopathy Complications include: • respiratory tract infection (pneumonia, tracheobronchitis, bronchiolitis) • encephalitis (acute and chronic) • keratitis

Inﬂuenza see Section 11.17

Yellow fever see Section 11.46

Primary HIV see Section 13

IRIS see Section 13 Drug-induced fever see Section 13

Rheumatic fever see Section 11.32 Acute strongyloidiasis see Section 11.36

Measles (in adolescents and young adults)

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Fever

Condition Relapsing fever (louseborne borreliosis – Borrellia recurrentis)

In favour Recurrent fever Spread from person-to-person among louse-infested populations (e.g. refugee camps, war, or famines with overcrowded populations with poor personal hygiene) Occurs in limited areas in Asia, east Africa and highlands of central Africa, and South America2 Rash, often petechial Jaundice, impaired liver function Spirochetes on Giemsa-stained thick or thin blood ﬁlm, or dark-ﬁeld preparation of blood, taken during a febrile period Good response to single dose tetracycline Jarisch-Herxheimer reaction (fever, rigors, hypotension within 2 hours of antibiotic administration) Exposure to fresh water in an endemic area (with sometimes skin itch just after exposure) Between 2 and 12 weeks after infection FBC – eosinophilia Exposure to fresh water, farming or contact with rodents or dogs Conjunctival suffusion Aseptic meningitis Jaundice, renal failure, haemorrhage (Weil’s disease) Exposure to aerosolized ﬂuid from birth products of farm animals (cows, goats, sheep); consumption of raw milk Flu-like illness, pneumonia, hepatitis in acute infection Lymphadenopathy Pharyngitis More common in adolescents than adults Persistent fatigue (up to 6 months) Splenomegaly FBC – >50% of WBC are lymphocytes Rash following antibiotic administration

Acute schistosomiasis (Katayama fever) see Section 11.34 Leptospirosis see Section 11.22

Acute Q fever

Mononucleosis

DDx: Fever more than 7 days without clinically obvious focus or site Condition Tuberculosis see Section 15 In favour Loss of weight, night sweats, fever, malaise Cough >2 weeks Signs of extrapulmonary disease – e.g. lymphadenopathy, pallor, abdominal pain Common complication of HIV See description in DDx table: Fever 7 days or less without clinically obvious focus or site See description in DDx table: Fever 7 days or less without clinically obvious focus or site Limb pain, often worse at night Local limb tenderness and swelling Risk factor may be present (IDU, sickle-cell disease) Contiguous skin infection or chronic ulcer X-ray showing periosteal reaction or bone destruction (after 2 to 4 weeks)

Typhoid see Section 11.43 Malaria see Section 11.25 Osteomyelitis

2 Heymann DL, ed. Control of communicable diseases manual, 19th ed. APHA and WHO, 2008.

Fever

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Endocarditis see Section 11.10

Low grade fever, night sweats New heart murmur (or change in old heart murmur) Signs of embolic disease (stroke, petechiae, splinter haemorrhage, abdominal pain) Signs of heart failure (difﬁculty breathing) Splenomegaly Risk factors: known cardiac valvular disease, IDU, previous rheumatic disease Right upper quadrant pain or tenderness Liver focal lesion at ultrasound Contact with farm animals (infected goats, pigs), consumption of raw milk Acute brucellosis: undulant fever Subacute localized brucellosis: lumbago due to spondylitis, mono or polyarthritis, osteomyelitis See description in DDx table: Fever 7 days or less without clinically obvious focus or site History of exposure to rodents or ﬂeas Unwell patient, sudden onset Rigors Extreme tiredness Large painful, tender lymph nodes-bubo (bubonic plague) Acute dyspnoea, pleuritic chest pain (pneumonic plague) Usually in advanced AIDS, but can rarely occur without HIV Meningo-encephalitis: headache, blindness Elevated intracranial pressure on LP, positive CSF India ink stain Pneumonia: cough, opacities on chest X-ray If available, positive serum or CSF cryptococcal antigen Usually in advanced AIDS, but can rarely occur without HIV Localized MAC: tuberculosis-like pneumonia, adenopathy, osteomyelitis Disseminated MAC: generalized lymphadenopathy, diarrhoea and abdominal pain AFB positive sputum, stool, or lymph node aspirate – conﬁrm on culture No response, or partial response to standard anti-tuberculous therapy Weight loss, night sweats Enlarged lymph nodes, hepatosplenomegaly Usually in advanced AIDS, but can occur without HIV Skin lesions Nodular or lobar opacities on chest X-ray Hepatosplenomegaly Endemic areas vary, depending on species Painful swallowing Diarrhoea Visual loss (CMV retinitis on fundoscopy) Complication of advanced AIDS Headache Focal neurological deﬁcit Complication of advanced AIDS

Liver abscess see Section 11.23 Brucellosis see Section 11.3

Yellow fever see Section 11.47 Plague see Sections 10.5 and 10.6

Cryptococcosis see Section 11.5

Mycobacterium avium complex (MAC) see Section 11.27 Lymphoma Deep fungal infections (histoplasmosis, penicilliosis, coccidiomycosis, paracoccidiomycosis) see Sections 11.16, 11.29 Cytomegalovirus (CMV) see Section 11.8 Toxoplasmosis see Section 11.40

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Fever

Condition African human trypanosomiasis (sleeping sickness) see Section 11.41

In favour Endemic areas in Africa May occur in patients without HIV Intermittent fever, headache Generalized lymphadenopathy, particularly in posterior cervical triangle Disturbed sleep Poor concentration and personality changes Endemic areas in Latin America Fever lasting for several weeks Swelling of both lids of one eye (Romaña sign), painful nodules (chagoma) Skin rash, localized enlarged lymph nodes Endemic area Fever, wasting syndrome, pallor of mucous membranes Generalized lymphadenopathy Splenomegaly, darkening of skin

Acute Chagas disease (American trypanosomiasis) see Section 11.42 Visceral leishmaniasis (Kala azar) see Section 11.20

DDx: Hyperthermia (temperature >40.5°C) Heat stroke Exposure to excess amount of sun Central nervous system dysfunction (e.g. anxiety, delirium, seizure, coma) Warm, red skin without sweating Signs of end organ damage: hypotension; hypoglycemia; elevated liver or kidney enzymes; disseminated intravascular coagulation (DIC) Haemorrhage (involving the pons) Stroke (involving the hypothalamus) Status epilepticus Tumor Toxicity from SSRIs, MAOI, anticholinergics (e.g. diphenhydramine, promethazine, amitriptyline, atropine), ﬂuoxetine or other SSRI – see Section 3.8 Withdrawal from alcohol (delirium tremens) – see Section 3.7 Malignant hyperthermia in response to halothane Neuroleptic malignant syndrome Thyrotoxicosis Adrenal crisis Pheochromocytoma Sepsis Brain abscess Meningitis Typhoid fever Malaria Relapsing fever

Intracranial injury

Drug effects

Endocrine conditions

Infectious causes

Fever

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10.1.3 Initiate treatment(s), monitor response, and reconsider diagnosis If the cause of fever is found, go to the relevant manual Section for management.

Relapsing fever (louse-borne borreliosis – Borrellia recurrentis) Treatment • Antibiotics, single dose orally: ° doxycycline 100 mg; OR ° erythromycin 500 mg; OR ° tetracycline 500 mg; OR ° If not able to take oral, procaine penicillin 600 000 to 800 000 IU IM once. Prevent transmission2 • Patients, clothing, contacts,and immediate environment must be deloused. Dust or spray patient, contacts, and their clothing with 1% permethrin. • Give antibiotic prophylaxis with single dose tetracyclines after exposure when risk of acquiring infection is high. • Use blood and body ﬂuid precautions.

Systematic approach to reassessment and empirical treatment if unclear diagnosis • Does the patient have an HIV-related condition (undiagnosed OI)? If the patient is HIV-infected, consider the following: ° TB is the most common cause of fever without localizing signs. ° Other opportunistic infections, particularly MAC, cryptococcal infection, and CMV may not present with focal signs and symptoms. ° If ART has recently been initiated (less than 6 months), the patient may have immune reconstitution inﬂammatory syndrome (IRIS) – see Section 13 Chronic HIV care. • Have malaria and tuberculosis been excluded? ° Consider multi-drug resistant (MDR)TB. ° Treat with antimalarials if RDT or blood smear positive (or if in endemic area and testing is not available). • Has anything been missed? Some often-missed sites that may cause fever include: ° dental abscesses ° sinusitis – percuss face and forehead ° endocarditis – ausculate for murmur, if possible perform blood cultures ° urinary tract infection ° prostatitis and pelvic inﬂammatory disease ° intra-abdominal, retroperitoneal, or paraspinal abscess ° cholangitis, liver abscess ° deep venous thrombosis – examine for lower limb swelling ° malignancy – check for breast lumps, cervical nodes, splenomegaly, hepatomegaly, prostate abnormalities ° connective tissue diseases (e.g. lupus, rheumatoid arthritis, small oral aperture, thickening of skin especially on face) ° fever due to medications ° pus that cannot drain (after trauma)

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• Has any new symptom or sign developed since presentation? Repeated, thorough examinations may be necessary – full body, roll over, look between the toes and behind the ears. • Consider nosocomial infections, such as urinary tract infection from a catheter or bedsore with infection. • Repeat important laboratory tests. Consider the possibility of an initial false negative result, especially if the clinical picture does not correlate with the laboratory result. • Treat according to the most likely clinical diagnosis based on symptoms and signs.

10.1.4 Management of the severely ill patient with fever Treat according to suspected causes, based on clinical examination and other Sections of the manual. If the febrile patient has a suspected infection with hypotension (systolic blood pressure <90), treat patient for septic shock (see Section 3.1.5 Manage septic shock).

Management of hyperthermia If the patient has hyperthermia (temperature >40.5°C) after long periods of sun exposure or other causes treat patient for hyperthermia: • Use Quick Check. • Assess volume status and hydrate appropriately. • Perform rapid cooling. ° Spray naked patient with a mist of lukewarm water while a fan or cool breeze is used to blow air over the moist skin (“evaporative cooling”). ° Give IV diazepam (5 mg IV) to suppress shivering induced by cooling. ° Give an antipyretic for infectious causes. Do not use antipyretic agents for heat stroke, intracranial injury, or drug-induced hyperthermia. ° Continuously monitor core temperature with a rectal probe to monitor for response to cooling therapy. If a rectal probe is unavailable, frequently monitor oral temperature. ° Cooling therapy should be stopped once the temperature is 38 to 39°C to avoid excessively low body temperatures. • Treat complications ° hypotension (see Quick Check page 19, Vol. 1 then Section 3.1) ° seizures (see Quick Check page 21, Vol. 1 then Section 3.5) ° disseminated intravascular coagulation (see Section 10.19.3) ° hypoglycaemia (see Quick Check page 41, Vol. 1)

Symptomatic management of fever in hospitalized patients • Give antipyretics – paracetamol/aspirin/NSAIDS (except in dengue endemic areas, where aspirin/NSAID should not be used). • Fan the patient and wipe the body with lukewarm water (tepid sponge). • Hydration (oral or IV, if patient unable to drink ﬂuids).

Fever

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10.1.5 Management of fever as an outpatient (not severely ill) • Give paracetamol or aspirin every 4 hours (no more than 4 g of paracetamol in 24 hours). • Make sure the patient stays well hydrated. Encourage oral rehydration. • Home care: ° Encourage frequent intake of oral ﬂuids such as water, diluted tea, fruit juices. ° Wipe the body with a damp cloth (tepid sponge) or give a lukewarm bath. ° Encourage the patient to wear only light clothes. ° Give paracetamol, aspirin, or ibuprofen to reduce the fever. Important: advise the patient and family to seek help or to return to the health facility if: • The fever does not improve or comes back after treatment. • The fever is accompanied by a cough, diarrhoea, severe pain, confusion, night sweats, rigors, stiff neck or change in consciousness. • A woman has fever in pregnancy, after birth, or after abortion (spontaneous or not).

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10.2 Skin disorders In this section: 10.2.1 Clinical approach to a patient with a skin disorder 10.2.2 Skin and soft tissue infections (with DDx tables) • Impetigo • Management of skin and soft tissue infections • Abscesses, furuncles, carbuncles, cellulitis (with or without purulent drainage) • Erysipelas • Table: How to choose antibiotics for skin and soft tissue infections • Complicated skin and soft tissue infections (including necrotizing fasciitis) 10.2.3 Papular lesions (with DDx tables) • Syndromic management of itchy papular lesions in PLHIV • Chiggers • Molluscum contagiosum • Viral warts • Eosinophilic folliculitis • Pityrosporum folliculitis • Papular urticaria • Drug reactions • Scabies • Cutaneous tuberculosis • Cutaneous histoplasmosis • Cutaneous cryptococcosis • Acne 10.2.4 Vesicular or bullous lesions (with DDx table) 10.2.5 Nodular lesions (with DDx table) • Erythema nodosum • Yaws 10.2.6 Maculopapular rash (with DDx table) • Viral exanthems 10.2.7 Plaques (with DDx tables) • Eczema • Dermatophytosis (ringworm) • Pityriasis versicolor • Psoriasis 10.2.8 Pruritus (with DDx table) • Xeroderma • Pediculosis • Symptomatic management of itching 10.2.9 Urticaria 10.2.10 Skin ulcers (with DDx table) • Diabetic ulcers • Venous ulcers • Arterial ulcers • Buruli ulcer • Pressure sores (bed sores) • Tropical ulcers • Anthrax

This Section provides an approach to the diagnosis and management of common skin and soft tissue conditions. For anorectal and genital lesions, see Sections 10.14 to 10.16. Skin lesions may be due to primary skin conditions, or may be a sign of a multisystem disease. Most skin problems can be diagnosed based on clinical examination. If a patient is HIV-infected, skin problems are very common, but the clinical presentation may be atypical. When using skin ointments or creams, follow the instructions in Section 8.4. Avoid use of potent topical steroids on the face. 30 Skin Vol. 2 • 10. Acute and subacute by symptom: July 2011

10.2.1 Clinical approach to a patient with a skin disorder Step 1: Perform Quick Check Use the Quick Check and ensure that there are no serious or life-threatening conditions. Exclude sepsis, anaphylaxis or severe drug reactions, bleeding disorders, and snake-bites. Step 2: Take a history and examine the patient. Take a thorough history speciﬁc to the skin lesions and a general history. Perform a complete cutaneous and systemic examination. Step 3: Assess HIV status Step 4: Classify the skin problem and work through the DDx table(s): • red, tender, warm with pus or crusts • papular lesions • vesicular or bullous lesions • nodular lesions • maculopapular rash • plaques and patches • generalized itching • skin ulcers. Step 5: Perform investigations if required. Step 6: Initiate management and monitor the response.

History A good medical history is important in the evaluation of cutaneous disorders. Speciﬁc history • What is the duration of the skin problem? • What is the mode of onset and progression of symptoms? • Site on the body – extensor versus ﬂexor, skin creases, exposed areas? • What are the associated symptoms: pain, itching, bleeding, discharge? • Are there any triggering, relieving factors: ° seasonal ° exposure to sun ° foods, cosmetics, drugs ° insect bites? • Is there a past history of similar rashes or lesions? General history • Is there evidence of systemic disease: ° constitutional symptoms (fever, night sweats, malaise, lymphadenopathy) ° speciﬁc system involvement (CNS signs, cough, abdominal complaints)? • Is there a history suggestive of co-morbidities: ° HIV status, clinical stage, or CD4 count ° autoimmune conditions, diabetes, rheumatoid conditions, any infectious diseases? • Is there a past history of atopy, allergies, or any other skin disease? • Medications – review all prescribed medications (IV, oral, and topical) including traditional medications.

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• Substance use – injecting drug use? • Sexual history – high risk behaviour, signs or symptoms of STIs now or in the past? • Family history – skin disorders, arthritic conditions, allergic conditions? • Travel history – the patient travels to or lives in an area endemic for relevant infectious diseases?

Examination Perform a full general physical examination to look for signs of multisystem disease (particularly lymphadenopathy, hepatosplenomegaly, fever, CNS, and respiratory signs). Examine the lesions Characteristics: • type of lesion – macule, papule, maculopapule, vesicle, bulla, plaque, patch, nodule, or tumour; • size; • shape – ﬂat-topped, umbilicated, cuniform, rough or verrucous, annular, round, oval, linear, irregular; • number – single or multiple; • colour – hyperpigmented, hypopigmented, depigmented, erythematous, black, blue. Distribution (map anatomically, noting the pattern of distribution): • unilateral; • dermatome; • sun-exposed areas, dust-exposed areas, covered areas; • generalized, localized; • speciﬁc areas spared, e.g. palms and soles; • mucosa – oral, conjunctival, vaginal, penile; • skin appendages – hair, nails; • consistency – hard, irregular. Assess for involvement of: • hair, nail, mucous membranes; • lymphadenopathy; • joints.

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Deﬁnitions or descriptions of skin lesions according to characteristics Blister Vesicle Bullae Erythema Nodules Papule Macule Plaque Patch Pustule Scale Crust Ulcer Licheniﬁcation Excoriation A collection of ﬂuid underneath the top layer of skin (epidermis) A raised lesion of <1 cm that is ﬁlled with clear ﬂuid Bullae are circumscribed ﬂuid-ﬁlled lesions that are >1 cm in diameter Redness or inﬂammation of the skin or mucous membranes A raised solid lesion of >1 cm, and may be in the epidermis, dermis, or subcutaneous tissue A discrete, solid, elevated lesion usually <5 mm in diameter; further classiﬁed by shape, size, colour, and surface change A ﬂat, colour change of the skin with a size of <1 cm A solid, raised, ﬂat-topped lesion >1 cm A macule >1 cm in size; may be referred to as a patch A small elevated skin lesion containing pus Flakes or plates that represent compacted desquamated layers of the superﬁcial layer of the skin Dry small plates of plasma or exudates over the skin Discontinuation or break in the skin or mucosa Characterized by an increase in pigmentation, prominent skin markings and thickening of skin due to chronic scratching Traumatized or abraded skin caused by scratching and rubbing, usually superﬁcial and linear

Investigations The diagnosis of skin lesions usually is clinical, but if it is unclear or conﬁrmation is required, consider the following investigations (see Section 7). Skin scrapings – microscopy or culture: • with KOH (potassium hydroxide) – useful for identifying causative organisms which directly infest the skin, e.g. mite or mite parts in scabies; yeasts or fungal ﬁlaments in fungal diseases; molluscum bodies in molluscum contagiosum; • slit skin smears – with appropriate staining to identify AFB or microﬁlaria or Donovan bodies in leishmaniasis; • Tzanck smears – to identify viral giant cells. Skin biopsy: • histology – to identify dysplasia or malignancy; • microscopy or culture; • Gram stain of ﬂuid or pus and sometimes culture.

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10.2.2 Skin and soft tissue infections DDx: Skin lesions: red, tender, warm with or without pus or crusts Condition Impetigo (superﬁcial bacterial skin infections) In favour Initially a vesicle or blister that ruptures to form small, superﬁcial ulcers Honey-coloured crusts Little or no surrounding erythema Pruritic No lymphadenopathy Lesions extend deeper into the dermis Dry, black, tightly adherent crust common Heals with scarring Often occur on the legs of children Predisposing – pruritic lesions( insect bites, scabies, or pediculosis); poor hygiene; malnutrition Superﬁcial, painful, yellow pustules Associated with hair follicle Localized No lymphadenopathy Painful, tender, warm, erythematous nodule Surrounding inﬂammation Fluctuation (soft, with or without pus) Large, inﬂamed, boggy swelling studded with pustules or cluster of furuncles With or without central ulceration Systemically ill Fever and systemically ill Ill-deﬁned diffuse swelling of the skin and subcutaneous tissues with redness, tenderness, and warmth – may ooze serous ﬂuid Spreads to involve signiﬁcant body surface area Lesions are more superﬁcial than cellulitis Well-deﬁned, raised margin Characteristics of cellulitis plus central area showing a blistering and greyish necrotic tissue Blistered area with lack of sensation under blister Intense pain or pain out of proportion to visible skin lesions Systemically ill X-ray – gas in soft tissue (only occasionally seen) Deep vein thrombosis, gout, drug reactions, insect bites or strings, malignant lesions, bursitis, osteomyelitis

Ecthyma a variant of impetigo

Folliculitis

Furuncle (boil)

Carbuncle

Cellulitis

Erysipelas Necrotising fasciitis

Other conditions to consider in DDx

Infections can develop on previously healthy skin, in pre-existing lesions, or lesions from other causes (such as impetiginized scabies). Potentially fatal systemic toxaemia may occur in patients with cellulitis, erysipelas, or other soft tissue infections that remain untreated.

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Impetigo Impetigo is contagious. Treatment • Soak and gently scrub crusts to clear collections of pus underneath. • For single lesions of impetigo or small areas of involvement, local treatment with topical mupirocin ointment 3 times daily for 7 days may sufﬁce. • For more extensive lesions, oral cotrimoxazole or doxycycline (effective against some MRSA) or amoxicillin for 7 days. Complications Glomerulonephritis may occur as a complication of impetigo caused by nephritogenic Streptococcus pyogenes. This occurs within 1–3 weeks (average 7–10 days). Prevention of spread • Add a spoonful of potassium permanganate into bathwater to make it pale pink. The family should bathe in this solution 2–3 times per week. • Clean shower and bath with bleach. • Do not share towels.

Management of skin and soft tissue infections If a patient is systemically ill, parenteral antibiotics should be administered.

Figure: Flowchart for the management of soft-tissue infections Soft - tissue infection (or cellulitis) • • • • Hospital admission Parenteral antibiotics Fluid resuscitation Prepare for surgery

Necrotizing infection No Signs of systemic illness No Focal cellulitis Yes Area of ﬂuctuance Yes • Drain purulence • Initiate antibiotics • Consider admission

Yes

Initiate antibiotics

Patient responsive to therapy No • • • • Re-evaluate antibiotic spectrum Reculture/review cultures Consider imaging Consider tissue biopsy Skin 35

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Abscesses, furuncles, carbuncles, cellulitis (with or without purulent drainage) Assess for signs of severity or risk factors: • severe or extensive disease; • signiﬁcant immunosuppression including AIDS, poorly controlled DM; • very young or old age; • difﬁcult area to drain, such as face, genitals, hands; • lack of response to incision and drainage alone. Treatment • Incision and drainage is the mainstay of treatment and is often all that is required. • Treatment in the absence of severe sign and risk factors, for 7–10 days: ° oral cloxacillin 500 mg 4 times daily (preferred); OR ° alternatives if allergy to penicillin or high rate of methicillin-resistant Staphylococcus aureus (MRSA): ◊ cotrimoxazole 1-2 DS tablets twice daily (if suspect MRSA, use higher dose); OR ◊ doxycycline 100 mg twice daily; OR ◊ clindamycin 300–450 mg 3 times daily. • Give parenteral therapy such as ceftriaxone if any of these severe signs or risk factors. Switch to oral options after signiﬁcant improvement, for total treatment of 7–10 days. • Patients who have diabetes or are immunocompromised require particularly careful management as carbuncles with multiple openings sometimes form as a result of invasion and necrosis of the dermis. See management of complicated skin infections below.

Erysipelas Patients with classic signs and symptoms of erysipelas who are not systemically ill and have small lesions may be managed with oral phenoxymethyl penicillin 500 mg every 6 hours for 5 to 10 days. If there are any systemic signs (fever, malaise), treat with IV antibiotics as for cellulitis above.

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Table: How to choose antibiotics for skin and soft tissue infections If a patient is systemically ill, parenteral antibiotics should be administered. Antibiotics with reliable coverage against group A Beta-haemolytic streptococci Antibiotics with reliable coverage against Staphylococcus aureus (methicillin-susceptible strains only) Penicillin, ampicillin, amoxicillin, cloxacillin, ﬂucloxacillin, all cephalosporins, clindamycin. Clindamycin is preferred in case of penicillin allergy. Note: Cotrimoxazole, doxycycline, and macrolides such as erythromycin have some activity, but there may be signiﬁcant resistance in some areas and they are not recommended as ﬁrst-line options. First-line: cloxacillin, ﬂucloxacillin, nafcillin, oxacillin, 1st generation cephalosporins (e.g. cefazolin or cephalexin), ampicillin/sulbactam, amoxicillin/ clavulanate. Second- line or penicillin allergic: clindamycin, ceftriaxone, cotrimoxazole, doxycycline. Note: Vancomycin has activity against all S. aureus, but is reserved for use against MRSA (methicillin-resistant Staphylococcus aureus). Clindamycin, cotrimoxazole, doxycycline, vancomycin. Note: Gram-negative organisms are not routinely associated with skin and soft tissue infections but, in some cases such as infected ulcers, necrotizing fasciitis, or penetrating injuries, Gram-negative coverage may be appropriate. Ceftriaxone, ciproﬂoxacin in higher doses (also has activity against Pseudomonas), gentamicin, and amoxicillin/clavulanate, cotrimoxazole

Antibiotics with activity against many MRSA strains Antibiotics with activity against Gram-negative organisms occasionally encountered in skin-related infections

Complicated skin and soft tissue infections (including necrotizing fasciitis) Treatment Antibiotic treatment should be based upon Gram stain, culture, and sensitivity where possible. Early empirical treatment should cover both aerobic and anaerobic organisms. IV antibiotics are the mainstay of therapy, there is no place for oral agents. • Treat with: ° cloxacillin 1 to 2 grams every 6 hours and clindamycin 900 mg IV every 8 hours; OR ° ampicillin 2 g IV every 6 hours and clindamycin 900 mg IV every 8 hours. • If previously hospitalized, consider adding Gram-negative coverage such as ceftriaxone, a ﬂuoroquinolone, or an aminoglycoside. • If MRSA is prevalent and clindamycin is not available, consider adding MRSA coverage with vancomycin, cotrimoxazole, or doxycycline. Consider surgical intervention, with debridement. If necrotizing fasciitis is suspected, this is mandatory.

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10.2.3 Papular lesions Ask: • Is there an itch? • Look for mouth lesions. • Is there a fever, or is the patient systemically ill? • Are others in the home affected? • Distribution of the lesions? • HIV status? • Drug history? • Recent introduction of ART?

DDx: Papular lesions with itching Condition Insect bite reaction (papular urticaria) (very common) In favour Scattered over exposed area; some insects, such as the blister beetle, cause linear rash Small papules and central crust Scratch marks mostly on exposed areas – face, arms, legs Exaggerated response in HIV – vesicular or bullous lesions Itching occurs several hours after bites of mites found in grassy ﬁelds, forests, parks, and gardens and the moist areas along lakes and streams. Severe itching with red pimple-like bumps Distribution rash on legs and waist line or parts of the body exposed to the sun; it may stop where the underwear meets the legs Secondary infection common following intense scratching Hyperpigmented papules and nodules Occasionally hyperkeratotic Symmetrical – affects arms, legs, lower back, and buttocks Residual hyperpigmentation after healing Resolves with ART Extremely itchy – resembles insect bites with a tendency to group Urticarial papules (wheal-like) Seborrhoeic areas – face, neck, scalp, chest, trunk (vs. PPE) Residual hyperpigmentation Occurs commonly as IRIS Numerous follicular papules or pustules Mostly on upper trunk and arms; may be extensive – affecting the scalp and face Gram stain: Gram-positive budding yeast cells Papules and burrows – on torso, web-space of hands and feet, wrist and ankles, elbows, axilla, umbilical, and groin Itching worse at night Similar problem in family or other contacts Clinical diagnosis or microscopy of skin scrapings – mites (KOH or mineral oil preparations) Sudden onset involving the trunk, extremities, and face History of starting on a new drug in recent past Mild or severe if mucosal involvement (Stevens-Johnson Syndrome) With or without fever

Chiggers

Pruritic papular eruption of HIV (PPE)

Eosinophilic pustular folliculitis

Pityrosporum folliculitis

Scabies Crusted scabies Norwegian scabies

Drug reactions

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Onchocerciasis see Section 11.28

Larger, pruritic, ﬂat-topped papules with licheniﬁcation Nodules Symmetric – over the buttocks, waist, and shoulders Surrounding skin may be depigmented and dry Endemic Clinical diagnosis or skin snip smears to demonstrate microﬁlaria Lump will develop in subcutaneous tissue as the larva grows. Develops into pustular lesion (furuncular myiasis) Sensation of movement under skin Stabbing pain May involve skin sores and open wounds May involve genitourinary or rectal oriﬁces

Myiasis (infection with a ﬂy larvae)

Syndromic management of itchy papular lesions in PLHIV • Document distribution, duration, involvement of palms or soles or mucosal surfaces. • Ask if anyone else at home itching? • Are there other symptoms of STI? • Obtain VDRL or RPR (if sexually active, if involvement of palms soles, or if mucosal lesions). It is often difﬁcult to make a speciﬁc diagnosis. An example of an approach to empirical treatment follows.. Stage I empirical treatment: • anti-scabetic or mite topical treatment (see scabies management below); • potent topical steroid with antifungal cream(s); • oral antipruritic agents: ° chlorphenamine 4 mg every 4 to 6 hours; • oral antibiotic (e.g., erythromycin or doxycycline). • Stage II empirical treatment if no response to Stage I: • continue Stage I regimen (including possible re-treatment for scabies or mites); • add systemic oral antifungal (ﬂuconazole or griseofulvin). Stage III Refer or biopsy.

Chiggers Treatment • Vigorous cleansing with soap and water may be helpful to remove the mites. • Topical antipruritics, such as menthol, calamine lotion, or topical corticosteroids, and oral antihistamines may help relieve the itching. • The condition heals without treatment. • Treat secondary infection (see impetigo above).

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DDx: Papular lesions – without itching Condition Molluscum contagiosum In favour Dome-shaped lumps with a dimple in the centre Involving face, neck, armpits, hands, and genitals Lesions may be chronic and numerous In PLHIV – may be large >1 cm and coalesce Small raised lesions with rough surface. Commonly involving the extremities Can appear anywhere May be recurrent and persistent in HIV Variable sizes, shapes and number – from small, ﬂat, to large and polypoid May be seen on any part of the genitalia, including intra-vaginal and intra-anal May be very large, recurrent, and persistent in patients with HIV Multiple lesions – papular or macular Generalized involving the palms and soles Dusky red-coppery Mucocutaneous lesions – moist erythematous patches over genital and oral mucosa Generalized lymphadenopathy Diagnosis – blood VDRL/RPR/TPHA Erythematous papule (at the site of a sand-ﬂy bite) Enlarges to a painless ulcerated nodule Raised and well-demarcated border Single or multiple lesions Skin snip or biopsy shows amastigotes Generalized raised umbilicated, ﬂeshy lesions (similar to molluscum contagiosum) Develops rapidly (within days) Fever Signs and symptoms of disseminated cryptococcosis, e.g. meningitis, lung infection Serum or CSF CrAg or CSF India ink Papulo-necrotic skin lesions May be umbilicated like molluscum contagiosum Usually on the face Associated constitutional symptoms or systemic involvement Endemic Skin biopsy – microscopy showing organism on Wright or Gram stain Erythematous maculopapular lesions with ulceration and purpura Oropharyngeal lesions Systemic involvement: lung, CNS, gastrointestinal, or eyes Diagnosis – tissue biopsy or microscopy: yeast forms on haematoxylin and eosin staining Endemic Blood or tissue culture Single or multiple purple-coloured lesions May be papular, nodular, patches, or plaques Can involve any part of the body including palate Lymphoedema may occur if on limbs

Common warts (verruca vulgaris)

Genital warts

Secondary syphilis see Section 11.37

Cutaneous leishmaniasis see Section 11.20

Cryptococcosis see Section 11.5

Penicilliosis see Section 11.29

Histoplasmosis see Section 11.16

Kaposi sarcoma see Section 11.19

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Mycobacterium avium complex (MAC) see Section 11.27

Papulo-pustular eruptions on trunk and extremities Fever Lymphadenopathy Pulmonary symptoms, diarrhoea, weight loss, night sweats Acid-fast bacilli on skin biopsy; blood culture The patient has advanced HIV Warty papules (may be nodular or an irregular plaque) Localized to 1 area – often the hands or extremities Often mistaken for verruca vulgaris Lesions may evolve and persist for years Multiple papules with black necrotic centres Scattered in 1 or 2 regions; not generalized Skin biopsy Pimples – visible lumps on the skin that may be papules, pustules, nodules, or cysts May be old or new scarring With or without active inﬂammation On face, neck, chest, back, and upper arms Common during adolescence

TB verrucosa cutis

Papulo-necrotic tuberculides Acne

Molluscum contagiosum This is a common viral infection of the skin. Key clinical features • pearly-white, umbilicated papular lesions on the face, trunk, and genital area • frequently seen among sexually active adults, especially those infected with HIV. Treatment • removal by enucleation (with forceps); OR • cautery – pierce the molluscum body with a needle and treat the base with silver nitrate or phenol or any other mild sclerosing agent; OR • cryotherapy – freeze using liquid nitrogen.

Viral warts Warts (verrucae) are caused by the human papillomavirus (HPV) and may regress spontaneously at any time within months or years of their ﬁrst appearance. Key clinical features • papules or nodules with a rough (verrucous) surface • occur most often on the hands and ﬁngers, but may be found on any area of the body. Genital warts (Condyloma accuminata) are sexually transmitted infections caused by HPV. The lesions may be seen on any part of the genitalia, including intra-vaginal and intra-anal. See Section 10.14.

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Treatment Alternative treatments include: • paints or lotions containing salicylic acid; • podophyllin resin; • cryosurgery – where available, liquid nitrogen applied with a cotton-tipped swab or a spray can be highly effective; • electrocautery can be used when available; • trichloroacetic acid may be another option for treatment of warts.

Eosinophilic folliculitis Key clinical features • Extremely pruritic rash seen in patients who are HIV-infected. • Primary lesions are urticarial papules that look like insect bites. • Pustules may be present. • Because of the intense itching, excoriations and post-inﬂammatory hyperpigmentation are seen. • Lesions are most prominent on the seborrhoeic areas of the skin (scalp, face, chest, upper back). Treatment • topical steroids – hydrocortisone 1%; OR • betamethasone 0.1% cream; • symptomatic relief – oral antihistamines such as chlorphenamine. If the patient is unresponsive to the above, give: • doxycycline 100 mg twice daily for 8–12 weeks.

Pityrosporum folliculitis Key clinical features • numerous pruritic follicular papules or pustules; • most commonly seen on the upper trunk and arms. Treatment • topical steroids – hydrocortisone 1%; OR • betametasone 0.1% cream; • ART if indicated for other reasons (the condition improves with immune recovery); • symptomatic relief – antihistamines (as above).

Papular urticaria This is an insect-related hypersensitivity reaction (Type IV).

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Key clinical features • commonly seen in children in developing countries; • characterized by crops of pruritic wheals that evolve into serum-ﬁlled papules and, less frequently, vesicles; • lesions seen predominantly on exposed body parts; • excoriations, due to scratching, lead to secondary bacterial infections; • spontaneous desensitization usually occurs by the age of 7 years; • in tropical climates, mosquitoes are the main cause of papular urticaria; ﬂies and bed bugs are the common causes in temperate climates. In patients who are HIV-infected, there is an exaggerated response to insect bites. Treatment • topical steroids: hydrocortisone 1% OR betamethasone 0.1% cream; • symptomatic relief with antihistamines such as chlorphenamine 4 mg twice daily; • topical antimicrobial (e.g. 2% mupirocin ointment) may be useful to treat secondary bacterial infection; • use insect repellents, screens, and bed nets; • disinfect pets if any.

Drug reactions (see also Section 13 Chronic HIV care) • Drug reactions may be localized to the skin or involve various organ systems. • The drugs most frequently involved include NNRTIs (NVP and EFV), ABC, sulfa drugs (cotrimoxazole and dapsone), antiepileptics (phenytoin, phenobarbital and carbamazepine), antibiotics (quinolones, penicillins, cephalosporins), and antituberculosis drugs. • The reaction may present 1–3 weeks after commencing the causative drug. But it may take up to 6 weeks with antituberculosis and antiepileptic medicines. Key clinical features Drug reactions or eruptions may be mild or severe. Mild drug reaction • Mild drug reactions typically present as an itchy papular or maculopapular rash with no constitutional symptoms or systemic ﬁndings. • Erythema multiforme is a special morphological type of drug eruption. It presents as a self-limiting symmetrical skin rash with “target lesions” (a pinkred ring around a pale centre). The rash begins abruptly and heals normally in 7–14 days. It is often triggered by HSV infection. It can be a manifestation of drug allergy.

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Severe drug reaction • A severe drug reaction may develop macules that rapidly spread and coalesce, leading to epidermal blistering, necrosis, and sloughing. • Constitutional symptoms and systemic involvement, such as an increase in liver enzymes, may be seen. • Stevens Johnson Syndrome (SJS) refers to skin changes affecting up to 10% of the body surface area, and involvement of >1 mucosal surface (oral, conjunctival, genital). • Toxic epidermal necrosis (TEN) refers to skin changes on large areas of the body, sometimes affecting >30% of the body surface area, and presents as sheets of erythema with blistering and skin peeling. Mucosal and systemic involvement may be seen as well. Treatment Mild drug reaction • Stop the suspect drugs. • Give antihistamines. • In some mild drug reactions, it may be possible to continue the drug if it is medically necessary. Erythema multiforme • If the cause is HSV infection, treat the HSV. • Discontinue suspected drug if the condition is drug-induced. • Supportive management includes: ° oral antihistamines ° topical calamine lotion. Severe drug reaction • Stop the suspect drugs (all drugs introduced within 1 month of the reaction should be considered suspect). • Hospitalize the patient in an intensive care or burns unit. • Referral to a tertiary dermatologic unit should be considered in toxic epidermal necrosis. • Give topical antibiotics. • Maintain hydration and electrolyte balance. • Give analgesics. • Use mouth washes and eyes ointments. • Screen and treat empirically for septicaemia. • Give systemic corticosteroids. Patient education The health worker should inform the patient about drugs that may have caused the eruption, drugs to avoid, and those drugs that can be used safely. This information should be noted in the patient’s record.

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Scabies Transmission is through close contact with infested persons and occurs in crowded spaces, conditions involving poor hygiene, and through sexual contact. A more severe form of scabies (Norwegian scabies) can occur if the patient is immunocompromised. Key clinical features Classical scabies • Itchy papular lesions. • Itching is typically most severe at night. • History of a similar problem in the family or contacts. • Typical lesion of scabies is the burrow of the adult mite, with excoriations from itching. • Secondary lesions commonly seen are papules and papulovesicles. • Typical distribution: ﬁnger webs, palms, wrists, elbow, axillae, areola, nipple, umbilicus, external genitalia, and feet. Norwegian (crusted) scabies • The lesions in crusted scabies are more widespread, crusted with thick, hyperkeratotic scales. There is infestation with a large number of mites. Little itching occurs because of immunocompromise, but this form is highly transmissible. • It resembles psoriasis: thick crusts, scales, and dystrophic nails. • These patches and plaques are commonly seen over elbows, knees, palms, and soles (but they can occur on almost any area of the body). Occasionally, only diffuse redness of skin is apparent. • Bacterial superinfections are common. Investigations • Diagnosis is usually clinical. • A burrow should be unroofed and scraped; examination under a light microscope will reveal a mite, eggs, or faecal pellets. Treatment With 1 of the following • 25% benzyl benzoate emulsion (dilute 1:1 for children; 1:3 for infants); OR • 5% permethrin cream; OR • ivermectin 0.2 mg/kg orally as a single dose, repeated in 2 weeks. If there are crusted scabies, repeat treatments on days 1, 15, and 29, or combine treatment with oral ivermectin and a topical scabicide (benzyl benzoate or permethrin cream). Method of application • The patient and all close contacts must be treated simultaneously, including the entire household and sexual partners, even if they are asymptomatic. • Clothing or bed linen used by the patient should be washed and dried well (or dry-cleaned).

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• Do not bathe before applying the treatment (this increases systemic absorption and does not help). • Apply the cream to the whole skin surface, giving particular attention to the ﬂexures, genitalia, intergluteal cleft, between the ﬁngers and under the ﬁngernails. Include the face, neck and scalp, but avoid areas near the eyes and mouth. • The cream may irritate the skin a little, especially if there are excoriations. • Keep the cream on for the treatment period: overnight treatment for 3 days. • If any cream is washed off during the treatment period (e.g. hands), reapply immediately. • Wash the cream off at the end of the treatment period. • Itching should start to diminish within a few days, but may persist for a number of weeks. This does not mean that the treatment has failed. Another cream may help with the itching (calamine lotion).

Cutaneous tuberculosis Cutaneous tuberculosis can present in many forms. Some of the common presentations include: • warty papules and plaques (tuberculosis verrucosa cutis); • well-circumscribed, dusky red, soft to ﬁrm papules and plaques with or without central scarring (lupus vulgaris); • multiple sinuses with ulceration at the mouth of the sinus (scrofuloderma); • chronic ulceration at the mouth or anal region (oriﬁcial tuberculosis). HIV-infected patients are more prone to developing tuberculosis and therefore are at increased risk of presenting with cutaneous hypersensitivity reactions to TB. In HIV-infected patients, these reactions occur with higher CD4 counts, are more ﬂorid, and several types may coexist. • Papulonecrotic tuberculid: papules, pustules, with central necrosis involving acral sites, such as earlobes, elbows, knee, extensors, and buttocks. • Lichen scrofulosorum: grouped papules on the trunk in association with underlying TB. • Erythema nodosum: erythematous, tender, evanescent nodules on the legs. Investigations Diagnose by biopsy, histopathology, and culture. Treatment As per WHO TB guidelines – see Section 15.

Onchocerciasis – see Section 11.28 Cutaneous histoplasmosis Key clinical features • Patients are usually ill with systemic involvement – fever, anaemia, respiratory symptoms, lymphadenopathy, hepatosplenomegaly, and skin lesions.

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• Skin involvement occurs in 5%–10% of patients. • Skin lesions are polymorphous: papules, nodules, plaques, abscesses, and characteristic gingival ulcers. • This condition may often resemble molluscum contagiosum. Investigations • Referral for biopsy and culture may be indicated (see Section 7).

Cutaneous cryptococcosis – see Section 11.5 Cryptococcosis This occurs with advanced HIV disease. Key clinical features • Skin involvement occurs in 10% of patients with systemic disease. • The typical lesions are haemorrhagic, ulcerated nodules and umbilicated papules resembling molluscum contagiosum. Investigations • A KOH preparation with or without India ink staining will show the characteristic round, thick-walled yeast cells of cryptococcosis.

Acne1 Key clinical features • comedones – whiteheads or blackheads with no redness (blocked hair roots or pores with white or black tips); • pustules – pus-ﬁlled pimples with no redness; • papules – pimples that appear red due to inﬂammation; • nodules – pimples that affect the deeper areas of the skin that can be disﬁguring due to inﬂammation (redness); • cysts – lesions formed by several nodules coming together; • scarring, which may or may not be inﬂamed. Treatment • Severe acne (nodules, cysts or scarring that is inﬂamed) ° Oral antibiotics taken for 3–6 months ◊ doxycycline 50 mg daily; OR ◊ tetracycline 500 mg twice daily; OR ◊ erythromycin 500 mg twice daily. ° Topical applications of: benzoyl peroxide 2.5%–5% or topical tretinoin twice daily until 2 weeks after lesions disappear. ° Wash face with mild soap twice daily (before topical application). ° In girls, if taking progesterone-only contraceptive pills or injections, consider changing to combined oral contraceptives. ° Review in 2 months. If there is no improvement: ◊ continue oral antibiotics for up to 6 months with review every 2 months; ◊ doxycycline dose can be increased up to 100 mg or 200 mg depending on response. 1 Adolescent Job Aid. WHO, 2010. Available at www.who.int/child_adolescent_health/documents/9789241599962/en/

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◊ If no improvement in a girl, consult with her about adding combined oral contraceptive pill. ◊ Refer for specialist care if very severe acne, if scarring is extensive or worsening, if acne is causing great psychological distress, or is not responding to treatment at 6 months. • Moderate acne (papules with no nodules, cysts, or inﬂamed scarring) ° Apply topical antibiotics twice daily and continue until 2 weeks after lesions disappear. ◊ clindamycin 1% gel or lotion; OR ◊ erythromycin 2% gel or lotion. ° Topical applications, face washing, and for girls, contraception change as above. ° Review in 2 months. Continue treatment if no improvement. If the condition worsens, give oral antibiotics as for severe acne. • Mild acne (only comedones or pustules): ° Topical applications as above, face washing, and for girls, contraception change as above. ° Review in 2 months. If no improvement, continue treatment. If acne is worse, treat as moderate or severe acne accordingly.

10.2.4 Vesicular or bullous lesions Assess the pattern of distribution and whether there is involvement of the mouth.

DDx: Vesicular or bullous lesions Condition Herpes simplex see Section 11.15 In favour Painful, grouped vesicles with surrounding mild erythema May evolve into a superﬁcial ulcer with crusting Associated with pain or tingling Usually localized to lips or genital area, may involve any site With or without a history of previous episodes Usually heals in 3–5 days Persistent ulcers for >1 month are more common in immunocompromised patients Crops of painful vesicles in dermatomal distribution Do not cross midline Intense pain In PLHIV: • recurrent, multidermatomal or disseminated herpes zoster • severe and takes longer to heal Fever Discrete (umbilicated) vesicles on a erythematous base Lesions in different stages of development Generalized, but predominantly involving the trunk, cephalocaudal spread Oral lesions In PLHIV, severe disseminated infection including pneumonia Lower extremity blister before ulcer forms when worm emerges See 10.2.10 below Anthrax See 10.2.10 below

Herpes zoster see Section 11.45

Chicken pox (varicella) see Section 11.45

Guinea worm (dracunculiasis)

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Pemphigus vulgaris

Middle-aged individuals Long history Fragile, ﬂaccid blisters – rupture leaves weeping, denuded skin Blisters extend readily on digital pressure Painful oral ulcers or erosions common Common sites: scalp, trunk, ﬂexures Elderly age group Tense blisters With or without itching Oral ulcers rare Common sites: trunk, extremities, ﬂexures History of recently starting a new drug (e.g. sulfas, NVP) Erythematous maculopapular rash with blisters Conﬂuent erythema with sheets of skin peeling and signiﬁcant oozing Oral, conjunctival, genital mucosal ulceration and crusting Fever Systemic illness

Pemphigoid

Severe drug reaction – Stevens Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) see Section 10.2.3

10.2.5 Nodular lesions DDx: Nodular lesions Condition Erythema nodosum In favour Crops of painful, tender, red bumps 1–2 cm in size Lesions appear and spontaneously heal, while new lesions appear Usually on the legs With or without fever Associated with tuberculosis, upper respiratory infection, leprosy, drugs, rheumatoid arthritis, malignancy Do a skin biopsy to conﬁrm Single or multiple purple-coloured lesions May be papular, nodular, patches, or plaques Lesions tend to follow lines of skin cleavage Can involve any part of the body including palate Lymphoedema may occur if on limbs Clinical diagnosis or skin biopsy to conﬁrm Single or multiple papules, nodules, and pedunculated lesions May appear suddenly and may be tender Flesh coloured, purplish, or red lesions May be large, friable, polypoid masses Signs of systemic illness: fever, lymphadenopathy, splenomegaly, or hepatomegaly Skin biopsy to conﬁrm Living in an area where this is present Cytopaenia Lymphadenopathy Amastigotes seen in samples of tissue or body ﬂuid under the microscope (Giemsa stain) Asymptomatic Skin-coloured nodules, papules, and plaques Commonly on face and extremities, but can occur at any site Other signs of leprosy: sensory loss, peripheral nerve thickening, loss of hair Slit skin smear for AFB

Kaposi sarcoma see Section 11.19

Bacillary angiomatosis see Section 11.2.4

Cutaneous leishmaniasis see Section 11.20

Lepromatous leprosy see Section 11.21

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Condition Mycosis fungoides Pruritic papular eruption (PPE)

In favour Pustules, nodules, ulcers, and papules in a patient with systemic symptoms Diagnosis by biopsy and histopathology Hyperpigmented papules and nodules Occasionally hyperkeratotic Symmetrical – affects arms, legs, lower back, and buttocks Residual hyperpigmentation after healing Resolves with ART Long history of nodules, plaques and patches Skin coloured or slightly erythematous; annular, doughnut-shaped Systemic signs with or without lymphadenopathy Hepatomegaly and splenomegaly Biopsy to conﬁrm Subdermal Painless Hard Roll easily over the bones underneath Do not suppurate Endemic Papules, or ulcerated nodular lesion with serous discharge Primary lesion – extremities Secondary lesions – mucocutaneous junctions Pain, with or without swelling of small joints Heal with scarring Hyperkeratosis and ﬁssuring of soles Bone deformities Residence in endemic area Positive syphilis test Skin biopsy

Cutaneous lymphoma

Onchocerciasis see Section 11.28

Yaws

Erythema nodosum Key clinical features • Present as reddish, painful, tender lumps, 1–5 cm in size. • Commonly located in front of the legs below the knees. • Usually resolves spontaneously; each of the nodular lesions shrink and then become ﬂat. They leave a bruised appearance and then resolve completely. • Simultaneously, as some lesions resolve, other lesions may continue to occur elsewhere. This may go on for weeks to months. • May occur as an isolated condition or may be triggered by other conditions – sulfa-related drugs, contraceptive pills, estrogens, streptococcal throat infection, fungal diseases, infectious mononucleosis, sarcoidosis, leprosy, and tuberculosis. Investigations • Diagnosis is mainly clinical. However, a skin biopsy may be needed to conﬁrm.

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Treatment Evaluate for the underlying cause and treat accordingly. • NSAID such as ibuprofen. • Colchicine 0.5 mg 2 or 3 times daily. • Elevate feet and advise the patient to have bed rest.

Yaws Yaws is a chronic condition caused by the spirochaete Treponaema pertenue, a subspecies of Treponaema pallidum that causes syphilis. Yaws affects skin, bone, and cartilage, and leads to disﬁgurement and disability. Children and adolescents less than 15 years are most commonly affected with peak incidence 6–10 years. Yaws is: • not a sexually transmitted infection • transmitted by direct skin contact with an infected person • endemic in certain tropical areas of Africa, Asia, and Latin America • spread in conditions of overcrowding, poor hygiene, and poor sanitation. Key clinical features There are 2 stages of Yaws disease, early (infectious) stage and late (non-infectious) stage. Early (infectious) stage • Skin ° Primary lesions: ◊ small papule or “mother yaw”, contains large numbers of spirochaetes and is usually on the face or leg; ◊ initial papule may heal, or persist for months as a raspberry-like “framboesia” lesion, or undergo ulceration. ° Secondary lesions: ◊ crops of macules or papules anywhere on the body; ◊ papillomatous or hyperkeratotic lesions on the palms and soles are painful and disabling. ° Tender regional lymphadenopathy. • Bone ° Periostitis of the long bones (sabre shin) and ﬁngers (dactylitis). ° Bone pain is usually worse at night. Late (non-infectious) stage • Occurs in 10–20% of untreated patients 5 or more years after infection. • Necrotic skin lesions and gumma of the bones cause disabling deformities, such as collapse of the nasal bridge (saddle nose). • Palmar and plantar hyperkeratosis may persist.

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Investigations • Demonstration of the spirochaete by darkﬁeld microscopy of exudate from lesions. • Serological tests: ° There are no speciﬁc blood tests for yaws. ° Non-treponemal tests (VDRL, RPR) and treponemal tests (TPHA, FTA) that are used for diagnosing syphilis can also be used for diagnosing yaws. They do not distinguish between yaws and syphilis. Treatment • Benzathine penicillin 1.2 million units as a single intramuscular injection is curative; OR ° Relapse is very rare. • Azithromycin oral 30 mg/kg (maximum 2000 mg) single dose.

10.2.6 Maculopapular rash DDx: Maculopapular rash Condition Drug eruption see Section 10.2.3 In favour History of recently starting a new drug (e.g. sulfas, NVP) Rash generalized or ﬁxed or discrete Red, itchy, maculopapular rash With or without mucosal involvement Fever Rash is asymptomatic (non-itchy) maculopapular or papular Starts on the face, spreads later to the neck, trunk, and limbs With or without oral lesions ( sometimes speciﬁc lesions, such as Koplik’s spots in measles) With or without lymphadenopathy Maculopapular lesions are the most common With or without maculopapular lesions

Viral exanthaema

Secondary syphilis see Section 11.37 Leprosy see Section 11.21

Viral exanthaema • Typically present with a prodrome of fever. Treatment • Usually asymptomatic and resolves spontaneously. • Symptom management only: paracetamol for fever.

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10.2.7 Plaques DDx: Plaques and patches with itching Condition Eczema In favour Inﬂamed, scaly patches with or without excoriation Pruritus and xerosis Oozing, wet rash arms, legs, trunk, face Any site Flexures in atopic eczema Relapses and remissions Responds to topical corticosteroids and antihistamines Scaly patches with central clearing (ring pattern) Intense itching May involve any site – commonly groin and buttocks On scalp produces localized loss of hair With or without nail involvement ( thickening of nail plate, white discoloration of nail plate, lifting of nail plate from nail bed) KOH preparation to demonstrate fungal ﬁlaments Plaques with well-demarcated borders Silvery white scales Commonly involving extensors: elbow, knees, back and scalp, hairline With or without nail involvement With or without joint pain or swelling Chronic course In patients with HIV – sudden exacerbations and resistant to therapy

Dermatophytosis (ringworm)

Psoriasis

DDx: Plaques and patches without itching Condition Pityriasis versicolor In favour Scaly, hypopigmented and hyperpigmented macules and patches Mainly over the upper trunk, stretching skin accentuates lesions Fine, bran-like scaling KOH to conﬁrm Asymptomatic and of long duration Nodules, plaques, and patches Skin coloured – slightly erythematous Systemic involvement – lymphadenopathy Hepatomegaly or splenomegaly Extensive crusting (psoriasis-like lesions) with thick hyperkeratotic scales on scalp, face, back, feet, and nails Commonly in immunocompromised persons Less itch KOH preparation to demonstrate mite – very high mite burden Single or multiple Hypopigmented or erythematous or coppery-coloured Decreased sensation, hair growth, and sweating over patch Peripheral nerve thickening Slit skin smear for AFB or skin biopsy

Cutaneous lymphoma

Crusted (Norwegian) scabies see Section 10.2.3

Leprosy see Section 11.21

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Eczema There are several types of eczema including seborrhoeic dermatitis, contact eczema, and nummular eczema. Seborrhoeic dermatitis Key clinical features • Occurs on the sebum-rich areas of the scalp, face, and trunk. • The scalp is the most common site of involvement and varies from mild, patchy, scaly areas to widespread, thick, adherent crusts. • Forehead, eyebrows, naso-labial folds, posterior part of the neck, and the postauricular skin may also show similar greasy and scaly lesions over red, inﬂamed skin. • In HIV-positive patients, seborrhoeic dermatitis tends to be more severe, to relapse frequently, and to improve on ART. Treatment • Aqueous cream. • Use of keratolytic shampoo containing active agents such as salicylic acid, coal tar, zinc pyrithione, and selenium sulphide reduces both the inﬂammation and scaling. • To apply: massage into the scalp and leave for 2–3 minutes before rinsing – good foaming action is required. • Preparations containing combinations of sulphur and salicylic acid can be applied to the scalp and other affected areas. Topical applications of corticosteroids, or azoles, such as ketoconazole, also are effective. Mild cases: • 2% ketoconazole shampoo for scalp (lather over hair, scalp). OR • 2% ketoconazole cream for body sites. Leave on for 5 minutes, then wash off. Repeat daily until cleared (usually 2 weeks). After clearance, continue to use once weekly for 2–3 months to prevent recurrence. OR • If there is no response to topical antifungals, use topical steroids: 1% hydrocortisone cream (including face) or 0.1% betamethasone cream (not on face) twice daily (for a maximum of 3–4 weeks). Once lesions clear, continue with topical ketoconazole for 2–3 months. Refractory cases: • Oral itraconazole 200 mg daily for a week followed by 200mg once every 2 weeks for several months. • Whenever apparent seborrhoeic dermatitis does not respond to appropriate therapy, the diagnosis should be reconsidered. For other eczemas such as contact eczema, nummular eczema • Find and avoid contact. • Severe eczema: use very potent corticosteroids for 3–4 weeks (such as clobetasol propionate); also apply emollient.

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• Infected eczema: treat with potassium permanganate (1:10000) compresses and oral antibiotics, followed by a combination of topical corticosteroid and antibiotic as for impetigo or antiseptic ointment. • Mild eczema: moderately potent topical corticosteroid (such as clobetasol butyrate); also apply emollient. • Weeping eczema: as for infected eczema, but without oral antibiotics.

Dermatophytosis (ringworm) This presents as scaly patches or plaques with an active raised edge and central clearing, and nail infections with thickening, scaling, deformity, and discolouration. • scalp ringworm (tinea capitis) typically appears as a patch of scaling alopecia (loss of hair), or a swollen inﬂammatory area (kerion); • ringworm of the trunk (tinea corporis); • foot ringworm (tinea pedis or athlete’s foot) – lesions most commonly and frequently ﬁrst appear in the fourth interdigital web; • ringworm of the groin (tinea cruris) – limited to the groin, inner thighs, and the skin of scrotum in contact with the thigh. In PLHIV There is a high incidence of coexisting nail infection, which has to be treated adequately to prevent recurrences of tinea infection of skin. Treatment Topical treatment • 1% terbinaﬁne hydrochloride2 • Other creams and powders containing an imidazole, undecyclinic acid, or tolnaftate. Systemic treatment when topical treatment has failed: • griseofulvin 500 mg – 1 g daily until cure – for extensive and generalized infections. Much longer courses of treatment are required when nails are affected (Note: Beware of interactions with ART. See Section 13.); OR • ﬂuconazole 150–300 mg/weekly until cure (6–12 months).

Pityriasis versicolor • Presents as scaly, hypopigmented and hyperpigmented macules and patches, mainly over the upper trunk. Fine, bran-like scaling is seen (more prominent on stretching skin). Treatment • sodium thiosulfate, 15%: twice daily for 4 weeks should be started; • selenium sulﬁde: a thin layer of undiluted 2% detergent-based suspension should be applied at bedtime to the trunk, groin, upper limbs, and axillae, and rinsed off after 5 to 15 minutes – treatment should be repeated after 3 and 6 days; 2 Both benzoic acid and salicylic acid (Whitﬁeld’s ointment) and gentian violet solution are inexpensive fungistatic compounds. Whitﬁeld’s ointment has been deleted from the WHO Essential Medicines List because it can have an irritating effect and requires lengthy treatment, but may be considered as an alternative fungistatic agent in resource-limited settings. Gentian violet has been deleted from the WHO Essential Medicines List due to reports of carcinogenicity. Vol. 2 • 10. Acute and subacute by symptom: July 2011 Skin 55

• ketoconazole, 2%: applied once or twice daily for several weeks; • ﬂuconazole: a single oral dose of 400 mg ﬂuconazole is reported to be very effective. • If there is a recurrence: use pulsed monthly ﬂuconazole or itraconazole for 3 months.

Psoriasis Key clinical features • Commonly present as erythematous plaques with profuse silvery scales. • Occurs on the scalp, extensor surfaces of the limbs and trunk. • Thickening, pitting, and discoloration of the nails are commonly seen. • Inﬂammatory arthritis may occur in some patients. • Erythrodermic psoriasis involves >90% of the body surface and usually presents as diffuse scaling. Treatment Many types of treatment are available. However, none have been shown to prevent relapses. Topical treatment: • dithranol ointment (0.1% initially, higher strengths later) – for 2–4 weeks; • crude coal tar ointment, in combination with ultraviolet B therapy can be very effective; • emollients containing low concentrations (1–2%) of salicylic acid are a useful adjunct to treatment; • topical corticosteroids – for short term treatments for face, ﬂexures, hands and feet. Systemic treatments • Give oral antibiotics for guttate psoriasis (amoxicillin for 7 days). • Systemic therapies are used for extensive involvement, and for psoriasis that is not responding to topical therapies. These involve the use of immunosuppressive drugs, which are expensive, have potentially serious side-effects, necessitate close monitoring of patients, and therefore require referral to a dermatology centre. • Systemic corticosteroids should not be used because of the risk of severe exacerbations on withdrawal.

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10.2.8 Pruritus DDx: Generalized itching without primary cutaneous lesions Condition Xeroderma In favour Generalized dry skin With or without scaling No evidence of systemic causes Intense pruritus Cutaneous lesions may be very few or hardly visible History of similar problem in family or other contacts Associated with overcrowding, poor hygiene May require therapeutic trial with antiscabetics Intense pruritus With or without excoriations With or without red punctae from bite Lice on inner seams of clothing Jaundice – liver failure Leukaemia, lymphoma, internal malignancy, iron deﬁciency, anaemia and thyroid disease are all causes to be excluded Evidence of renal disease Elevated urea

Scabies see Section 10.2.3

Pediculosis (lice)

Obstructive jaundice see Section 10.8 Uraemia

Xeroderma • Xeroderma is generalized dry scaly skin that may be itchy. • Causes include: malnutrition, chronic diseases, such as chronic renal failure, liver failure, HIV infection, and internal malignancy. Treatment Rule out the underlying causes. • Keep the skin moist. Avoid detergents and other degreasing agents, use soap sparingly or replace with aqueous cream or bath oils. • Avoid hot baths – rather, advise tepid water. In cold climates, use adequate protective clothing. • Emollients: preparations such as aqueous creams, emulsifying ointments, or urea should be applied to affected skin once or twice daily. Regular and proper application of emollients is the mainstay of therapy. • Consider treating for scabies if there is persistent itching in an HIV-positive patient, even if there are no typical lesions. • Use chlorphenamine or other oral antihistamines to reduce itching. • Use topical steroids for areas of skin that are very itchy due to secondary eczema.

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Pediculosis Infection with lice is usually transmitted directly, by contact, or indirectly, via clothing and linens of infested persons. Key clinical features • Poor hygiene tends to increase the chance of body lice infestations. • The infection may be localized to the scalp (pediculosis capitis) or the pubic region (pediculosis pubis). • Pediculosis is characterised by intense itching, with excoriations from scratching. • Close inspection of the skin reveals both the characteristic red punctae from bites, and lice. • Exclude secondary bacterial infection. Treatment Benzyl benzoate can be used for all types of pediculosis. Apply to affected area AND wash off 24 hours later (further applications possibly needed after 7 and 14 days). Other options follow below. Pediculosis capitis (head lice) • 1% permethrin preparations should be applied to damp hair and left for 10 minutes before rinsing; OR • 0.5% malathion preparations should be massaged into the scalp and left for at least 12 hours. Do not use malathion more than once a week or for more than 3 consecutive weeks. • Treat all household contacts, and soak all combs and brushes in any of the above preparations for at least 2 hours. Pediculosis corporis (body lice) • Use powdered preparations of permethrin 5%. Dust clothes, and wash in boiling water. Pediculosis pubis • The treatment (the medication and duration of application) is the same as for head lice and should be applied to the pubic area, thighs, axillae, trunk, and head (including eyebrows). • Sexual partners should be treated simultaneously.

Symptomatic management of itching Home care: • If the affected person has dry skin, moisturize with aqueous cream or petroleum jelly mixed with water. • Use 1 spoon of oil (bath or vegetable) in the bath water when washing. • Apply diluted chlorhexidine (0.05%) after a bath.

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• Rub the itchy skin with local remedies (examples: effective and safe herbs, cucumber, or wet tea bags or leaves put in a clean piece of cloth and soaked in hot water). • Advice to the patient on care-seeking: seek help from a trained health worker for painful blisters or extensive skin infection. Outpatient medication or clinical: • Assess for bacterial, fungal ,or viral cause – if present, treat (see other sections in this manual). • Consider that this may be the side-effects of medication. • Local steroid creams may be useful if inﬂammation is present in the absence of any infection (bacterial, fungal, or viral). • Chlorphenamine 4 mg twice daily, up to 4 mg every 4–6 hours (maximum 24 mg daily), or another antihistamine, may be useful for severe itching. If the itching still persists, a short-acting antihistamine and a long-acting antihistamine (from different groups) could be combined for better symptom relief. • Consider treating for scabies if there is persistent itching in an HIV-positive patient, even if there are no typical lesions. • If there are multiple skin infections, use a chlorhexidine (0.05%) rinse after bathing. Speciﬁc management options • Candidiasis – see Section 11.4. • Eczema or skin allergies will usually respond to topical steroids, e.g. hydrocortisone, betamethasone, or other. General management options • Non-speciﬁc itch: ° avoid heat and hot water ° moisturise and hydrate dry skin ° apply calamine lotion ° menthol 1% in aqueous cream. • Moisturize and hydrate the skin: ° generous use of aqueous cream as a soap substitute and bland bath oils can restore skin hydration; ° apply an emollient (liquid parafﬁn, coconut oil) immediately after a bath.

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10.2.9 Urticaria Key clinical features • Lesions are intensely pruritic, erythematous, circumscribed plaques (often with central pallor). • Individual lesions appear over minutes and disappear within a few hours and are often coalescent • Sometimes accompanied by angioedema. • Often triggered by allergens (e.g., food or drug), insect stings or infection. Evaluate the patient • Use Quick Check to evaluate emergency signs – make sure patient is breathing normally and that circulation is not compromised. • Quickly assess the patient, including a medical history and any history of allergies, with an aim to establishing the cause of hypersensitivity. ° Any recent exposure to something new or unusual? ° Did the patient swallow medicine bought from a local drug store? ° Carry out a thorough medication review and stop all medicines that can potentially cause an allergic reaction. Treatment For severe urticaria • Manage as an inpatient. • Ensure the airway is not compromised. • Establish IV access. • If shock, give epinephrine (see Quick Check page 19, Vol.1) and follow management in Section 3.1.3 Anaphylactic shock. For all urticaria • Ensure there is adequate hydration. • Give an antihistamine, such as chlorphenamine. • If rash is severe, give IV hydrocortisone 100 mg once then repeat every 6–8 hours. Parenteral steroids can be changed to oral steroids once the rash is under control.

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10.2.10 Skin ulcers DDx: Skin ulcers Condition Diabetic ulcer In favour Diabetes, poor blood sugar control Ulcers mainly over extremities (predominately feet) May be deep, with greenish yellow slough and foul-smelling discharge Trophic changes: dry, lustreless skin, hair loss, dystrophic nails With or without peripheral pulses With or without pain Starts as a painless nodule, an area of induration, or a diffuse swelling of the limbs Develops into massive ulcers Most commonly on the legs Undermined margins No pain, no fever Ulcers heal with scarring Can be diagnosed clinically or by direct smear examination, culture, or skin biopsy Painless ulcers Mainly over extremities Sensory loss over the extremity Peripheral nerve thickening With or without other features of leprosy Very painful lower leg ulcer – often the foot Intensely painful oedema, blister then an ulcer caused by emergence of the long worm Accompanied by intense generalized pruritus Fever, nausea, vomiting, diarrhoea, urticaria may accompany or precede vesicle formation Ulcers often develop secondary bacterial infection Drinking stagnant water in 1 of the 5 endemic countries (Ethiopia, South Sudan, Chad, Ghana, and Mali reported cases in 2010) Evolve from papular lesions through to vesicular lesions over 1-6 days Can appear as a depressed eschar with accompanied oedema Link to other suspected cases or to contaminated animal products May be associated with other clinical forms – gastrointestinal, pulmonary, or CNS Large irregular ulcers Typically above the malleoli, medial side of leg Surrounding skin hyperpigmented or eczema Varicose veins, oedema of lower limbs With or without pain Intensely painful ulcers, pain at rest Mostly on the legs or feet, more on the lateral side The surrounding skin does not show the pigmentation that is usually seen in venous ulcers Clean ulcers, may show areas of necrosis Absent peripheral pulses with claudication pain

Buruli ulcer

Leprosy (trophic ulcers) see Section 11.21

Guinea worm (dracunculiasis)

Anthrax (cutaneous form)

Chronic venous ulcers

Arterial ulcers

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Condition Sickle-cell disease see Section 10.18 Tropical ulcers

In favour Ulcers most common over lateral malleoli Susceptible to secondary infection Ulcers with raised, slightly undermined border and a yellowish necrotic base Common sites – legs, feet May heal spontaneously May extend, resulting in deep lesions and penetrate into muscle, tendon, bone Heal with much scar tissue Patients bedridden, underweight, malnourished, or dehydrated Common sites: bony areas, such as the head, elbows, heels, hips, shoulders, and tailbone.

Bed sores (pressure ulcers)

Diabetic ulcers Peripheral arterial occlusive disease is common in diabetics. Assess for risk factors that predispose the skin to ulcer formation and infection. • Signs or symptoms of claudication: pain occurring in the arch or forefoot at rest or during the night, absent popliteal or posterior tibial pulses, thinned or shiny skin, absence of hair on the lower leg and foot, redness of the affected area when the legs are dependent, and pallor when the foot is elevated. • Lack of protective sensation (from sensory neuropathy). • Decreased sweating (from autonomic neuropathy) leading to dry skin and ﬁssure formation. • Foot deformities due to atrophy of intrinsic musculature are common in diabetic patients, and lead to focal areas of high pressure. • Poor glucose control leading to impaired wound healing. • Poor footwear. • Obesity. Investigations • Blood glucose. • Plain-ﬁlm X-rays should be obtained to look for soft tissue gas and foreign bodies, and to evaluate the ulcer for bone involvement. • The involvement of underlying structures and the presence or absence of ischaemia or infection must be determined before an appropriate wound classiﬁcation can be made and a subsequent treatment plan instituted. Treatment • Control blood sugar (follow national guidelines for chronic management of diabetes). • Protective footwear. • Send pus for culture and treat with appropriate empirical antibiotics. • Debride as necessary. • May require referral for specialist management.

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Venous ulcers These are a common problem causing considerable morbidity due to chronic venous insufﬁciency and ulceration. • Usually shallow, less painful, with oedema, eczema, or hyperpigmentation of the surrounding skin. • Commonly seen just above the medial malleolus. Treatment • Control underlying medical and metabolic disorders, e.g. diabetes, hypertension. • Leg elevation: elevation of the legs as often as possible promotes venous return. • Compression: apply an elastocrepe bandage from the ankle to the knee, with higher compression applied to the foot, and decreasing compression as the bandage approaches the knee (see ﬁgure below). Compression stockings, if available, may be an effective alternative. • Secondary bacterial infection should be treated empirically (with broad spectrum penicillin or macrolide, or quinolone antibiotics). Treatment for 2 weeks should cover S. aureus. If no response, treatment should include MRSA and Gram-negative organisms (see table in Section 10.2.2). • Topical antibiotics should be avoided due to the risk of increasing bacterial resistance and contact dermatitis. • Refer for an evaluation of leg veins or ulcer in order to decide on the need for surgical intervention.

Figure: How to apply a pressure bandage

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Arterial ulcers These are commonly caused by atherosclerosis of the medium- and large-sized arteries. Other causes include diabetes, thromboangiitis, vasculitis, thalassaemia, and sickle-cell disease. • These ulcers typically occur over the toes, heels, and bony prominences of the foot. The surrounding skin may exhibit dusky erythema and may be cool to touch, hairless, thin, and brittle, with a shiny texture. The toenails thicken and become opaque and may be lost. • There may be gangrene of the extremities with decreased or absent pulse in the dorsalis pedis and posterior tibial arteries. • Pain may be present when the patient is at rest, and may be alleviated by hanging the foot over the side of the bed or sleeping in a chair. Treatment • Stop smoking. • Control diabetes, hypertension, and hyperlipidaemia, if present. • Patients may ﬁnd beneﬁts from sleeping in a bed raised at the head end. • Infection can cause rapid deterioration in an arterial ulcer, and treatment with systemic antibiotics should be started. • Patients with rest pain or worsening claudication, or both, and a non-healing ulcer should be referred to a vascular surgeon. • Opioid analgesia may be necessary during the wait for surgery.

Buruli ulcer3 This is caused by environmental mycobacterium – Mycobacterium ulcerans. The disease causes extensive destruction of skin and soft tissue. It can affect any part of the body but most commonly the limbs, and particularly the lower limbs. It is not usually associated with pain, fever, or lymph nodes. More than 50% of those infected are children and adolescents under 15 years of age. Key clinical features Pre-ulcerative stage: • subcutaneous nodule, papule, or plaque in the skin; OR • oedematous form: ° diffuse, extensive, non-pitting, swelling; ° ﬁrm, painless, ill-deﬁned margins; ° involves part or all of a limb or other part of the body (e.g. face); ° may be accompanied by fever. Ulcerative stage; • Ulcer is chronic and painless (can be massive). • Undermined edges, indurated peripherally and necrotic “cotton-wool” base. • May have multiple ulcers that communicate beneath the skin. • May involve underlying bone and joints. • May be painful if secondarily infected. • Spontaneous healing can occur after months or years. 3 Buruli ulcer. WHO. Available at: http://www.who.int/buruli/en/

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• Healing causes scarring that can cause contractures, restricted movement as well as cosmetic disﬁgurement. • Squamous cell carcinoma can develop in chronically active ulcers. Investigations Diagnosis often made clinically by experienced health workers in endemic areas. Laboratory tests used are as follows. • Direct smear examination ° On swabs from ulcers or smears from tissue biopsies. ° Can be done at facilities where TB microscopy is done. ° Sensitivity is low because M. ulcerans bacilli are not uniformly located within tissue and their numbers decrease over time. • Culture of M. ulcerans ° On swabs from ulcers or tissue biopsies. ° Takes 6–8 weeks or more. ° Sensitivity is about 20%–60%. • Polymerase chain reaction (PCR) ° On swabs of ulcers or tissue biopsies. ° Results within 2 days. ° Sensitivity is about 98%. ° Not widely available. Newer dry-reagent based PCR has been developed for use in the ﬁeld and may be used in some district hospital laboratories. • Histopathology ° On tissue biopsies. ° Sensitivity is about 90%. ° Useful when the results of the above methods are negative. ° Not widely available. Treatment • Antibiotics for all active disease. ° rifampicin 10 mg/kg daily orally for 8 weeks, PLUS streptomycin 15 mg/kg daily IM for 8 weeks (amikacin is an alternative to streptomycin)4; OR ° rifampicin plus streptomycin for 4 weeks followed by rifampin plus clarithromycin for 4 weeks (alternative regimen); OR ° rifampicin plus clarithromycin for 8 weeks (alternative regimen). Dose of clarithromycin is 7.5 mg/kg twice daily (not to exceed 500 mg twice daily); ° nodules or uncomplicated cases can be treated without hospitalization. • Surgical interventions may be needed in addition to antibiotics. ° Debridement to remove necrotic tissue. ° Skin grafting to cover skin defects. ° Correction of deformities and contractures. ° Amputation. ° Recurrence after surgery alone is 16–30%. • Prevention of disability. ° Adequate wound care (cleaning, dressing, bandaging). ° Anti-deformity positioning. ° Control of oedema (compression, elevation). ° Minimize scarring, ﬁbrosis and adhesions (lubricate skin, massage soft tissue, joint stretching exercises). ° Active participation in daily activities. 4 Amikacin is an alternative to streptomycin.

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Pressure sores (bed sores) Pressure sores are blisters or breaks in the skin caused when the body’s weight stops the ﬂow of blood to a certain area. They are often seen in bedridden, underweight, malnourished, and dehydrated patients over bony areas. The head, elbows, heels, hips, shoulders, and tailbone are the most common sites of involvement. Prevention It is important to note the following: • Pressure damage occurs more rapidly if the skin is also subject to friction (skin damage) or lateral shearing forces (capillary damage), both of which occur if patients are pulled instead of lifted. • All carers need to be taught the correct techniques of lifting and turning patients, paying attention to frequent repositioning in immobile patients (every 2 hours is recommended). • Prevention of pressure sores is better than cure (which is often impossible). • Specialized dressings (very expensive) promote healing only if pressure is relieved. • A pressure area will heal if kept clean and relieved of pressure. Adequate pressure-relieving techniques are needed. Symptom management: bedsores Hospital • Routine irrigation of pressure sores with warm saline helps remove exudates. • Antiseptics can delay healing. • If sores are infected or smelly, the exudates can be removed with 10% betadine solution, diluted to 5% with normal saline to avoid damage to new tissue. • Avoid remedies, e.g. hypochlorites, that damage granulation tissue. • Pressure-relieving aids ° Make sure that the patient does not lie on pressure sores. ° Use foam pads or pillows or water beds to take pressure off the sore. ° Use pillows to keep the knees and ankles apart. ° When the patient is laying on the back, place a pillow under the lower calves to lift the ankles slightly off the bed. ° Change the patient’s position at least every 2 hours. Advise health workers accordingly if the patient is immobile. • Physical methods of treatment to promote granulation tissue formation: ° Use ice therapy (to reduce oedema in early pressure areas). ° Treat with ultraviolet light. ° Avoid massage – it can increase skin damage. ° Surgical excision of black necrotic tissue can reduce infection and smell. ° Pain in a deep pressure sore is unusual and suggests pus under a necrotic slough. • Drugs: ° Oral zinc sulfate improves skin healing. ° Vitamin C given daily (especially if nutrition has been poor). ° Broad-spectrum antibiotics with anti-staphylococcal action (if there is cellulitis). ° Anaerobic antibiotics, such as metronidazole, should be included if there is a foul smell or the patient is ill. ° Barrier creams – applied generously and covered with gauze.

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Outpatient or primary care All patients and health workers need advice on good skin care to avoid pressure problems: • Check for signs of infection. Exclude other skin diseases. Home care Do the following to soothe the pain of bedsores and quicken healing. • For small sores, clean gently with salty water and allow to dry. • If painful, use paracetamol or aspirin. • For deep or large sores, clean daily with diluted salt water and cover with a clean, light dressing to encourage healing. ° Advise how to relieve pressure as in hospital care advice. • Signs of an infected pressure sore include the following (seek help from a health worker): ° thick yellow or green pus ° a bad smell from the sore ° redness or warmth around the sore ° swelling around the sore ° tenderness around the sore. Advice to the patient on care seeking Seek help from a trained health worker for any discoloured skin, or bedsores that are getting worse.

Tropical ulcers Key clinical features • necrotic painful lesions that result from a mixed bacterial infection; • occur on the lower legs or feet of children and young adults; • typically, have a raised, slightly undermined border and a yellowish necrotic base; • can heal spontaneously, or extend into deep lesions that penetrate into muscles, tendons, or bone; • untreated – can result in much scar tissue and disability. Treatment • Daily dressing with 0.01% potassium permanganate or 0.005% silver nitrate solution. • Systemic treatment with procaine benzylpenicillin, 600 000 IU daily (25 000–50 000 IU/kg for children and adolescents under 12 years) for 2–4 weeks.

Anthrax5 Anthrax is a notiﬁable, infectious disease, and is transmitted from infected domestic animals or wild game to humans directly or by indirect contact (their products). See Section 21.

5 Heymann DL, ed. Control of communicable diseases manual, 19th ed. APHA and WHO, 2008.

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Key clinical features • Varies from cutaneous, gastrointestinal, or inhalational involving the respiratory tract. • Skin lesions vary from papule to a blister to an ulcer with a black scab. • Blister or ulcer usually surrounded by much oedema. Investigations • Swabs from vesicular ﬂuid, or from the base of the ulcer. • Punch biopsy of papule. • Blood culture prior to antimicrobial treatment. • Gram stain isolating a Gram-positive rod-shaped Bacillus anthracis. Treatment Treat localized or uncomplicated cutaneous anthrax for 7 to10 days: • ciproﬂoxacin oral 500 mg twice daily (preferred); OR • doxycycline oral 100 mg twice daily; OR • if there is known antibiotic sensitivity, amoxicillin 500 mg 3 times daily; OR phenoxymethylpenicillin 500 mg 3 times daily are an alternative. If serious systemic illness or possible inhalation of anthrax, give multidrug IV antibiotic therapy for 10 to 14 days: • IV ciproﬂoxacin 400 mg IV twice daily (preferred) OR in ciproﬂoxacinintolerant patients, IV doxycycline 100 mg twice daily; PLUS • one or additional IV antibiotics active against B. anthracis such as rifampicin, macrolides, aminoglycosides, vancomycin, chloramphenicol, penicillin, ampicillin, clindamycin, or clarithromycin is recommended. Use at least one antibiotic with good CNS penetration (rifampicin, vancomycin, penicillin or ampicillin) and consider clindamycin as a third agent due to its potential inhibition of toxin production. If in shock, follow septic shock guidelines in Section 3.1.5. Prevention • Prolonged antibiotic prophylaxis is recommended only for persons known to have been, or are strongly suspected of having been, exposed to substantial doses of aerosolized spores in a deliberate release scenario. Report and seek expert advice if suspected bioterrorism. Treatment of bioterrorism-related cutaneous anthrax and post-exposure prophylaxis should be for 60 days, preferably with ciproﬂoxacin. • Restricted availability of vaccines for humans, reserved for persons in at-risk occupations. • See Control of communicable diseases manual5 for prevention of naturallyoccurring anthrax spread from animals, including livestock vaccination, education of persons in risk occupations, etc.

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10.3 Weight loss and malnutrition In this section: 10.3.1 Clinical approach to a patient with weight loss • Assess and classify nutritional status using anthropometric measures and nutritional oedema • Assess for underlying causes of weight loss and malnutrition 10.3.2 Consider the likely cause of loss of weight • DDx Loss of weight • DDx Weight loss while on antiretroviral therapy 10.3.3 Treat weight loss and malnutrition and its underlying causes • Treat moderate malnutrition in outpatient care • Treat severe malnutrition • Hospital care of malnutrition 10.3.4 Prevent malnutrition

Malnutrition occurs when a dietary intake is not balanced with nutritional needs. This Section provides guidance on how to assess, classify, and treat patients with malnutrition as a consequence of inadequate dietary intake or disease, exhibited by thinness, weight loss, or nutritional oedema. Micronutrient deﬁciencies are also a form of malnutrition. Micronutrient deﬁciencies are a consequence of reduced micronutrient intake or absorption in the body. The most common forms of micronutrient deﬁciencies are related to iron, vitamin A, and iodine deﬁciency. See Section10.18 for treatment of anaemia. Signiﬁcant weight loss is deﬁned as the loss of 5% or more of the body weight over a period of 6 months. A body mass index of <18.5 is deﬁned as malnutrition, although the deﬁnition of malnutrition varies in different settings.1 Malnutrition can occur as a primary disorder in adolescents and adults in conditions of extreme deprivation and famine. Malnutrition can also be caused by underlying medical and psychiatric conditions, including: • infectious diseases such as HIV, TB, parasitic infections, other chronic infections • cancers • intestinal malabsorption and liver diseases • endocrine and autoimmune diseases • psychiatric and behavioural causes leading to anorexia • alcohol and other substance dependence • medications and their side-effects • situations of dependency or insufﬁcient diet, for example the elderly, and people in prisons. This Section provides guidance on how to approach patients presenting with signiﬁcant weight loss, as well as how to manage patients presenting with poor nutritional status.

1 Nutrition landscape information system interpretation guide. WHO, 2010. Available at http://whqlibdoc.who.int/ publications/2010/9789241599955_eng.pdf

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10.3.1 Clinical approach to a patient with weight loss Step 1: Perform Quick Check to assess life-threatening conditions and treat urgently. Step 2: Assess and classify nutritional status using anthropometric measures, and clinical signs of nutritional oedema. Step 3: Assess for underlying causes of malnutrition, including manifestations of immunosuppression and opportunistic infections (such as chronic diarrhoea, fever, generalized lymphadenopathy, oral lesions, and cough), and tuberculosis. Step 4: Assess HIV status. Step 5: Treat symptomatic and underlying causes of malnutrition. Step 6: Treat and monitor patients with malnutrition.

The approach to patients presenting with malnutrition includes assessing and classifying malnutrition, as well as determining and then treating the underlying cause. It is important to assess, classify, and manage malnutrition, no matter what is the underlying cause. Current nutritional status is an important indicator of treatment outcome in many conditions. For instance, in persons with HIV, baseline malnutrition has a higher mortality even following ART initiation, and nutritional interventions support treatment retention. ART improves nutritional status, but it can also create additional issues with nutritional implications, such as dyslipidaemia and impaired glucose tolerance.

Assess the patient for life-threatening conditions and treat urgently Use the Quick Check at the front of this manual to identify and manage emergency conditions. Patients with significant weight loss could present with severe complications of an underlying systemic disease, or severe complications of malnutrition that require urgent interventions.

Assess and classify nutritional status using anthropometric measures and clinical signs of nutritional oedema The following anthropometric measures are essential for nutritional assessment and monitoring response to interventions: • weight in kg • height in cm • mid upper arm circumference (MUAC) in cm Then determine: • extent of unintentional weight loss – compare with prior measurements • body mass index (BMI) • extent of malnutrition

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Unintentional weight loss Unintentional weight loss is calculated as the percentage of weight lost from the baseline body weight (BBW) using the following formula: % of weight lost = [(BBW – current body weight)/BBW] x 100 Signiﬁcant weight loss is deﬁned as the loss of 5% or more of the body weight over a period of 6 months. However, any unintentional weight loss should carefully be investigated for underlying systemic causes and treated. Percentage of weight loss is used for WHO clinical staging of HIV disease, but is not recommended for classiﬁcation of malnutrition. Body mass index (BMI) BMI is an indicator used to classify underweight, overweight, and obesity in adolescents and adults. It is deﬁned as the weight in kilograms divided by the square of the height in metres. BMI = (kg/m²) weight in kilograms height in meters²

See the table below. For adolescents, it is recommended to calculate the genderspeciﬁc BMI for age.2 See the table on the next page. BMI requires the accurate measurement of both height and weight. Measurement of weight and height require equipment that must be calibrated and maintained. Basic calibration of weighing scales is included in the clinical practice sessions of IMCI, use of WHO Growth Standards and other courses. Quality assurance is required to ensure that reasonable accuracy of the measurements is maintained. BMI can be inaccurate in several circumstances: • Oedema complicating malnutrition or other disorders. Note that patients with malnutrition may exhibit nutritional oedema, presenting as bilateral pitting oedema. • Pregnancy. Thus, interpretation of these measurements must always be made within a clinical context.

2 WHO Gender-speciﬁc BMI for age for adolescents 5-19 years. Available at http://www.who.int/growthref/ who2007_bmi_for_age/en/index.html

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Table: Classiﬁcation of nutritional status of adults who are not pregnant or post-partum and are >18 years of age3 BMI <16.0 16.0 to 17.0 17.0 to 18.5 <18.5 18.5 to 24.99 25–29.9 >30 Classiﬁcation Severe thinness Moderate thinness Mild thinness Underweight Normal Overweight – pre-obese Obese

For adolescents, WHO recommends the use of BMI-for-age as the best indicator of malnutrition, the cut-off value being <3rd percentile2. For adolescent patients below 18 years of age, use the BMI-for-age graph at the end of this Section to assess nutritional status. Table: Classiﬁcation of nutritional status in non-pregnant, non-postpartum adolescents by body mass index-for-age <18 years of age2 Body mass index <-3 SD <-2 SD -2 SD to +1 SD +1 SD to +2 SD Classiﬁcation Severe thinness Thinness Normal Overweight

MUAC MUAC measures the circumference of the left upper arm in centimetres (cm). It is taken at a point midway between the tip of the shoulder and the elbow. MUAC is a proxy measure of nutrient reserves in muscle and fat that are not affected by pregnancy or oedema and are independent of height. MUAC has often been used as an alternative indicator of nutritional status where the collection of height and weight measurements is difﬁcult, such as during emergencies, famine, or refugee crises, or when reliable scales and height boards are not available. Although there are no normative WHO guidelines for use of MUAC among persons older than 5 years of age, some programmes use MUAC to assess adults and adolescents. However, data are limited on thresholds to classify nutritional status among adults and adolescents based on MUAC. New evidence for its utility in assessing adults may emerge from ongoing evidence reviews.

3 WHO BMI classiﬁcations. Available at http://apps.who.int/bmi/index.jsp?introPage=intro_3.html

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In the IMAI Acute Care guidelines for the health centre level, adolescents and adults can be classiﬁed as having severe malnutrition (“severe undernutrition”) and referred to therapeutic feeding if they have a MUAC <160 mm or a MUAC 161–185 mm plus one of the following4: • pitting oedema up to the knees on both sides; OR • cannot stand; OR • sunken eyes. This has been used to identify patients for admission to therapeutic feeding.

Measuring MUAC 1. Have the patient bend her or his left arm to a 90 degree angle. Locate the top of the shoulder and the elbow bone. 2. Using a string between the top of the shoulder and elbow, ﬁnd the mid of the upper arm and mark with a pen. 3. With the patient’s arm relaxed and resting at her or his side, wrap MUAC tape around the arm at the pen mark. There should not be any space between the patient’s skin and the tape, but avoid wrapping the tape too tight. 4. Read the MUAC in mm from middle window exactly where the arrows point inward. Record the MUAC to the nearest 1 mm (0.1 cm).

Assess for underlying causes of weight loss and malnutrition Look for clinical manifestations of immunosuppression and opportunistic infections (chronic diarrhoea, fever, generalized lymphadenopathy, oral lesions and cough). Assess for TB (see Section 15). Evaluate the patient by taking a history, a thorough physical examination, and performing laboratory investigations: • to assess the signiﬁcance and intentionality of the weight loss • to look for underlying systemic causes of weight loss Refer to the DDx tables Loss of weight and Weight loss while on antiretroviral therapy for the likely differential diagnosis.

4 IMAI Acute care. WHO, 2009. Available at http://www.who.int/hiv/pub/imai/primary_acute/en/index.html

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History Use the history to help identify root causes and rate of weight loss. Ask about: • weight change and how much, changes in belt notch, changes in the ﬁt of clothing • fever and night sweats • diarrhoea • pain • cough or shortness of breath • skin changes • dietary history ° loss of appetite ° difﬁculty eating, dysphasia, sore throat ° anorexia ° nausea ° change in food availability, income, or number and health of persons in household • use of alcohol • medications • presence of pregnancy or LMP • risk factors for HIV or HIV status, if known • polyuria, polydipsia, polyphagia, nocturia, blurry vision • gynaecological symptoms (vaginal bleeding, discharge, pelvic pain) • water supply, sanitation, and hygiene.

Physical examination Look for: • general appearance: weak, hunched over, slowed movements, wasted appearance, distribution of fat (lipodystrophy or lipoatrophy); • vital signs: hypotension, tachycardia, fever or hypothermia, tachypnoea; • skin: pallor, jaundice, hyperpigmentation, turgor, non-healing sores, hair loss, lanugo; • mouth: dry mucous membranes, thrush, ulcers; • neck: lymphadenopathy, thyromegaly; • musculo-skeletal and extremities: ° muscle wasting or contraction;

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° oedema of extremities: examine ankles and lower legs for pitting oedema. If symmetrical, oedema is present and its cause must be determined. In adults, nutrition-associated oedema frequently presents as bilateral pitting oedema, facial oedema, and ascites. In addition to malnutrition, causes of oedema include pre-eclampsia (in pregnant women), severe proteinuria (nephrotic syndrome), nephritis, acute ﬁlariasis (the limb is hot and painful), heart failure, and wet beriberi. Non-nutritional causes of oedema can readily be identiﬁed by the history, physical examination, and urinalysis. See Section 10.4; • cardiac, pulmonary, abdominal exam; • rectal and vaginal examination; • neurological and psychiatric assessment.

Investigations Essential • HIV testing and CD4 count, if positive • stool examination (for occult blood, ova, or parasites) • haemoglobin • full blood count (FBC) • sputum AFBs, or other additional investigation, if smear-negative, or pulmonary or extrapulmonary, TB is suspected (see Section 15) • check glucose – blood or urine to exclude diabetes mellitus • urine dipstick – protein, blood, or glucose. Additional • blood tests as necessary – check renal, liver, thyroid functions • ultrasound • cancer screening (for example, VIA for cervical cancer, feel for masses or abnormal lymph nodes – see Section 10.15). A detailed nutrition and diet history, as well as an assessment of symptoms associated with weight loss, helps in identifying any underlying diseases. The availability of adequate food and household food security should also be assessed.

10.3.2 Consider the likely cause of loss of weight Use the ﬁrst differential diagnosis table for all patients to identify a diagnosis or underlying cause of weight loss. In PLHIV on ARV therapy, there are additional causes for weight loss that should be considered; these appear in the second DDx table below. If the patient is a known HIV-positive individual or is taking antiretroviral treatment, also see Section 13 for the management of weight loss in people with HIV after using this Section.

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DDx: Loss of weight Consider as diagnosis or underlying cause Poorly controlled diabetes If patient has Polyuria and polydipsia Orthostatic hypotension Dehydration Raised blood glucose

Other chronic diseases: CHF, COPD, other chronic lung disease Peptic ulcer disease, gastritis Hyperemesis in pregnancy Substance use Thyrotoxicosis Chronic vomiting Pregnancy, especially ﬁrst trimester see Section 17 Thyroid enlargement and proptosis Fatigue Palpitations and tachycardia Heat intolerance, excessive sweating, tremor Nervousness Brisk reﬂexes Low TSH Fever Night sweats Cough (especially chronic or persistent) Lymphadenopathy Sputum or FNA AFB positive Exudative ascites or pleural effusion Chest X-ray – suggestive changes Ultrasound – abdominal lymphadenopathy Loss of weight >10% from baseline (WHO clinical stage 3) Chronic diarrhoea or fever longer than 1 month with unexplained cause (WHO clinical stage 3) Known HIV-positive Diarrhoea >1 month Not responsive to empirical therapy Known HIV-positive Low CD4 count Other WHO clinical stage 4 deﬁning condition

Tuberculosis see Section 15

HIV wasting syndrome

Chronic diarrhoea, e.g. cryptosporidiosis, isosporiasis, HIV enteropathy see Section 10.7 Other neglected tropical diseases (NTD)

Mycobacterium avium complex (MAC) see Section 11.27

Fever Lymphadenopathy Diarrhoea Known HIV-positive Low CD4 count Oral candidiasis Odynophagia, dysphagia, and retrosternal chest pain Responsive to ﬂuconazole

Oesophageal candidiasis see Sections 10.7b Painful or difﬁcult swallowing and 11.4 Candida

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Malabsorption syndromes, e.g. celiac disease, sprue Malignancy

Loss of appetite Distended abdomen with bloating Loose fatty stools (steatorrhoea) Symptoms vary according to site of malignancy, e.g. cervical, Kaposi Sarcoma, liver Evidence of primary tumour, evidence of metastases Poverty and lack of availability of food Sad or low mood Fatigue or loss of energy Loss of appetite Sleep disturbances Previous history of depression Abnormal focus on eating behaviour, body shape, and weight Avoidance of food Adequate food available, no organic cause found Delusions about food

Starvation Depression see Section 10.11

Eating disorders, e.g. anorexia nervosa, bulimia Other psychiatric disorders, e.g. psychosis see Section 10.11 Dementia with poor care see Section 10.11

Forgetfulness Misplacing things Difﬁculty in carrying out daily routines Lack of care taker or support system

DDx: Weight loss while on antiretroviral therapy – consider all of the above, plus: Diagnosis or underlying cause IRIS (Immune reconstitution inﬂammatory syndrome) see Section 13 In favour Usually starts within 2–3 weeks of initiating ART Fever, sweats Possibly enlarging lymph nodes Cough Evidence of pathogen or disease, e.g. chest X-ray changes Symptoms of speciﬁc OI, e.g. fever, night sweats, cough, lymphadenopathy, diarrhoea Low CD4 count Many months on ART, good adherence On AZT or d4T-containing regimen (or ddI) Nausea and vomiting Abdominal pain Dyspnoea (late stage) with deep breathing Dehydration No evidence of new OIs Low bicarbonate, high anion gap High lactate High CD4 count Undetectable viral load

Opportunistic infection, e.g. tuberculosis

Symptomatic hyperlactataemia or lactic acidosis See Section 13

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Diagnosis or underlying cause Lipoatrophy (as part of lipodystrophy)

In favour Months to years of successful ARV therapy d4T-containing ARV regimen Fat wasting, particularly of face, arms, and legs No constitutional symptoms Normal chemistries High CD4 count Viral load undetectable On antiretroviral drugs >6 months Features of HIV – new Stage 2, 3, 4 events Decreasing CD4 – see ART failure section High viral load (failing ARV regimen) Non-tender, enlarging nodes Systemic symptoms: fever, weight loss, night sweats, malaise, itch Evidence of spread to skin, CNS, gut, lung, bone marrow Low CD4 count Histology – B or T cell proliferation Good adherence, no evidence of OIs, insufﬁcient food or no stable livelihood

Treatment failure and HIV disease progression

Lymphoma

Inadequate food security

10.3.3 Treat weight loss and malnutrition and its underlying causes Having used the differential diagnosis tables to determine the diagnosis or underlying cause contributing to the weight loss or malnutrition, treat both the immediate symptomatic, as well as the underlying causes at all levels. For example, in the case of oral or oesophageal candidiasis, symptomatic treatment for mouth pain and odynophagia should be offered, as should treatment with antifungal agents. Stage HIV disease using clinical (WHO clinical stage 3 and 4) or immunological (CD4 count ≤350 cells/mm3) criteria, and initiate ART if eligible. See Section 13. Refer to various Sections of this manual based on likely diagnoses. Treat and monitor patients with poor nutritional status5

Treat moderate malnutrition in outpatient care Moderately thin adolescents and adults require an additional 20–30% caloric intake that should be provided, in addition to their normal intake, in the form of frequent smaller amounts of locally available nutrient-rich food. Recommend diet considering those needs. If available, enrol the person in a programme where nutritional assessment, counselling, and support including supplementary feeding are available.

5 The WHO Department of Nutrition for Health and Development (NHD) is developing evidence-based guidelines for nutritional interventions and has established the Nutrition Guidance Expert Advisory Group (NUGAG) to conduct evidence reviews and recommendations. These should be available by mid 2012. A training course in nutritional care and support for people living with HIV is available at http://www.who.int/nutrition/publications/ hivaids/9789241591898/en/index.html

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Determine and treat the underlying cause of malnutrition. Offer nutritional counselling and information for weight gain. Encourage small and frequent meals. Treat nausea, thrush, and diarrhoea when indicated. Link or refer to community or home-based nutritional interventions or food security initiatives, if possible. Ensure follow-up visits and assessment.

Treat severe malnutrition Adolescents and adults with severe malnutrition may be managed as outpatients in a food-by-prescription programme, providing that they are ambulatory (good Karnovsky score) and do not have a medical condition that requires hospital admission. Those with severe malnutrition should be treated as inpatients if an outpatient therapeutic feeding programme does not exist.

Hospital care of malnutrition Initial treatment (stabilization): If able to consume food, patients with severe malnutrition require ready-to-use therapeutic foods; therapeutic foods should not be combined with additional vitamins and minerals, since they are already fortiﬁed at levels considerably higher than the RDA, to correct deﬁciencies and allow rebuilding of lost tissues. The initial goal of treatment is to prevent further tissue loss. The amount of food given per kg of body weight is much less for adults than for children, and decreases with increasing age reﬂecting the lower energy requirements of adults. Recommended amounts for different ages are given in the table on the next page. These amounts will meet all nutrient requirements of adolescents and adults. Nasogastric tube feeding should only be used when there is no alternative. Adolescent and adult patients who have severe malnutrition can be given any or all of the following: ready-to-use food, fortiﬁed blended ﬂours, formula milks (F75, F100), as available. Table: Dietary requirements for initial treatment of severely malnourished adolescents and adults6 Age (years) Daily energy requirementsa (Kcal /kg) 7–10 11–14 15–18 19–75 >75 75 60 50 40 35 (KJ/kg) 315 250 210 170 150 Volume of diet required (ml/kg per hour) F-75b 4.2 3.5 2.8 2.2 2.0 F-100b 3.0 2.5 2.0 1.7 1.5

a Individual needs may vary up to 30% from these ﬁgures depending on sex, activity level, infections and other factors. b F-75 and F-100 are therapeutic milk products designed to treat severe malnutrition. Ingredients include concentrated milk powder, food oil, and dextrin vitamin complexes. The designations mean that the product contains respectively 75 and 100 kcals per 100 ml.

6 Management of severe malnutrition: A manual for physicians and other senior health workers. WHO, 1999. Available at http://whqlibdoc.who.int/hq/1999/a57361.pdf

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Severely malnourished adults and adolescents are also susceptible to hypothermia, hypoglycaemia, and dehydration. Treat and prevent hypothermia, hypoglycaemia (see Quick Check page 19), and dehydration (see Section 10.7). Adolescent and adult patients who have severe malnutrition should be assessed for co-existing medical conditions and provided with appropriate treatment. Ready-to-use food has been shown to be very effective for children with severe acute malnutrition. It has recently been used for PLHIV. Ready-to-use food has potential in this area as it is energy- and nutrient-dense, can be made with an appropriate balance of nutrients, and does not require cooking. Its high energy density means that sufﬁcient calories can be delivered without the patient being expected to digest large bulky meals. Adaptations and alternative formulations for adults and speciﬁc patient groups are underway. These are relatively expensive, and cost-effectiveness is a consideration. Care should be taken when administering intravenous feeds and ﬂuids to patients with unknown cardiac status and albumin levels, as severe oedema (including pulmonary oedema) may result. In patients with HIV, antiretroviral medication should not be stopped during refeeding, unless there are other reasons to stop the medications. For a patient who is not yet receiving ARVs, ART should not be initiated during the initial management of severe acute malnutrition (stabilisation phase) but should start during or after the rehabilitation phase. The rehabilitation phase after which ART should be initiated is short (several days up to 2 weeks). When possible, ﬁnd out what might be causing the loss of weight and manage accordingly. Use the above differential diagnosis tables of Loss of weight and Weight loss while on antiretroviral therapy. Rehabilitation An improving appetite indicates the beginning of rehabilitation. During rehabilitation, it is usual for adolescents and adults to become very hungry, sometimes refusing the specialized foods and requesting enormous amounts of other foods. When this happens, a diet should be given that is based on traditional foods, but with added oil, mineral mix, and vitamin mix. Provide a wide variety of nutrient-dense foods, and allow the patient to eat as much as she or he desires. In the rehabilitation phase, adolescent and adult patients recovering from severe malnutrition should continue to receive therapeutic foods plus traditional foods with added oil, vitamins, and minerals, as tolerated. If possible, continue to give the formula feed with the vitamin and mineral mixes between meals and at night. If necessary, present the formula feed as a medicine. Criteria for discharge Severely malnourished adolescents and adults can be discharged when: • they are eating well and gaining weight • they have a reliable source of nutritious food outside the hospital • any other health problems have been diagnosed and treatment has begun.

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Adults should continue to receive a supplemented diet as outpatients until their BMI is >18.5; for adolescents, their diets should be supplemented until their BMIfor-age is >5th percentile of the median NCHS/WHO reference values.2 Failure to respond to treatment Failure to respond to treatment in adults and adolescents is usually due to an unrecognized underlying illness, a nutrient deﬁciency, or refusal to follow the treatment regimen.

10.3.4 Prevent malnutrition Encourage the sick person to eat, but do not use force as the body may not be able to accept it, and the patient may vomit. • Offer smaller, attractive meals of what the sick person likes more frequently. • Let the sick person choose the foods she or he desires to eat from what is available. • Encourage the patient to eat nutrient-dense foods that are locally available. Monitor weight and address causes of weight loss before the patient develops malnutrition. Advice to patient on care seeking: Seek help from a trained health worker if you notice rapid weight loss or if the sick person consistently refuses to eat any food or is not able to swallow. Community nutrition delivery mechanisms have been shown to be effective in many programmes. Community-based feeding programmes and home-based care share many common components, including emphases on physical care, a continuum of care, health education, local capacity-building, ensured access, sustainable support, and community-based case-ﬁnding strategies. If available, enrol the person in a programme where nutritional assessment, counselling, and support, including supplementary feeding, are available. Determine and treat underlying causes of malnutrition. Offer nutritional counselling and information for weight gain. Encourage small and frequent meals. Treat nausea, thrush, and diarrhoea when indicated. Link or refer to community- or home-based nutritional interventions or food security initiatives, if available. To prevent malnutrition in PLHIV, where feasible, recommend home care for all adolescents and adults living with HIV.7

7 More detailed advice on home-based prevention of malnutrition is provided in: Living well with HIV/AIDS. FAO and WHO, 2002. Available at http://www.fao.org/DOCREP/005/Y4168E/Y4168E00.HTM

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10.4 Swelling of the limbs In this section: 10.4.1 Clinical approach to swelling of the limbs 10.4.2 Differential diagnosis of oedema (with DDx tables) • DDx: Unilateral limb swelling • DDx: Bilateral limb swelling or generalized swelling 10.4.3 Treatment of limb swelling with pitting oedema 10.4.4 Symptom management of pitting oedema 10.4.5 Manage lymphoedema (non-pitting oedema)

Swelling of the limbs may be: • bilateral, usually due to: ° oedema (deﬁned below) OR • unilateral, due to: ° infections (e.g. cellulitis) ° blocked veins (e.g. by blood clot or compression) ° blocked lymphatic duct (e.g. by tumour or infections) ° trauma and bleeding. The swelling may be subtle and only found on examination, or the patient may complain of: • swollen limbs • unexplained weight gain • tightness of rings or shoes • other symptoms associated with the primary cause. If the swelling involves the whole body the patient may complain of: • facial swelling or pufﬁness. Oedema is ﬂuid collecting in the interstitial spaces and is found in dependant areas, e.g. the legs (in ambulant patients) or the sacrum (in bed-bound patients). Anasarca is when the oedema and swelling is generalized and affects the whole body and not just the legs.

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10.4.1 Clinical approach to swelling of the limbs Step 1: Perform Quick Check. In women, consider pre-eclampsia (pregnancy with raised blood pressure). Ask about a possible snake or other animal bite, as this may require urgent attention. Step 2: Take a history and examine the patient. Determine the extent and duration of the swelling. Step 3: Assess HIV status. Step 4: Classify using DDx tables and consider likely differential diagnoses. Step 5: Perform investigations that may conﬁrm your diagnosis. Step 6: Initiate treatment and monitor response.

History General Is the limb swelling unilateral or bilateral? • Is the onset: ° acute (within the previous day) ° subacute (over the past week) ° chronic and long-standing? • Is there associated pain or tenderness? • Is there associated lymphadenopathy? • Does the patient have fever? • Ask about the possibility of pregnancy. For generalized oedema, ask about symptoms that may indicate an underlying cause. • cardiac: ° dyspnoea on exertion ° orthopnoea (difﬁculty lying ﬂat) ° paroxysmal nocturnal dyspnoea (PND) (shortness of breath at night) ° known cardiac disease. • liver: ° history of liver disease or jaundice. • renal disease • low-protein states: ° malnutrition ° chronic diarrhoea.

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Examination General • Assess the extent of the swelling: ° Is it bilateral or unilateral? ° Does it involve only the upper or lower limbs or the whole body? • Is the swelling pitting? ° Pitting can be demonstrated by applying ﬁrm pressure to the swollen area with the thumb (preferably over a bone, e.g. the anterior tibia). Pressure is applied for a few seconds, and if an indentation persists after the release of the pressure, it is referred to as pitting oedema. Look for an underlying cause • Blood pressure – particularly if pregnant • Look for local causes: ° tumours or nodules on the skin – e.g. Kaposi sarcoma ° any infection or inﬂammation of the limb ° enlarged lymph nodes draining the site. • Look for other causes: ° evidence of congestive cardiac failure, particularly elevated JVP ° evidence of liver disease – assess the size and consistency of the liver, look for signs of chronic liver disease (see Sections 10.8 Jaundice and 10.9 Ascites). • Assess other systems: ° pulmonary oedema or pleural effusion ° ascites (see Section 10.9 Ascites) ° evidence of Kaposi sarcoma elsewhere. Assess HIV status See Section 9.

10.4.2 Differential diagnosis of oedema Classify the swelling according to the: 1. extent – unilateral (conﬁned to a single limb) or bilateral or generalized and 2. duration – acute or subacute in onset or long-standing.

DDx: Unilateral limb swelling Condition Acute onset Deep vein thrombosis (DVT) Low grade fever <38.5°C Risk factors – immobilization or trauma to pelvis, limb, long haul bus or plane travel, pregnancy, malignancy Calf pain and tenderness Swelling of leg with pitting oedema, erythema Systemically ill – fever and tachycardia Redness and inﬂammation of the skin and subcutaneous tissue Old bite or sore Lab – high WCC History of trauma or sprain Bruising Pain with movement or weight-bearing In favour

Cellulitis see Section 10.2

Local injury

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Snake-bite see Section 3.9 Subacute or chronic Kaposi sarcoma see Section 11.19 Lymphatic obstruction

History of bite Rapidly progressive swelling Pain

HIV-positive Purple plaques and nodules History of malignancy (e.g. Kaposi sarcoma, breast, pelvic), surgery or radiation to the area Non-pitting oedema Hyperpigmentation Enlarged lymph nodes Insidious onset Non-tender Endemic area Prior history of DVT Distended veins

Lymphatic ﬁlariasis see 11.12 Venous insufﬁciency e.g. post DVT

DDx: Bilateral limb swelling or generalized swelling Condition Acute onset Cardiac failure History of heart disease Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea Pitting oedema of legs Hepatomegaly Crackles in chest, S3 gallop Elevated JVP Hypertension, oliguria Urine dipstick: macroscopic haematuria, red cell casts, dysmorphic RBCs, leukocytes and some proteinuria In favour

Renal disease – acute nephritic syndrome see Section 11.31 Subacute or chronic Renal disease – nephrotic syndrome see Section 11.31

Pitting oedema Anasarca with periorbital oedema Urine dipstick: proteinuria Abnormal renal function tests Wasted Hair loss Hyperpigmentation Facial oedema Ascites may be present Low serum albumin Jaundice, palmar erythema, spider angiomata, caput medusae Splenomegaly, ascites Fetor hepaticus Gynaecomastia Duputren’s contracture Elevated LFTs: elevated AST, ALT, alkaline phosphatase Low serum albumin level Prolonged INR

Severe malnutrition see Section 10.3

Chronic liver disease, cirrhosis see Section 10.9

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Condition Pretibial myxoedema – hyperthyroidism

In favour Heat intolerance, sweating, tremor, tachycardia Weight loss Constipation Fatigue Irregular menstrual ﬂow Non-pitting oedema – nodular appearance above the malleoli Known history Abdominal distension Splenomegaly Normal LFTs

Portal vein obstruction

Perform investigations • urine dipstick – protein, glucose • blood glucose • serum albumin, protein • renal function test (serum creatinine, BUN) • liver function tests • ultrasound of the abdomen or pelvis • doppler ultrasound of the limbs – if DVT suspected.

10.4.3 Treatment of limb swelling with pitting oedema • It is important to identify the underlying cause in order to give speciﬁc treatment. ° For bilateral pitting oedema due to interstitial ﬂuid (such as cardiac, renal, or liver failure), give diuretics. ° Do not give diuretics for lymphatic obstruction or other causes of nonpitting oedema (lymphoedema). • furosemide 40–80 mg ° diuresis should occur within 1 hour and lasts 6 hours; preferred treatment in most cases of oedema. ◊ hypotension can occur ◊ hypokalaemia can occur (see Section 5.2) ◊ avoid at night (sleep disturbance) ◊ high doses needed in renal failure (see Section 11.31) ° Infuse furosemide slowly (not more than 4 mg/minute). • amiloride 5–10 mg daily ° potassium-sparing diuretic ° given with furosemide to prevent hypokalaemia. ° Do not give if hyperkalaemia or renal failure. • spironolactone 100–200 mg daily (can give up to 400 mg), given with furosemide ° preferred combination in cirrhosis and end-stage heart failure ° potassium sparing diuretic ° causes nausea, gynaecomastia ° contraindicated in hyperkalaemia and hyponatraemia.

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• hydrochlorothiazide 25 mg daily ° use in combination with furosemide for resistant generalized oedema but not in cirrhosis ° avoid if the patient also has gout ° hypokalaemia can occur.

10.4.4 Symptom management of pitting oedema In addition to treatment of infection or diuretic treatment for pitting oedema, several interventions can reduce morbidity. • Exercise ° Flex the ankles. ° Walking reduces ankle oedema. • Elevation of the legs ° Legs should be above horizontal. ° Support the whole limb. • Compression stockings • Compression pump ° Shifts soft oedema very rapidly. ° Beware of precipitating heart failure by sudden shift of ﬂuid. ° Keep pressure below 60 mm Hg. ° Follow up with a support stocking. • Skin care ° Use bland non-scented products for daily cleansing and moisturizing. ° Compression and good skin care can reduce the occurrence of leakage, lymphocele, papilloma. ° Non-adherent dressings can reduce leakage. ° Try support stockings (above the knee). Stop if uncomfortable. ° Provide good skin care to prevent cellulitis and infection (see Sections 10.2 and 20).

10.4.5 Manage lymphoedema (non-pitting oedema) • Treatment ° diuretics not indicated, and not effective ° elevation ° exercise ° bandages ° compression garments ° massage (manual lymph drainage) ° compression pump ° antibiotics if cellulitis develops – see Section 10.2. • Prevention ° Careful skin hygiene to prevent infection – encourage the use of moisturizers and topical antibiotics after even small breaks in the skin. ° Elevate affected extremities as much as possible, even while asleep. ° Avoid tight-ﬁtting clothes. ° Avoid medical procedures (except IV lines or blood draws) on affected extremities.

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10.5 Lymphadenopathy and lumps In this section: 10.5.1 Clinical approach to lymphadenopathy and lumps 10.5.2 Classify the lymphadenopathy and consider the differential diagnosis • DDx: Localized or regional lymphadenopathy • DDx: Generalized lymphadenopathy 10.5.3 Approach to lymphadenopathy in PLHIV 10.5.4 Symptom management of lymphadenopathy

This Section provides an approach to the patient with a swelling or lump that may be an abnormal enlargement of lymph nodes.

10.5.1 Clinical approach to lymphadenopathy and lumps Step 1: Use Quick Check. Ensure that there are no serious or life-threatening conditions. Be aware that lymph nodes can cause compression of the upper airway and difﬁculty breathing. Suppurating lymph nodes may be infective – separate these patients at triage. Step 2: Take a history and examine the patient. • Conﬁrm that it is lymphadenopathy. • Look for underlying cause and associated conditions. Step 3: Assess HIV status. Step 4: Classify the lymphadenopathy and consider the likely differential diagnosis using the DDx table(s). • DDx localized or regional lymphadenopathy • DDx generalized lymphadenopathy Step 5: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response. Always consider TB.

History • • • • • • How long has it been there, and is it changing in size? Is it painful? Is it draining pus or ﬂuid? Prior TB or contact with TB? Travel or occupational exposure? Constitutional symptoms? Lymph node groups

Examination Conﬁrm lymphadenopathy • Exclude other possible causes for a mass such as: ° hernia ° aneurysm ° lipoma ° abscess ° foreign body ° cyst

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° neoplasm ° neuroﬁbroma. • Position: see ﬁgure for sites. Remember that each group of lymph nodes drains a speciﬁc area and local pathology will occur in the drainage area. • quality – assess lymph nodes for: ° size: (remember that the lymph nodes grow progressively until the age of late childhood, and then undergo progressive atrophy during puberty. It is therefore normal to have palpable anterior cervical, inguinal, and axillary nodes in children). Check for: • erythema • tenderness • warmth • consistency (Are they ﬁrm? Are they ﬂuctuant?) • mobility (Are the lymph nodes matted together? Are they ﬁxed to the adjacent structures?). • pulsatile? • bowel sounds? Classify the lymphadenopathy as localized or regional, or generalized. • Localized or regional lymphadenopathy – nodes are localized to a single site. The cause is often apparent if the area is thoroughly examined. Look for evidence of local pathology such as: ° dental, or ear, nose, or throat disease ° STIs ° skin problems – infections, bites, dermatitis, phlebitis ° malignancy ° breast pathology. • Generalized lymphadenopathy is the enlargement of lymph nodes at two or more sites. Look for evidence of underlying systemic disease. ° Perform general examination looking particularly for pallor, wasting, fever, petechiae, or other rash. ° Examine the liver, spleen, and other organ systems. ° Feel for bone tenderness. Nodes may be enlarged within the chest and abdomen. These may be seen on a chest x-ray or an abdominal ultrasound. Assess HIV status See Section 9.

Investigations • Full blood count: ° look for evidence of infection, disseminated disease or malignancy. • Perform sputum examination for TB. • Chest x-ray (see Section 10.6): ° lymphadenopathy is often apparent as hilar shadows ° look for evidence of TB.

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• Ultrasound: ° abdominal lymphadenopathy, organomegaly or free ﬂuid in the abdomen. • Fine needle aspiration (FNA) of lymph node (see Section 7.2.5). Pay special attention to the choice of lymph node on which to perform FNA. ° Send sample for AFB smear. • Additional tests may include: ° Cytology – look for presence of malignant cells (use ﬁxative on the slide). ° Culture – identify speciﬁc organisms (if enough ﬂuid or pus is aspirated). DO NOT DO a FNA if the mass is pulsatile or has bowel sounds. It could be an aneurysm or a hernia. • Lymph node biopsy (see Section 7.2.6 Procedures): ° microscopy – identiﬁcation of organisms (speciﬁc stains may be required for certain organisms) ° culture – speciﬁc organisms may be isolated ° histology – characteristics of tissue architecture ° cytology – evidence of malignancy and severity of dysplasia. Consider locally common diseases that may require speciﬁc investigations. See DDx tables below.

Treatment For focal infection: • Start broad-spectrum antibiotics that include coverage for Staphylococcus aureus and Streptococcus pyogenes. • Expect an improvement within 48 hours and a response to treatment within a week. • If there is poor response to treatment, consider TB or malignancy. A biopsy may be indicated. For management of conditions requiring speciﬁc treatment, see Section links in the differential diagnosis tables.

10.5.2 Classify the lymphadenopathy and consider the differential diagnosis Assess whether the lymphadenopathy is localized or regional, or generalized, and consult the relevant DDx table below to consider the likely differential diagnosis.

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DDx: Localized or regional lymphadenopathy Condition In favour Unilateral – in neck May be ﬂuctuant or discharging Single or multiple nodes – not red, painful, or inﬂamed; may be matted Constitutional symptoms – night sweats, loss of weight, fever Evidence of TB elsewhere (e.g. typical chest X-ray, sputum AFB) FNA – AFB positive Acute onset Painful, red, inﬂamed Local source of infection Tender inguinal lymphadenopathy Coalescence of nodes – may be ﬂuctuant or discharging History of genital ulcers Dark purple, painless lesions or nodules Associated lymphoedema Non-tender, enlarging nodes Systemic symptoms – fever, weight loss, night sweats, malaise, itch Evidence of spread to skin, CNS, gut, lung, bone marrow Low CD4 count Histology – B or T cell proliferation Non-tender, hard, irregular node Node ﬁxed to surrounding tissue Evidence of primary malignancy in the area drained by the lymph node Petechiae Pallor Splenomegaly Weight loss Fever Sweating Extreme fatigue FBC-anaemia, thrombocytopenia, neutropaenia, lymphocytosis Blast cells in peripheral blood, bone marrow, or tissue biopsy Recent initiation of ART with very low CD4 count Painful, enlarging lymph nodes – neck or axilla Fever Acute: recurrent episodes of fever, tender localized lymphadenopathy, and epididymitis Chronic: lymphoedema of associated limb Generalized lymphadenopathy, particularly in posterior cervical triangle Papule or indurated nodule (site of tsetse ﬂy bite) Intermittent fever, headaches Disturbed sleep, poor concentration, and personality changes Epidemiological evidence (patient coming from endemic area or has travelled to endemic area) Unwell patient with fever, extreme tiredness Large, painful, very tender lymph gland – bubo History of exposure to possibly infected rodents or ﬂeas

TB lymphadenitis see Section 15

Focal infection

Sexually transmitted infection see Sections 10.14, 10.15, and 10.16 Kaposi sarcoma see Section 11.19 Lymphoma

Malignancy

Leukaemia

Immune reconstitution inﬂammatory syndrome (IRIS) see Section 13 Lymphatic ﬁlariasis (endemic areas) see Section 11.12 African human trypanosomiasis (sleeping sickness) see Section 11.41

Plague – bubonic

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DDx: Localized or regional lymphadenopathy Condition Viral infections In favour Prodrome of malaise, fever, upper respiratory tract symptoms, body or joint pain Generalized rash and lymphadenopathy Possible causes – measles, rubella, EBV, CMV or this may be an HIV seroconversion illness Night sweats, loss of weight, fever Evidence of TB elsewhere (e.g. chest X-ray, sputum or FNA – AFB positive) May have associated hepatosplenomegaly Unwell patient Persistent fever and night sweats, diarrhoea, with or without pulmonary symptoms May have hepatomegaly and anaemia Lymph node FNA – AFB positive (culture needed to distinguish from TB) Advanced HIV infection: CD4 <100 Symmetrical nodes >3 months Early HIV disease and often asymptomatic, but can coexist with more advanced manifestations Occipital and epitrochlear lymph nodes enlarged Multiple abscesses in skin and lungs Recurrent fever Immunocompromised patient CD4 <100 Unwell patient – fever, malaise, skin lesions with or without lung involvement Immunocompromised patient: CD4 <100 Firm, discrete, and mildly tender nodes Fever Maculo-papular rash – involving palms and soles History of previous chancre or residual genital chancre (25%) Syphilis test positive Cough, chest pain, dyspnoea Fatigue, loss of weight, malaise, low-grade fever Chest X-ray: hilar lymphadenopathy LN biopsy: histology shows non-caseating granulomas Endemic areas in Africa Generalized lymphadenopathy, particularly in posterior cervical triangle Papule or indurated nodule (site of tsetse ﬂy bite) Intermittent fever, headaches Disturbed sleep, poor concentration, and personality changes

Miliary TB see Section 15

Mycobacterium avium complex (MAC) see Section 11.27

Persistent generalized lymphadenopathy see below Nocardiosis

Fungal infections e.g. penicilliosis, histoplasmosis, cryptococcosis see Section 11 Secondary syphilis see Section 11.37

Sarcoidosis

African human trypanosomiasis (Sleeping sickness) see Section 11.41

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Bubonic plague1 Treatment: • streptomycin 1 gram every 12 hours IV (preferred); OR • gentamicin 5 mg/kg/day in 3 equal doses every 8 hours or 5 mg/kg once daily (alternative); OR • doxycycline 200 mg loading dose then 100 mg oral or IV twice daily (alternative); OR • chloramphenicol 50 mg/kg/day in 4 equal doses (preferred for plague meningitis). • Treatment is for 7-10 days. • Consider post-exposure prophylaxis for close contacts (e.g. household, care providers), especially contacts of pneumonic plague: ° doxycycline 100 mg oral twice daily for 7 days (preferred); OR ° ciproﬂoxacin 500 mg twice daily for 7 days (alternative). Note: Notify all cases of suspected plague within 24 hours. See Section 21.

10.5.3 Approach to lymphadenopathy in PLHIV Lymphadenopathy in PLHIV is an important ﬁnding at any stage. For all patients with HIV all sites should be examined regularly for the presence of nodes and any change in node size or consistency. If signiﬁcant lymphadenopathy is present, every effort should be made to ﬁnd a cause, as this may be due to opportunistic infections, IRIS, or persistent generalized lymphadenopathy.

Opportunistic infections • Look for infections and treat before commencing ART to reduce the risk of IRIS. • Tuberculosis is very common.

Persistent generalized lymphadenopathy (PGL) • WHO Stage 1 condition – PGL is a clinical diagnosis after exclusion of opportunistic infections. ° Deﬁned as non-tender, enlarged lymph nodes of >1 cm in 2 or more noncontiguous sites (excluding inguinal) and persisting for ≥3 months. ° Lymphadenopathy is symmetrical and often involves the posterior cervical, axillary, occipital, and epitrochlear nodes. ° No speciﬁc treatment is required. • Generalized lymphadenopathy in advanced HIV disease is often due to an underlying opportunistic infection.

1 Heymann DL, ed. Control of communicable diseases manual, 19th ed. APHA and WHO, 2008.

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Immune reconstitution inﬂammatory syndrome (IRIS) IRIS commonly presents with lymphadenopathy. It may be necessary to aspirate or biopsy the lymph node for a deﬁnitive diagnosis. Common IRIS conditions include: • TB • MAC • cryptococcosis • Kaposi sarcoma • lymphoma. Treat the underlying condition and continue ART. See Section 13 Chronic HIV care for more details.

10.5.4 Symptom management of lymphadenopathy • Provide adequate analgesia. • If the swelling is severe steroid therapy may be required, but only when speciﬁc treatment for the cause is also provided. • Ensure discharging lymph nodes are covered.

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10.6 Chest symptoms: cough and shortness of breath In this section: 10.6.1 Clinical approach to a patient with chest symptoms • Interpretation of chest X-ray ﬁndings 10.6.2 Differential diagnosis of chest complaints • DDx: X-ray abnormalities in patients with acute chest symptoms • DDx: Difﬁcult breathing or cough – with fever • DDx: Difﬁcult breathing or cough – without fever • DDx: Chest pain • Evaluation and differential diagnosis of pleural effusion 10.6.3 Pneumonia • Determining the need for hospitalization • Outpatient management of non-severe pneumonia • Pneumocystis jirovecii pneumonia • Inﬂuenza pneumonia • Varicella pneumonia 10.6.4 Asthma • Classify asthma severity • Table: Examples of increasing dosage and choice of medications by asthma severity 10.6.5 Chronic obstructive pulmonary disease • Classify COPD severity • Example of approach to management of COPD

This Section provides an approach to patients presenting with the most frequent chest symptoms: shortness of breath, cough, and chest pain. This approach is intended for patients who do not have conditions that require emergency management (described in Quick Check) or have been stabilized after emergency treatment and require more deﬁnitive diagnosis and management that can be approached more slowly. This Section should be viewed as part of a continuum of care, beginning with Quick Check, and proceeding through Section 3.2 (Severely ill patient with respiratory distress) for patients who require urgent care.

10.6.1 Clinical approach to a patient with chest symptoms Step 1: Use Quick Check. on every patient and initiate emergency management as needed. In patients with severe difﬁculty breathing, proceed with diagnosis and urgent management as described in Section 3.2. In patients with chest pain, proceed as described in Section 3.3. Step 2: Take a history and examine the patient. Step 3: Assess HIV status. Step 4: Consider likely differential diagnosis using the DDx table(s). Utilize the appropriate differential diagnosis tables and establish a list of possible diagnoses ranked in order of likelihood. Step 5: Perform investigations as required, based on the possible diagnoses. Step 6: Initiate treatment and monitor the response.

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The key features of an illness or symptom are its severity and rapidity of progression. Severe or rapidly progressive conditions should be managed as per Quick Check (emergency illness) and Section 3 (severe illness). Occasionally, conditions requiring emergency or urgent management will have been missed in triage, so all patients should have a repeated Quick Check to be certain they have been appropriately evaluated for emergency conditions and treated. Shortness of breath, cough, and chest pain may occur alone or in combination and may be the result of either infectious or non-infectious diseases. In some patients, particularly those with compromised immune systems, multiple infectious and non-infectious processes may be present at the same time. The clinician should consider additional diagnoses, even after establishing one diagnosis.

History Obtaining a medical history is a critical component of the diagnostic evaluation and should both help direct the physical examination and prompt more targeted questions. The history should be linked to the physical examination. While taking the history, observe the general status, e.g. whether too short of breath to speak in full sentences or answering questions inappropriately. For all of the chest symptoms, the history should include certain standard questions: • What is the nature of the symptoms? For example, is it a single symptom such as shortness of breath or combined with cough and chest pain? • Is fever (or feeling hot) present? • Have there been chills? • When did the symptoms begin? • Did the symptoms begin gradually or suddenly? • How severe are the symptoms? • How rapidly are the symptoms progressing (minutes, hours, days, weeks)? • What makes the symptoms worse? • What makes the symptoms better? • Are there associated non-chest symptoms, such as nausea, vomiting, diarrhoea, muscle aches, headache, weight loss, irregular heart beat? • Does the patient have other illnesses, particularly chronic obstructive pulmonary disease (COPD), asthma, previous lung infections, heart disease, hypertension, HIV infection? • Are there symptoms that suggest an underlying illness? • Does the patient take any medications or traditional remedies? • Has there been exposure to persons with lung infections? • Has there been any recent trauma or bite? • Have any of the symptoms happened in the past? If shortness of breath, also ask: • Is the difﬁculty breathing only with exercise or at rest as well? • Is it affected by body position (upright or lying down or lying on one side or the other)?

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• • • •

Is the breathing noisy? Does the chest feel tight? Is there fever or chills? Is there cough?

If cough, also ask: • Is fever present? • Is the cough dry or is mucus produced? • If mucus is produced ° What is the colour (green, yellow, white)? ° What is the quantity (scanty, profuse)? ° Is it blood-stained? • Is there gross blood? • When is the cough most likely to occur (especially at night or in the morning on arising)? • Are there any aggravating factors (exertion, particular seasons, particular environments such as the workplace, speciﬁc positions, exposure to dust, pollens, or other allergens or irritants such as smoke)? • Has there been a recent upper respiratory infection or sinus infection? • Is there a prior history of similar cough? If chest pain, also ask: • Where is the pain? • What is the quality of the pain? • Has there been any chest trauma? • Does the pain radiate anywhere? To the jaw, arm, or back? • How rapidly is it progressing (minutes, hours, days, weeks)? • What makes it worse (e.g. exercise, taking a deep breath)? • What makes it better (e.g. certain positions, non-steroidal medications)? • Does it resolve spontaneously or with antacid medications (may suggest oesophageal spasm)? Obtain a past medical history and social history to help identify the cause of symptoms: • history of asthma, COPD, or heart disease; • medication use currently or in recent past; • previous TB; • HIV status and latest CD4 count; • immunisation history, including pertussis, inﬂuenza, Streptococcus pneumonia; • occupational history or environmental exposure (e.g. mining, exposure to dust, fumes or strong odours, farming, animals); • known close contact with a person with TB; • smoking and exposure to second-hand tobacco smoke;

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• exposure to indoor smoke from cooking or heating, open ﬁres using wood, grass, dung, or other fuels in poorly ventilated structures; • sinus pain or previous sinus infections; • substance use including alcohol and inhaled cocaine. Examination The physical examination will help to determine whether the problem is primarily from the lungs, the heart, or another organ system and will be guided by the information obtained in the history. • Vital signs. The initial vital signs serve to quantify the severity of illness and as the baseline for monitoring the response to treatment. ° temperature (<36°C, >38°C abnormal) ° blood pressure (systolic blood pressure <90 and diastolic <60 is low) ° heart rate (>110 beats/minute is abnormally fast and <60 beats/minute abnormally slow) ° respiratory rate (normal 12 to 16/minute; use Section 3.2 if >25/minute) ° pulse oximetry (normal: SpO2 >95%, give oxygen if <90%; SpO2 <90 is abnormally low but may be normal at high altitude). • General examination ° Does the patient appear acutely or chronically ill? ° Is the patient too short of breath to speak in full sentences? ° Is the patient having severe pain? ° Does the patient respond to questions appropriately? ° Is there confusion or disorientation? ° Does the patient appear cyanotic (bluish discoloration around lips or under the tongue)? ° Is the patient pale or ﬂushed? ° Are there visible lymph nodes? ° Does the patient have digital clubbing? • Examination of the respiratory system ° Does breathing appear difﬁcult or easy? ° Is there nasal ﬂaring? ° What is the pattern of breathing (deep and sighing or rapid and shallow) ° Are accessory muscles (especially the muscles in the neck) being used? ° Is there retraction of the intercostal spaces? ° Is the trachea in the midline? ° Do both sides of the chest move evenly? ° Is any part of the chest tender to the touch? ° Is there dullness or hyper-resonance when the chest wall is percussed? ° Listen to the breathing for audible noise and by auscultation. ◊ Is there audible noise with inspiration or expiration, and is it coming from the upper or lower airways? ◊ Is there wheezing (high-pitched breath sounds) or prolonged expiratory phase? ◊ Are breath sounds equal on both sides? ◊ What is the quality of breath sounds? Are there crackles or rales or harsh breath sounds? ◊ Are the abnormal breath sounds localized or diffuse? ° Are there palpable lymph nodes? • Examination of the heart and cardiovascular system ° Are the jugular veins elevated? (This may be difﬁcult to determine in a patient who is breathing rapidly.)

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° Is there swelling of one leg or both legs? ° Is the apex beat displaced from the left midclavicular line in the ﬁfth intercostal space? ° Are the heart sounds decreased? ° Is there a heart murmur? ° Is there an extra heart sound (gallop or rub)? ° Is the liver enlarged? (The edge of the liver should not be felt below the rib cage on the right side of the abdomen.) ° Is the abdomen swollen? Investigations • Generally, a productive cough for 2 or more weeks is an indication for obtaining sputum for molecular testing with a nationally or WHO-approved test such as Xpert MTB/RIF test where available, or for an acid-fast smear microscopy or other tests to detect mycobacteria. In HIV-positive patients or in HIV-prevalent settings, suspect TB and send sputum test in patients presenting with cough. See Section 15 Tuberculosis. • Check Hb (for anaemia) and WBC (if elevated, suspect infection). • If suspect malaria, check malaria smear or RDT. • Pulse oximetry (SpO2). • Chest X-ray. • Peak ﬂow measurements for acute management of asthma. • Spirometry (measurement of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)). Spirometry is the most accurate means of quantifying the degree of airways obstruction in the chronic management of COPD and asthma. Reversibility of airﬂow obstruction is deﬁned as either an increase in FEV1 ≥12 % from baseline AND ≥200 ml after inhalation of a shortacting bronchodilator such as salbutamol. • ECG to look for evidence of cardiac disease.

Interpretation of chest X-ray ﬁndings The chest X-ray can assist in narrowing the differential diagnosis or making speciﬁc diagnoses. There are several books available that can guide interpretation of chest X-rays1 and also describe appropriate quality control for X-ray examination. The table in the Section 10.6.2 (DDx: Chest X-ray abnormalities in patients with acute chest symptoms) presents the X-ray patterns associated with various diagnoses. Common terms for chest X-ray ﬁndings • Inﬁltrate or opacity: A generally ill-deﬁned density on the X-ray ﬁlm. • Lucency: An area that is less dense than the surrounding tissue, thus appearing dark compared to the surrounding area. • Focal inﬁltrate or opacity: An area of increased density that is localized to one part of the lung, usually no more than a single lobe. • Diffuse inﬁltrate or opacity: Increased density that involves multiple areas of the lungs in either a patchy or uniform distribution. • Masses and nodules: Focal densities that are solid and well-deﬁned. Masses are ≥3.0 cm in size whereas nodules are between 0.2–3.0 cm. Both may be 1 The WHO manual of diagnostic imaging: Radiographic anatomy and interpretation of the chest and pulmonary systems. WHO, 2006. Available at http://whqlibdoc.who.int/publications/2006/9241546778_eng.pdf

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•

single or multiple. Miliary nodules are tiny, ≤2 mm in size, and are usually associated with tuberculosis (see Section 15), but may be caused by other infections and occasionally by malignancies. Pleural effusion: Fluid that has accumulated in the pleural space between the chest wall and the lung. The collection may be on one or both sides of the chest. Pneumothorax: Air in the pleural space associated with partial or complete collapse of the lung. A tension pneumothorax will cause a shift of the heart and mediastinum to the opposite side of the chest. Cavity: A rim of high density containing an area of decreased density in the lung. Is usually the result of an infection that causes death of lung tissue. Some lung cancers (for example, squamous cell carcinoma) may also present as a cavity. Cavities caused by infection are usually surrounded by an area of inﬁltrate. Lymphadenopathy: Enlargement of lymph nodes in the chest (e.g. mediastinal or hilar), may also be associated with tuberculosis (see Sections 10.5 and 15) or cancer.

10.6.2 Differential diagnosis of chest complaints A list of possible diagnoses can be developed based on the history, physical examination, chest X-ray, and other investigations and local epidemiological factors, e.g. the prevalence of HIV infection or TB, and the season of the year (is there seasonal inﬂuenza circulating). The list will vary according to the patient’s age and should be roughly in order of likelihood. Generally, the ﬁrst diagnosis on the list will be the working diagnosis, for which empirical treatment may be necessary. Other diagnoses lower on the list may be sufﬁciently likely that treatment may be indicated. However, if more than one disease or condition is treated empirically, the response to treatment cannot be used to infer a diagnosis.

DDx: Chest X-ray abnormalities in patients with acute chest symptoms Chest X-ray ﬁndings Focal inﬁltrate or opacity Figure 1a Right middle lobe inﬁltrate pneumonia (PA view) and Figure 1b (lateral view) Diffuse inﬁltrates or opacities Figure 2 Most likely causes (may differ in different areas according to the most common conditions) • Pneumonia (bacterial, viral, fungal) • TB (see Section 15)

• • • • •

TB (see Section 15) Pneumonia (particularly viruses such as inﬂuenza and CMV; PCP) Fungal infections Heart failure (pulmonary oedema) Malignancy (including Kaposi sarcoma and lymphoma)

Multiple small nodules Figure 3 Masses and nodules Figure 4 Cavity Figure 5

• Infection (especially disseminated TB, see Section 15) • Metastatic malignancy (including from a primary lung cancer) • Lung cancer • Metastatic malignancy (especially if multiple masses are present) • Infection (especially TB or fungal, see Sections 11 and 15) • TB (see Section 15) • Bacterial infection – especially caused by aspiration pneumonia (associated with alcoholism, epilepsy, poor dentition) • Fungal infection • Malignancy, particularly if wall thickness is >1.5 cm

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Pleural effusion Figures 6a and 6b

• • • • • • •

Bacterial pneumonia (including empyema) TB, particularly if there is pleural calciﬁcation (see Section 15) Malignancy (including Kaposi sarcoma and lymphoma) Heart failure (usually bilateral or right-sided) Chest trauma (haemothorax) Pulmonary embolism Any condition associated with a low serum protein concentration (severe liver disease, nephrotic syndrome, renal insufﬁciency, severe malnutrition – usually bilateral) TB (see Section 15) Malignancy including Kaposi sarcoma and lymphoma Fungal infections Metastatic cancer Inhalational anthrax Spontaneous pneumothorax (no underlying disease) TB (see Section 15), PCP COPD, asthma Chest trauma

Hilar or mediastinal lymphadenopathy Figures 7a and 7b

• • • • • • • • •

Pneumothorax Figure 8

Normal Figure 9

• Asthma • Pulmonary embolism • PCP

DDx: Difﬁcult breathing or cough – with fever Disease or condition Acute bronchitis In favour • • • • • • Shortness of breath mild, if present Cough may be productive Acute onset Mild or absent fever No chest ﬁndings on physical examination except wheezing in asthmatics Normal chest X-ray

Pneumonia

• Shortness of breath mild to severe • Productive cough with bacterial pneumonia and non-productive cough with nonbacterial pneumonia (but considerable overlap) • Acute onset hours to a few days • Focal chest pain with deep breaths or coughing • Fever and chills • Fast breathing (>30 breaths/min) • If SBP <90, patient has septic shock (see Section 3.1.5) • Focal signs – bronchial breath sounds, crackles, or rales on auscultation • With pleural effusion, dullness to percussion and decreased breath sounds over affected side • Chest X-ray may show focal or diffuse inﬁltrates particularly in non-bacterial pneumonia • • • • • • • • • Inﬂuenza known or suspected to be circulating Fever Cough Sore throat Rhinorrhoea or nasal congestion Headache Muscle pain or malaise Gastrointestinal illness such as diarrhoea or vomiting If shortness of breath, consider inﬂuenza with pneumonia (below)

Uncomplicated inﬂuenza (may be pandemic or seasonal) see Section 11.17

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Disease or condition Inﬂuenza with pneumonia see below and Section 11.17

In favour • Inﬂuenza known or suspected to be circulating • History of inﬂuenza-like illness • Risk factors: age <2 years or ≥65 years, pregnancy (up to 2 weeks postpartum), any chronic disease (pulmonary, cardiac, diabetes, metabolic, renal, hepatic, hematologic, or neurologic) or immunosuppression (HIV, malignancy, chemotherapy) • Shortness of breath, pleuritic pain, cough, coloured sputum, fever • Rapid respiratory rate • Bilateral crackles, possible wheezing • Chest X-ray may show focal or diffuse inﬁltrates Note: Both uncomplicated inﬂuenza and inﬂuenza pneumonia may be complicated by secondary bacterial pneumonia with features of pneumonia as described above.

Pulmonary tuberculosis see Section 15

• • • • • • • •

Shortness of breath mild to moderate but occasionally severe Possible history of exposure to a person with TB Usually gradual in onset Cough with or without bloody or blood-tinged sputum Weight loss Fever, night sweats, occasionally chills Occasionally, chest pain Xpert MTB/RIF positive (or other nationally- or WHO-approved molecular test) where available, sputum AFB positive (possible for AFB smear to be negative in patients with smear-negative pulmonary TB) – see Section 15.

Chest X-ray in patients without immune system compromise: unilateral or bilateral upper lobe inﬁltrates with or without cavitation; pleural effusion; miliary nodular pattern; other nodular opacities and ﬁbrosis. A normal chest X-ray does not exclude TB. Chest X-ray in patients with advanced immune deﬁciency (advanced immune system compromise, advanced HIV): non-speciﬁc pattern, with patchy inﬁltrates in the lower and mid lung zones; hilar and mediastinal lymphadenopathy may also be seen. Routine chest X-ray is not indicated for the diagnosis of TB. See Section 15.

Pneumocystis jirovecii pneumonia (PCP)

• • • • • • • •

Shortness of breath mild initially but may become severe Subacute onset – days to weeks Non-productive cough Low grade to moderate fever Fast breathing >30 breaths/minute Nasal ﬂaring Usually no ﬁndings on physical examination of the chest Chest X-ray bilateral diffuse inﬁltrates without lymph node enlargement or pleural effusion. In mild cases, X-ray may be minimally abnormal or normal. • CD4 cell count <200 • Hypoxaemia (SpO2 <90) – particularly on exertion • • • • • • • • • Shortness of breath is mild to moderate Subacute or chronic onset Cough may be productive or non-productive Generally moderate fever Weight loss Mild or no respiratory symptoms Lymphadenopathy and skin lesions may be present Enlargement of liver and spleen Chest X-ray – various abnormalities including focal or diffuse inﬁltrates, single or multiple masses or nodules, hilar or mediastinal adenopathy, and pleural effusions

Disseminated fungal infection (endemic fungi vary from place to place) see Section 11.16

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Immune reconstitution inﬂammatory syndrome (IRIS) see Section 13

• Shortness of breath if the lungs are involved • HIV-positive with ART initiated in past 3 months, often with CD4 <50 cells/mm3 at initiation • Common in patients with tuberculosis • Cough, if present, is generally non-productive • Moderate fever is common • Physical examination of the chest depend on the manifestations of IRIS • Extra thoracic lymphadenopathy commonly increases • Usually an increase in CD4 cell count • Chest X-ray may show worsening of inﬁltrates, pleural effusion, and increasing intra-thoracic lymphadenopathy • • • • • • Shortness of breath is mild if present Onset is subacute, generally over several weeks Fever is moderate Cough is productive with copious thick, yellow to brown, foul-smelling sputum Poor dentition may be present Chest may reveal crackles and coarse bronchial breath sounds over the involved area • Chest X-ray – focal inﬁltrate or mass with cavitation • Note: Lung abscess is generally the consequence of a necrotizing pneumonia, but may also be secondary to endobronchial obstruction (e.g. from cancer). • Shortness of breath moderate or severe • Risk factors – use of corticosteroids, other immunosuppressive drugs, or HIV infection • Acute onset • Moderate fever • Cough usually non-productive but may have blood-tinged sputum • Abdominal pain, nausea, vomiting, diarrhoea may be present • Skin rash possible • Chest usually normal but wheezing may be present. • Chest X-ray – diffuse inﬁltrates • Peripheral eosinophilia may be noted • Larvae on wet mount and Giemsa stain of sputum • History of exposure to animals • Oropharyngeal anthrax: eschar lesions in mouth, tongue, tonsils, or posterior pharynx. Symptoms of sore throat, dysphagia, regional lymphadenopathy. Swelling of neck and anterior chest wall. • Inhalation anthrax: fevers, chills, sweats, fatigue, cough, shortness of breath, confusion, nausea and vomiting. Chest X-ray – mediastinal lymphadenopathy plus pleural effusions and pulmonary inﬁltrates. • • • • • • Sudden onset of fever, chills, headache, severe malaise Chest pain Difﬁculty breathing Cough with blood-stained sputum or haemoptysis Fulminant course (100% case fatality rate if not treated rapidly) May or may not have painful swelling of lymph nodes

Lung abscess

Strongyloides hyperinfection see Section 11.36

Anthrax see Section 10.2

Plague see Section 10.5

Varicella pneumonia see Section 11.45

• Pneumonia may complicate chickenpox in adults, particularly pregnant women and persons who are immunocompromised • Usually presents 1–6 days after the onset of rash • Associated with cough, dyspnoea, fever, tachypnoea, and chest tightness, although chest signs are often minimal • The diagnosis is usually based on ﬁnding skin lesions characteristic of varicella • (see Sections 10.2 and 11.45) • Chest X-ray – diffuse interstitial opacities

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DDx: Difﬁcult breathing or cough – without fever Disease or condition Pneumothorax see Quick Check page 46, Vol. 1 for emergency management of tension pneumothorax In favour • • • • • • Shortness of breath sudden, rapidly progressive and severe Sudden onset over minutes or hours Chest pain on affected side May be associated with trauma or underlying lung disease such as PCP, COPD Cyanosis may be present If tension pneumothorax, low blood pressure and trachea shifted from mid-line to the side opposite the pneumothorax • Hyper-resonance on percussion and diminished or absent breath sounds on the affected side. Subcutaneous emphysema (“crunchy” feel when pressure applied to chest wall or neck) • Chest X-ray – completely or partially collapsed lung with no lung markings between collapsed lung and chest wall. If tension – the midline structures (trachea, heart) are shifted away from the affected side • Patients commonly feel short of breath • Subacute onset • Always an underlying cause – diabetic crisis, renal failure, aspirin toxicity or other poisoning (methanol, ethanol, paraldehyde), lactic acidosis (e.g. side effects of ARV drugs, commonly d4T- or ddI-containing regimens, more common in women or overweight persons) • Cough not present • Respiratory rate rapid and respirations deep and sighing, in the absence of cough • Physical examination – chest is normal • Chest X-ray is normal • Shortness of breath mild to severe • History of previous wheezing episodes associated with chest tightness • Identiﬁable triggers common (upper respiratory infection, allergen exposure, exercise, cold air, extreme emotion) • Breathing or cough commonly worse at night • Non-productive cough is common • Chest examination can be normal between attacks • During attacks or when asthma is poorly controlled, wheezing or prolonged expiration (compared to inspiration) throughout all lung ﬁelds (not focal) • In severe attacks, absent breath sounds, fast breathing, use of neck muscles • Chest X-ray may be normal, or show signs of hyperinﬂation like hyperlucent lung ﬁelds and ﬂattened diaphragms, and thickened bronchial walls • Shortness of breath generally mild • Often afebrile • Cough chronic and copious production of yellow/green sputum is common, occasional blood • Often history of recurrent chest infections and worsening symptoms usually associated with infections • Examination may reveal crackles and wheezes over the involved area(s) and uncommonly digital clubbing (rounded deformity of the ﬁngernails) • Chest X-ray may show streaky peribronchial inﬁltrates and dilated bronchioles

Metabolic acidosis (such as lactic acidosis or diabetic ketoacidosis)

Asthma

Bronchiectasis

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Chronic obstructive lung disease (COPD)

• Shortness of breath is chronic but worsens with exacerbations that may be caused by acute infections or heart failure • Unlike asthma, symptoms are usually persistent, not intermittent • Chronic productive cough • Often a history of tobacco smoking, occupational exposures, or exposure to biomass fuel smoke • In an exacerbation, fast breathing with prolonged expiratory phase and wheezing; fever may be present (if infection) • Examination shows engorged jugular veins as evidence of right heart failure, often hard to assess if breathing is laboured; decreased breath sounds, prolonged expiratory phase, and wheezing • Chest X-ray – hyperinﬂation (hyperlucent lung ﬁelds and ﬂattened diaphragms) • • • • Shortness of breath mild to moderate Subacute or chronic onset over weeks Cough is common often with bloody or blood-tinged sputum Characteristic purple lesions or nodules of Kaposi sarcoma on the skin or oral mucus membranes • Chest examination generally normal • Chest X-ray – perihilar patchy interstitial inﬁltrates, ill-deﬁned nodular densities • Shortness of breath uncommon in lung malignancies unless other disease present (COPD, pneumonia) • Tobacco smoking is a common but not universal risk factor • Onset insidious – usually over months • Cough non-productive but there may be haemoptysis • Weight loss, anorexia are common • May have enlarged supraclavicular lymph nodes • Chest examination normal • The chest X-ray usually shows single or multiple nodules or masses often with enlarged hilar or mediastinal lymph nodes; pleural effusion may be present • Shortness of breath may be severe • Onset sudden, possibly preceded by shortness of breath on exercise and at night • Possible history of an underlying condition (rheumatic heart disease, hypertension, severe anaemia) • Chest pain may be present • Cough is common and non-productive • May have signs of right ventricular failure (elevated jugular venous pressure, liver enlargement, pitting oedema of the both legs) or left ventricular enlargement (displaced apex beat) • Gallop rhythm (extra heart sound) or murmur (if associated valve disease) may be present • Chest examination shows bibasilar crackles and sometimes wheezing • Chest X-ray – an enlarged heart, bilateral pulmonary vascular congestion and diffuse inﬁltrates; pleural effusions may be present • • • • Shortness of breath is generally less prominent than weakness and tiredness Gradual onset – often inﬂuenced by the underlying cause Cough is absent Examination: marked general pallor, pallor of the nail beds and oral mucus membranes • Chest examination is normal • Chest X-ray may be normal or may show heart enlargement • Low Hb (<7 g/dl in pregnancy, <8 g/dl in non-pregnant women, <9 g/dl in men) • • • • • • Shortness of breath may be severe Sudden onset Young patients with no underlying disease and have had previous attacks There is no cough Physical examination is normal Chest X-ray is normal

Pulmonary Kaposi sarcoma see Section 11.19

Lung malignancy

Heart failure

Severe anaemia see Section 10.18

Panic attack see Section 10.11

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DDx: Chest pain Disease or condition Pneumothorax see Quick Check page 46, Vol. 1 In favour • Chest pain on affected side, sudden onset, often severe, and increased with inspiration • Shortness of breath rapidly progressive and severe • Associated with trauma or underlying lung disease such as PCP or emphysema, but may be primary with no known underlying disease • Cyanosis may be present • If tension pneumothorax, blood pressure will be low. This requires emergency treatment – see Quick Check page 46, Vol. 1 • Trachea shifted from mid-line away from side of pneumothorax • Hyper-resonance on percussion, diminished or absent breath sounds on affected side • Subcutaneous emphysema (“crunchy” feel when pressure is applied to the chest wall or neck) • Chest X-ray– radiolucent area with no lung markings between the visceral (retracted or collapsed lung) and the parietal pleura (chest wall). In tension pneumothorax, midline structures (trachea, heart) shifted away from affected side • • • • • • • • • • • • • • • • • • • • • Localized sharp pain worse on inspiration or coughing Acute onset Associated with shortness of breath Fever present, depending on cause Chest exam demonstrates decreased expansion of the affected side Possible pleural friction rub, crackles not heard unless underlying pneumonia Chest X-ray may demonstrate a pleural effusion or atelectasis Pain located in anterior chest, improves with leaning forward Acute onset Fever present depending on cause Examination shows rapid heart rate, pericardial friction rub may be present Chest X-ray – may be normal or show heart enlargement Electrocardiogram – diffuse S-T segment and T wave abnormalities If blood pressure low, consider cardiac tamponade: urgent treatment is required Pain is crushing, substernal pressure, radiating to the left arm or jaw Pain on exertion and sudden in onset Associated with shortness of breath, sweating, and nausea Risk factors – tobacco smoking, hypertension, diabetes, and obesity Examination often normal Chest X-ray is normal Electrocardiogram localized S-T segment and T wave abnormalities

Pleuritis, pleurisy without pneumonia

Pericarditis see Section 3.3

Acute coronary syndrome, myocardial infarction see Section 3.3

Aortic dissection or rupture

• Pain sudden and severe radiating to the back • Fainting may occur • Dissection may occur spontaneously (or rupture just distal to left subclavian artery may occur in blunt trauma) • Hypotension possible. • Aortic insufﬁciency murmur may be heard • Chest X-ray – widened mediastinum • • • • Onset of pain – subacute, somewhat worse on inspiration No cough or fever Examination – tenderness on palpation of costochondral junctions Chest X-ray is normal

Costochondritis

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Oesophagitis and spasm see Section 10.7b

• • • • •

Pain sub-sternum sudden and severe, like pain of cardiac origin Pain increased with swallowing No shortness of breath, cough, or fever Physical examination is normal Chest X-ray is normal

Rib fracture associated with severe cough

• Bony crepitation (“grating” feeling ) may be palpated • Chest X-ray may be normal, show the rib fracture or demonstrate the underlying process that caused the coughing • Pain – sudden onset, with vigorous coughing and may be severe; increases with inspiration, coughing, or movement • Focal pain

Evaluation and differential diagnosis of pleural effusion Many diseases and conditions may cause or be associated with pleural effusion. A presumptive cause of the effusion often can be determined based on the underlying condition or disease. For example: • bilateral effusions in a patient with heart failure are likely caused by heart failure • an effusion in a patient with bacterial pneumonia is likely associated with the infection. However, if the cause of the effusion is not a clear presumptive diagnosis, the ﬂuid must be analysed to distinguish if the effusion is due to an infectious or a non-infectious cause. • First, detect the ﬂuid on a chest X-ray. • Second, perform a thoracentesis to obtain a sample of the ﬂuid. • Third, analyse the ﬂuid using the algorithm below.

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Figure: Evaluation and differential diagnosis of pleural effusion

Presence of pleural effusion on chest X-ray No evident diagnosis Send sputum for Xpert MTB/RIF if available or AFB Perform thoracentesis (see Section 7.4.1) Bloody ﬂuid • Trauma • Malignancy • Pulmonary embolism Cloudy, thick ﬂuid • Likely to be exudate (e.g. empyaema) Clear, thin ﬂuid • Likely to be transudate

Examination of ﬂuid • Visual inspection (Is ﬂuid bloody, cloudy, clear, thick, thin?) • Laboratory investigations ° protein (serum and pleural ﬂuid) ° glucose ° LDH (serum and pleural ﬂuid) ° cell count and differential white cell count ° Gram stain and AFB smear ° culture for bacteria and mycobacteria if available

Fluid is exudate if any of the following criteria are met • Pleural ﬂuid/serum protein concentration ratio >0.50 • Pleural ﬂuid/serum LDH concentration ratio >0.60 • Pleural ﬂuid protein concentration ≥30 g/litre Fluid is LIKELY exudate if cloudy OR viscous OR WBC >5000/µl

Fluid is not an exudate (transudate)

Cells are mainly neutrophils

Cells are mainly lymphocytes Main differential diagnosis • Heart failure • Severe liver disease • Nephrotic syndrome • Severe malnutrition

Main differential diagnosis • Bacterial pneumonia (especially if glucose <60 mg/dl) • Pulmonary embolism (may be lymphocytic)

Main differential diagnosis • Tuberculosis (see Section 15) • Malignancy

If diagnosis is unclear, consider empirical treatment for tuberculosis.

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10.6.3 Pneumonia Pneumonia can be caused by many categories of infectious organisms including viruses, bacteria, fungi, certain parasites, and mycobacteria (most commonly M. tuberculosis). The relative proportion of the different categories of organisms will depend on factors such as prevalence of HIV infection and tuberculosis, and the season of the year. Pneumonia is an inﬂammatory condition that involves the air-containing sacs (alveoli) and the airways. Because the alveoli are predominately involved, most pneumonias interfere with the transfer of oxygen from inspired air into the blood and result in hypoxaemia, which can be severe. The lung inﬂammation may extend to the outer membrane (pleura) of the lung and cause pleuritis, pleural effusions, and chest pain. Key clinical features Symptoms can vary substantially, depending on the category of infecting organism and severity, but there is considerable overlap. • Cough and shortness of breath are common. Sharp chest pain on inspiration or cough from pleuritis may occur. • Virtually all categories cause fever and elevated respiratory rate. However, increased heart rate and low blood pressure should raise suspicion of severe sepsis or shock from the infection or dehydration. • On examination of the respiratory system, chest inspection may note asymmetry of expansion. Possible ﬁndings on auscultation include decreased breath sounds on one side if a pleural effusion is present, and crackles and (increased) bronchial breath sounds over the involved area. A pleural friction rub may also be heard. Investigations • Hypoxaemia is common and can be severe. • Chest X-ray

Determining the need for hospitalization In the ﬁrst-level IMAI Acute Care guidelines, adult patients will be referred to hospital with severe pneumonia or other very severe disease based on very fast breathing (>30 breaths/minute), pulse 120 or higher, high fever, lethargy, inability to walk unaided, discomfort lying down, or severe chest pain. Second or third trimester pregnant women with signs of non-severe pneumonia (fast breathing >20 breaths/minute, night sweats, or chest pain) are also referred to hospital, rather than receiving oral antibiotics as an outpatient. The same ‘’upgrade’’ for hospital referral is recommended for PLHIV in clinical stage 4 or with a low CD4 count. At the district hospital, Quick Check triage will identify patients who have emergency signs of airway and breathing (severe respiratory distress, cyanosis, appears obstructed), count the respiratory rate and measure SpO2. If the patient also has a fever, then empirical antibiotics for possible pneumonia will be given.

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Suspect severe pneumonia if the following criteria are met and use Section 3.2.3 to guide management: • fever or suspected infection • cough • respiratory rate >30 • signs of severe respiratory distress • SpO2 <90. There are other approaches to determining that a patient may have severe pneumonia and need hospitalization. A large multicentre study in a high-resource setting2 derived and validated the «CURB-65» prognostic score based on the following factors (each worth one point): • Confusion (altered mental status) • Urea >7 mmol/litre • Respiratory rate ≥30 breaths/minute • Blood pressure (systolic) <90 mmHg or diastolic <60 mm Hg • age ≥65 years. Increasing CURB-65 scores are associated with increasing mortality. In some professional society guidelines, it is recommended that patients having 2 or more factors be admitted to the hospital. The utility of CURB-65 may be decreased in resource-constrained settings. Empirical treatment is usually based on a presumptive determination of the likely category of organism causing the pneumonia and on an assessment of severity. It is important to have knowledge of the local epidemiology of communityacquired pneumonia. In high TB prevalence areas, or if HIV infection is known or suspected, TB should always be a consideration in patients presenting with respiratory infection. If the patient has severe pneumonia, see Sections 3.2.1–3.2.3 for management.

Outpatient management of the patient with non-severe pneumonia • Patients who have signs and symptoms of pneumonia but do not meet criteria for severe pneumonia can be managed as outpatients. • Counsel the patient regarding the importance of adherence to the medication regimen and the need for follow-up to determine response. • The patient should be advised to return for evaluation if there is no improvement or there is a worsening of symptoms. • Treatment should be given for 5–7 days, assuming there is a good, prompt response. Empirical antibiotic regimens for non-severe pneumonia • amoxicillin 500–1000 mg 3 times daily; OR • erythromycin 500 mg 4 times daily; OR • doxycycline 100 mg 2 times daily (avoid in pregnancy). 2 Lim WS, et al. Deﬁning community acquired pneumonia severity on presentation to hospital: an international derivation and validation. Thorax, 2003, 58:377-82.

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Follow national guidelines for alternative antibiotics regimens that may include: • azithromycin 500 mg once daily; OR • clarithromycin 500 mg twice daily, OR • oral respiratory quinolone (for example, levoﬂoxacin) – see below for cautions. Send sputum for Xpert MTB/RIF if available, or for AFB if TB is suspected. See Section 15. It is important not to treat patients suspected of having TB with a respiratory quinolone as it may mask or partially treat underlying tuberculosis. Respiratory quinolones should also be avoided in high-prevalence TB settings unless TB is excluded. Safety of respiratory quinolones in pregnancy has not been established. If not improving after 3 days and the patient has been adherent to the antibiotic regimen, review and consider switching to an IV regimen. • ceftriaxone 1–2 grams once daily PLUS erythromycin 500 mg (oral or IV) 4 times daily; OR • ampicillin 2 grams IV 4 times daily PLUS gentamicin (see Section 8.4 for dosing) PLUS erythromycin 500 (oral or IV) 4 times daily. If the patient has a non-anaphylactic allergy to penicillin (for example, skin rash only), then ceftriaxone can be used. Consider other infections, including TB and, if HIV-positive, consider PCP.

Pneumocystis jirovecii pneumonia (PCP) PCP is caused by a fungus, Pneumocystis jirovecii (formerly known as Pneumocystis carinii). The organism is present in soil, transmitted through inhalation, and distributed worldwide. Most people have been exposed to it by the age of ﬁve. PCP occurs only in immunocompromised patients, particularly those who are infected with HIV and whose CD4 count is <200 cells/mm3. It is associated with high mortality in HIV patients. Patients who have recently received steroids or other immunosuppressive therapy are also at increased risk. Key clinical features • PCP can be associated with many of the manifestations described above for pneumonia in general. • Shortness of breath that is slow in onset (over 1–2 weeks). • Cough that is non-productive. • Fast pulse. • Fast respiratory rate. • Cyanosis may be present and is a sign of severe hypoxaemia. • Auscultation of the chest is generally unremarkable, but some crackles may be present. Investigations • SpO2 is decreased. • Elevated lactate dehydrogenase (LDH), which is a non-speciﬁc marker of pulmonary inﬂammation.

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• Experienced microscopists with special training may be able to identify the organism in induced sputum samples with special stains: methenamine (Grocot) silver, calcoﬂour white, and Wright-Giemsa. The sensitivity is diminished in patients using cotrimoxazole prophylaxis. • On chest X-ray, bilateral peri-hilar inﬁltrates are common, but nodular densities, lobar consolidations, and cavitation also can occur. At ﬁrst presentation, in 25% of cases, the chest X-ray can be (misleadingly) normal. Pleural effusion is rare. Treatment • If patient has severe pneumonia, see Section 3.2.3 for additional management recommendations regarding oxygen and ﬂuid therapy. • Treatment should be initiated early and empirically, based on history and clinical presentation, while awaiting deﬁnitive diagnosis. • Antimicrobial treatment is most effective when started early: ° cotrimoxazole 400 mg trimethoprim/80 mg sulfamthoxazole tablets (SS): dose based on trimethoprim (TMP) 5 mg/kg divided 4 times daily orally or IV for 21 days (preferred); OR ° clindamycin 600 mg IV or orally 4 times daily PLUS primaquine 15 mg twice daily orally for 21 days (alternative); OR ° pentamidine 4 mg/kg IV daily for 5 days, then reduce dose to 2 mg/kg daily IV to complete 21 days (alternative if unresponsive to cotrimoxazole or cotrimoxazole not tolerated). • If the patient is hypoxaemic with SpO2 <90 on room air, give IV therapy initially and add prednisone, 40 mg twice daily for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days to complete 21 days of treatment. Prophylaxis • Primary prophylaxis is indicated for HIV-positive patients in WHO clinical stage 2, 3, or 4 irrespective of CD4 count, or with CD4 count <350/mm3 irrespective of clinical stage. See Section 13. Follow national guideline recommendations. • Secondary prophylaxis should be given to all patients following treatment of PCP. • Primary and secondary prophylaxis is the same: cotrimoxazole 1 double strength tablet daily. • Patients should at least be continued on PCP prophylaxis until there is evidence of immune recovery on antiretroviral therapy (CD4 counts >350 cells/ mm3 after at least 6 months of antiretroviral therapy). See Section 13.

Inﬂuenza pneumonia (see Section 11.17) Key clinical features • Inﬂuenza is suspected or known to be circulating. • History of inﬂuenza-like illness. • Progressive symptoms, such as worsening cough, purulent or bloody sputum, shortness of breath (at rest or with exertion) or chest pain. • Signs of respiratory distress, such as fast respiratory rate, cyanosis, and hypoxaemia (if severe) and, on chest auscultation, there may be crackles or rales or wheezing.

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Investigations • Chest X-ray usually shows diffuse interstitial inﬁltrates. • See Section11.17 for use of rapid diagnostic tests for an indication of the presence of inﬂuenza in the community (not for routine individual patient care). Treatment (see Section 11.17) • Treatment should be based on clinical diagnosis and suspicion of inﬂuenza infection based on local epidemiology and should not be delayed for results of laboratory investigations. • Treat with antiviral, oseltamivir 75 mg orally twice daily or zanamivir, as soon as possible. • Co-existing pneumonia due to other pathogens may be difﬁcult to exclude in a patient with suspected inﬂuenza infection. If you suspect communityacquired pneumonia, or another infectious pneumonia based on local epidemiology, then treat with appropriate antimicrobials. Bacterial infection by S. pneumoniae and S. aureus, both methicillin-sensitive and methicillinresistant, are common (see Section 3.2.3). • Occasionally, bacterial pneumonia will develop in a person who seems to be recovering from inﬂuenza infection. In these instances, the presentation is as described for bacterial pneumonia and empirical treatment for bacterial pneumonia should be started as described previously. Infection prevention and control – see Section 6 for respiratory hygiene and droplet precautions.

Varicella pneumonia Pneumonia may complicate chickenpox in adults, particularly pregnant women and immunocompromised persons. The disease can progress rapidly to fulminant respiratory failure. Varicella pneumonia usually presents 1–6 days after the onset of rash, and is associated with cough, dyspnoea, fever, fast breathing, and chest tightness, although chest signs often are minimal. The diagnosis usually is based on ﬁnding skin lesions characteristic of varicella (see Sections 10.2 and 11.45). A chest X-ray shows diffuse interstitial opacities. Treat with: • IV aciclovir 10–15 mg/kg 3 times daily for 7–10 days. • Switch to oral regimen once there is evidence of clinical improvement to complete the 10–14-day course.

10.6.4 Asthma Asthma is an inﬂammatory disease of the airways causing reversible airways obstruction and characterized by recurrent acute attacks (exacerbations). The inﬂammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli. The diagnosis is usually established from the episodic history of symptoms and by the ﬁnding of wheezing on auscultation of the chest. Key clinical features • Recurrent episodes of cough and shortness of breath often associated with noisy breathing (wheezing) and chest tightness.

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• Symptoms may be worse at night and interfere with sleep. • Episodes commonly occur in response to speciﬁc exposures, such as pollens or other allergens, acute respiratory infections, dust, exercise, or cold air. Investigations • Spirometry demonstrating reversibility is consistent with the diagnosis of asthma. However, many patients with asthma have normal spirometry when they are not having an exacerbation. Reversibility of airﬂow obstruction may be incomplete in some patients with asthma, especially those with longstanding asthma. • Peak ﬂow can also demonstrate airﬂow reversibility.

Classify asthma severity A classiﬁcation of chronic asthma severity and examples of its treatment according to severity follow. Table: Classiﬁcation of severity of asthma Classiﬁcation Episodes of breathlessness Frequency of night symptoms Peak ﬂow or spirometry (FEV1), % predicted or personal best Intermittent asthma <1 per week <2 per month >80% Mild persistent asthma 1 or more per week, but <1 per day >2 per month >80% Moderate persistent asthma Daily >1 per week Between 60–80% Severe persistent asthma Continuous daily Frequent <60%

WHO and partners3 are working to support the availability of basic asthma medications at the primary care level. Inhaled salbutamol and beclometasone are on the WHO essential medicine list and WHO guidelines for management of asthma at the primary care level are in development . District clinicians will often see patients with an acute exacerbation of wheezing (see Section 3.2.3) or with persistent symptoms despite use of these basic asthma medications. There are several schematic approaches (shown in the table below, Examples of increasing dosage and choice of medications by asthma severity) to increasing the intensity of treatments to control asthma. Inhaled salbutamol by metered-dose inhaler (MDI) as needed is used as a reliever medication in all categories. Inhaled steroids (for example, beclometasone) are the most important therapy to control symptoms. All patients should be counselled to stop smoking and referred for specialist care for severe persistent asthma if available.

3 For example, IUATLD has established an Asthma Drug Facility to support availability of more affordable salbutamol and beclametasone metered-dose inhalers. Available at http://www.globaladf.org/

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Refer to national or other local guidelines for speciﬁc recommendations. It may be necessary to advise patients to purchase more effective medications that are not on the national formulary to control moderate or severe persistent asthma. Although sustained release (SR) theophylline is not on the WHO essential medicines list, it is widely available; low dose SR theophylline can be used and stopped if there is evidence of toxicity.4 Theophylline is not as effective or as safe as the other options listed. Where available, theophylline blood levels should be used to adjust dosing. Table: Examples of increasing dosage and choice of medications by asthma severity Asthma severity Intermittent Derived from WHO model formulary 20085 Inhaled salbutamol as needed (100–200 mcg up to 4 times daily) Inhaled salbutamol as needed Beclometasone 100–250 mcg twice daily OR SR theophylline OR a leukotriene antagonist Moderate persistent Inhaled salbutamol as needed Beclometasone 100–500 mcg twice daily PLUS if needed EITHER Long-acting beta-agonist or SR theophylline or leukotriene antagonist OR Beclometasone high dose >1 mg/day (divided doses) Severe persistent Inhaled salbutamol as needed Beclometasone >1 mg/day (divided doses) PLUS Longacting beta-agonist PLUS if needed SR theophylline or leukotriene antagonist or long-acting beta-agonist or oral prednisolone in lowest dose possible, given once daily in the morning Derived from IUATLD guidelines6 Inhaled salbutamol as needed Inhaled salbutamol as needed Beclometasone 200 mcg daily Derived from BTS/SIGN guidelines7 Inhaled salbutamol as needed Inhaled salbutamol as needed Beclometasone 200 mcg twice daily

Mild persistent

Inhaled salbutamol as needed Beclometasone 200 mcg twice daily

Inhaled salbutamol as needed Beclometasone 200 mcg twice daily and a long-acting beta-agonist (must always be used with beclometasone) OR Beclometasone up to 400 mcg twice daily Inhaled salbutamol as needed Beclometasone 1000 mcg twice daily OR Beclometasone 1000 mcg twice daily AND 6 week trial of SR theophylline. OR Beclometasone 1000 mcg twice daily and daily prednisolone at lowest dose needed for adequate control

Inhaled salbutamol as needed Beclometasone 400 mcg twice daily and prednisolone 0.5 mg/kg/day (reassess weekly; taper when patient stable for 1 week)

4 If theophylline blood levels are available, they should be used to adjust dosing. See Adaptation Guide. 5 WHO model formulary. WHO, 2008. Available at http://www.who.int/selection_medicines/list/WMF2008.pdf 6 IUATLD asthma guidelines available at http://www.theunion.org/index.php/en/resources/scientiﬁcpublications/ lung-health 7 BTS/SIGN guidelines. Available at http://www.sign.ac.uk/guidelines/fulltext/101/index.html

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10.6.5 Chronic obstructive pulmonary disease (COPD) Chronic obstructive pulmonary disease is characterized by airﬂow limitation that is not fully reversible. The airﬂow limitation is usually progressive and associated with an abnormal inﬂammatory response to noxious particles or gases in the lung. The most common inhaled toxin is cigarette smoke, but smoke from indoor biomass fuel consumption, air pollution, and pulmonary infections also play a role. Key clinical features • Symptoms of chronic cough and progressive shortness of breath, with or without sputum production, in a person with an exposure history such as cigarette smoking. • On examination, patients commonly have a fast respiratory rate, and breath sounds are usually reduced throughout all lung ﬁelds on chest auscultation. • At advanced stages, patients may use accessory muscles to breathe, have clinical signs of heart failure (e.g. elevated JVP, liver enlargement and bilateral leg oedema). Investigations • Spirometry demonstrating ﬁxed airﬂow obstruction with an FEV1/FVC <70% after inhalation of short-acting bronchodilator is suggestive of COPD. • Severity of airﬂow obstruction is based on FEV1 (% predicted).

Classify COPD severity Severity can be based on subjective criteria (symptoms) or physiological criteria (spirometry); there is often not a good correlation between the two classiﬁcation schemes.

Table: Classiﬁcation of severity of COPD8 COPD severity Mild Moderate FEV1 Symptoms Short of breath when hurrying on level ground or walking up slight hill Walks slower than people of same age on the level because of breathlessness, or stops for breath when walking on level ground at own pace. Stops for breath after 100 metres or a few minutes on level Too breathless to leave house or when dressing or undressing

more than 80% between 50–79%

Severe Very severe

between 30–49% less than 30%

Treatment See table below on management of COPD. For treatment of an acute episode of severe wheezing, see Section 3.2.3. Moderate exacerbations of COPD present with increased shortness of breath and possibly more purulent sputum (increase in the volume and change in colour).

8 Questions are from MRC questionnaire, cited in NICE COPD guideline at http://guidance.nice.org.uk/CG101. The relationship of symptoms to COPD severity (deﬁned by FEV1) is approximate.

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Management consists of the following: • Give higher dose salbutamol and ipratropium. • Give prednisolone 30 mg/day for 7–14 days. • Do chest X-ray to rule out pneumonia, pneumothorax, or pleural effusion. • If sputum more purulent compared to baseline, and: ° if evidence of pneumonia, treat as per above guidance. ° if no evidence of pneumonia, give amoxicillin, erythromycin,9 or doxycycline. Chronic COPD management is determined by the following factors: • symptoms of breathlessness or exercise limitation • frequency of exacerbations • severity of airﬂow obstruction • presence of complications. In the management of COPD, inhaled salbutamol or ipratropium as needed are used as reliever medications in all categories. All patients should be counselled to stop smoking and avoid indoor air pollution. Give pneumococcal and annual inﬂuenza vaccinations. Refer for specialist care for severe or very severe COPD (for example, to consider long-term home oxygen therapy and treatment of right heart failure in very severe disease). Commonly used inhaled medications include: • Short-acting bronchodilators, such as salbutamol metered-dose inhaler or ipratropium MDI. • Long-acting bronchodilators, include long-acting beta-agonists (LABA, e.g. formoterol or salmeterol) or long-acting muscarinic antagonist (LAMA, e.g. tiotropium). Regular dose ipratropium (2 puffs 4 times daily) could be substituted for LAMA. The table that follows provides an example of an approach to the management of chronic COPD. Refer to national or local guidelines. It may be necessary to advise patients to purchase more effective medications that are not on the national formulary to control COPD. WHO guidelines for management of COPD at the primary care level are in development.

9 Follow national guidelines. Clarithromycin or azithromycin are alternatives.

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Table: Example of approach to management of stable COPD Severity Mild Moderate Derived from NICE10 Short-acting bronchodilator (salbutamol 100-200 mcg up to 4 times daily or ipratropium 20-40 mcg up to 4 times daily) as needed Short-acting bronchodilator (salbutamol or ipratropium) as needed

LABA (salmeterol or formoterol) or LAMA (tiotropium) Severe Short-acting bronchodilator (salbutamol or ipratropium) as needed

LABA (salmeterol or formoterol) and beclometasone (400 mcg twice daily) OR LAMA (tiotropium) or ipratropium 4 times daily OR LABA and LAMA or ipratropium 4 times daily Very severe Short-acting bronchodilator (salbutamol or ipratropium) as needed

LABA and beclometasone OR LAMA or ipratropium 4 times daily AND LABA OR LABA AND (LAMA or ipratropium 4 times daily) and beclometasone Maintenance prednisolone is not normally recommended. Some patients may require maintenance prednisolone when it cannot be stopped after an exacerbation. The dose should be kept as low as possible. SR theophylline should only be used after a trial of short-acting bronchodilators and LABA/ LAMA, or in patients who are unable to use inhaled therapy.

10 Management of chronic obstructive pulmonary disease in adults in primary and secondary care. NICE, 2010. Available at http://guidance.nice.org.uk/CG101

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Fig 1a Right middle lobe inﬁltrate pneumonia (PA view)

Fig 1b Lateral view

Fig 2 Diffuse inﬁltrates or opacities

Fig 3 Multiple small nodules

Fig 5 Cavity Fig 4 Masses and nodules

Fig 6a Pleural effusion

Fig 6b Pleural effusion

Fig 7a Hilar or mediastinal lymphadenopathy

Fig 7b Hilar or mediastinal lymphadenopathy

Fig 9 Normal Fig 8 Pneumothorax

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10.7 Abdominal complaints Each symptom is dealt with in its own subsection. Patients may present with several combinations of the symptoms discussed below, e.g. abdominal pain plus diarrhoea. Therefore, it is important to determine each major symptom, work through the differential diagnosis tables for each, and develop a coherent treatment plan. Section 10.7 includes: • 10.7a Abdominal pain • 10.7b Painful or difﬁcult swallowing • 10.7c Nausea and vomiting • 10.7d Diarrhoea (and constipation)

10.7a Abdominal pain In this section: 10.7a.1 Clinical approach to abdominal pain 10.7a.2 Differential diagnosis of abdominal pain and management of speciﬁc conditions • DDx: Generalized abdominal pain • DDx: Upper abdominal or epigastric pain • Management of speciﬁc conditions causing abdominal pain • Dyspepsia, gastritis, peptic ulcer disease • Pancreatitis • Cholecystitis and cholangitis • Peritonitis • Ascariasis 10.7a.3 Approach to abdominal pain in PLHIV

This Section provides an approach to the diagnosis and management of a patient with abdominal pain, either upper or epigastric, or generalized pain. Lower abdominal pain is also addressed in Section 10.15.2 Female genitourinary problems.

10.7a.1 Clinical approach to abdominal pain Step 1: Use Quick Check. Ensure that there are no serious or life-threatening conditions. Be aware that a patient with abdominal pain could have a surgical abdomen (see below) or a gynaecological emergency that requires surgery. The patient should not eat until this diagnosis has been ruled out. Step 2: Take a history and examine the patient. Step 3: Assess HIV status. Step 4: Classify the abdominal pain and use the DDx tables to work through a differential diagnosis. • DDx: Generalized abdominal pain • DDx: Upper abdominal or epigastric pain Step 5: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response.

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Emergency treatments Always consider the possibility of an acute surgical abdomen or gynaecological emergency, e.g. an ectopic pregnancy. Patients should not eat or drink before this is ruled out. A “surgical abdomen” is any abdominal condition which would result in a rapidly worsening prognosis in the absence of surgical intervention. A high level of suspicion should be maintained in immunocompromised patients when typical signs of peritoneal inﬂammation may be reduced or absent. • General signs and symptoms of a surgical abdomen: ° a very ill patient with or without fever and shock ° little pain relief from analgesics ° localized, generalized, or rebound tenderness on palpation ° distended abdomen ° diminished or absent bowel sounds ° no ﬂatus or bowel movements. • X-ray ﬁndings suggestive of a surgical abdomen include: ° hollow organ perforation: free intra-peritoneal air, or air under the diaphragm on upright chest or abdominal X-ray (note that this ﬁnding, although uncommon, is speciﬁc for a surgical abdomen and should prompt immediate surgical consultation); ° hyper-inﬂated bowel- consider peritonitis. • Use ultrasound to exclude other causes of an acute surgical abdomen. If a surgical abdomen is strongly suspected, refer to the Quick Check for urgent interventions and the WHO manual Surgical care at the district hospital1 for deﬁnitive care.

History The history of the presenting complaint should include: • nature of the pain – onset, duration, location, quality, and radiation; • exacerbating or relieving factors (e.g. food, antacids, exertion, defecation); • associated symptoms (e.g. fevers, chills, weight loss or gain, nausea, vomiting, diarrhoea, constipation, blood in the stool, change in the colour of urine or stool, yellow discoloration of the eyes). • Medical history ° previous history of similar abdominal pain ° history of peptic ulcer ° symptoms suggestive of systemic disease (e.g. cough, fever, night sweats) ° substance use including alcohol ° immune status. • Medication history ° ART (duration of therapy is important) ° over-the-counter medications (e.g. paracetamol, aspirin, NSAIDs) ° traditional remedies ° antibiotic therapy.

1 Surgical care at the district hospital., WHO, 2003. Available at www.who.int/surgery/publications/scdh_manual/ en/index.html

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• Menstrual and pregnancy history • Geographic location for diseases speciﬁc to certain regions (notably, prevalence of schistosomiasis and soil-transmitted helminths) ° If the patient is from a schistosomiasis endemic area, treat empirically with praziquantel (see Section 11.34).

Examination • Targeted general examination ° vital signs ° jaundice, pallor, lymphadenopathy ° signs of chronic liver disease (e.g. scratch marks, palmar erythema, ascites, spider naevi, caput medusa, bruising, oedema) • Abdominal examination ° look for abdominal distension ° palpate for masses, tenderness, peritoneal signs (rebound tenderness and guarding) ° listen for bowel sounds ° percuss for ascites – shifting dullness ° do rectal examination and also look for blood in stool ° examine the groin and the scrota for inguinal masses and hernias. • Pelvic examination ° in women with lower abdominal pain. • Other organs ° look for pneumonia or heart failure – may cause abdominal pain ° shingles can cause localised abdominal pain.

Classify abdominal pain and use the differential diagnosis tables Classify the pain based on the clinical presentation. Refer to the respective DDx tables below to help work through a differential diagnosis. • Generalized abdominal pain (DDx table) See also lower abdominal pain in 10.15.2 Female GU problems. • Upper abdominal or epigastric pain (DDx table).

Perform investigations • Laboratory investigations: The following are recommended investigations for all patients: ° urine analysis (dipstick and microscopy – for haematuria and S. haematobium ova) ° pregnancy test ° U&E, FBC, glucose • Investigations based on clinical ﬁndings include: ° liver functions ° amylase ° serum lactate if the patient is taking ART. ° Stool for macroscopic and microscopic examination – look for occult blood and various helminth infections, including Schistosoma ova. This may require repeated examinations or concentration procedures.

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• Imaging: ° abdominal X-ray ° chest X-ray ° abdominal ultrasound is useful to identify: ◊ abdominal lymph nodes ◊ liver and spleen pathology ◊ appendix mass ◊ gall stones, cholecystitis ◊ renal stones or hydronephrosis ◊ pelvic inﬂammatory disease with collections or a mass ◊ ectopic pregnancy.

Initiate treatment and monitor response For management of speciﬁc conditions associated with abdominal pain, see the text after the DDx tables.

10.7a.2 Differential diagnosis of abdominal pain and management of speciﬁc conditions The differential diagnosis differs for generalized abdominal pain and for upper abdominal or epigastric pain. Use the appropriate table below. In women with lower abdominal pain, see also Section 10.15.2 Female genitourinary problems.

DDx: Generalized abdominal pain Condition Surgical abdomen* In favour Rebound tenderness, guarding Pain not responding to analgesics Abdominal distension Vomiting Decrease in ﬂatus or stool Abdominal X-ray – dilated loops of bowel, air ﬂuid levels Chest X-ray – free air under the diaphragm *Consider bowel obstruction or perforation, appendicitis, peritonitis, mesenteric infarct, ruptured ectopic pregnancy. Manage according to Quick Check page 8. See Section 10.15 for female genitourinary problems. See the WHO Manual Surgical Care at the District Hospital. Ectopic pregnancy see Section 10.15 Positive pregnancy test (or may be negative) Pain usually in lower abdomen Abnormal vaginal bleeding Back pain Cervical motion tenderness on pelvic exam Shock (if ruptured) History of previous ectopic pregnancy Low grade fever Early – peri-umbilical pain Later – pain localized to right lower quadrant FBC – high WCC Colicky abdominal pain Abdominal distension Vomiting No stool or ﬂatus Bowel sounds – none, or if partial obstruction, high-pitched tinkling with rushes Hernia detected

Appendicitis

Bowel obstruction

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Abdominal TB see Section 15

Pain usually non-speciﬁc and chronic Constitutional symptoms – fever, weight loss, night sweats Abdominal swelling, mass, or ascites Chest X-ray – evidence of pulmonary TB Ultrasound – para-aortic lymph nodes or ascites Biochemistry – low SAAG ascites (see Section 10.9) Seriously ill without other apparent cause Prolonged high fever Abdominal tenderness Relative bradycardia compared with fever Geographic area FBC – decreased WCC Patient taking ARVs for >6 months Patient taking an NRTI, e.g. d4T, ddI, or AZT Female, overweight Loss of weight, fatigue, malaise Nausea or vomiting Serum lactate >5 mmol/l Arterial pH <7.3, widened anion gap >13 Elevated ALT/AST, LDH, and amylase Most common cause of severe gastroenteritis in the young, the elderly, and people who have suppressed immune systems Abdominal pain, diarrhoea, nausea, vomiting Chills, clammy skin, excessive sweating, fever, joint stiffness Leakage (incontinence) of stool Muscle pain Poor feeding, vomiting blood (very rare), weight loss Abdominal pain in the left lower quadrant Fever Nausea Change in bowel habits Peritoneal signs – guarding and rebound High worm burdens may cause abdominal pain and intestinal obstruction Eggs on stool exam by direct wet mount or after concentration Chronic watery diarrhoea Wasting and malnutrition Geographic area Other symptoms of advanced HIV Diarrhoea – may have blood Cough Serpiginous (snake-like) skin lesions Visible parasites on stool or sputum examination Abdominal cramping, bloating, and a change in bowel habits between constipation and diarrhoea More often in women than men No known cause of IBS

Typhoid see Section 11.43

Lactic acidosis see Section 13

Viral gastroenteritis

Diverticulitis

Helminthic infections – ascaris Protozoan infections

Strongyloidiasis see Section 11.36

Irritable bowel syndrome (IBS)

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Condition Inﬂammatory bowel disease (ulcerative colitis and Crohn’s disease)

In favour Peak incidence in young adults (15–25 years old) Ranges from mild disease (insidious onset, non-bloody diarrhoea, poor weight gain) to severe (fulminant presentation, severe abdominal pain, bloody diarrhoea, tenesmus, and fever) Abdominal tenderness Perianal involvement (ﬁstulae, anal tag, or ﬁssure) Extraintestinal manifestation: eye involvement (e.g., uveitis), skin involvement (e.g., rash, erythema nodosum, pyoderma gangrenosum), peripheral arthritis (involving large joints and ankylosing spondylitis), sclerosing cholangitis, thromboembolism, lung disease, renal stones, anemia, and digital clubbing Palpable abdominal mass (suggestive of a ﬁstula) and oral ulcerations can occur in Crohn’s disease Diagnosis based on characteristic history and endoscopy Offensive smelling urine Painful urination Frequency of urination Urgency of urination Cloudy urine Urine dipstick – leucocytes, nitrites, blood Urine microscopy – leucocytes, RBCs, bacteria Fever Rigors Flank pain Painful urination Cloudy urine Costovertebral angle tenderness Urine microscopy– leucocytes, protein, RBCs, WBC, bacteria Acute attacks of severe colicky back or ﬂank pain, radiating to groin (loin to groin radiation) History of previous attacks Taking indinavir or sulphadiazine Urine dipstick – blood Urine microscopy – red cells and crystals Abdominal X-ray – stones may be visible in renal tract Ultrasound – urethral dilatation, hydronephrosis, stones Persistent fever Diarrhoea Hepatomegaly Wasting FBC – severe anaemia and neutropaenia Elevated ALP and GGT CD4 <50 History of medications known to cause abdominal side-effects Sudden onset severe pain Shock Abdominal pain radiating to the back Pulsatile abdominal mass with peritonism Ultrasound – aortic dilatation, intimal ﬂap dissection

Urinary tract infection, cystitis see Section 11.44

Acute pyelonephritis see Section 11.44

Renal stones

Mycobacterium avium complex (MAC) see Section 11.27

Drug induced Dissecting abdominal aortic aneurysm

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DDx: Upper abdominal or epigastric pain Condition Gastritis, peptic ulcer disease In favour Burning epigastric pain and tenderness Relieved by food and antacids (more likely gastric ulcer) History of alcohol or NSAID use Complications – signs of upper GI bleed or perforation Upper epigastric and retrosternal pain Worse on eating and swallowing See Section 10.7.b Delayed gastric emptying, commonly occurring in diabetes Heartburn or pain in the upper abdomen with spasms in the stomach area Nausea or vomiting of undigested food – sometimes several hours after a meal Early feeling of fullness after only a small amount of food Weight loss due to poor absorption of nutrients or low calorie intake Abdominal bloating Fluctuating blood glucose levels – high and low Lack of appetite Gastro-oesophageal reﬂux Jaundice Malaise Loss of appetite Exposure to hepatotoxic drugs – TB medications, NVP, EFV History of heavy alcohol intake Right upper quadrant pain High ALT, AST, bilirubin Nausea, vomiting, loss of appetite Pain is steady and severe – patient is often reluctant to move Pain worse after eating Right upper quadrant pain radiating to right shoulder or back Guarding Jaundice if duct obstruction Tender hepatomegaly or tenderness over site of gallbladder Low grade fever or chills High WBC, ALP, AST/ALT, amylase, bilirubin Ultrasound –gall stones or sludge, thickened gall bladder wall, dilated common bile duct if obstruction, pericholecystic ﬂuid, sonographic Murphy’s sign (pain when gallbladder is pushed by transducer) Abdominal X-rays usually normal HIV patients – acalculous cholecystitis (no stones seen) Similar to above, but with: • high grade fever • jaundice • rigors • shock Abdominal pain, fever, loss of appetite, nausea, vomiting, jaundice Risk factors – previous history of gallstones (can occur if gall bladder has been removed)

Oesophagitis CMV see 11.8 Herpes see Section 11.15 Candida see Section 11.4 Gastroparesis

Viral hepatitis see Section 11.14

Cholecystitis (inﬂammation of the gall bladder)

Cholangitis (inﬂammation of the bile ducts)

Choledocholithiasis

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Condition Pancreatitis

In favour Pain radiating to the back Pain is exacerbated by eating and when lying down and relieved by sitting up or leaning forward Nausea, vomiting Fever, tachycardia Dehydration May be severely ill with shock History of excessive alcohol intake Exposure to NRTIs – d4T, ddI, 3TC, ritonavir Purple hue on the skin around the ﬂanks may signify retroperitoneal bleeding from haemorrhagic pancreatitis Amylase >3 times normal, increased lipase, increased TG, high AST, high ALT, high ALP, increased bilirubin Ultrasound – gallstones, pancreatic oedema, abdominal ﬂuid Patient taking ARVs for >6 months Patient taking an NRTI, e.g. d4T, ddI, or AZT Female, overweight Loss of weight, fatigue, malaise Nausea or vomiting Serum lactate >5 mmol/l Arterial pH <7.3, widened anion gap >13 Elevated ALT/AST, LDH, and amylase Left upper quadrant pain Fever Pain referred to left shoulder Splenomegaly Ultrasound – splenic abscesses Associated signs of TB May present as right or left upper quadrant pain Chest examination reveals consolidation of the lung adjacent to site of abdominal pain

Lactic acidosis see Section 13

Splenic abscess see Section 10.20

Pneumonia see Section 10.6

Management of speciﬁc conditions causing abdominal pain Dyspepsia, gastritis, and peptic ulcer disease Treatment • Empirical therapy before investigations is acceptable (gastroscopic or barium studies). • Advise the patient to discontinue NSAIDS, alcohol, caffeine, cigarettes. • Treat with proton pump inhibitors: ° omeprazole 20 mg once daily for 4–8 weeks • In refractory cases: consider diagnosis of Helicobacter pylori. It is better to conﬁrm the diagnosis of H. pylori before treating. Test according to national guidelines with available tests. These may include rapid tests on blood, breath, or stool, or may require endoscopy to obtain a biopsy sample. Have a high index of suspicion for malignancy, which will require a gastroscopy and biopsy to exclude.

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• If test is positive, give triple therapy2: amoxicillin 1 g twice daily: + clarithromycin 500 mg twice daily + omeprazole 20 mg twice daily then omeprazole 20 mg once daily for 4–6 weeks ° For patients with allergy to amoxicillin, use metronidazole 400 mg twice daily. ° If clarithromycin is unavailable, use amoxicillin 1 g twice daily and metronidazole 400 mg twice daily. ° For second-line therapy, replace clarithromycin with doxycycline 100 mg twice daily. • Patients who do not respond should be referred for further investigations, e.g. endoscopy.

for 7 days

Pancreatitis Common causes • alcohol • gall stones • high triglyceride levels (more than 1000 mg/dl) – protease inhibitors may cause elevated lipid levels • toxins, such as scorpion bite or organophosphate insecticides • in patients with HIV infection: ° medications ◊ ART – ddI or d4T, especially if used in combination ◊ for OIs – cotrimoxazole, pentamidine, sulfonamides ° patients with CMV or MAC infection • other medications – valproic acid, furosemide, tetracycline, ACE inhibitors, sulfur drugs. Pancreatitis usually presents as an acute process, but can lead to chronic pancreatitis if the insult recurs.

2 18th expert committee on the selection and use of essential medicines. WHO, 2011. Available at http://www.who. int/selection_medicines/committees/expert/18/en/index.html

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Calculate the severity of acute pancreatitis using Ranson’s criteria. At admission: • age in years >55 years • white blood cell count >16 000 cells/mm3 • blood glucose >10 mmol/l (more than 200 mg/dl) • serum AST >250 IU/l • serum LDH >350 IU/l If the Ranson score is ≥3, severe pancreatitis is indicated, and rapid intervention is necessary. It indicates poor prognosis. If the score is <3, the pancreatitis is less severe and could resolve with symptomatic management. Re-evaluate after 48 hours.

Treatment Mild acute pancreatitis • Nothing by mouth. • Aggressive IV hydration, especially in the ﬁrst 24–48 hours, to replace the large amount of ﬂuid lost to the third space. • Analgesia – an opioid such as morphine is usually required. • Stop toxic medications (see Section 13.8 toxicity and drug substitutions). • Re-assess regularly and re-evaluate Ranson’s criteria after 48 hours. • Close clinical monitoring to recognize complications early: ° monitor intake and output (urine output of 0.5 ml/kg/hour is desirable) ° monitor pain control ° monitor for signs of septic shock (low BP, tachycardia, poor perfusion) ° monitor for early signs of respiratory failure (tachypnoea, acidotic breathing). Severe acute pancreatitis • Supportive treatment as above and referral to a higher level for surgical consultation and nutritional support. Complications of pancreatitis • Prolonged pancreatitis with haemodynamic instability, fever, and poor response to medical therapy should be referred for surgical opinion and management at an intensive care unit. • A deterioration in clinical condition may indicate complications. ° Early complications (within days of onset) ◊ pancreatic necrosis ◊ acute lung injury or acute respiratory distress syndrome with hypoxaemia (see Section 3.2.3) ◊ septic shock – hypotension, tachycardia, low urine sodium concentration (see Section 3.1.5) ◊ haemorrhage ° Late complications (within 4 weeks, seen on a contrast-enhanced CT scan) ◊ pancreatic pseudocyst ◊ abscess.

Cholecystitis and cholangitis Treatment • Check for danger signs using Quick Check. • Administer IV ﬂuids.

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• Insert a nasogastric tube for drainage, or suction if vomiting. • No oral intake (except for medication). • Treat with antibiotics and expectant (conservative) management and then, once stabilized, arrange and refer for surgical assessment. • Empirical antibiotic therapy according to local patterns of resistance, availability, and severity of illness. For cholangitis, for 10–14 days: ° ampicillin 2 g IV every 4 hours PLUS gentamicin IV 1.5 mg/kg every 8 hours PLUS metronidazole 500 mg IV or orally 3 times daily; OR ° ceftriaxone 1 g IV once daily PLUS metronidazole (1 g rectally or 500 mg orally 3–4 times daily or 500 mg IV 3 times daily); OR ° ciproﬂoxacin 400 mg IV (or 500 mg orally) twice daily plus metronidazole as above. • For cholecystitis- no jaundice or rigors and able to take oral medication: ° amoxicillin-clavulanic acid 1 g orally 3 times daily (1 g orally 4 times daily if more severe); OR ° ciproﬂoxacin 500 mg orally twice daily plus metronidazole 500 mg orally 3–4 times daily. Early surgical assessment or referral should be done for those with complications or those not responding to treatment. Complications of cholecystitis and cholangitis • Gangrene or perforation of the gallbladder requiring surgical intervention to remove the gall bladder.

Peritonitis3 Peritonitis is an acute, life-threatening condition caused by bacterial contamination of the peritoneal cavity. The major causes of peritonitis include: • appendicitis • perforated peptic ulcer • anastomotic leak following surgery • strangulated bowel • pancreatitis • cholecystitis • intra-abdominal abscess • haematogenous spread of infective agents such as typhoid or TB • typhoid perforation • ascending infection, for example, in salpingitis and postpartum infection.

Key clinical features • • • • sharp pain that is worse on movement or coughing fever abdominal distension, tenderness, and guarding diminished or absent bowel sounds

3 Adapted from Surgical care at the district hospital. WHO, 2003. Available at www.who.int/surgery/publications/ scdh_manual/en/index.html

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• shoulder pain (referred from diaphragm) • tenderness on rectal or vaginal examination (suggests pelvic peritonitis). These features may be minimal in elderly patients or those who are immunosuppressed. Therefore for these patients it is important to maintain a high index of suspicion for the condition. Treatment The treatment of peritonitis is the treatment of the underlying cause. • Administer IV ﬂuids. • Insert a nasogastric tube for drainage. • Give IV antibiotics, providing aerobic, Gram negative and anaerobic coverage, e.g. ampicillin 2 g IV every 6 hours, PLUS gentamicin 1.5 mg/kg IV every 8 hours, PLUS metronidazole 500 mg IV every 8 hours. • Record ﬂuid balance and vital signs on the bedside chart every 6 hours. Assess or refer for surgical intervention as appropriate. The nature of the intervention will depend on the cause of the peritonitis, e.g. appendectomy for appendicitis, repair of a perforated viscus, or drainage of an abscess.

Ascariasis Treatment • albendazole 400 mg oral once; OR • mebendazole 500 mg oral once or 100 mg twice daily for 3 days. Ascariasis can uncommonly cause intestinal and biliary obstruction that may require surgical intervention.

10.7a.3 Approach to abdominal pain in PLHIV The approach to patients with abdominal pain is similar in HIV-infected and uninfected patients (see ﬂow chart below), except that HIV-infected patients may present atypically due to underlying immune suppression. The common causes of abdominal pain listed above occur also in PLHIV, and these should remain high on the differential diagnosis list. However, there are some additional conditions to consider including: • MAC, CMV, fungal and protozoal infections causing diarrhoea and associated intermittent, dull abdominal pain; • drug side-effects (e.g. pancreatitis, lactic acidosis) – take a full drug history; • HIV-related lymphomas, which can cause abdominal pain with intestinal obstruction.

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Figure: Approach to HIV-infected patient with abdominal pain

Abdominal pain

Check for danger signs: guarding, distension, loss of bowel sounds, high temperature, shock

See Quick Check page 23, Vol. 1

Is the patient on ART?

See Section 13, table on ARV toxicities

Look for associated symptoms and location of pain

Epigastric or upper abdominal pain, +/- nausea and vomiting

Generalized +/- fever, vomiting, or nausea

Generalized +/- diarrhoea

Lower abdominal pain

Check for: gastritis, PUD, gallbladder stones, hepatitis, cholecystitis, malignancies

Check for: malaria, TB, liver or spleen abscess, UTI, typhoid fever, other OIs (CMV, crypto, MAC)

See Section 10.7d Diarrhoea

Check for: UTI, appendicitis, PID, pelvic abscess. In females check gyn history and complications (See Section 10.15)

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10.7b Painful or difﬁcult swallowing In this section: 10.7b.1 Clinical approach to painful or difﬁcult swallowing 10.7b.2 Differential diagnosis and treatment of painful or difﬁcult swallowing (with DDx table) 10.7b.3 Approach to oesophagitis in PLHIV

Painful or difﬁcult swallowing may occur with liquids or solids, and patients may complain of problems at the onset of swallowing or a sensation of food getting “stuck” in their throats.

10.7b.1 Clinical approach to painful or difﬁcult swallowing Step 1: Use Quick Check. Ensure that there are no serious or life-threatening conditions. Be aware that a patient with difﬁculty swallowing may present with dehydration and electrolyte imbalances as a result of poor oral intake. Refer to Quick Check for management of these patients. Step 2: Take a history and examine the patient. Step 3: Assess the patient’s HIV status. Step 4: Consider likely differential diagnosis using the DDx table(s). Step 5: Perform investigations as required. Step 6: Initiate treatment and monitor the patient’s response.

History • • • • Is it painful to swallow, or is there difﬁculty in swallowing? Is it associated with liquids or solids? What is the duration of symptoms? Are there any associated symptoms – cough, fever, heartburn, weight loss, nausea, vomiting, vomiting blood, breathing problems, or other?

Examination • Check the patient’s weight and temperature. • Check the oral cavity for white plaques or ulcers. • Assess hydration and nutritional status. Assess the patient’s HIV status HIV infection will change the possible differential diagnoses for painful or difﬁcult swallowing, as a number of opportunistic infections can cause these symptoms, such as CMV and Candida oesophagitis. An HIV test and CD4 count are helpful in determining the underlying cause. See Figure below for approach to painful or difﬁcult swallowing in patients with HIV.

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Investigations • FBC, urea, and electrolytes.

10.7b.2 Differential diagnosis and treatment of painful or difﬁcult swallowing DDx: Painful or difﬁcult swallowing Condition In favour Painful swallowing Oral thrush (Candida) Pain in chest behind the sternum Responds to ﬂuconazole Fever Severe pain on swallowing Pain in chest behind the sternum Painful oral ulcers Associated visual loss or CMV retinitis on fundoscopy CD4 <50 History of object lodging in throat Vomiting or increased salivation (complete salivation) Choking (see Quick Check) Pain or burning sensation in chest (heartburn) Bitter or sour taste in back of mouth Worse after eating or at night Chronic reﬂux can lead to strictures and difﬁculty in swallowing (initially solids, then liquids) Purple lesions on the palate or gums Lesions can be painful or ulcerate Lesions may become infected Associated painless purple nodules on skin Pain on swallowing Ulcer or abscess may be seen Enlarged or inﬂamed tonsils Fever Enlarged lymph nodes in the neck Painful or difﬁcult swallowing Ulcers or masses that do not heal Dental changes Weight loss Bleeding Loss of appetite Weight loss Progressive difﬁculty in swallowing (initially solids, then liquids) Painful swallowing Anaemia

Candida oesophagitis see Section 11.4

CMV or HSV oesophagitis (see Section 11.8 or 11.15)

Foreign body in throat

Gastric reﬂux

Kaposi sarcoma see Section 11.19

Mouth or throat infection see Section 10.17

Oral cancer

Oesophageal cancer

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Condition Oesophageal stricture or web, or diverticula

In favour Difﬁculty swallowing Discomfort with swallowing A feeling that food gets stuck in the oesophagus Regurgitation of food Weight loss Risk factors – gastro-oesophageal reﬂux (GERD) Prolonged use of a nasogastric tube Ingestion of corrosive substances Viral or bacterial infections Injuries caused by endoscopes Difﬁculty in swallowing solids and liquids Weight loss Chronic cough Hiccups Heartburn Regurgitation

Achalasia

Initiate treatment and monitor the patient’s response • Initial empirical treatment is recommended for symptoms suggestive of gastro-oesophageal reﬂux (give a trial of omeprazole) or of Candida oesophagitis (give ﬂuconazole – see Section 11.4) until symptoms resolve. • For treatment of speciﬁc conditions, see text and referenced Sections below.

10.7b.3 Approach to oesophagitis in PLHIV Key clinical features • Common causes of oesophagitis in patients with HIV include: Candida, CMV, aphthous ulcers, HSV (see Figure below). • Oral Candida associated with painful or difﬁcult swallowing is highly suggestive of Candida oesophagitis. However, its absence does not exclude the diagnosis – especially in patients who have been using topical antifungals. • Gastro-oesophageal reﬂux disease (GERD) may present like oesophagitis, and should be considered in the differential diagnosis. Treatment • Empirical management as above with ﬂuconazole for patients with recent onset of symptoms. ° If symptoms suggest reﬂux disease, give trial of antacid therapy. ° If empirical Candida therapy fails, consider treating for CMV, HSV, or reﬂux disease. ° If still failing to respond, referral for gastroscopy plus biopsy can be considered. Pain management • Pain medication may be required according to analgesic ladder (see Section 20). • Crush and disperse aspirin 600 mg in a small amount of water and rinse the mouth; gargle if throat is painful. Diet • Introduce soft diet to decrease discomfort. • Avoid extremely hot, cold, or spicy foods. • Increase ﬂuid intake when swallowing pills.

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Figure: Approach to painful or difﬁcult swallowing in PLHIV

Odynophagia or dysphagia

Treat presumptively for oesophageal candidiasis

Improved after 7 days

No*

Treat presumptively for HSV (Section 11.15)

Improved after 7 days

Consider treating for reﬂux disease, if no improvement, refer for oesophagoscopy for diagnosis

Continue treatment for 14 days Commence ART

Continue aciclovir for 14 days Recurrence is likely unless ART is commenced Consider prophylaxis with aciclovir 400 mg twice daily

* At any point, if symptoms are suggestive of gastro-oesophageal reﬂux disease, consider treatment with acid blockers. * Consider CMV disease especially if ﬁndings are suggestive of CMV in other sites (i.e. retinitis). See Section 11.8. * Kaposi sarcoma, lymphoma, and oesophageal carcinoma can cause painful and difﬁcult swallowing. Further investigations including barium studies, endoscopy, and biopsy may be required for a deﬁnitive diagnosis.

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10.7c Nausea and vomiting In this section: 10.7c.1 Clinical approach to nausea and vomiting 10.7c.2 Differential diagnosis and treatment of nausea or vomiting (with DDx table) 10.7c.3 Symptom management for nausea and vomiting

This Section discusses an approach to the diagnosis and management of nausea, with or without vomiting. There are many causes for nausea and vomiting such as: • gastric causes (e.g. peptic ulcer, infection, gastro-oesophageal reﬂux); • central causes (e.g. headache, motion sickness, inner ear problems, raised intracranial pressure, offensive smells); • pregnancy (hormone changes, pressure on stomach by the uterus); • drugs and toxins; • other illnesses (e.g. hepatitis, myocardial infarction).

10.7c.1 Clinical approach to nausea and vomiting Step 1: Use Quick Check. Ensure that there are no serious or life-threatening conditions. Step 2: Take a history and examine the patient. Step 3: Assess the patient’s HIV status. Step 4: Consider likely differential diagnosis using the DDx table(s). Step 6: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response.

History • History of presenting complaint: ° number and timing of episodes (after food, in the morning, after certain medications) ° contents of vomitus (food, blood, bile, or coffee grounds) ° association with changes in position or motion ° associated symptoms (abdominal pain diarrhoea, fever, headache, visual changes, heartburn). • Exposure to toxins: ° food history (are others sick who ate the same food) ° medications and treatments (such as chemotherapy) ° drug or alcohol use. • travel history • menstruation, contraception, pregnancy.

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Examination • Targeted general exam: ° signs of dehydration (increased thirst, dry lips or mouth, decreased skin turgor) ° concentrated or reduced urine ° jaundice ° weight loss ° rashes, spider naevi. • CNS exam: ° level of consciousness ° eyes for pupil size ° neck stiffness. • Abdominal exam: ° presence of abdominal distension or tenderness ° bowel sounds (present, reduced, or absent, high pitched or normal) ° liver for hepatomegaly. Assess the patient’s HIV status HIV infection changes the possible differential diagnoses for nausea and vomiting, and should be considered in all patients presenting with these symptoms.

Investigations • • • • • • • • FBC – low Hb or low WBC electrolytes (Na, K, Cl) urea and creatinine stool for macro or microscopic examination and occult blood pregnancy test in women liver proﬁle – AST, ALT, bilirubin abdominal X-ray ultrasound (for hepatomegaly, gallstones, thickened gallbladder wall, dilated common bile duct).

10.7c.2 Differential diagnosis and treatment of nausea or vomiting Use the DDx table below to work through a differential diagnosis based on ﬁndings. Initiate treatment and monitor the patient’s response Treatment will depend on the differential diagnosis. For symptom management of nausea and vomiting, see 10.7.c.2 below. For management of speciﬁc conditions, see referenced Sections or other guidelines.

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DDx: Nausea or vomiting Condition Gastrointestinal causes Gastroenteritis Associated diarrhoea Acute onset Fever Cramping abdominal pain Blood in vomitus – see Quick Check Epigastric pain, discomfort, or tenderness Nausea Loss of appetite History of alcohol or NSAID use Delayed gastric emptying, commonly occurring in diabetes Heartburn or pain in the upper abdomen with spasms in the stomach area Nausea or vomiting of undigested food – sometimes several hours after a meal Early feeling of fullness after only a small amount of food Weight loss due to poor absorption of nutrients or low calorie intake Abdominal bloating Fluctuating blood glucose levels – high and low Lack of appetite Gastro-oesophageal reﬂux Painful or difﬁcult swallowing Pain or burning sensation in the chest (heartburn) Bitter or sour taste in back of mouth Worse at night, after eating or when lying down. Candida in the mouth (may suggest Candida oesophagitis) Associated right upper quadrant abdominal pain with radiation to right shoulder or back Pain often severe – patient reluctant to move Pain worse after eating Tender hepatomegaly or tenderness over site of gallbladder Low grade fever or chills Jaundice FBC – leukocytosis Laboratory results – high ALP, high AST/ALT, increased amylase, increased bilirubin Ultrasound – hepatomegaly with or without abscesses, gall stones, thickened gall bladder wall, dilated common bile duct Abdominal X-rays usually normal In HIV patients acalculous cholecystitis (without stones) occurs Pain – radiates to the back, worse after eating and when lying down Fever, tachycardia, dehydration Vomiting after eating History of excessive alcohol intake May be severely ill with shock – see Quick Check Exposure to NRTIs – d4T, ddI, 3TC, RTV Purple hue overlying skin Laboratory results – amylase more than 3 times normal, increased lipase Ultrasound – gallstones Diffuse abdominal discomfort Constipation Abdominal distension Abdominal X-ray: air ﬂuid levels Diminished bowel sounds In favour

Gastritis or peptic ulcer disease

Gastroparesis

Oesophagitis see Section 10.7a

Cholecystitis see Section 10.7a

Pancreatitis

Ileus

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Acute hepatitis (viral, alcohol, drugs, toxins) see Section 11.14

Mild fever Jaundice Malaise, loss of appetite Exposure to drugs (TB medications, NVP, RTV, EFV, ABC), alcohol, toxins Right upper quadrant pain Laboratory results – high ALT, AST, bilirubin Gastrointestinal – initially non-speciﬁc nausea, vomiting, anorexia, mild diarrhoea, and abdominal pain. May progress to severe abdominal pain, haematemesis, bloody diarrhoea, massive ascites, and signs suggestive of acute abdomen Fainting spells, asthenia Fever and headache. Crampy abdominal pain Abdominal distension Vomiting Not able to pass ﬂatus or stool History of previous abdominal surgery Bowel sounds – high-pitched, can be decreased

Anthrax (gastrointestinal)

Intestinal obstruction or constipation

Non-gastrointestinal causes Association with general febrile illness (e.g. malaria) Endemic area Fever, chills Sweats Headache Malaise, myalgia Splenomegaly, hepatomegaly, jaundice Headache, stiff neck Fever Confusion Petechial rash (if meningococcal) History of previous episode Preceding aura Moderate to severe headache, photophobia, nausea Headache and visual disturbances Hypertension Unequal pupils Focal neurologic deﬁcit Fundoscopic examination – loss of retinal vein pulsation, papilloedema History of being in a boat, plane. or car Associated dizziness, vertigo, nystagmus Pain, discomfort, or blocked ear Fatigue, confusion Loss of appetite, constipation Muscle weakness Evidence of associated malignancy Plasma calcium >2.6 mmol/l Known renal disease Hiccups, confusion, and loss of appetite Convulsions Uraemic frost on skin Lab high urea and creatinine

Meningitis see Section 10.10b Migraine see Section 10.10b Headache Raised intracranial pressure see Section 10.10b Headache Inner ear problems (motion sickness, labyrinthitis) Hypercalcaemia see Section 5.2

Uraemia see Section 11.31

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Condition Symptomatic hyperlactataemia or lactic acidosis

In favour On ART >6 months On NRTI, e.g. d4T, ddI, or AZT Female, >40, high BMI Loss of weight, fatigue, malaise Abdominal pain Fast, deep breathing Serum lactate >5 mmol/l Low pH (<7.3), low bicarbonate, high anion gap (>13) Elevated ALT/AST, LDH, and amylase First 16–18 weeks pregnancy Worse in the mornings Loss of weight Dehydration, ketoacidosis History of using morphine Nausea, drowsiness, constipation Constricted pupils (miosis) AZT, ABC (hypersensitivity), protease inhibitors ; rifampicin; NSAIDs Severe, crushing, retrosternal chest pain or discomfort Radiation of pain to left shoulder, arm, jaw Associated sweating, anxiety, nausea History of smoking, hypertension, cholesterol, diabetes Previous episodes of angina Exposure to heat and lack of adequate hydration Hot, ﬂushed, dry skin with reduced sweating, rapid pulse, rapidly rising temperature over 40.5ºC (heat stroke) Pale, cold, clammy skin, weak pulse, low BP, high temperature (heat exhaustion) Confusion, convulsions Related to speciﬁc sights, smells or sounds Related to emotional states – anxiety, fear

Pregnancy-related vomiting and hyperemesis gravidarum see Section 14 Opioids see Section 20 Other drugs Myocardial infarction

Heat-related (heat stroke or exhaustion) see Section 10.1.4 Psychogenic see Section 10.11

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10.7c.3 Symptom management for nausea or vomiting • Home care For vomiting of less than 24 hours with no associated danger signs (e.g. blood in vomit, dehydration, headache or stiff neck, severe abdominal pain): ° drink plenty of ﬂuids ° eat favourite, available foods that cause less nausea ° eat frequent, small portions of food ° use effective and safe local remedies, e.g. licking ash from wood. Advise the patient to seek help at a health facility if: ° they have been vomiting for more than 24 hours; OR ° if they have a dry tongue; OR ° are passing little urine; OR ° have abdominal pain. • Medications ° Antiemetics: ◊ metoclopramide 10 mg IV/orally 3 times daily; OR ◊ chlorpromazine 25–50 mg IM/orally four times daily; OR ◊ ondansetron 4–8 mg IV twice daily or orally (for 24–48 hours) for moderate or severe vomiting, vomiting related to chemotherapy, or in hyperemesis gravidarum (see Section 14.1.6). Metoclopramide should not be used in bowel obstruction or severe constipation. Haloperidol 1.5 mg at bedtime is also an effective antiemetic if other agents are not available.

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10.7d Diarrhoea4 (and constipation) In this section: 10.7d.1 Clinical approach to abdominal pain 10.7d.2 Classify and manage diarrhoea (with DDx tables) • Acute diarrhoea (<14 days), with no blood • Cholera • Drug-induced diarrhoea • Clostridium difﬁcile colitis • Diarrhoea with blood 10.7d.3 Approach to persistent or chronic diarrhoea in PLHIV (with DDx table) • Protozoan infections • HIV enteropathy 10.7d.4 Constipation

This Section discusses an approach to managing patients with: • acute diarrhoea (<14 days) including cholera • diarrhoea with blood • chronic or persistent diarrhoea (14–30 days) in an immunocompromised patient.

10.7d.1 Clinical approach to diarrhoea Step 1: Use Quick Check. Use Quick Check to ensure that there are no serious or life-threatening conditions. Step 2: Take a history and examine the patient. Step 3: Assess the patient’s HIV status. Step 4: Classify dehydration and diarrhoea to work through differential diagnosis. • Acute diarrhoea, no blood • Acute diarrhoea with blood • Persistent diarrhoea in immune compromised patients Step 6: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response.

History Ask about: • diarrhoea ° frequency of stools ° duration of diarrhoea ° blood or mucous in stool • nausea, vomiting • abdominal pain • fever • recent antibiotic or other drug treatment • other co-morbid conditions, especially HIV status and CD4 count 4 The treatment of diarrhoea: A manual for physicians and other senior health workers. WHO, 2005. Available at www.who.int/child_adolescent_health/documents/9241593180/en/

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• travel history or local outbreaks of disease • food history.

Examination Assess the severity of the dehydration. • Targeted general exam: ° What is severity of dehydration? ° Is the patient lethargic? ° Does the patient have sunken eyes? ° Do the eyes appear unusually sunken in their sockets? ° Ask the family if the patient’s eyes are more sunken than usual. ° Does a skin pinch go back very slowly (more than 2 seconds)? ° Pinch the inner skin of the forearm for 1 second, then release and observe. Does it go back very slowly, more than 2 seconds? ° Note: The inside of the forearm is suggested because it is still feasible in a pregnant woman, and because it does not require the adult patient to get undressed. ° Is the patient not drinking, drinking poorly, or drinking eagerly? ° Are there signs of severe malnutrition or wasting? ° Are there signs of chronic illness or immune compromise? • Abdominal exam. ° Is there tenderness or masses? ° Is there abdominal distension with increased bowel sounds? ° In a rectal examination, note characteristics of the stool, including blood. Assess the patient’s HIV status HIV infection will change the differential diagnoses for diarrhoea, and should be considered in all patients presenting with diarrhoea. If the patient is HIV-infected, what is the CD4 count?

Investigations • • • • • • • FBC – anaemia or leucocytosis electrolytes stool for macro and microscopic examination, and occult blood pregnancy test in women liver proﬁle – AST, ALT, bilirubin abdominal X-ray ultrasound – hepatomegaly, gallstones, thickened gallbladder wall, dilated common bile duct • urinalysis – dipstick, macroscopic, and microscopic examination (S. haematobium ova, WBCs, RBCs).

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10.7d.2 Classify and manage diarrhoea Dehydration should be assessed, classiﬁed, and treated in all patients with diarrhoea. Empirical treatment algorithms are suggested for the management of acute diarrhoea and diarrhoea with blood. Most patients will respond to empirical treatment, so diagnostic tests often are not necessary. If the situation is different, follow national guidelines and use clinical judgement. Table: Classify and treat dehydration Signs Two of the following signs: • Lethargic or unconscious • Sunken eyes • Not able to drink or is drinking poorly • Skin pinch goes back very slowly Classify as SEVERE DEHYDRATON Treatments Rehydration with IV or NG – Plan C Consider causes and treat. If there is cholera in your area, give appropriate antibiotic for cholera (according to sensitivity data). Report cases (see Section 21 Recording and reporting disease outbreaks). Give ﬂuid and food – Plan B Immediately advise patient when to return. Follow up in 5 days if not improving. Treat diarrhoea at home – Plan A Advise when to return. Follow up in 5 days if not improving

Two of the following signs: • Sunken eyes • Drinks eagerly, thirsty • Skin pinch goes back slowly Not enough signs to classify as severe or some dehydration

SOME DEHYDRATION

NO DEHYDRATION

Acute diarrhoea (<14 days), with no blood Acute diarrhoea with no blood is most commonly due to viral infections, but may be due to bacterial infections. In an outbreak, consider cholera. Patients may present with fever. Diagnosis • Diarrhoea generally of limited duration and does not require investigations. • Cholera should be suspected if there are cases of diarrhoea with severe dehydration in the community (see management of cholera below). Treatment • Usually no antimicrobial therapy is needed. • Manage dehydration according to severity (see table above): ° Use an appropriate ﬂuid plan (see below) depending on the classiﬁcation of dehydration. ° Give adequate oral ﬂuids and oral rehydration salts. ° If severe dehydration, give intravenous therapy. • In addition to ﬂuids, in all cases of diarrhoea it is important to continue eating.

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Cholera5 Key clinical features It is most important to ascertain whether all patients thought to have cholera do in fact have the same disease. • Cholera may occur as an outbreak or be locally endemic. • Signs and symptoms include: ° profuse watery stools (rice-water stools) ° large volumes of ﬂuid are vomited ° severe dehydration ° abdominal pain not marked. • According to the WHO case deﬁnition, a case of cholera should be suspected if: ° in an area where the disease is not known to be present, a patient aged 5 years or more develops severe dehydration or dies from acute watery diarrhoea; OR ° in an area where there is a cholera epidemic, a patient aged 5 years or more develops acute watery diarrhoea, with or without vomiting. • Cholera is conﬁrmed if Vibrio cholerae O1 or O139 is isolated from a patient with diarrhoea. ° Stool samples should be sent for culture or a rapid dipstick test should be performed. ° Laboratory conﬁrmation of the ﬁrst 10–20 cases is essential to determine an outbreak of cholera. ° It is not necessary to take a sample from every patient with acute diarrhoea, once the cholera outbreak is conﬁrmed. • If tests to conﬁrm a diagnosis are not available, empirical treatment can be started. The clinical case deﬁnition allows detection and treatment of cholera. • Stool samples should be taken before giving antibiotics to the patient. See Section 7.2.17 on taking stool samples in Cary-Blair medium for cholera. Treatment • Rehydration is the mainstay of treatment. ° Classify dehydration and follow ﬂuid plans above. ° 80% of cases can be treated with ORS. • Provide antibiotics for patients with severe disease (according to local guidelines and sensitivities). ° doxycycline 300 mg in a single dose; OR ° tetracycline 500 mg (or 25 mg per kg) 4 times daily for 3 days; OR ° erythromycin 250 mg 4 times daily for 3 days (for areas with tetracyclineresistant strains); OR ° ciproﬂoxacin 1 g in a single dose. Prevention • Other important measures include: ° Ensure a safe water supply. ° Supervise careful preparation of food and drinks. ° Isolate patients in a separate ward from other patients. ° Wash hands with soap before and after taking care of the patient (see Section 6). 5 Cholera, WHO, 2011. Available at http://www.who.int/topics/cholera/en/

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° Cut nails (health worker). ° Note that the stools, vomit, and soiled clothes of patients are highly contagious. ° Wash and disinfect latrines and patients’ buckets with chlorine. ° Provide a supply of nutritious food (small frequent meals). Home care advice for patients with diarrhoea • Increase ﬂuid intake. ° Encourage the patient to drink plenty of ﬂuids to replace lost water. ° Ensure safe water for the patient – boiled or disinfected. ° Give the patient frequent drinks in small amounts, such as rice soup, porridge, water (with food), other soups or oral rehydration solution (ORS), but avoid sweet drinks. • The patient should continue eating. • Advise the patient when to return to the clinic, and to seek help from a health worker if: ° The patient is vomiting and has fever. ° There is blood in the stool. ° The diarrhoea continues more than 5 days. ° The patient becomes even weaker. ° There is broken skin around the rectal area. To prevent dehydration • The patient should drink extra ﬂuids frequently – see Fluid Plan A for adults. • The patient should use ORS if there is a large volume of diarrhoea or there is persistent diarrhoea. • Advise the patient to continue eating.

Fluid plans A, B and C (ﬂuid and food) Plan A: Treatment of diarrhoea at home Counsel the patient on the 3 rules of home treatment. 1. Drink extra ﬂuid. 2. Continue eating. 3. Advise the patient when to return to the health facility. 1. Drink extra ﬂuid • Drink extra ﬂuid: ° as much as the patient will take ° safe ﬂuid that is clean or has been boiled or disinfected ° ORS or other ﬂuid (except ﬂuids with high sugar or alcohol) ° drink at least 200–300 ml after each loose stool ° continue drinking extra ﬂuid until the diarrhoea stops. • It is especially important to provide ORS for use at home if the patient cannot return to the clinic if the diarrhoea worsens. • If ORS is provided: ° teach the patient how to mix and drink ORS ° give 2 packets to take home. • If the patient is vomiting, they should continue to take small sips. Anti-emetics are usually not necessary. 2. Continue eating 3. Return to the health facility when: • diarrhoea becomes worse • the patient has persistent diarrhoea or a large volume.

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Plan B: Treatment of patient with some dehydration using ORS 1. Determine amount of ORS to give during ﬁrst 4 hours. • The approximate amount of ORS required (in ml) can be calculated by multiplying the patient’s weight (in kg) times 75. • Use the patient’s age if you do not know the weight. • If the patient wants more ORS than shown, give more. • Give the recommended amount of ORS in the clinic over a 4-hour period. • If the patient is weak or vomits: ° give frequent small sips from a cup. After a vomit, wait 10 minutes then continue, but more slowly. Age Weight In ml 2. • • • 5–14 years 20 to <30 kg 1000–2200 ≤15 years 30 kg or more 2200–4000

After 4 hours Reassess the patient and classify for dehydration. Select the appropriate plan to continue treatment. Begin feeding the patient in the clinic.

3. If the patient must leave before completing treatment • Show the patient how to prepare ORS solution at home. • Show the patient how much ORS is needed to ﬁnish a 4-hour treatment at home. • Give enough ORS packets to complete rehydration. Give 2 packets as recommended in Plan A. 4. Explain the 3 rules of home treatment 1. Drink extra ﬂuid. 2. Continue eating. 3. Return to the health facility if needed.

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Plan C: Treat severe dehydration quickly Follow the arrows. If the answer is “yes” go across. If “no”, go down. START HERE

Can you give intravenous (IV) ﬂuid immediately?

Yes

Is IV treatment available nearby (within 30 minutes)

Yes

No Are you trained to use a naso-gastric (NG) tube for rehydration? No Yes

Can the patient drink?

Refer URGENTLY to hospital for IV or NG treatment.

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• Start IV ﬂuid immediately. If the patient can drink, give ORS by mouth while the drip is set up. Give 100 ml/kg Ringer’s lactate solution (or, if not available, normal saline), divided as follows: Age Infants (under 12 months) Older (12 months or older, including adults) First give 30 ml/kg in: 1 hour* 30 minutes* Then give 70 ml/kg 5 hours* 2½ hours

*Repeat once if radial pulse is very weak or not detectable. • Reassess the patient every 1–2 hours. If hydration status is not improving, give the IV drip more rapidly. Also give ORS (about 5 ml/kg/hour) as soon as the patient can drink, usually after 3– 4 hours (infant) or 1–2 hours for children, adolescents, and adults. • Reassess an infant for 6 hours and older patient after 3 hours. Classify dehydration. Then choose the appropriate plan (A, B, or C) to continue treatment. • Refer URGENTLY to hospital for IV treatment. • If the patient can drink, provide a relative or friend with ORS solution and show how to give frequent sips during the trip. • Start rehydration by tube (or mouth) with ORS solution. Give 20 ml/kg/hour for 6 hours (total of 120 ml/kg). • Reassess the patient every 1– 2 hours: ° if there is repeated vomiting or increasing abdominal distension, give the ﬂuid more slowly; ° if hydration status is not improving after 3 hours, send the patient for IV therapy. • After 6 hours, reassess the patient. Classify dehydration. Then choose the appropriate plan (A, B or C) to continue treatment.

Drug-induced diarrhoea Clinical features Diarrhoea is a common side-effect of many medications, especially antibiotics. In patients who have a history of antibiotic therapy or hospitalization, consider Clostridium difﬁcile (see below). Patients on antiretroviral therapy have an increased likelihood of drug-induced diarrhoea: • protease inhibitors (PI) such as LPV/ritonavir; • AZT and ddI (buffered). Treatment Treatment in these patients is symptomatic. In cases of severe ARV-induced diarrhoea, a switch of treatment regimen should be considered – see Section 13.8 ARV toxicity and management.

Clostridium difﬁcile colitis Clostridium difﬁcile may be underestimated as a cause of diarrhoea. It may cause severe abdominal pain, fever, megacolon, and rupture. C. difﬁcile colitis is also called pseudomembranous colitis.

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Key clinical features • Leucocytes and blood in stool supports the diagnosis. • Frequent hospitalization and prior exposure to antibiotics are risk factors for C. difﬁcile colitis. • Severe cases may present with toxic megacolon. • Toxin assay may be available in a referral laboratory. Table: Antibiotics associated with C. difﬁcile colitis Frequently associated • Ciproﬂoxacin, moxiﬂoxacin, levoﬂoxacin • Clindamycin • Amoxicillin, ampicillin, amoxicillinclavulanic acid • Ceftriaxone, ceﬁxime Occasionally associated • • • • • Erythromycin, azithromycin Trimethoprim Sulfonamides Cotrimoxazole Cloxacillin Rarely associated • Aminoglycosides gentamicin, streptomycin • Tetracycline, doxycycline • Chloramphenicol • Metronidazole • Vancomycin

Treatment • Stop any other antibiotics if possible. • Metronidazole 500 mg orally 3 times daily for 10 days. • Relapse occurs in 5% to 30% of the patients diarrhoea associated with C. difﬁcile. • In very severe cases, colonic perforation may require surgical intervention. Prevention • Take contact isolation precautions if the patient is hospitalized; advise strict hand hygiene for the patient and caregiver.

Diarrhoea with blood6,7 Diarrhoea with blood is most commonly due to an infection. Shigella is the most common cause. Fever may be present and is more likely associated with shigellosis than amoebiasis. The patient’s stool generally contains blood and mucous, is of relatively low volume, and may be associated with abdominal pain and tenesmus. Non-infectious inﬂammatory causes of bloody diarrhoea are signiﬁcantly less common. Acute presentation is more likely in: • Shigella • Other bacteria: Campylobacter, Salmonella, certain strains of E. coli • Entamoeba histolytica (amoebiasis) • Schistosoma • Balantidium coli • Clostridium difﬁcile – post-antibiotic

6 Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae type 1. WHO, 2005. Available at http://whqlibdoc.who.int/publications/2005/9241592330.pdf 7 Antibiotics in the management of shigellosis. WHO Weekly Epidemiological Record, 2004, 79:355–356. Available at http://www.who.int/wer/2004/en/wer7939.pdf

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• Viral haemorrhagic fevers such as Ebola • other causes. Persistent diarrhoea is more likely and (except for inﬂammatory bowel disease) more common in immunosuppressed patients. This includes: • CMV • mycobacterial infections including TB, MAC • disseminated fungal infections • Kaposi sarcoma • inﬂammatory bowel disease. Management of acute presentation of diarrhoea with blood (dysentery) • Assess and manage ﬂuid status and need for hospitalization (use the appropriate Fluid Plan A, B, or C above depending on the classiﬁcation of dehydration). • The use of an effective antimicrobial against shigellosis alleviates the dysenteric syndrome, fever, and abdominal cramps, reduces the duration of pathogen excretion, interrupts disease transmission, and reduces the risk of potential complications. In ideal situations, a stool or rectal swab sample should be processed for laboratory conﬁrmation of diagnosis and drug sensitivity testing before institution of antimicrobial therapy. However, this is rarely possible, and empirical antimicrobial therapy is instituted based on the knowledge of the antimicrobial resistance pattern of Shigella strains circulating locally. • Initiate treatment with an antibiotic with good local activity against Shigella (adjusting for local sensitivities and national guidelines). Possible antibiotics include: ° ciproﬂoxacin 500 mg orally twice daily for 5 days (the oral form can be used for outpatients and hospitalized patients because of its excellent bioavailability). ° If the patient is unable to take oral medications: ◊ ciproﬂoxacin 400 mg IV twice daily for 5 days; OR ◊ ceftriaxone 1 g IV daily for 5 days. Note: Widespread resistance has been reported to cotrimoxazole, ampicillin, and nalidixic acid. • Reassess the patient 2 days after they start antibiotics, but advise them to return immediately if the diarrhoea becomes worse. • If there is no improvement: ° consider resistance to ﬁrst line Shigella treatment and amoebiasis. Give second antibiotic usually effective against Shigella locally. • If there is no improvement or the diarrhoea becomes worse, consider other causes. Obtain a stool culture and do stool microscopy for parasites and AFB. • After giving 2 different antibiotics that are usually effective against Shigella locally, but without clinical improvement, consider treating empirically for amoebiasis. See Section 11.1. If diarrhoea persists in PLHIV, see management below. • If the patient is severely ill and no deﬁnitive diagnosis is possible, start treatment for both amoebiasis and Shigella.

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10.7d.3 Approach to persistent or chronic diarrhoea in PLHIV Persistent diarrhoea is deﬁned as having 3 or more loose stools a day, intermittently or continuously, for 14 days or more. It is a very frequent and frustrating problem in immunocompromised patients, and has a signiﬁcant impact on quality of life. It is considered WHO clinical stage 3.

DDx: Persistent or chronic diarrhoea in HIV Condition Protozoan infections Isospora belli cryptosporidiosis see sections 11.18; 11.6 Microsporidiosis see Section 11.26 In favour • • • • • Profuse watery diarrhoea Sudden onset of fever, abdominal pain, vomiting Weight loss Might present as IRIS Diagnosis by modiﬁed AFB of stool specimen

• Chronic, watery, non-bloody diarrhoea; sometimes abdominal pain and cramping, nausea, vomiting, and weight loss • Can be associated with disseminated disease: cholecystitis and biliary tract infections, hepatitis and peritonitis, kerato-conjunctivitis; infections of the lungs, muscles, and brain • • • • Diarrhoea associated with epigastric pain aggravated by food Nausea, vomiting, constipation GI bleeding, weight loss Large worm loads and hyperinfection syndrome can occur in immunocompromised patients

Strongyloidiasis see Section 11.36

HIV enteropathy CMV see Section 11.8 Mycobacterium MTB (see Section 15), MAC see Section 11.27

• Only if all investigations are inconclusive • Diagnosis of exclusion • Abdominal pain, weight loss, and (bloody or non-bloody) diarrhoea • Can be associated with other system involvement (oesophagitis, pancreatitis, gastritis, retinitis, CNS) • Can be associated with disseminated disease – prolonged fever and night sweats, wasting, enlarged liver and spleen, abdominal pain, symptoms of anaemia • Or with localized disease generalized lymphadenopathy, papulo-pustular eruption on trunk and extremities

Key clinical features • Generally watery with no blood or mucus. • Accompanied by nausea, weight loss, abdominal cramps, fever, and dehydration. • Identiﬁed infectious agent in about 50% of patients with HIV-associated diarrhoea. • Causes in HIV patients include: Cryptosporidia, Isospora, microsporidia, and Giardia. • In addition, mycobacteria, CMV, and disseminated fungal infections can cause persistent diarrhoea that may or may not be bloody. • Invasive bacterial pathogens, such as Campylobacter, Shigella, and Salmonella species can cause severe and prolonged illness in immunocompromised patients, but are not a frequent cause of persistent diarrhoea.

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• Intestinal tuberculosis can cause diarrhoea, especially in severely immunocompromised individuals who may also have constitutional symptoms such as fever and weight loss. Investigations It is difﬁcult to distinguish the different causative agents of persistent diarrhoea without stool culture. Therefore treat empirically. • Stool microscopy and culture • If you suspect tuberculosis infection, obtain a chest X-ray and an abdominal ultrasound. Empirical management If there is persistent diarrhoea in immunocompromised patients, treat empirically with the 2-step approach below. Step 1 • Give cotrimoxazole 2 double strength (800/160 mg) or 4 single strength (400/80 mg) twice daily for 14 days, followed by 1 double strength twice daily for 3 weeks, then cotrimoxazole prophylaxis with 1 double strength daily; PLUS • Give metronidazole 500 mg 3 times daily for 7 days. Step 2 • If no response, do stool investigations. ° stool microscopy – 3 specimens on separate days ◊ wet mount ◊ ova and parasites stain (Giemsa) ◊ modiﬁed AFB smear ◊ AFB smear ° stool culture. • Give albendazole 400 mg twice daily for 5 days OR mebendazole 500 mg twice daily for 5 days. • If appropriate investigations do not lead to the diagnosis of a speciﬁc cause in patients with HIV, start the patient on ART. Most patients will improve. • Look for evidence of tuberculosis – consider empirical anti-tuberculosis treatment (see Section 15). • Provide supportive and symptomatic care:8 ° Increase ﬂuid intake to prevent dehydration. ° Advise on special care of the rectal area (see IMAI-IMCI Palliative Care guideline module9). ° Advise on nutrition. ° Monitor weight.

8 If there is still debilitating, chronic, or repeated severe diarrhoea in PLHIV, consider a constipating drug (do NOT give if there is blood in stool, if the patient has fever, is a child younger than 5, or is elderly). Although these indications are not included in the WHO EML, and do not have the support of randomized trials, patient and palliative health workers’ experience support considering codeine 10 mg 3 times daily (up to 60 mg every 4 hours); or even morphine 2.5–5 mg orally every 4 hours in an ill patient, on an individual basis. 9 Palliative care: symptom management and end-of-life care. WHO, 2004. Available at http://www.who.int/hiv/ capacity/modules/en/index.html

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Prevention • The patient needs to pay attention to personal hygiene (hand washing), drink boiled water, eat thoroughly cooked meat, and eat cooked or thoroughly washed fruit and vegetables. • The patient should take cotrimoxazole prophylaxis.

Protozoan infections Isospora belli and cryptosporidiosis are the most common protozoal infections that cause persistent diarrhoea in immunocompromised patients, and are clinically indistinguishable. However, these infections have a different response to empirical therapy. Both organisms can be detected in the stool by using a modiﬁed acidfast stain. See Section 11.18 for the management isosporiasis. ART for immune reconstitution is recommended for both and is the only effective treatment for cryptosporidiosis (see Section 11.6). For Strongyloides stercoralis, see Section 11.37.

HIV enteropathy Clinical features Symptoms may be diarrhoea and weight loss. This is a diagnosis of exclusion. Treatment AIDS enteropathy responds to ART.

10.7d.4 Constipation Constipation has been deﬁned as a stool frequency of <3 per week, but is often difﬁcult to deﬁne. Patients may complain of difﬁculty passing stools or decreased stool volume. • It is important to exclude intestinal obstruction. • Consider what medicines may be contributing. • Perform a rectal examination to decide whether impacted. Treatment • Stop offending medicine if feasible • Give laxative, e.g. senna, initially 15 mg at night. Increase if necessary to 30 mg at night. • Give frequent oral ﬂuids. • Encourage high ﬁbre foods, such as fruits with the skin, vegetables, nuts, and grains. • Encourage ambulation, if possible. • If impacted (a solid, immobile bulk of stool in the rectum): ° gently apply petroleum jelly or insert soapy solution into the rectum by enema. ° manual disimpaction – start with manual fragmentation if necessary. After this is accomplished, an enema with mineral oil will help to soften the stool and provide lubrication.

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10.8 Jaundice In this section: 10.8.1 Clinical approach to a patient with jaundice • Table: Laboratory ﬁndings used to classify jaundice • DDx pre-hepatic jaundice • DDx hepatic jaundice • DDx post-hepatic jaundice

Yellow discoloration of the skin, eyes, and mucous membranes is called jaundice or icterus. Jaundice occurs when levels of bilirubin in the blood are too high and it is deposited in the tissue. Bilirubin is a yellow pigment formed from the breakdown of haemoglobin. Jaundice can be detected clinically once bilirubin levels exceed 3 mg/dl (51.3 µmol/l). This section discusses how to approach a patient presenting with jaundice and how to establish a differential diagnosis. Jaundice is always the result of an underlying process, and it is always important to evaluate for the underlying disease. Bilirubin metabolism occurs in a 3-step process. Problems in any of these steps can lead to jaundice. The approach to a patient with jaundice requires an understanding of this process, as the 3 steps are used to categorize jaundice into 3 types, each with its own differential diagnosis. • Pre-hepatic – Most bilirubin is produced from the breakdown of red blood cells. Bilirubin is then transported to the liver for conjugation. ° Problems here include red blood cell haemolysis, resulting in increased unconjugated (indirect) bilirubin levels. • Hepatic – Unconjugated (indirect) bilirubin is metabolized to conjugated (direct) bilirubin in the liver. Conjugation is required for the removal of bilirubin from the body. ° Problems here include direct liver injury (hepatitis) resulting in a decreased capacity to metabolize bilirubin. • Post-hepatic – Once conjugated, bilirubin passes through the biliary ductal system to the gall bladder or is excreted into the intestine. ° Post-hepatic problems (e.g. gall stones) may obstruct the ﬂow of bile through the common bile duct causing conjugated hyperbilirubinaemia.

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10.8.1 Clinical approach to a patient with jaundice Step 1: Use Quick Check to assess the patient. Make sure that the patient has no emergency or life-threatening conditions. Check for any signs or symptoms requiring urgent attention. Exclude shock and the complications of severe anaemia. If abdominal pain and fever are present, consider cholangitis. Consider referral to or consultation with a specialist if urgent surgical intervention or further investigation is needed. Step 2: Take a history and examine the patient looking for signs and symptoms of underlying or co-morbid disease. Step 3: Assess the patient’s HIV status. Step 4: Classify jaundice – pre-hepatic, hepatic, or post-hepatic. (mixed pictures may occur) Step 5: Perform investigations. Step 6: Initiate treatment and monitor the response.

History • Duration of jaundice • associated symptoms: ° itching of the skin, fever, pain (dull or colicky) ° dark urine and pale stool – associated with post-hepatic jaundice ° abdominal pain and vomiting. • Contact with a jaundiced patient: ° viral hepatitis. • Constitutional symptoms (fever, night sweats, weight loss, and loss of appetite) are indicative of TB or malignancy. • Symptoms of underlying infection suggesting sepsis as the cause. • History indicating cardiac failure or ischaemic hepatitis • History of travel to malaria endemic area • Blood transfusions: ° malaria, HBV, and HIV can be transmitted through unsafe blood transfusion. • Tattoos and body piercing are risk factors for hepatitis C. • Medications can be a cause, especially TB medications, ART, over-the-counter (pain) medication, bush tea, traditional remedies. Note: The time of onset of jaundice in relation to the start of the medication can be helpful in determining whether a drug can be the cause. • Alcohol consumption • Intravenous drug use • Past surgical or medical interventions • Sexual activity • Family history of jaundice • Current or recent pregnancy.

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Examination • Do a thorough examination of the liver: ° Check for hepatomegaly (liver span of more than 12 cm along right midclavicular line or a palpable left lobe of the liver under the epigastrium). ° Feel for tenderness (may indicate the presence of hepatitis or cholangitis or TB-IRIS of the liver). ° Feel the consistency (soft or hard) and the surface of the liver (smooth or nodular). (Hard consistency is usually consistent with tumours and end stage cirrhosis. ° Check for palpable gall bladder (suggestive of obstruction). • Signs of chronic liver disease, including: Note: It is not uncommon to see jaundice in the early stages of chronic liver disease. ° white nails ° clubbing ° palmar erythema ° large or small liver ° spider angiomata ° gynaecomastia ° pedal oedema, ascites. • Signs of hepatic encephalopathy, including: ° altered mood and behaviour ° sleep disturbance ° confusion, slurred speech, restlessness, and coma ° hepatic foetor ° asterixis (hand ﬂap, ﬂapping tremor). • Generalized lymphadenopathy • Associated splenomegaly • Signs of sepsis • Signs of HIV infection (oral candida, oral hairy leukoplakia, lymphadenopathy) • Signs of cardiac failure: increased central venous pressure, cardiac rub, cardiac murmurs, tachycardia (could be a sign of shock), ascites, peripheral oedema • To establish jaundice, inspect the sclerae under natural light. In dark-skinned individuals, the mucous membrane below the tongue can show jaundice and in fair-skinned individuals the skin can be yellow-coloured. • Signs of anaemia – pale conjunctivae • If anaemia or signs of chronic liver disease are present, consider gastrointestinal blood loss and perform a rectal examination and test stool for blood (see 7.2.17).

Laboratory investigations • Liver function tests (direct and indirect bilirubin, ALT, AST, ALP, GGT; albumin and INR to assess synthetic function). ° Marked elevations of transaminases are seen in viral hepatitis and toxic liver injuries. ° ALP usually increases in obstructive jaundice.

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• Urine dipstick, urinalysis (to check for bilirubin and urobilinogen). • FBC ° Anaemia can indicate a GI bleed; also consider stool occult blood if this is a concern. ° The platelet count can be low in patients with portal hypertension and splenomegaly, or in patients with severe sepsis and haemolysis. • A blood smear looking for schistocytes or malaria. • Rapid test for malaria • Serologic tests for viral hepatitis (HbsAg, HbcIgM, anti-HCV antibody, antiHAV IgM). See Section 11.14. • Check alpha-fetoprotein (AFP) (increases in hepatocellular carcinoma and cirrhosis). • An ultrasound, which can detect: ° hepatomegaly, gallstones, dilatation of the bile duct, mass in the liver or pancreas, ascites, obstructed hepatic or portal circulation, features of abdominal TB, e.g. lymphadenopathy and splenic lesions. ° look for normal collapsing of the inferior vena cava – absent in heart failure.

Classiﬁcation A combination of liver function tests are needed to arrive at a possible diagnosis as no one of the individual tests can differentiate between the various diseases. The table below displays the results of liver function tests in jaundice. Nevertheless, it is important to remember that deﬁnitive diagnosis might require some additional work. Table: Laboratory ﬁndings used to classify jaundice Pre-hepatic jaundice Total bilirubin Unconjugated (indirect) bilirubin Conjugated (direct) bilirubin ALT and AST levels ALP level Serum albumin level Urobilinogen normal/increased increased normal normal normal normal increased Hepatic jaundice increased normal/increased normal/decreased increased normal decreased normal/increased Obstructive (post hepatic jaundice) increased normal increased normal increased normal decreased/absent

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DDx: Jaundice Pre-hepatic Severe malaria see Section 11.25 In favour Fever Positive rapid test or blood smear Living in or travelled to an endemic area Lab – low Hb, low platelet, high bilirubin (mostly unconjugated) Evidence of haemolysis on blood smear (schistocytes) Predisposing conditions such as sickle-cell disease, G6PD, recent blood transfusion Urine – blood or urobilinogen Lab – low Hb, high bilirubin (mostly unconjugated), high LDH, low haptoglobin (Hp) Inherited: sickle-cell disease (may be mixed direct or indirect), G6PD deﬁciency, thalassaemias Red blood cell destruction: valvular and splenic disorders Medications causing haemolysis: e.g. AZT dapsone, ribavirin No other signs Increased bilirubin only – no other increased liver function tests History of right-sided heart failure, e.g. cor pulmonale May have massive hepatomegaly Lab – mild unconjugated hyperbilirubinaemia (although may be very high if CHF acute), high ALT and AST, but no more than 2–3 times ULN* Occurs in pregnancy, mostly in women with pre-eclampsia; usually in third trimester but may occur before or postpartum Abdominal pain, nausea, vomiting, malaise; may present with severe disease (DIC, abruption) Lab – haemolysis with characteristic helmet cells (schistocytes), platelets <100 000, LDH >600, AST >70

Haemolysis

Inherited disorders: Gilbert’s syndrome, Crigler-Najjar syndrome Congestive heart failure

HELLP syndrome (haemolysis, elevated liver enzymes, low platelets)

* ULN = upper limit of normal

Hepatic jaundice Viral hepatitis (Hepatitis A, B,C, E) see Section 11.14 In PLHIV consider HSV and CMV see Sections 11.8 and 11.15 HSV, Epstein-Barr virus Drug-induced liver injury

In favour Fever Anorexia preceding jaundice Tender hepatomegaly Lab – high ALT and AST >10 times ULN, predominantly conjugated bilirubin, positive hepatitis serology

Recent initiation of new medication, e.g. NVP, EFV, anti-TB treatment, ﬂuconazole; paracetamol overdose Nausea, vomiting, abdominal pain Lab – high ALT >3 times ULN, conjugated bilirubin Recent consumption of a potentially toxic substance including mushrooms, herbs, traditional remedies, arsenic Nausea, vomiting, abdominal pain Lab – high ALT >10 times ULN History of alcohol use Stigmata of chronic liver disease Lab – conjugated bilirubin, AST/ALT ratio >2, elevated MCV and disproportionately high GGT Ultrasound may show small cirrhotic liver

Toxin-induced liver injury see Section 3.8

Alcoholic liver disease see Section 16

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Hepatic jaundice Non-alcoholic steatohepatitis (NASH)

In favour History of obesity, diabetes mellitus, medications including amiodarone, glucocorticoids, tetracycline, d4T Frequently asymptomatic Lab – AST/ALT ratio <1 Fever, hypotension, sepsis Should rule out other causes: viral hepatitis, drug-related Lab – high ALT and AST >1000 along with very high LDH History of HBV, HCV, iron overload, or any other form of cirrhosis Hepatomegaly Wasting, cachexia Chest X-ray – pulmonary metastases Ultrasound – liver mass Lab – high AFP Hard, irregular enlarged liver Evidence of primary tumour (breast lump, skin lesions) Lab – high ALP, mixed hyperbilirubinaemia Ultrasound – multiple masses Loss of weight, night sweats, malaise Pallor Hepatomegaly Lab – increased bilirubin, high ALP (obstructive or inﬁltrative lesions) Positive TB contact Ultrasound – hepatic abscesses, intra-abdominal lymphadenopathy Concurrent congestive heart failure, especially right-sided Symptoms similar to those of acute hepatitis Lab – increased ALT and AST >1000 along, with very high LDH History of cirrhosis, recent abdominal surgery, or hypercoagulable state Commonly presents with oesophageal or gastric variceal haemorrhage; massive splenomegaly may also be present Lab – liver function tests may be normal, low albumin Usually during second half of pregnancy, third trimester most common; many women have preeclampsia Nausea, vomiting, abdominal pain, anorexia Lab – AST and ALT may be as high as 1000, may have decreased platelets, distinguishable from HELLP by increased coagulation studies, low glucose, high ammonia Occurs in the second and third trimesters Intense pruritis; abdominal pain, and signs of liver failure are uncommon Lab – high ALP, normal GGT, AST and ALT may be >1000, high serum bile acids: increased cholic acid and chenodeoxycholic acid, increased cholic acid or chenodeoxycholic acid ratio Ultrasound usually normal History of recurrent episodes that resolve spontaneously Known sickle-cell disease Very high conjugated hyperbilirubinemia Lab – mild elevation of ALT

Bacterial sepsis see Section 3.1.5 Hepatocellular carcinoma

Metastases in PLHIV consider Kaposi sarcoma or lymphoma Tuberculosis In PLHIV also consider atypical mycobacteria and periportal TB. Lymphadenopathy may also cause obstructive jaundice. see Section 15 Ischaemic hepatitis

Portal vein thrombosis – decreased blood ﬂow into the liver Acute fatty liver of pregnancy

Intrahepatic cholestasis of pregnancy

Benign hyperbilirubinemia secondary to sickle-cell anaemia see Section 10.18

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Post-hepatic (obstructive) Cholangitis, cholecystitis, or pancreatitis see Section 10.10a

In favour Right upper quadrant abdominal pain that is worse after eating Fever, chills, rigors Tender hepatomegaly Lab – high WBC, increased ALP, high AST and ALT, high amylase, high conjugated bilirubin Ultrasound – hepatomegaly, gall stones, thickened gall bladder wall, dilated common bile duct Pruritis and dark urine Epigastric mass or palpable gall bladder Lab – high conjugated bilirubin, high ALP Ultrasound – dilated common bile duct, enlarged gall bladder, mass Right upper quadrant or epigastric abdominal pain, diarrhoea Lab – CD4 <100, high ALP, high GGT, mildly increased AST and ALT Ultrasound useful, but cholangiography is diagnostic High index of suspicion in all patients in endemic areas presenting with biliary colic Lab – eosinophilia Stool microscopy may detect eggs or parasites Abdominal X-ray may reveal large collections of worms Ultrasound can image the biliary tree Associated with haematological malignancies Commonly present with ascites, hepatomegaly Variable increased AST and ALT, high ALP Ultrasound with Doppler most useful

Cholestasis – gallstone, head of pancreas tumour AIDS cholangiopathy – cryptosporidium. Also CMV, microsporidium, and cyclospora. Biliary parasitosis (some may also be intrahepatic): Ascaris lumbricoides, Clonorchis sinensis, Fasciola hepatica, Echinococcus granulosus, schistosomiasis) Budd-Chiari syndrome (hepatic vein or inferior vena cava thrombosis) – decreased blood ﬂow out of liver

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10.9 Ascites In this section: 10.9.1 Clinical approach to a patient with ascites 10.9.2 Classify ascites and consider the likely differential diagnosis • Classify the ﬂuid as a transudate or exudate and calculate the SAAG. • DDx ascites with SAAG >1.1 (portal hypertension) – transudate • DDx ascites with SAAG <1.1 (no portal hypertension) 10.9.3 Manage ascites according to cause • Manage ascites with SAAG > 1.1 • Manage ascites with SAAG < 1.1 • Manage cirrhosis • Spontaneous bacterial peritonitis • Schistosomiasis

Ascites is the abnormal accumulation of fluid within the peritoneal cavity, presenting with: • abdominal discomfort • increase in belt or clothing size • shortness of breath (cardiac failure, pleural effusion) • peripheral oedema. It may be secondary to: • local causes in the peritoneum or other systemic diseases • increase in the portal venous pressure observed in cirrhosis and heart failure • direct peritoneal involvement by an infectious or neoplastic process • a low serum albumin state with decreased oncotic pressure (nephrotic syndrome and kwashiorkor); • less frequently, end-stage renal disease or other medical conditions.

10.9.1 Clinical approach to a patient with ascites Step 1: Perform Quick Check Use the Quick Check to assess the patient for serious and life-threatening conditions. Patients with ascites may present with: • shortness of breath or respiratory failure from pulmonary oedema secondary to CHF or a huge abdomen that interferes with normal breathing; • shock or hypotension caused by circulatory failure; or • severe subacute bacterial peritonitis leading to sepsis; or • bleeding disorders in patients with chronic liver disease (cirrhosis). Step 2: Take a history and perform a physical examination. Step 3: Assess HIV status. Step 4: Perform investigations. Step 5: Consider the likely differential diagnosis using the DDx tables. Step 6: Initiate treatment and monitor the patient’s response.

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History Speciﬁc Ask about: • abdominal discomfort and a stretching sensation of the ﬂanks and groin • increase in belt or clothing size • early satiety (fullness) • shortness of breath – in cardiac failure, or pleural effusion • swelling of the legs • facial or upper extremity swelling, or generalized swelling – in case of nephrotic syndrome or end-stage renal disease • lower back pain • abdominal pain in hepatosplenic conditions, or irritation of the parietal peritoneum by infection or cancer. General • co-morbid diseases – chronic hypertension with chronic heart failure, chronic liver disease (cirrhosis, cancer, hepatitis, schistosomiasis, malignancies) • alcohol use • TB, HIV • food security or dietary history • protein-losing enteropathies – bowel disorders • chronic renal diseases – proteinuric state.

Examination General • Conﬁrm the ascites by the presence of: ° shifting dullness to differentiate ascites from other causes of abdominal swelling ° ﬂuid thrill. ° Look for evidence of chronic liver disease or decompensation ° signs suggestive of cirrhosis ° jaundice; ° spider naevi ° palmar erythema ° overt encephalopathy or ﬂapping tremors. • The presence of heart failure: ° distended jugular veins ° heart gallop rhythm ° pulmonary crackles (pulmonary oedema). • Generalized oedema (anasarca): ° involving both upper and lower extremities ° most commonly associated with nephrotic syndrome and end-stage renal disease ° can be seen in severe heart failure. • Cachexia (wasting) and diffuse lymphadenopathy (tuberculosis or a neoplastic disease).

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Speciﬁc Inspection: • distended abdomen; • stretched skin marks; • bulging ﬂanks, and occasionally an umbilical hernia; • visible abdominal venous pattern (caput medusa) with the direction of ﬂow away from the umbilicus (portal hypertension). Palpation: • splenomegaly (in marked portal hypertension, tuberculosis, lymphoma); • liver – small and ﬁrm or non-palpable in cirrhosis; • enlarged in schistosomiasis (pre-sinusoidal portal hypertension) and BuddChiari syndrome (post-hepatic portal hypertension); • hard nodular in primary liver cancer or metastatic disease – suggesting that direct peritoneal seeding is the cause of ascites; • pelvic and rectal examination to look for genitourinary and gastrointestinal malignancies.

Perform investigations • See Section 7.4.3 for instructions on diagnostic paracentesis (abdominal tap). ° Observe gross appearance. ° ° Send ascitic ﬂuid for: ◊ protein (albumin level) ◊ cell count (WBC, RBC) ◊ Gram stain, AFB, and culture ◊ cytology (if malignancy suspected). • LFTs – AST, ALP; bilirubin; albumin • FBC • INR (PT) and PTT or crude clotting time (Section 7.2.18) if not available • stool microscopy • urine dipstick or 24-hour urine albumin (an albumin level <2.5 g/dl and 24hour proteinuria >3 g are diagnostic of nephrotic syndrome) • ESR • abdominal ultrasound (detects small amounts of ascites and deﬁnes abnormalities present in the liver parenchyma and portal circulation) • doppler ultrasound – to look for venous obstruction.

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10.9.2 Classify ascites and consider the likely differential diagnosis Classify the ﬂuid as a transudate or exudate, and calculate the SAAG Classify according to protein measurement of the ﬂuid. • transudate: protein <30 g/litre in peritoneal ﬂuid • exudate: protein >30 g/litre in peritoneal ﬂuid Calculate the SAAG (serum-to-ascites albumin gradient) SAAG = (serum albumin) – (ascitic ﬂuid albumin)

• A SAAG >1.1 g/dl (11 g/litre) indicates that the patient has portal hypertension: ° cirrhosis ° heart failure ° Budd-Chiari syndrome and schistosomiasis. • A SAAG <1.1 g/dl (less than 11 g/litre) rules out portal hypertension: ° ascites caused by infectious or neoplastic peritoneal disease ° severe acute pancreatitis ° a low albumin state (nephrotic syndrome and kwashiorkor). Consult the relevant differential diagnosis table.

DDx: Ascites with SAAG >1.1 (portal hypertension) – transudate Conditions Cirrhosis In favour Known risk factor – alcoholism, history of jaundice, chronic HBV or HCV (see Section 11.14) Small nodular liver, jaundice Signs of chronic liver disease – gynaecomastia, caput medusae, palmar erythema, spider naevi, ﬂapping tremor Upper gastrointestinal bleeds from varices Peritoneal ﬂuid analysis (straw coloured, WBC <250 predominantly mesothelial, RBC <10 000, protein <2.5 g/dl) High bilirubin and INR Low serum albumin Distended jugular veins, heart gallop, pulmonary crackles (pulmonary oedema), hepatomegaly, oedema of lower limbs Peritoneal ﬂuid analysis – straw coloured, protein >2.5 g/dl, WBC <250 Abdominal ultrasound – hepatomegaly, distended IVC with minimal respiratory cycle change Risk factors for thrombosis (haematological and other malignancies, contraceptives containing estrogen) Consistent features on ultrasound – see below Upper GI bleeding from varices Stool positive for ova Ultrasound – periportal ﬁbrosis, splenomegaly, enlarged veins, collateral vessels

Congestive heart failure

Budd-Chiari syndrome

Schistosomiasis see Section 11.34

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DDx: Ascites with SAAG <1.1 (no portal hypertension Condition Bacterial peritonitis see Section 10.7a In favour Acute abdomen – see Section 10.7a Abdominal pain Systemically ill Peritoneal ﬂuid analysis – turbid or purulent; protein >2.5 g/dl; WBC often >1000 and predominantly PMN; RBC <10 000; positive Gram stain and culture Abdominal X-ray – free air under diaphragm. If perforation of hollow organ suspected, titrate bile and amylase from sample. Fever, abdominal pain, encephalopathy Peritoneal ﬂuid analysis – turbid or purulent WBC >250 Positive Gram stain and culture Constitutional symptoms – low grade fever, weight loss, night sweats, generalized lymphadenopathy, hepatosplenomegaly More common in HIV with evidence of immunosuppression Peritoneal ﬂuid analysis – clear, haemorrhagic or chylous; protein >2.5 g/dl; WBC often >500 predominantly lymphocytes; RBC occasionally >10 000 Positive AFB or culture (not always), High ESR Ultrasound – hepatosplenomegaly, peritoneal thickening, abdominal lymphadenopathy, micro-abscess in spleen or liver Systemic symptoms – weight loss, night sweats Peritoneal ﬂuid analysis – straw-coloured, haemorrhagic, mucinous or chylous; protein >2.5; WBC often >500 with variable cell types; RBC occasionally >10 000; positive cytology, high ESR Ultrasound – liver mass, abdominal mass or peritoneal thickening History of heavy alcohol intake Epigastric or central abdominal pain Peritoneal ﬂuid analysis – turbid, haemorrhagic, chylous; protein >2.5 g/dl; variable WBC and RBC counts High serum and ascites amylase levels Ultrasound – oedematous pancreas, may be normal Peritoneal ﬂuid analysis – straw coloured, protein <2.5 g/dl, WBC <250, RBC <10 000 Serum albumin <2.5 g/dl Urine dipsticks, proteinuria, and 24-hour proteinuria >3.5 g Ultrasound may show enlarged kidneys Rarely causes clinical ascites in adults Peripheral oedema is common Peritoneal ﬂuid analysis – straw coloured, protein <2.5 g/dl, WBC <250, RBC <10 000 Serum albumin <2.5 g/dl Urine dipstick – no protein Slow progression of fever, malaise, and weight loss Marked cachexia, splenomegaly, hepatomegaly, jaundice Low platelets or pancytopaenia Demonstration of parasite by smear or culture in bone marrow or spleen

SBP in cirrhosis

Tuberculous peritonitis

Neoplasms

Pancreatitis see Section 10.7a

Nephrotic syndrome see Section 11.31 Malnutrition see Section 10.3

Visceral leishmaniasis see Section 11.20

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10.9.3 Manage ascites according to cause It is important to establish the underlying cause of the ascites since the management differs in relation to different causes.

Manage ascites with SAAG >1.1 (portal hypertension) – transudate General management • Salt restriction <2 grams (less than half a teaspoon) per day. • Combined oral diuretics – keep the ratio between the 2 drugs constant: ° spironolactone 100 mg increased up to a maximum dose of 400 mg/day PLUS furosemide 40 mg to a maximum of 160 mg/day. ° Caution in rapid diuresis. ° Monitor daily weights and urine output. ° Therapeutic peritoneal tap if indicated – assess for ascites and see box below. ° Intractable ascites need to be referred for further investigations. ° Refer patients who are not responding for shunt operations or possible liver transplantation. Therapeutic paracentesis in portal hypertension (see Section 7.4.3) The amount of ﬂuid taken out daily by paracentesis should be 2–3 litres. Exception: occasionally, patients with massive ascites will develop abdominal discomfort and severe shortness of breath and will require a large volume therapeutic paracentesis (4–5 litres) for control of the symptoms. Diuresis Patients with peripheral oedema tolerate mobilization of a high ﬂuid volume (2 litres/day) without developing intravascular depletion and azotaemia. Patients with ascites but without oedema can develop hypovolaemia and acute renal failure if the rate of ﬂuid removal exceeds 500 ml/day. Diuretic-resistant ascites is deﬁned by a lack of response to maximum doses of spironolactone and furosemide in a patient on a low sodium diet. These patients often need serial large volume therapeutic paracenteses, not exceeding 4–5 litres to avoid intravascular volume depletion and acute renal failure.

Manage cirrhosis Prevent complications from cirrhosis: • Look for a cause – serology for hepatitis B, C (see Section 11.14). • Advise the patient to avoid alcohol. • Determine the severity of cirrhosis using the modiﬁed Child-Turcotte-Pugh classiﬁcation (use Table below). • If available, refer for endoscopy to look for oesophageal varices. If varices present, use a low-dose non-selective beta blocker (e.g. propranolol titrated to achieve a 25% reduction in the heart rate), as primary prevention for upper gastrointestinal bleeding secondary to documented oesophageal varices. • Consider whether patient has hepatic encephalopathy (see Section 3.4.1).

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• Consider long-term lactulose, titrated to achieve 2–4 bowel movements per day, if signs of hepatic encephalopathy (see instructions in 8.4). • Be careful about ﬂuid management and avoid nephrotoxic drugs (e.g. NSAIDs and aminoglycosides) to prevent hepatorenal syndrome. • Refer patients with severe cirrhosis, hepatic encephalopathy and metabolic complications to a specialist for management of complications and for evaluation for other therapies. Scoring to determine the severity of cirrhosis • The score uses 5 markers of liver disease. Each measure is scored 1–3; with 3 indicating the most severe derangement. Table: Child-Turcotte-Pugh classiﬁcation Measure Bilirubin (total) Serum albumin 1 point <34 µmol/l (<2 mg/dl) >35 g/l <1.7 None None 2 points 34–50 µmol/l (2–3 mg/dl) 28–35 g/l 1.71–2.20 Suppressed with medication Grade I–II (or suppressed with medication) B 7–9 3 points >50 µmol/l (>3 mg/dl) <28 g/l >2.20 Refractory Grade III–IV (or refractory) C 10–15

INR Ascites Hepatic encephalopathy Classiﬁcation Total points

A 5–6

Manage ascites SAAG <1.1 (no portal hypertension) – transudate Ascites caused by neoplastic or infectious processes and secondary to acute pancreatitis and a low albumin state should be managed differently. • Treat the primary disease. See Section 10.7.1.4 if peritonitis is suspected. • Avoid sodium restriction and diuresis as this can be harmful and lead to unwanted intravascular volume depletion and acute renal failure. • May require large volume therapeutic paracentesis (4–5 litres) to manage or alleviate symptoms of discomfort.

Spontaneous bacterial peritonitis • Suspect in patients with cirrhosis and ascites presenting with: ° fever ° abdominal pain ° altered mental status ° hepatorenal syndrome.

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Investigations • Paracentesis (see Section 7.4.3) – WBC count ≥500, neutrophils ≥250 cells/ mm3. Treatment • Give ceftriaxone 2 grams daily for 5–10 days. • If available, albumin 25% IV 1.5 g/kg on day 1 and 1 g/kg on day 3. Prevention • Antibiotic prophylaxis – for all patients with: ° a history of SBP ° a current upper gastrointestinal bleeding episode ° ascitic ﬂuid albumin level less than 1 g/dl. • cotrimoxazole (1 double-strength tablet daily); OR • ciproﬂoxacin 250–500 mg daily; OR • norﬂoxacin 400 mg daily.

Schistosomiasis (see Section 11.34) Schistosomiasis leads to granulomatous inﬂammation and the obstruction of the blood ﬂow to the liver. • Referral is usually needed if a shunt operation for portal hypertension is available upon referral.

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10.10 Neurological problems A patient presenting with headache, meningeal signs, change in mental status, seizures, or neurological deﬁcit could require urgent management. You will need to use different parts of this Section and of the manual to work through a differential diagnosis for the problem. Use this Section 10.10 • 10.10a Neurological deﬁcit without meningeal signs (no headache, stiff neck, vomiting – if present, also see Section 10.10b) ° patient with a stroke-like syndrome ° patient with spinal cord problem (myelopathy) ° patient with peripheral motor or sensory nervous system problem ° patient with a cranial nerve abnormality. • 10.10b Headache ° headache with no abnormal physical ﬁndings ° headache with abnormal physical ﬁndings (including meningeal signs, fever, neurological deﬁcit, seizures). • 10.10c Seizures or convulsions ° seizures due to a systemic illness ° seizures due to intracranial infection or lesion ° chronic recurrent seizures. Use Section 2 – Quick Check • for emergency management of a convulsing or comatose patient • for patients with a history of head trauma. Use Section 3 – Approach to the severely ill patient • for a patient with a decreased level of consciousness, confusion, intoxication, or agitation (Section 3.4) • for a patient who is convulsing or in status epilepticus (Section 3.5). Use Section 10.12 – Eye problems • for acute visual loss. Key points • It is possible to recognize and treat common neurological problems without the use of complex diagnostic tests. • HIV-related conditions of the central nervous system and spinal cord are common. • Patients recently started on ART may develop an immune reconstitution inﬂammatory syndrome (IRIS) that complicates the clinical picture. • Toxoplasmosis can be prevented with cotrimoxazole prophylaxis. • Secondary prophylaxis with ﬂuconazole is mandatory after an episode of cryptococcal meningitis.

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10.10a Neurological deﬁcit (without meningeal signs) In this section: 10.10a.1 Clinical approach to a patient with neurological deﬁcit 10.10a.2 Classify the neurological deﬁcit and consider the likely differential diagnosis 10.10a.3 Stroke-like syndrome (with DDx table) • Approach to HIV-infected patients with stroke-like syndrome 10.10a.4 Spinal cord problem (myelopathy) (with DDx table) 10.10a.5 Peripheral motor or sensory nervous system problem (with DDx table) 10.10a.6 Peripheral neuropathy (with DDx table) 10.10a.7 Common cranial nerve palsies and their differentials

This Section addresses the management of a patient who presents with a neurological deﬁcit and without meningeal signs. Use this Section for a patient presenting with the following symptoms: • motor deﬁcit (weakness, paralysis, loss of balance, difﬁculty speaking) • sensory deﬁcit (tingling, numbness, pain) • cranial nerve deﬁcits (facial weakness, vertigo, double vision). For the management of patients with headache or meningeal signs, also refer to Section 10.10b Headache. For the management of patients with cognitive problems, see Sections 3.4 and 10.11.

10.10a.1 Clinical approach to a patient with neurological deﬁcit Step 1: Use Quick Check. Ensure that there are no serious or life-threatening conditions. Use the Quick Check for management of life-threatening conditions, such as coma and convulsions. Step 2: Take a history and perform a physical examination. If the patient has difﬁculty speaking or is confused, obtain a good history from the family. Step 3: Assess the patient’s HIV status. Step 4: Classify the deﬁcit using the table Classiﬁcation of motor and sensory neurological deﬁcit. Step 5: Use the DDx tables to work through a differential diagnosis: • DDx: Stroke-like syndrome • DDx: Spinal cord problem (myelopathy) • DDx: Peripheral motor or sensory nervous system problem • DDx: Peripheral neuropathy (distal – DSPN) • DDx: Cranial nerve abnormalities Step 6: Perform investigations. Perform investigations according to the differential diagnosis and availability of tests. It is possible to diagnose and manage neurological problems without the use of complex diagnostic tests. Step 7: Initiate treatment and monitor response.

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Quick Check Ensure that there are no serious or life-threatening conditions. Use the Quick Check for patients with coma and convulsions. Ask speciﬁcally about any history of head injury.

History • History of the following presenting complaints, including onset (sudden or insidious) and duration: ° motor changes (e.g. difﬁculty combing hair, writing, squatting, climbing stairs) ° sensory changes ° vision, hearing, or speech problems ° difﬁculty with balance or walking ° meningeal signs – headache, stiff neck ° associated fever, constitutional symptoms ° associated nausea, vomiting, dizziness ° associated seizures ° change in consciousness, behaviour, mood ° change in memory or cognition ° bowel and bladder disturbances. • Medical history: ° risk factors for stroke (hypertension, diabetes, heart disease, obesity, bleeding disorders, clotting, pregnancy) ° HIV infection (CD4 count, ART) ° TB infection (current TB symptoms, previous TB, or TB contact) ° malignancy ° syphilis ° history of head injuries ° medications (e.g. aspirin, anticoagulants, oral contraceptive pill).

Examination General signs • vital signs • signs of immune compromise • level of consciousness • neck stiffness, meningeal signs (if present, also see Section 10.10b). Examine the fundi • Perform fundoscopy (see Section 10.12). • Look for loss of spontaneous venous pulsations, blurred optic disc margins, and elevated optic head as evidence of papilloedema. Assess higher functions • orientation to person, place, or time • memory • speech ° difﬁculty articulating words (dysarthria) ° difﬁculty understanding or expressing words (aphasia) • gait, ability to walk

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• assess for cognitive deﬁcits (see Sections 3.4 and 10.11) ° In PLHIV, assess for possible HIV-associated cognitive disorders Examine cranial nerves • See Table: Common cranial nerve palsies and their differentials. Examine motor system • power, tone, reﬂexes. Examine the sensory system • Examine for touch, pain, temperature, and position sense. • Screen for peripheral neuropathy ° In PLHIV, assess for HIV-associated distal sensory polyneuropathy Examine cerebellar function • Assess for intention tremor, hypotonia, nystagmus, broad-based gait, and incoordination. Assess HIV status There are a number of neurological conditions associated with immune suppression from HIV infection. The HIV status of a patient will impact on the differential diagnosis and management.

10.10a.2 Classify the neurological deﬁcit and consider the likely differential diagnosis Neurological deﬁcit can result from a number of different conditions that cause injury to the brain, spinal cord, or peripheral nerves. Classifying the deﬁcit will help you to work through a differential diagnosis and determine the most likely cause. Table: Classiﬁcation of motor and sensory neurological deﬁcit Condition Stroke-like syndrome (due to injury to the brain – results in upper motor neuron deﬁcit) Features in favour Onset acute (stroke) or subacute Unilateral Weakness or numbness in face, arm, or leg Difﬁculty speaking, swallowing Dizziness, blurred vision, loss of balance Confusion Cerebellar signs Slow, subacute onset, or acute trauma to the spinal cord. May present abruptly or gradually. Bilateral or unilateral Paraparesis or quadriparesis Loss of motor function and sensation (touch, temperature) Loss of bladder or bowel control Acute or subacute onset Motor – weakness, cramps, spasms Sensory – tingling, numbness, pain Autonomic – BP instability, reduced sweating, incontinence, sexual problems HIV positive, alcohol use, malnutrition Isolated or multiple cranial nerve palsies Eye and vision changes Difﬁculties with balance or hearing

Spinal cord problem (myelopathy) (due to injury to the spinal cord)

Peripheral motor or sensory nervous system problem (neuropathy) (due to injury to the peripheral nerves) Cranial nerve problems

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Once you have classiﬁed the deﬁcit, use the DDx tables below to ﬁnd a likely cause. • DDx: Stroke-like syndrome • DDx: Spinal cord problem (myelopathy) • DDx: Peripheral motor or sensory nervous system problem • DDx: Peripheral neuropathy (distal sensory peripheral neuropathy) • DDx: Cranial nerve abnormalities

Perform investigations Perform investigations according the likely differential diagnosis. • Lumbar puncture to examine the CSF (see Section 7.4 for Procedure and Section 10.10b for further work-up): ° perform fundoscopy to exclude papilloedema; ° this is especially important if HIV infection; ° important if you suspect meningitis or subarachnoid bleed; ° may be considered in the presence of focal signs if no signs of impending herniation (see Section 10.10.b); ° may be considered for headache, for more information see Section 10.10b; ° CSF for opening pressure, appearance, microscopy for cells and other microorganisms, chemistry, cryptococcal antigen, rapid syphilis test, TB. • Bloods: ° FBC ° cryptococcal Ag ° toxoplasma IgG ° rapid syphilis test. • Spinal X-rays: ° for neurological deﬁcit with a spinal level. • CT scan (if indicated and available).

Initiate treatment and monitor response Management of patients with a neurological deﬁcit and no meningeal signs will depend on the availability of CT scanning. As a rule of thumb, 80–90% of patients can be managed at district level without CT scan. Very few district hospitals have CT scanners, but CT scanning may be available at a referral hospital for speciﬁc patients. If there is no access to CT scanning and LP is contraindicated (see Section 10.b Headache), then empirical therapy should be started for TB and toxoplasmosis or any other diagnosed conditions, especially in the case of HIV-infected patients.

10.10a.3 Stroke-like syndrome Problems affecting the brain or central nervous system can cause stroke-like syndromes due to damage to the upper motor neurons. The differential for a patient presenting with a stroke-like syndrome is broad; however, in settings of high HIV prevalence, certain conditions occur more commonly.

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Use the DDx table below to work through a differential diagnosis for a patient presenting with a stroke-like syndrome.

DDx: Stroke-like syndrome* Condition Cerebrovascular accident Ischaemic or haemorrhagic stroke Sudden onset Hypertensive, diabetic, history of smoking Unilateral weakness or numbness in face, arm, or leg Difﬁculty speaking or swallowing Dizziness or blurred vision Difﬁculty walking or problem with balance Confusion No progression of deﬁcit (may have some improvement over time) In favour

Intracranial masses Cerebral toxoplasmosis see Section 11.40 Subacute onset over days to weeks Headache With or without fever Focal signs Dull affect, impaired level of consciousness Seizures CT scan – multiple ring enhancing lesions HIV infection – CD4 <100 Subacute onset over days to weeks Fever, malaise, headache Skin lesions resembling molluscum contagiosum LP – high opening pressure HIV infection – CD4 <50 CSF: increased lymphocytes, low glucose, high protein, + India ink, + CRAG N.B.: CSF may be normal. Gradual onset over days to weeks Focal neurological deﬁcit Evidence of TB elsewhere CSF – increased lymphocytes, low glucose, high protein May result from contiguous spread or bacteraemia Gradual onset over weeks Headache, neck stiffness, altered mental status, signs of increased ICP Focal deﬁcits beginning days after headache, seizures LP should be avoided Insidious onset Cranial nerve palsies, mental status change Focal neurology

Cryptococcoma see Section 11.15

Tuberculoma

Bacterial brain abscess

Tumours (benign tumour, lymphoma, metastases) Other infections Progressive multifocal leucoencephalopathy (PML)

Clumsiness Visual changes, hemiparesis, dysarthria, aphasia; seizures Progression over 1–9 months HIV infection – CD4 < 100

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Condition Neurocysticercosis see Section 11.7

In favour Seizures Headache, nausea, vomiting, altered mental status Endemic area CSF – high WBC, eosinophils Skull X-ray – multiple calciﬁed cysts CT – multiple calciﬁed cysts and active ﬂuid-ﬁlled cysts Subacute onset of headache, dizziness, personality changes followed by stroke-like syndrome CSF – normal glucose high protein, high WBC + CSF VDRL (not RPR or FTA) VDRL or RPR Acute or subacute onset Prodrome of high fever, headache, nausea, lethargy, myalgia Frontal or temporal lobe focal signs Seizures, confusion, altered level of consciousness, bizarre behaviour CSF – increased lymphocytes, normal glucose, mildly elevated protein

Neurosyphilis – meningovascular see Section 11.37 Viral encephalitis (herpes, CMV) see Sections 11.8 and 11.15

*Other disorders with neurologic manifestations: American or African human trypanosomiasis (Sections 11.141 and 11.42), and schistosomiasis (Section 11.34).

Approach to HIV-infected patients with stroke-like syndrome Assess patient for clinical signs and symptoms of disseminated infections such as TB, syphilis, cryptococcal infection. • Investigate according to ﬁndings: ° CD4 count ° toxoplasma serology ° cryptococcal serology (serum or CSF) ° syphilis serology ° platelet count/coagulation studies ° investigations for TB if suggestive – CXR, sputum AFB, lymph node FNA. • CD4 count and degree of immunosuppression help guide diagnosis. • Toxoplasmosis or TB are common causes: ° TB is more likely if there are signs of TB elsewhere. ° Toxoplasmosis is unlikely if CD4 >200. Commence empirical treatment without delay • If a CT scan is immediately available: ° Interpret CT ﬁndings. ° If a lumbar puncture is safe (see Section 10.10b), do CSF investigations. ° Based on CT or CSF ﬁndings, treat for the most likely cause (if uncertain, always cover for toxoplasmosis). ° If no response to treatment – review diagnosis. • If a CT scan is not immediately available: ° Weigh the risks of a lumbar puncture versus empirical therapy. ° Initiate empirical treatment for toxoplasmosis and TB (if evidence of TB infection elsewhere in body); ° Review patient and revise diagnosis depending on CD4 count, results of other investigations, subsequent CT scan, and response to treatment. ° Consider referral for CT if available and patient not responding to empirical treatment.

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Table: Neurological conditions according to immune status HIV-negative or CD4 >500 (but all can also occur with lower CD4 count) • benign and malignant brain tumours • CVA • neurosyphilis • tuberculoma or TB meningitis • neurocysticercosis • secondary malignancy or brain metastases CD4 200–500 • HIV-associated neurocognitive disorders (HAND) CD4 <200 • toxoplasmosis (usually CD4 <100) • tuberculoma or TB meningitis • primary CNS lymphoma (usually CD4 <50) • CVA – intracerebral haemorrhage related to thrombocytopenia • progressive multifocal leukoencephalopathy • bacterial causes/abscesses • cryptococcal meningoencephalitis • neurocysticercosis • HIV-associated neurocognitive disorders (HAND)

10.10a.4 Spinal cord problem (myelopathy) Problems affecting the spinal cord cause damage to the lower motor neurons and sensory nerves. The differential for myelopathy is broad; however, in settings of high HIV prevalence, certain conditions occur more commonly than others.

DDx: Spinal cord problem (myelopathy) Condition Compressive Spinal cord compression (herniated disc, tumour – benign, malignant, or metastatic – abscess) Slow onset Back pain Numbness or tingling in toes, ﬁngers, or buttocks Weakness, unsteadiness, difﬁculty walking Urine or faecal retention or incontinence Evidence of primary cancer (breast, lung, prostate, lymphoma) Slow onset Pain or stiffness in neck, thoracic, or lumbar spine – radiation down arm or leg, worse in the morning, worse with movement Numbness or tingling in the arms, legs, hands, or feet Weakness, unsteadiness, difﬁculty walking Loss of bladder or bowel control In favour

Spondylosis (osteoarthritis of the spine)

Infectious/inﬂammatory Tuberculosis of the spine see Section 15 Onset over months Back pain (lasting weeks to months), muscle spasm Fever Weight loss Night sweats Spinal deformity (kyphosis) Slow onset Progressive weakness or stiffness in the legs (sometimes arms) Sensory loss, sphincter dysfunction, incontinence Increased reﬂexes, up-going plantar response (Babinski) Erectile dysfunction in men Difﬁculty walking Advanced HIV disease Associated HIV dementia or peripheral neuropathy

HIV-associated myelopathy

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Condition Transverse myelitis (herpes, varicella, CMV, HIV, TB, polio, rabies, measles, syphilis, hepatitis, schistosomiasis, bartonella, mycoplasma, MS, paraneoplastic, AV malformation) see Section 11 for more on speciﬁc diseases Tertiary syphilis see Section 11.37

In favour Acute onset Back pain Sensation of a tight band around the trunk Numbness or tingling below a certain spinal level Weakness in legs (arms involved less often) Muscle spasms Bowel and bladder dysfunction Associated headache, fever, loss of appetite Other symptoms depending on the cause Slow onset Numbness or tingling in the hands or feet Weakness of limbs, unsteadiness, wide-based walk Loss of reﬂexes, incontinence Memory loss, psychiatric problems, visual loss

Metabolic Vitamin B12 deﬁciency Subacute onset Megaloblastic anaemia Numbness or tingling in the hands or feet Weakness in legs, ataxia, wide-based walk Absent ankle reﬂexes Poor joint position and vibration sense Peripheral neuropathy Dementia, depression

10.10a.5 Peripheral motor or sensory nervous system problem Problems affecting the peripheral nervous system can cause motor or sensory disturbances, and occur as a result of damage to the peripheral nerves and nerve roots. The differential for a patient presenting with weakness, numbness, tingling and pain is broad. However, in settings of high HIV prevalence, certain conditions occur more commonly due to the effect of HIV on the nerves, as well as the effect of opportunistic infections, neoplasms, and medications. The most common conditions are mononeuropathies (focal disorders affecting a single nerve or nerve group) and radiculopathies (disorders of the nerve roots). Different disorders can be roughly distinguished by whether or not they are focal or multifocal, symmetrical or asymmetrical, and whether they are primarily sensory or have a motor or autonomic component. On taking the patient’s history, the following information is important: • onset and progression of symptoms • symmetrical or asymmetrical, distal or proximal, focal or multifocal • bladder control problems • sweating, temperature or pulse instability (autonomic involvement) • HIV infection (if positive, CD4 count) • exposure to drugs (INH, d4T, ddI) or toxins (alcohol, lead). On examination, pay particular attention to the following: • sensory function (pain, light touch, vibration, proprioception) • motor function (power, tone, reﬂexes)

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• spinal examination • sphincter function • cranial nerves abnormalities. Investigations • CSF analysis may be helpful for distinguishing between various conditions that have involvement at the spinal cord level (see differential diagnosis table). • In the absence of sophisticated nerve conduction tests, diagnosis is commonly based on clinical context and pattern recognition. • Speciﬁc investigations according to the clinical suspicion of underlying problems.

DDx: Peripheral motor or sensory nervous system problem Condition Focal or asymmetrical deﬁcits Compression of nerve or nerve root (lymphoma, TB, carpal tunnel syndrome, bleed) Mononeuritis multiplex (hepatitis B, hepatitis C, HIV, CMV, VZV, leprosy) Weakness and sensory disturbance in the distribution of affected nerve and indicative of the level of the lesion Pain, weakness, and paraesthesias in the distribution of affected nerve or nerves Pain over area Weakness of related muscles If CD4 <50, can have severe form affecting multiple nerves of the shoulder girdle Radiating back pain Loss of feeling and paraesthesias in lower limbs Reduced or absent reﬂexes in lower limbs Flaccid paralysis with no speciﬁc spinal “level” Urine retention, loss of bowel function Low CD4 count (usually <50) CSF – high polymononuclear cell, normal glucose, high protein Evidence of CMV disease elsewhere (retinitis, GE, encephalopathy) In favour

Polyradiculopathy (commonly CMV, also VZV, lymphoma, syphilis)

Symmetrical neuropathy (motor or sensory) Distal symmetrical sensory polyneuropathy (DSPN) (HIV, medication, nutritional deﬁciencies, alcohol, diabetes) Distal, symmetrical – glove and stocking distribution Painful tingling and numbness Usually no motor weakness Other causative factors have been excluded CSF – no cells, N glucose See below for more information Presentation depends on the agent: motor, sensory, or both Can affect cranial nerves History of exposure to toxin Onset related to exposure to toxin Gradual onset (over months) Sensory and motor deﬁcit with no speciﬁc “level” Responds to steroids CD4 200 – 500 CSF – increased mononuclear cell, normal glucose, high protein

Toxic neuropathy (toxins, solvents, insecticides, alcohol, drugs including heroin and amphetamines) Chronic inﬂammatory demyelinating polyneuropathy (CIDP)

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Condition Acute inﬂammatory demyelinating polyneuropathy (AIDP) e.g. Guillain-Barré syndrome Tetanus

In favour Acute (over hours to weeks) Ascending, painless, ﬂaccid weakness Sensory loss distally Areﬂexia CSF – normal WCC, high protein Recent open wound Irritability Jaw or neck stiffness (lockjaw) Spasm of neck, back, abdominal muscles, respiratory muscles Brisk reﬂexes Autonomic dysfunction: hypertension, tachycardia, high temperature, sweating Normal level of consciousness Difﬁculty swallowing or speaking Facial weakness Double vision Trouble breathing Nausea, vomiting, and abdominal cramps Paralysis

Botulism

Symmetrical neuropathy (motor or sensory) Rabies see Section 11.30 Wild animal, unimmunized domestic animal, or bat bite (bat bite may not be remembered) Fever Headache Altered mental state, insomnia, agitation, confusion, hallucinations Hypersensitivity or spasms in response to stimuli (noise, touch, visual) Hydrophobia Excessive salivation Paralysis Pain or paraesthesia Autonomic dysfunction: big pupils, increased saliva, sweat, and tears Muscle weakness, headache, stiff neck, fever Spinal poliomyelitis: paralysis of shoulder girdle often precedes intercostal and diaphragmatic paralysis Bulbar poliomyelitis: facial weakness, dysphagia, dyspnoea, nasal voice, inability to swallow saliva, weak sternocleidomastoid and trapezius muscles. Can progress to respiratory paralysis.

Acute poliomyelitis*

Systemic causes Hypokalaemia see Section 5.2 Generalized motor weakness, atrial or ventricular arrhythmias Hyporeﬂexia ECG changes – ST depression, ﬂattened (or absent) T waves, U waves (positive deﬂection after the T wave), prolonged P–R interval Lab: very low potassium Chronic diarrhoea

* Acute ﬂaccid paralysis in person <15 years or acute paralytic illness at an age where polio is suspected should be reported immediately and investigated (see Section 21).

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10.10a.6 Peripheral neuropathy (See also Section 13.8 – Peripheral neuropathy as an ART toxicity.) Peripheral neuropathy is a term used to describe dysfunction in one or more of the peripheral nerves. In this section, the term "peripheral neuropathy" (PN) is used speciﬁcally to refer to distal symmetrical sensory polyneuropathy (DSPN) – a condition that starts at the base of the feet and progresses upwards causing numbness, paraesthesias, and pain. There are a number of different causes of PN including: nerve compression, autoimmune or inﬂammatory conditions, toxin- or drug-induced damage, and inherited conditions. It is important to look for the cause as early detection and treatment will stop and may even reverse the progression of symptoms. Pain due to PN may become irreversible if left for too long. In settings with a high HIV and TB prevalence, PN is a common problem that can be irreversible and debilitating for patients who are affected by it. Peripheral neuropathy is the most frequent neurological complication of HIV infection. This could be either primarily due to HIV infection (after all other co-morbid causes have been excluded) or secondary to ART.

DDx: Peripheral neuropathy Condition HIV infection In favour Symmetrical, glove-stocking distribution: • starts in toes and balls of feet • spreads to rest of foot, ankle, and up the legs • in severe cases ﬁngers or hands involved Sensory changes (often worse at night): • numbness or increased sensitivity to touch • progresses to tingling, burning, or pain • impaired vibration sensation and temperature perception • in severe cases: super-sensitivity to touch (unable to wear shoes or lie under bed sheets) Motor function usually preserved: • weakness uncommon • reduced or absent ankle jerk reﬂexes • walking and balance may appear abnormal due to pain • if rapidly progressive weakness and high lactate, consider HIVassociated neuromuscular weakness syndrome associated with lactic acidosis Medicines, substance use Patient taking one or more offending medicine: • most common: INH, d4T, or ddI • other medicines: ethambutol, ethionamide, dapsone, vincristine, thalidomide, lithium carbonate, metronidazole, high-dose vitamin B6, cisplatin • Heroin or amphetamine use Symptoms: • similar to peripheral neuropathy caused by HIV (see above) • reports of deep aching pain across the top of the foot High lactate: • associated with NRTI-mediated neuropathy

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Condition Diabetes

In favour Glove-stocking distribution: • starts in toes or soles • spreads to ankles and calf Poor glycaemic (blood sugar) control Evidence of other diabetic complications: • peripheral vasculopathy, nephropathy, retinopathy Sensory changes: • numbness or pain

Nutritional deﬁciency Alcohol Other infections: (VZV, CMV, hepatitis C, syphilis, Cryptococcus, leprosy)

Low serum vitamin B12 Clinically malnourished History of alcohol overuse Other evidence of chronic alcohol abuse Other evidence of the infection that is causing the neuropathy (see Section 11 for more on speciﬁc diseases)

Diagnosis • The brief peripheral neuropathy screen (BPNS) should be used to assess for HIV-associated distal sensory polyneuropathy (DSPN). ° Subjective – ask for symptoms of pain, burning, pins and needles, or numbness in the hands or feet ° Objective – assess sensation of the hands and feet, vibration sense, and ankle tendon reﬂexes. Treatment • Treat or remove the cause. • Give thiamine if known history of alcohol use. • If the patient is on TB treatment or on ART – refer to Sections 15 and 13 respectively for management and drug substitution. • After discontinuation of the offending drug, it may take a few weeks for the pain to decrease, and in that time the pain may even worsen. • Peripheral neuropathy primarily due to HIV infection may improve once the patient is put on effective ART: ° also give one pyridoxine 50 to 75 mg daily. • Pain control by anticonvulsants and tricyclics for neuropathic pain: ° amitriptyline is widely used for peripheral neuropathy; dose: start at 25–75 mg at night (increase as needed if side-effects are tolerated) to a maximum dose of 300 mg daily; OR ° carbamazepine – start at 100 mg twice daily and increase to a total of up to 1600 mg daily. ° If HIV-positive and on ART with poor response to amitriptyline, then the use of gabapentin is recommended: ◊ Dose: day 1, an initial dose of 300 mg daily; day 2, 300 mg twice daily; day 3, 300 mg 3 times daily. Dose can then be titrated 100 mg increments every 3 days as needed, to a maximum of 3600 mg daily (given as either 1200 mg 3 times daily or 900 mg 4 times daily).

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• Analgesics including opiates may provide some relief – see Section 17 for a stepwise approach to controlling pain. ° Low-dose opioids may be required for relief of neuropathic pain, following trial with tricylic antidepressant agents. Prevention • It is desirable to give pyridoxine (vitamin B6) 10 mg daily to patients taking INH as prophylaxis or as part of TB treatment. • Avoid the use of stavudine, see Section 13. • Educate and monitor patients taking stavudine and substitute if any toxicity. • Control diabetes and hypertension.

10.10a.7 Common cranial nerve palsies and their differentials Problems affecting the cranial nerves can occur as a result of central or peripheral nervous system conditions. See the table below for likely signs and symptoms. Cranial nerve palsies Second nerve palsy (optic nerve) Third nerve palsy (occulomotor nerve) Presentation Acute visual loss Fixed, dilated pupil Ptosis Eye looks downwards and outwards Double vision Double vision Restricted eye movement up in adduction Concurrent third and sixth nerve palsy Recent head injury Pain or paraesthesias in face Weak jaw clenching Wasting of temporalis and masseter muscles Double vision Unilateral paresis of eye abduction Facial muscle weakness Lower motor neuron (LMN) = forehead paralysed Upper motor neuron (UMN) = forehead is spared Ramsay Hunt = facial weakness + vertigo + loss of taste Eighth nerve palsy (vestibulo-cochlear nerve) Onset acute, chronic or recurrent Sensorineural hearing loss Vertigo (hallucination of movement) Associated nausea, vomiting, tinnitus, Nystagmus Common causes see Section 10.12 Eye problems Ruptured aneurysm Subarachnoid haemorrhage HIV vasculopathy Diabetes mellitus Syphilis Often idiopathic Head injury Aneurysms Tumours Multiple sclerosis Trigeminal neuralgia Herpes zoster

Fourth nerve palsy (trochlear nerve)

Fifth nerve palsy (trigeminal nerve)

Sixth nerve palsy (abducens nerve) Seventh nerve palsy (facial nerve)

Raised intracranial pressure Tumours or masses Meningitis LMN: Bell's Palsy – idiopathic Ramsay Hunt – varicella zoster (treat with steroid + aciclovir) UMN: Stroke Tumour Brainstem stroke Menieres disease Aminoglycoside antibiotics Labyrinthitis (acute onset) Benign paroxysmal positional vertigo (recurrent)

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10.10b Headaches In this section: 10.10b.1 Clinical approach to a patient with headache 10.10b.2 Consider the likely differential diagnosis • DDx: Primary headache • DDx: Secondary headache 10.10b.3 Treatment of speciﬁc conditions • Acute bacterial meningitis • Tuberculosis meningitis 10.10b.4 Symptom management of headache

This Section provides an approach to the patient with headache, with or without meningeal signs or fever. Headache is a common complaint in clinical practice, and it is important to distinguish benign headaches from those due to a serious condition. If the patient reports the headache as the “ﬁrst or worst” of its kind, then it is more likely to be due to a serious cause. Headaches are most thoroughly classiﬁed by the International Headache Society's International Classiﬁcation of Headache Disorders (ICHD) 2004. This classiﬁcation is accepted by WHO. 1. Primary headaches • migraine • tension-type headache • cluster headache and other trigeminal autonomic headaches • other primary headaches (e.g. primary cough headache, exertion headache, headache associated with sexual activity). 2. Secondary headaches • head or neck trauma • cranial or cervical vascular disorder • non-vascular intracranial disorder • substance use or its withdrawal • infection • homeostasis • facial pain attributed to a disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structures • psychiatric disorders. 3. Cranial neuralgias, central and primary facial pain, and other headaches Secondary headaches may be further sub-divided, as in the differential diagnosis tables below, into: • headache with meningeal signs, with or without fever • headache with no meningeal signs, with or without fever • headache with no meningeal signs and no fever • extracranial causes of headache.

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10.10b.1 Clinical approach to a patient with headache Step 1: Perform Quick Check. Use the Quick Check and ensure that there are no serious or life-threatening conditions, such as altered consciousness or convulsions. Step 2: Take a history and examine the patient. Determine whether the onset is acute or chronic. Look for meningeal signs, fever, rash, and agitation or confusion. Step 3: Assess the patient’s HIV status. Step 4: Perform investigations. If in doubt, do a lumbar puncture (LP). If the patient is HIV-positive, do an LP. There are few contraindications to an LP, and the diagnostic beneﬁt is signiﬁcant. Ask whether a CT scan will change management and whether it is available through referral. Step 5: Work through the differential diagnosis using the DDx tables: • DDx: Headache with no abnormal physical ﬁndings • DDx: Headache with abnormal physical ﬁndings. Step 6: Initiate management and monitor the patient’s response. • Flow chart 1: Approach to headache in a patient with HIV infection or unknown HIV status and suspected CN infection. • Flow chart 2: Approach to headache in HIV-negative patient with suspected CN infection.

Take a history and examine the patient A good history and examination will help determine the cause of the headache. Headache syndromes show a typical pattern in the history and an absence of unexplained physical signs. As noted, a headache that is the ﬁrst of its kind or the worst of its kind is more likely to be from a serious cause.

History • History of presenting complaint: ° onset (sudden or gradual) ° duration (hours, days, weeks, months) ° stiff neck ° associated dizziness, nausea, or vomiting ° motor or sensory abnormalities ° vision, hearing, or speech problems ° trouble with balance or walking ° associated seizures, change in level of consciousness ° change in behaviour, mood, memory, or cognition ° constitutional symptoms (fever, weight loss, night sweats). • Medical history: ° risk factors for stroke (hypertension, diabetes, heart disease, obesity, bleeding disorders, clotting, pregnancy) ° TB, HIV (if positive, CD4 count and ART history) ° malignancy ° syphilis ° history of head injury ° current medications. • Exposure to infectious diseases: ° TB contact ° Living in or travelled to endemic area (malaria, dengue, rickettsia). Vol. 2 • 10. Acute and subacute by symptom: July 2011 Headache 189

Examinations General signs • vital signs • level of consciousness, using AVPU or Glasgow Coma Scale • rash: ° Look for petechiae or purpura. It may look like bruises and can be difﬁcult to see on dark skin. Check paler areas such as palms, soles, torso, conjunctiva, palate. ° Look for signs of viral infection, sinusitis, toothache, or ear infection. Meningeal signs • neck stiffness • Kernig’s sign (resistance to straightening of the leg while hip is ﬂexed) • Brudzinski’s sign (ﬂexing the neck causes ﬂexion of the hip or knee). Fundoscopy for papilloedema See Section 10.12. Higher functions • orientation to person, place, or time • speech, cranial nerves, motor and sensory system, cerebellar function (as indicated). See Section10a Neurological deﬁcit. • ability to walk. Assess the patient’s HIV status. HIV infection inﬂuences the likely differential diagnosis for headache, as there are a number of opportunistic infections that can present with headache. Whenever possible, an HIV test should be done, and the CD4 count should be checked if a patient is HIV-positive. LP in patients with HIV infection Lumbar puncture carries no excessive risk in patients with TB meningitis or cryptococcal meningitis, even in the presence of papilloedema, vomiting, or an altered mental state. In advanced HIV these infections are very common, and you should have a low threshold for performing an LP in these patients. See ﬂow diagram below for management approach.

Perform investigations Bloods • full blood count with white cell differential count to look for infection • malaria smear if endemic area (coinfection with malaria and meningitis is common) • ESR if temporal arteritis suspected.

Lumbar puncture (LP) For more on how to perform an LP, see Section 7.4 Procedures. LP is recommended in the following situations: • If blood or pus is suspected in subarachnoid space: ° sudden onset severe headache and suspected subarachnoid bleed ° recent onset headache with fever or neck stiffness or pain and meningitis is suspected. • If a headache is the ﬁrst of its kind or the worst of its kind, it will need investigation after considering a migraine. • If the patient is HIV-positive with signs and symptoms of meningitis. 190 Headache Vol. 2 • 10. Acute and subacute by symptom: July 2011

DO NOT perform an LP if there is: • local skin or soft tissue infection at LP site • known or suspected bleeding disorder (risk of spinal haematoma) • any sign of impending brain shift (herniation) is present ° rapidly deteriorating level of consciousness ° recent seizure (within 30 minutes) or status epilepticus ° brainstem signs ◊ unequal pupils ◊ abnormal posturing ◊ irregular respirations. ° If signs of impending brain shift are present, do the following: ◊ Refer to Quick Check for emergency management. ◊ Commence empirical antibiotics if you suspect CNS infection. ◊ Do a CT scan to look for evidence of brain shift before doing an LP. Cerebral spinal ﬂuid (CSF) analysis See the table below for characteristic CSF ﬁndings for various diagnoses. • Opening pressure ° Measure routinely. This can be done with an intravenous infusion set and is useful for the diagnosis and management of cryptococcal meningitis. ° Assess the macroscopic appearance (to the naked eye). Is it clear, cloudy, purulent, straw-coloured, blood-stained? • Microscopy ° Routine ◊ cell count ◊ glucose (compare with blood glucose for CSF: plasma glucose ratio) ◊ protein ◊ Gram stain. ° If the patient is HIV-infected or of unknown HIV status, perform the following: ◊ India ink ◊ cryptococcal latex agglutination test (CrAg) ◊ If clinical signs of syphilis are present or if diagnosis uncertain: ◊ Perform CSF rapid syphilis test (RPR/VDRL) – low sensitivity but high speciﬁcity. A positive test conﬁrms the diagnosis of neurosyphilis. ° Mycobacterial microscopy is not recommended due to low sensitivity. • Culture ° Bacterial culture ◊ If limited resources, use selectively, in cases of poor response to treatment, suspected drug resistance, very ill patient with inconclusive CSF ﬁndings. ◊ If readily available, use if Gram stain is positive. ° Mycobacterial culture ◊ Usefulness is limited during initial diagnosis (time delay for results). ◊ Consider using if there is suspected drug-resistant TB, previous TB, unsure of diagnosis (MAC versus TB). ° Fungal culture ◊ useful for previously treated cryptococcal meningitis in HIV-infected patients on ART to distinguish reinfection from immune reconstitution inﬂammatory syndrome (IRIS). • Cytology ° if CNS malignancy is suspected.

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CT scan If a CT scan is available, do it before an LP in the following circumstances: • Clinical ﬁndings suggest a space-occupying lesion. • signs of brain shift (herniation) • coma of unknown cause. Start empirical antibiotics while waiting for CT in all cases of suspected meningitis. Table: Characteristic CSF ﬁndings White cell count (cells/ mm3) Usually >100 PMNs CSF glucose: blood glucose ratio Low (<50%)

Condition Bacterial meningitis

Onset Hours to days

Protein High

Other Cloudy or purulent CSF Organisms on Gram stain Positive culture India ink, CrAg positive High opening pressure CrAg positive India ink may be negative Cryptococcal culture negative Cloudy CSF Evidence of TB elsewhere Focal neurology Evidence of TB elsewhere VDRL positive (FTA not used in CSF) VDRL or RPR positive Gram stain and culture negative (consider acute HIV infection) Active ﬂuid-ﬁlled cysts on CT

Cryptococcal meningitis

Days to weeks

Usually >501 lymphocytes

Low (<50%)

Normal or high

Cryptococcal IRIS meningitis

Days (recent initiation of ART)

Usually >100 lymphocytes

Low (<50%)

High

TB meningitis

Days to weeks

Usually >100 lymphocytes Raised lymphocytes Variable lymphocytes >5 cells Variable lymphocytes

Low to very low (<30%) Low (<50%)

High

Tuberculoma (cerebral) Syphilitic meningitis Neurosyphilis latent Aseptic or viral meningitis

Days to weeks

Very high

Days to weeks Months to years (decades) Hours to days

Normal (60%) Normal (60%) Normal (60%)

Slightly elevated Slightly elevated Slightly elevated

Neurocysticercosis

New onset seizures

High eosinophils

Normal (60%)

Normal

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Bacterial brain abscess Lymphomatous meningitis Viral encephalitis (herpes, CMV, PML) Subarachnoid haemorrhage

Days

Slightly high WBC Variable; lymphocytes High lymphocytes Red cells often seen Increased red blood cells

Normal (60%)

Normal

Evidence of sinusitis, otitis, or abscess in other organs Cytology Other evidence of systemic lymphoma Focal neurology (frontal or temporal) Seizures Normal or severe neurological deﬁcit with or without meningeal signs

Days to weeks

Normal to low

Elevated

Hours to days

Normal (60%)

Slightly elevated

Sudden onset severe headache

Normal (60%)

Elevated

1 Unless IRIS, in which case typically >50.

10.10b.2 Consider the likely differential diagnosis Use the differential diagnosis tables to work through a likely differential diagnosis.

DDx: Primary headache Condition Tension headache In favour Mild to moderate dull, aching head pain Pressure or tightness band around the head Tenderness of the scalp, neck, shoulders Fatigue Can last up to a week Intense throbbing, unilateral pain History of previous attacks Pain preceded by aura or prodrome Nausea, vomiting May have visual defects Sensitivity to light and sound Lasts hours; can last days Acute onset – within minutes – usually at the same time each day History of previous attacks Excruciating, deep, piercing pain Unilateral, pain around the eye Excessive tearing Conjunctival injection on the side of the pain Blocked or runny nose on the side of the pain Horner’s syndrome (droopy eyelid, constricted pupil, reduced sweating)

Migraine

Cluster headache

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DDx: Secondary headache Condition In favour

Headache with meningeal signs (with or without fever) Bacterial meningitis see Management, below Acute onset: hours to days Fever Meningeal signs Purpuric rash (if meningococcal) CSF – high PMNs, very low glucose, very high protein; Gram stain may be positive Subacute onset: days to weeks Fever Meningeal signs Focal neurological deﬁcit Evidence of TB elsewhere CSF – high lymphocytes, low glucose, higher protein Subacute onset: days to weeks HIV infection, signs of weak immune system Meningeal signs (may be absent), fever (may be absent), malaise Skin lesions resembling molluscum contagiosum LP – high opening pressure CSF – high lymphocytes, low glucose, high protein, positive India ink, positive CrAg (CSF may be normal in severe immunocompromise – AIDS) Acute onset: hours to days Can be part of acute HIV infection Meningeal signs Maculopapular rash Usually self-limiting CSF – high lymphocytes, normal glucose, mildly elevated protein Acute onset: hours to days Acute HIV infection Rash, pharyngitis Meningeal signs CSF – increased lymphocytes, normal glucose, mildly elevated protein Acute or subacute onset Prodrome of high fever, headache, nausea, lethargy, myalgia Frontal or temporal lobe focal signs Seizures, confusion, altered level of consciousness CSF – increased lymphocytes, normal glucose, mildly elevated protein

TB meningitis see Section 15

Cryptococcal meningitis see Section 11.5

Aseptic or viral meningitis

HIV meningitis

Viral encephalitis (herpes, CMV, PML)

Headache with no meningeal signs (with or without fever) Cerebral toxoplasmosis see Section 11.40 Subacute onset: days to weeks Dull affect, altered level of consciousness Focal signs Seizures Fever CT scan – single or multiple ring-enhancing lesions HIV-infected or signs of immune compromise CD4 <100/mm3 Very acute onset Severe headache, “worst ever” Neurological deﬁcit Meningeal signs (may be absent) No fever CSF – very high RBCs, high protein

Subarachnoid haemorrhage

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Neurosyphilis – syphilitic meningitis see Section 11.37 Bacterial brain abscess

Subacute onset: days to weeks Meningeal signs (may be absent) CSF – high WBC, normal glucose, high protein, positive VDRL or RPR In HIV-negative patients may result from contiguous spread or bacteraemia. Gradual onset: weeks Headache, neck stiffness, altered mental status, signs of increased ICP Focal deﬁcits beginning days after headache, seizures LP should be avoided. Subacute onset: days to weeks Focal neurological deﬁcit No meningeal signs Constitutional symptoms (including fever, weight loss, night sweats) Evidence of TB elsewhere CSF – high lymphocytes, low glucose, higher protein Haemorrhagic leptomeningitis Neck pain with or without ﬂexion Headache, changes in mental state Vomiting and high-grade fever Markedly elevated CSF pressure and the appearance of blood in the CSF are followed rapidly by disorientation, loss of consciousness, and death. Presents as a meningoencephalitis in HIV-positive patients A DDx for toxoplasmosis, with a pseudo tumour located in the white matter of the brain Can progress to seizures and paralysis Acute onset (after injury or exposure) Muscle rigidity (jaw, neck, shoulders, back) Neck stiffness With or without fever Autonomic dysfunction (hypertension, tachycardia, sweating) Increased deep tendon reﬂexes Alert mental state

Cerebral tuberculoma see Section 15

Anthrax

Chagas disease see Section 11.42

Tetanus see Section 11.39

Headache with no meningeal signs and no fever Stroke (CVA) see Section 10.10a Sudden onset Focal signs – hemiparesis, aphasia, unilateral facial weakness Raised BP Normal CSF New onset seizures Cognitive deﬁcits, personality changes CSF – high WBC, eosinophils CT – multiple ﬂuid-ﬁlled active cysts Onset over days to weeks CSF – high protein, high WBC RPR or VDRL positive on CSF Insidious onset Seizures Neurologic deﬁcit – cranial nerve palsies, mental status change Immunocompromised, CD4 <50/mm3 Headache – worse at night Vomiting, low-grade fever Focal signs, seizures Deterioration in mental status Evidence of the primary tumour, e.g. breast

Neurocysticercosis see Section 11.7

Neurosyphilis – syphilitic meningitis see Section 11.37 Primary CNS lymphoma

Brain metastases

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Condition Human African trypanosomiasis see Section 11.41

In favour Worsening headache Confusion, behaviour changes, depression Somnolence Convulsions Sensory disturbance, poor coordination BP >180/110 mmHg Confusion Fundoscopy – sclerosis, exudates, haemorrhages, papilloedema With or without abnormal renal function (if severe) With or without raised cholesterol Pregnant 2nd or 3rd trimester BP >140/90 Oedema or anasarca Visual disturbances, confusion Urine – proteinuria Increased uric acid, increased urea, increased creatinine, high ALT/AST, low platelets (HELLP syndrome)

Severe hypertension

Severe pre-eclampsia or eclampsia see Quick Check page 23, Vol. 1

Extra-cranial causes of headache Malaria see Section 11.25 Acute onset Fever Positive malarial RDT or microscopy FBC – anaemia Pain behind the eyes Fever, joint pains, myalgia Petechiae Travel to or living in endemic area Positive dengue IgM or IgG Tender sinuses, pain or pressure in the face Nasal discharge, blocked nose or post-nasal drip Fever History of previous episodes Labs – all normal Headache severe Fever Rash – often involves palms and soles Eschar (dark scab) at the site of the bite or history of contact with tick or ﬂea High ALT/AST Pain starts in the mouth Pain on chewing Dental caries Fever Increased WCC (high PMN) in blood Pain starts in the mouth Pain on swallowing Fever If severe – difﬁculty breathing, meningism, headache Increased WCC (high PMN) on blood Sudden, severe, brief, stabbing, recurrent pain in the distribution of one or more branches of the ﬁfth cranial (trigeminal) nerve Usually unilateral Facial muscle spasms with severe pain Triggers include touching affected area, chewing, talking, brushing teeth, cold air, smiling, or grimacing.

Dengue fever see Section 11.9

Sinusitis see Section 11.35

Rickettsial diseases see Section 11.32

Toothache see Section 10.17

Tonsillitis

Trigeminal neuralgia

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Initiate management and monitor response For primary headache not due to a treatable cause, refer for deﬁnitive diagnosis and management. Secondary headache Empirical treatment: • Empirical treatment differs depending on the patient’s immune status. ° If HIV-infected, do a CD4 count as soon as possible to guide the differential diagnosis. Use ﬂow chart 1, below, for management. ° If HIV status unknown, manage initially as HIV-infected and perform HIV test as soon as possible. Use ﬂow chart 1, below, for management. ° If HIV-negative, use ﬂow chart 2, below, for management.

Flow chart 1: Approach to headache in a patient with HIV infection or unknown HIV status and suspected central nervous system infection HIV-positive

No LP performed Focal neurological or brainstem signs present? No Treat: bacterial meningitis toxoplasmosis Start investigation for TB Take serum CrAg Yes Treat: bacterial meningitis toxoplasmosis Refer to empirical approach for focal neurological deﬁcit

LP performed CSF analysis: cell count, glucose, protein Gram stain, India ink, CrAg

India ink or CrAg positive

Gram positive or CSF ﬁndings consistent with bacterial meningitis

CSF ﬁndings consistent with TB meningitis

Improvement by 48 hours? No Continue treatment Do LP when safe Yes Reconsider LP Add treatment for: TB meningitis (if other evidence of TB) cryptococcal meningitis (if serum CrAg positive) Refer DDx table

Treat: cryptococcal meningitis (see below)

Treat: bacterial meningitis (see below)

Treat: TB meningitis and bacterial meningitis (see below)

Improvement by 48 hours? No Continue treatment Yes Repeat LP Consider wrong or dual diagnosis Refer DDx table

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Flow chart 2: Approach to headache in HIV-negative patient with suspected central nervous system infection Assess risk of herniation – consider LP

No LP performed Focal neurological or brainstem signs present? No Yes

LP performed CSF analysis: cell count, glucose, protein Gram stain

Treat: bacterial meningitis Add steroids

Refer to focal neurological deﬁcit section

Gram positive or CSF ﬁndings consistent with bacterial meningitis

CSF ﬁndings consistent with TB meningitis

Other

Improvement by 48 hours? Yes Continue treatment Do LP when safe No

Treat: bacterial meningitis (see below)

Clinical evidence of TB elsewhere in body?

Refer DDx tables

Reconsider LP Look for TB elsewhere If found, treat TB meningitis Refer DDx table

Yes

No Repeat LP at 1 week If no resolution consider TB Rx Refer DDx tables

Treat: TB meningitis

Improvement by 48 hours? Yes No Repeat LP Refer DDx table

Continue treatment

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10.10b.3 Treatment of speciﬁc conditions Acute bacterial meningitis Acute bacterial meningitis is the most common cause of meningitis with an acute onset. It is a medical emergency. If it is clinically suspected, start treatment immediately while waiting for results to conﬁrm the diagnosis. On taking the patient’s history, look for: • prodrome of non-speciﬁc symptoms • classic triad of ° fever ° headache ° neck stiffness • photophobia, vomiting • confusion, seizures. On examination look for: • very unwell or rapidly deteriorating patient • meningeal signs ° neck stiffness ° positive Kernig's or Brudzinski's sign • rash – petechial or purpuric (non-blanching) – meningococcal meningitis • focal neurological deﬁcit (may develop in later stages). If CSF findings are consistent with bacterial meningitis, refer to the table Characteristic CSF ﬁndings, above. Treatment If acute bacterial meningitis is suspected, begin empirical therapy immediately without waiting for the laboratory conﬁrmation. Refer to national guidelines and epidemiology of local resistance patterns for individual cases and meningitis epidemics. Empirical therapy • ceftriaxone 2 g IV or IM twice daily (preferred): ° 5–7 days for Neisseria meningitidis and Haemophilus inﬂuenzae ° 10–14 days for Streptococcus pneumoniae or unknown organism. • empirical therapy if ceftriaxone is unavailable: ° ampicillin 2 g IV every 4 hours AND cotrimoxazole 10–20 mg per kg (based on the trimethoprim component) IV per day divided into 2–4 doses (alternative). • modiﬁcations to empirical therapy ° If there is a high prevalence of pneumococcal resistance to penicillin, add vancomycin 1 g IV twice daily, if available. ° If risk factors are present for L. monocytogenes (see below), add ampicillin 2 g IV every 4 hours. ° If patient has anaphylactic allergy to penicillin, give chloramphenicol 1 g IV every 6 hours PLUS cotrimoxazole 10 to 20 mg per kg (based on the trimethoprim component) IV per day divided into 2–4 doses.

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• oily chloramphenicol 100 mg/kg IM (maximum dose 3 g) single dose (repeat after 24–48 hours if necessary), only in meningococcal epidemics. An alternative to oily chloramphenicol is ceftriaxone 2 grams.1 • In adults with suspected bacterial meningitis, consider giving dexamethasone 10 mg IV every 6 hours for 4 days immediately prior to antibiotics. The administration of steroids should not delay the administration of antibiotics. If antibiotics are started ﬁrst, do not administer dexamethasone. Therapy for conﬁrmed infections • Treatment should be guided by local microbial epidemiology, resistance patterns, and results of CSF cultures, if available. • Neisseria meningitidis, Haemophilus inﬂuenzae, Streptococcus pneumoniae: ° ceftriaxone: see above (can be used for patients with a non-anaphylactic allergy to penicillin); ° ampicillin (dose above) may be used for sensitive H. inﬂuenzae isolates; ° benzylpenicillin (4 million units [2.4 g] IV every 4 hours) may be used for sensitive S. pneumoniae and N. meningitidis isolates; ° If anaphylaxis to penicillin, give chloramphenicol and cotrimoxazole (see doses above). • Listeria monocytogenes (more common in the elderly, pregnant women, and those with impaired immunity, including HIV): ampicillin 2 g IV every 4 hours for at least 21 days PLUS gentamicin 5 mg per kg per day divided into 3 doses until patient improves (at least 1 week). ° In patients with anaphylactic allergy to penicillin, alternative is cotrimoxazole 10 to 20 mg per kg (based on the trimethoprim component) IV per day divided into 2–4 doses. Protection of contacts of conﬁrmed cases of bacterial meningitis (not in outbreak situation)2 • N. meningitidis: Prophylaxis is recommended for close contacts (household members, roommates, intimate contacts, individuals at a child-care center, young adults in dormitories, military recruits in training centers, and sitting next to an index patient for more than 8 hours on an airplane; individuals who have been exposed to oral secretions (for example, by kissing, mouth-to-mouth resuscitation, endotracheal intubation or endotracheal tube management). If a close contact develops fever, prompt evaluation is recommended. Recommended prophylaxis: ° ciproﬂoxacin 500 mg orally as a single dose; OR ° ceftriaxone 250 mg IM as a single dose; OR ° rifampicin 600 mg orally 2 times daily for 2 days. • H. inﬂuenzae: Prophylaxis of all household contacts (including adults) is recommended only when the index case has H. inﬂuenzae serotype b (Hib) AND the household has at least one child under 1 year old (excluding the index case) or has a child 1–3 years old who is not adequately immunized. Recommended prophylaxis: ° ciproﬂoxacin 500 mg orally as a single dose; OR ° ceftriaxone 250 mg IM as a single dose; OR ° rifampicin 400 mg orally once daily for 4 days. • S. pneumoniae: Prophylaxis of household contacts is not recommended. 1 Standardized treatment of bacterial meningitis in Africa in epidemic and non epidemic situations. WHO, 2007. Available at http://www.who.int/csr/resources/publications/meningitis/WHO_CDS_EPR_2007_3/en/index.html 2 Heymann DL, ed. Control of communicable diseases manual, 19th ed. APHA and WHO, 2008.

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Cryptococcal meningitis and IRIS (see Section 11.5) Cryptococcus is the most common cause of meningitis in patients with advanced HIV infection. Note: Without the results of a lumbar puncture, other concomitant infections cannot be excluded and should be covered with empirical therapy.

Tuberculosis meningitis TB meningitis occurs more commonly in HIV-infected patients, but it may also occur in HIV-negative patients. The meningeal inﬂammation is due to the spread of the TB to the meninges via the blood or rupture of a tuberculoma in the brain. TB is usually found in another part of the body, e.g. pulmonary TB. On history look for: • night sweats, loss of weight • gradual onset headache • low-grade fever • neck stiffness • symptoms of TB in other systems, i.e. cough • TB contact. On examination look for: • meningism • cranial nerve palsies • decreased conscious state • focal neurological deﬁcit • evidence of TB elsewhere (lymphadenopathy, chest signs). Investigations For the CSF analysis, refer to table Characteristic CSF ﬁndings, above. • may appear cloudy • high protein (40–100 mg/dl) • low glucose (<20 mg/dl) • cell count 500/mm3 – lymphocytes. The CSF ﬁndings can often be ambiguous. If the ﬁndings are unclear, look for evidence of TB elsewhere in the body (see Section 11 Tuberculosis). Treatment • for treatment guidelines refer to Section 15 Tuberculosis.

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10.10b.4 Symptom management of headache In-hospital management • Work through differential diagnosis for headache as outlined above in this chapter. • Treat pain using the WHO pain ladder: begin with analgesics such as paracetamol or NSAIDS and change to analgesic-opioid combinations and ultimately to strong opioids if the patient has continued pain. • If there is raised intracranial pressure: ° If due to inﬂammation or intracranial masses, give a high dose of corticosteroids, e.g. dexamethasone 16 mg IV daily for about 5 days. ° If due to intracranial haemorrhage, do not give corticosteroids. Outpatient or primary care management • Ask the patient about the nature of the headache and whether he or she has had a seizure. • Give paracetamol or ibuprofen. • Give nasal decongestants if paranasal sinus congestion is suspected. • Refer to the hospital if the patient fails to respond. Home care • The patient should rest. • The patient should try self-steaming, using a basin with hot water (but warn them to be careful of being burned by the water). • The patient should take an over-the-counter pain medicine, e.g. paracetamol. • Advise patients to seek medical help if the headache is not responding to treatment.

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10.10c Neurological problems: seizures (without meningism or fever)1 In this section: 10.10c.1 Clinical approach to a patient with seizures 10.10c.2 Consider the likely differential diagnosis (with DDx table) • Seizures without meningism or fever

Seizures result from a number of different causes and are associated with a variety of conditions. Taking a good history is essential for all patients presenting with seizures, as it helps determine a possible cause and guides your management approach. An eyewitness account is essential for determining whether the episode was in fact a seizure. Injury to the brain, such as trauma, infection, toxin damage, drug withdrawal, severe hypertension, and mass lesions with pressure effect can all result in seizures. Epilepsy is deﬁned as two or more seizures in a patient without a reversible condition. Epilepsy may be due to a structural brain abnormality or previous brain damage. However, in many cases, the cause is unknown (idiopathic). Acute causes of seizures must be excluded before a diagnosis of epilepsy is made.

10.10c.1 Clinical approach to a patient with seizures Step 1: Perform Quick Check. Ensure that there are no serious or life-threatening conditions. Use Quick Check for the emergency management of convulsions remembering to protect the airway and keep the patient away from danger. DO NOT put anything into the mouth. Remember to check glucose and consider pregnancy in women. Step 2: Take a history and examine the patient. An eyewitness account helps establish whether the patient has had a seizure. Determine the type of seizure, and whether this is the ﬁrst episode. Examine the patient for a possible cause. If you suspect meningitis (fever, neck stiffness), proceed to Section 10.10b Headache. Step 3: Assess the patient’s HIV status. HIV infection alters the differential diagnosis of seizures. Step 4: Consider a differential diagnosis using the DDx table. * See DDx: Seizures without meningism or fever, on next page. Step 5: Perform investigations. Bloods, lumbar puncture, and CT scanning are useful in helping to ﬁnd a cause for the seizure. Always ask yourself whether a LP or CT scan will aid diagnosis and management. Step 6: Initiate treatment and monitor the patient’s response. After initial emergency management of the convulsing patient, further management of seizures will depend on the differential diagnosis and the likely cause. See the management approach below.

1 mhGAP Intervention Guide for mental, neurological and substance use disorders in non-specialized health settings. WHO, 2010. Available at http://www.who.int/mental_health/evidence/mhGAP_intervention_guide/en/ index.html

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History • Determine if the patient had a seizure. ° Ask an eyewitness if someone else was present at the time of the episode. • Obtain a description of the event: ° the type of seizure (parts of body involved, generalized or focal) ° whether there was loss of consciousness ° loss of bladder or bowel control. • Take a medical history to determine: ° associated headache, fever, neck stiffness ° history of previous seizures and possible precipitating factors and events ° other illnesses – HIV infection, renal dysfunction, hypertension ° medications including antiepileptics, antidiabetic agents, antiretrovirals ° toxin exposure ° alcohol or drug use or withdrawal ° prescription drug overdoses ° use of traditional remedies or medicines ° other toxins (organophosphates, cleaning liquids) ° current pregnancy.

Examination • Look for evidence that a seizure occurred (bitten tongue, soiled clothes, postictal mental state). • Conduct a focused neurological exam to look for possible cause. • Assess the following: ° altered conscious state (AVPU/GCS) ° localizing signs ° papilloedema ° meningeal signs (see Section 10b Headache for details). Assess the patient’s HIV status HIV infection inﬂuences the likely differential for seizures. There are a number of opportunistic infections that can present with seizures, and it is important to consider HIV infection when investigating a patient with new onset seizures.

10.10c.2 Consider the likely differential diagnosis Assess whether the seizure is related to a systemic illness or condition, to an intracranial lesion or infection, or is part of an ongoing chronic seizure pattern. Consult with the relevant section of the DDx table below.

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DDx: Seizures without meningism or fever* Condition In favour criteria

Seizures as part of a systemic illness or condition Cerebral malaria see Section 11.25 Fever Positive smear or rapid malaria test Hypoglycaemia Living in or travelled to an endemic area Sudden onset repeated seizures Use of diabetic medication Unresponsive or confused Responds to administration of glucose BP >180/110 mmHg Confusion Fundoscopy – sclerosis, exudates, haemorrhages, papilloedema Pregnant 2nd or 3rd trimester BP >140/90 Oedema or anasarca Visual disturbances, confusion Urine – proteinuria Lab – increased uric acid, increased urea, increased Cr, high ALT/AST, low platelets Recent illness, e.g. diarrhoea Electrolyte disturbances, e.g. hypoNa+ hypoMg++, hypoCa++, and uraemia Known history of substance abuse History of cocaine, amphetamine, ecstasy, or other Track marks at injection sites Pinpoint or dilated pupils On tricyclic antidepressants (TCA) History of alcohol use Tremor Other evidence of chronic liver disease

Hypoglycaemia see Quick Check and Section 3.4 Hypertensive encephalopathy

Eclampsia see Section 2

Metabolic disturbances see Section 5.2 Overdose (drug or prescription) see Section 3.6

Alcohol withdrawal see Section 3.7

Seizures due to intracranial infection or lesion Brain abscess see Section 10.10a Fever, headache Local spread: from sinuses, ear, teeth – discharging ear, tender mastoid, tender bridge of nose, dental caries, haematogenous spread. e.g. from lungs, heart, skin, abdomen Fever Headache Neck stiffness Lethargy and altered mental status Focal neurological deﬁcit Papilloedema Tremor Onset over days to weeks Focal signs Impaired level of consciousness CD4 less than 100 CT scan – single or multiple ring enhancing lesions

Meningitis see Section 10.10b Viral encephalitis, e.g. herpes simplex

Toxoplasma encephalitis see Section 11.40

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Condition Masses (lymphoma, tuberculoma, tumours) Trauma

In favour criteria Insidious onset Cranial nerve palsies, mental status change Focal neurology History of trauma or whiplash injury Contusions or lacerations on head or face X-ray or CT scan evidence of trauma

Chronic, recurrent seizures Neurocysticercosis see Section 11.7 Cognitive deﬁcits Personality changes CSF – high WBC, eosinophils CT – multiple calciﬁed cysts active ﬂuid ﬁlled cysts Known history of epilepsy Previous history of seizures Family history of epilepsy No reversible causes found

Epilepsy (see below)

* Consider other causes of seizures: schistosomiasis, Bartonellosis (cat scratch disease), African human trypanosomiasis. See Section 11 Multisystem diseases list for details on these diseases.

Perform investigations For all convulsing patients, take: • blood glucose ° Give IV glucose D50, 25–50 ml if unable to test. See Quick Check page 41, Vol.1. Do investigations according to the differential diagnosis: • malaria microscopy (if not immediately available, RDT can be performed while waiting for the result of the blood smear); • electrolytes: ° Electrolyte disturbances can cause seizures (see Section 5.2.2). Measure electrolytes if available. • CSF analysis (see Section 10.10b Headache): ° if you suspect blood or pus (i.e. subarachnoid bleed or meningitis). Note: Do not delay antibiotic therapy if meningitis is suspected and you are unable to do a CSF analysis.

Often CT scans are not widely available. If CT is available at a referral centre, refer the patient for a CT in the following circumstances: • unexplained neurological ﬁndings • intractable or worsening epilepsy (in a patient who is compliant) • onset of seizures late in life (where a cause is unclear). Treatment Acute seizure control – see Quick Check page 21, Vol. 1 and Section 3.5 for the management of a convulsing patient. • Identify and treat reversible causes (blood glucose, electrolytes, blood pressure, infection, drug overdoses).

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After acute seizure control, a decision needs to be made regarding ongoing management. Management of seizures with no apparent cause depends on the history and number of episodes A patient presents having had 1 or 2 seizure episodes but now looks completely well. What should be done? • Do not treat a ﬁrst episode seizure. ° The risk of second seizure is less than 50%. ° Are you sure that in fact the patient really had a seizure? ° Wait to see if another or others occur. A patient presents having had at least 2 convulsions in the last year (recurrent). • Investigate if there are unexplained neurological or physical ﬁndings. • Treat any underlying cause. • Start antiepileptics. Monotherapy with any of the standard antiepileptic drugs: • carbamazepine: start 100–200 mg once daily, maintenance at 400–1400 mg daily • phenobarbital: start 60 mg daily, maintenance at 60–180 mg daily • phenytoin: start at 150–200 mg daily, maintenance at 200–400 mg daily • valproic acid: start at 400 mg, maintenance 400–2000 mg daily (should be considered in children and adults with convulsive epilepsy) However, given the costs of these drugs, phenobarbital may be considered as a ﬁrst option. In some settings its availability is constrained by regulatory issues. Carbamazepine might be considered with partial onset seizures. Phenobarbital is a good antiepileptic but interacts with antiretrovirals (NNRTI, PIs) to lower drug levels via the cytochrome P450 system in the liver. Valproic acid is a good alternative as it does not interact with antiretrovirals. However, it is expensive. It should be used in patients who are already on ART and are to be started on antiepileptics. Valproic acid and the use of multiple drugs to control seizures should be avoided in pregnant women. A patient with a history of seizures in the past presents after 2 years of being seizure-free. • In this circumstance, the decision to withdraw or continue antiepileptic drugs (AEDs) should be made after consideration of several clinical, social, and personal factors, and with the involvement of the patient and the family. • Among clinical factors, those discouraging treatment withdrawal include: ° presence of an underlying neurological condition; ° epilepsy syndrome with high potential for seizure relapse (e.g. myoclonic epilepsy or any symptomatic epilepsy);

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° history of high seizure frequency or status epilepticus. • Social and personal factors play a role in the ﬁnal decision: ° patient preference; ° extremely infrequent seizures; ° occupational stigma and psychological effects of continued AED use. Additional intervention details • Psychological treatments such as relaxation therapy, treatments based on CBT principles, psycho-educational programmes, and family counselling may be considered as additional treatments for epilepsy. • People with epilepsy can lead normal lives. They can marry and have children. • People with epilepsy can work in most jobs. However, they should avoid certain jobs, such as working with or near heavy machinery. • People with epilepsy should avoid cooking on open ﬁres and swimming alone. • People with epilepsy should avoid excessive alcohol and any recreational substances, sleeping much less than usual, or going to places where there are ﬂashing lights. • National laws related to the issue of driving and epilepsy need to be observed.

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10.11 Approach to patients with mental health problems In this section: 10.11.1 Clinical approach to mental health problems • History and physical examination • Approach to good clinical practice and balanced care • Special considerations in adolescents 10.11.2 Suicide and deliberate self-harm assessment and management • Suicide risk assessment • Management of the suicidal patient • Pharmacotherapy in patients with suicide risk 10.11.3 Abnormal behaviour or thinking (with DDx table) • Assessment of abnormal behaviour • Delirium • Intellectual disability in adolescents and adults • Dementia 10.11.4 Psychosis • Deﬁnitions of brief and persistent psychotic disorders • Clinical management of psychosis not accompanied by mania or severe depression • Use of antipsychotic medications: some basic principles and cautions • Considerations for long-term antipsychotic therapy 10.11.5 Bipolar disorder • Psychosocial interventions in bipolar disorders • Pharmacologic management of bipolar disorders 10.11.6 Sad or low mood including depression (with DDx table) • Assessment of patients with sad or low mood or depression • Depressive symptoms due to medical conditions • Depressive symptoms due to adverse life events • Acute management of depression • Use of antidepressant medications: some basic principles and cautions • Use of antidepressant medication in the management of a depressive episode (moderate to severe) • Management of severe depression with psychotic symptoms 10.11.7 Anxiety • Assessment and diagnosis of anxiety • Management of anxiety • Psychotropic therapy for anxiety • Making a speciﬁc anxiety disorder diagnosis (with DDx table) • Management of speciﬁc anxiety disorders Appendix 1 Psychotherapy and mental health counselling Appendix 2 Medical conditions to consider before starting treatment for mental disorders and when patients do not respond to initial psychiatric therapy

Importance • Mental health problems are as disabling as physical problems, but their treatment often is overlooked or delayed. • Mental health disorders are very common in primary care populations. • Mental health problems frequently coexist with other medical and physical disorders. • Consider mental health problems if there are unexplained medical symptoms, recurrent multiple complaints, or sexual dysfunction.

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10.11.1 Clinical approach to mental health problems Symptoms that alert the clinician to the possibility of a mental disorder Any of the following signs or symptoms can indicate the presence of a mental disorder. • A notable change in mental status. • The development or new onset of unusual or bizarre behaviour. • A diminished level of functioning or symptoms in one or more of the following areas: ° self-care, such as bathing, dressing, eating ° family relations – spouse, children, relatives ° attendance or performance at work or school ° doing housework or household tasks ° social activities, seeing friends ° remembering things ° subjective distress (sadness, fear, anxiety, irritability) ° agitation, outbursts of anger, potential for violence, homicidal thoughts ° suicidal thoughts or recurrent thoughts of death ° disturbed sleep and appetite ° diminished concentration, impairment in complex thinking, difﬁculty in learning new tasks ° emotional numbing or lack of a full range of emotions ° delusions and hallucinations ° confusion. As outlined in the steps below, the clinical approach to assessing these symptoms begins by ensuring the patient’s safety and then excluding any life-threatening or signiﬁcant medical conditions.

Clinical approach to all patients Step 1: Ensure the patient’s safety. See Section 10.11.2 and note the guidelines for managing suicidal, violent, or agitated patients. Step 2: Ensure that the patient does not have any life-threatening medical conditions, especially delirium, or any other signiﬁcant medical conditions. Use Section 3.4 – the approach to the severely ill patient, and follow the guidelines for decreased level of consciousness or confusion or intoxication or agitation. Step 3: Take a present history from the patient and family. • Assess symptoms of abnormal behaviour and sad or anxious states of mind. • Assess the impact on function. • Assess stressful life events and recent losses. • Ask about drug and alcohol use. • Ask for treatments received for the presenting problem and the response to it. Step 4: Take a past history from the patient and family. • Has the person had similar symptoms in the past? • Is there a history of psychiatric hospitalizations? • Is there a history of past use of psychotropic medication? • What was the response to treatment and mental health interventions? • Is there a history of suicide attempts or violence toward others? • Is there a history of exposure to traumatic events? • Is there a history of alcohol or substance use? • Is there a childhood history of learning or developmental disabilities?

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Step 5: Perform a mental status evaluation. Assess: • appearance and behaviour • orientation • speech • mood quality, range and appropriateness of emotions • thinking processes and clarity of content • perceptual abnormalities • suicidal ideation, intent, or plans • violent or homicidal ideation, intent, or plan • cognitive functioning • awareness of illness and need for its treatment. Step 6: Conduct or review baseline investigations. Ask yourself: • Have I considered underlying medical conditions and side-effects of medication or home remedies? • What is the person’s HIV status? • Have I considered alcohol or substance use or withdrawal? • Have I reconsidered delirium? If you think the patient may have delirium, use Section 3.4. Step 7: Determine whether the patient is experiencing abnormal behaviour or a sad or anxious state of mind. • If both abnormal behaviour and a sad or anxious state of mind are present, assess abnormal behaviour ﬁrst. Step 8: Based on your assessment and classiﬁcation, institute appropriate treatment. • Based on steps 1 and 2, consider whether hospitalization or other urgent mental health intervention is needed. • Provide the patient and family with counselling and psycho-education (see Appendix 1). • Enlist psychosocial support (family, friends, peers). • Institute psychotherapies as available and appropriate (see Appendix 1). • Give medication as available and appropriate. • Assess for long-term care referral as available and appropriate. Step 9: If the patient does not respond to the initial course of psychiatric treatment, then reconsider assessment for medical conditions (see Appendix 2). Step 10: If the patient continues to have a poor response to treatment at a second level care facility, refer to specialty care for: • clariﬁcation of the diagnosis • the development of an optimal treatment regimen • stabilization of the patient. Back-referral from specialty care with suggestions for further management is often the most efﬁcient and affordable means for continuing the patient’s treatment.

History and physical examination Start by taking a good history Enquire about the symptoms that are common to many mental disorders and that may alert the provider to the presence of a mental health concern. Whenever possible, and after obtaining consent to do so from capable patients, include family members and friends when obtaining this history.

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Important elements of a history • The time of onset of the current episode. • Type and severity of the symptoms. • Current medical problems or diagnoses. • Decrease in the level of functioning, including social isolation and decreased productivity. • Precipitating stressful life events. • Past or recent exposure to traumatic events. • Occurrence of gender-based or domestic violence. • Current medications or home remedies, particularly those that have been initiated recently. • Personal history of drug or alcohol abuse. • Family history of drug or alcohol abuse. • Personal history of prior mental disorder and treatment. • Family history of mental disorder and treatment. • Available social and family support. Co-morbidity of mental disorders with each other • Co-morbidity is common because the presence of one mental disorder increases the risk for other mental disorders. • Co-morbid alcohol or substance use disorders increase the complexity of treating other mental health symptoms and disorders. Treatment for both disorders is required. • Many patients do not ﬁt neatly into diagnostic categories. In those cases, treatment is often targeted to symptoms. • Use the following hierarchy when symptoms of multiple disorders are present. ° If patient is actively using alcohol or substances, reassess symptoms after patient is no longer intoxicated (see Section 17 Substance use). ° If the patient is withdrawing from alcohol or other substances, provide medical care for withdrawal, and reassess symptoms (see Section 17 Substance use). ° If the patient has abnormal behaviour and a sad or anxious state of mind, treat abnormal behaviour as the primary condition and then address the sad or low mood. ° If the patient has a sad or low mood and an anxious state of mind, treat the sad and low mood as the primary condition. Co-morbidity of mental disorders with medical conditions • Co-morbidity is common between mental disorders and medical conditions, and each increases the risk for the other. • When compared to the general population, people with mental health disorders have increased morbidity and mortality from medical conditions. • As people age or acquire medical conditions, mental and medical disorders commonly are found to coexist.

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Approach to good clinical practice and balanced care Management of patients with mental health disorders involves the provision of a supportive, safe, and healing environment and the development of a trusting and therapeutic working relationship. The way in which this environment is created will vary across settings depending on resources and local approaches to mental health care. Non-specialist health-care providers should acquire appropriate knowledge and skills for, and follow good clinical practices in, their interactions with people with mental, neurological, and substance use disorders and their families. These should include the following: • attentive or active listening; • effective and cultural, language, or gender-sensitive communication, including communication with behaviourally disturbed, anxious, and withdrawn patients; • obtaining important psychosocial information (including family, living, ﬁnancial and social circumstances) from the patient and family; • assessing psychosocial stress; • being non-judgemental towards patients and families; • providing adequate privacy in interactions with patients and families; • planning treatment in consultation with the patient and family, keeping in mind their preferences; • providing appropriately detailed information and advice in a supportive manner; • communicating a realistic hope for better functioning and recovery; • responding sensitively to the disclosure of private and emotional events (such as sexual violence or suicide attempts, especially where illegal); • providing information on the patient's health status and diagnosis in a clear, accurate, empathetic, and culturally appropriate way, keeping in mind the patient's preferences, and in consultation with the family; • monitoring progress and encouraging self-monitoring of symptoms; • monitoring adverse effects of any treatment; • facilitating necessary follow-up and treatment continuation; • facilitating necessary specialist referral; • facilitating necessary linkages with community-based supports. Non-specialist health-care providers should ensure the protection of and respect the rights of people with mental, neurological, and substance use disorders and their families. This should include the following: • respecting the rights of patients and families within the health-care facilities • obtaining full and informed consent for all diagnostic and treatment interventions • observing the conﬁdentiality of patients and promoting their participation in all aspects of their treatment. Psychosocial support and psycho-education are helpful interventions in all mental health disorders. Psychotherapies are often effective in treating speciﬁc mental health symptoms and disorders. Depending on the resources and expertise that exist, psychotherapy may be delivered in individual or group settings. Psychotropic medications, alone or combined with psychotherapies, have been shown to be effective in treating many mental health disorders. Many mental health disorders have a chronic and recurring course and require longer term approaches to care, including psychosocial rehabilitation, to minimize disability.

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General principles in prescribing psychotropic medications • Weigh the effectiveness of the medication in reducing symptoms against the impact of adverse side-effects. • Keep in mind that the metabolism of psychotropic medications can vary by race and ethnicity, and, within any given group, the metabolism of psychotropic medications can vary widely among individuals. • The elderly and medically ill often require lower doses than younger, physically healthy adults. • Ensure that medication management adheres to local principles of informed consent, including a determination of the patient’s capacity to make treatment decisions. • Assess the patient’s acceptance of the treatment and anticipate the possibility of non-adherence. • Manage non-adherence with a non-judgemental approach. • It is best when a family member or friend can help a patient with medication management. However, it is essential that a capable patient consents to communication with those family members or friends. • Explain the following to patients and, as appropriate, family members or friends: ° the symptoms may not immediately respond to the medication; ° medication side-effects often diminish or disappear over time; ° adherence to psychotropic medications over time is required to maintain a therapeutic response; ° medications that have been used for more than several weeks should be tapered rather than abruptly stopped, to reduce discontinuation symptoms and relapse risk.

The categorization of mental health symptoms can be confusing and overwhelming to the busy clinician. In this Section, a simpliﬁed approach is presented based on the differential diagnosis of two main categories, abnormal behaviour (which is characteristic of possible delirium, dementia, intellectual disability, or psychosis) and sad or anxious states of mind (which may indicate a mood or an anxiety disorder). It is anticipated that this will enable more efﬁcient assessment and diagnosis of major mental disorders by non-specialist clinicians. The following algorithm illustrates where speciﬁc symptoms are addressed in these guidelines. Manage suicide or deliberate self-harm (see Section 10.11.2) Consider the patient’s symptomatic picture

Agitation, frightening, or unusually impulsive behaviour? Unkempt appearance and odd ways of relating to others or odd mannerisms? Disorganized or strange speech, thoughts, or behaviour? Reporting or responding to hallucinations (e.g. reacting to false or imagined perceptions)? Reporting or responding to delusions (e.g. ﬁxed false beliefs)? Yes Refer to 10.11.3 Abnormal behaviour No Sad or low mood? Fatigue, loss of energy, tiredness? Loss of interest or pleasure? Guilt or loss of self-conﬁdence? Loss of sexual desire? Disturbed appetite (weight loss or gain)? Feeling tense, anxious, excessively worried, or frightened? Unexplained somatic symptoms? • aches and pains • tingling, numbness (e.g. pins and needles sensations) • shortness of breath (e.g. sense of suffocation) • palpitations • gastrointestinal distress. Reliving past traumas in thoughts, images, dreams, or acts?

Refer to 10.11.6 Sad or low mood including depression

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Special considerations in adolescents Adolescent mental health1 Adolescence is a time of rapid physical, psychological, and social changes that can be accompanied by anxious, sad, and angry thoughts and feelings. But if symptoms persist, become strange or abnormal, or prevent a teen from being able to carry out their usual activities, including school work or healthy socialization, this may be an indication of a mental health disorder. Points to consider regarding adolescent mental health • Adolescence is both a common time of developmental stress and a common time of onset of mental disorders. Differentiating between the two can be challenging. Adolescents can experience any of the conditions mentioned in this Section; however, their presentation may vary from the adult presentation. • Educating adolescents and their families about the normal development of teens and the signs of mental health problems is critical for preventing, identifying, and treating mental disorders. • Adolescents are often reluctant to discuss substance use, sexual activity, suicidal ideation, or conduct problems with parents and adults. Health-care workers can best overcome this barrier by creating youthfriendly, trusting, and conﬁdential relationships with teens. Share information with family members and others only with the adolescent’s permission. • Finding an individual identity and separating from family can cause turmoil and the rejection of parental advice. But difﬁcult behaviours may also reﬂect mental health problems that can put young people at higher risk for abuse and neglect, suicide, substance abuse, school failure, violence, and health-jeopardizing impulsive behaviours. • Teens who have experienced sexual and physical abuse are at increased risk for the onset and persistence of suicidal behaviour and mental health problems. Social isolation and academic failure, bullying, and harsh or humiliating punishments may also be tied to adolescent depression and anxiety. • Alcohol and drug use are common behaviours in adolescents. Concurrent substance misuse can worsen mental health problems and render standard mental health interventions less effective. Concurrent treatment of both substance use and other mental disorders is the ideal way to offer care.

10.11.2 Suicide and deliberate self-harm assessment and management2 • Suicide is the act of deliberately killing oneself. • Self-harm is the intentional injury or poisoning of oneself, which may or may not have a fatal outcome. This is generally a sign of serious underlying mental disorder even when the intent is not suicide. For poisoning see Section 3.8. Regardless of the diagnosis, an assessment for risk of suicide should always be performed. Asking about self-harm does NOT provoke acts of self-harm. It often decreases anxiety associated with thoughts or acts of self-harm and helps the person feel understood. Attempt to establish a therapeutic working relationship with the patient and then directly ask about suicide and self-harm behaviours. • Do you feel that you would be better off dead?

1 Derived from Adolescent Job Aid. WHO, 2010. Available at http://www.who.int/child_adolescent_ health/documents/9789241599962/en/index.html 2 mhGAP Intervention Guide for mental, neurological and substance use disorders in non-specialized health settings. WHO, 2010 and mhGAP Evidence Resource Centre. Available at http://www.who.int/mental_health/ evidence/mhGAP_intervention_guide/en/index.html. The mhGAP Guidelines and the mhGAP-IG will be reviewed and updated in 5 years. Any revision and update before that will be made to the online version of the document.

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• Do you have thoughts of hurting yourself? • Have you ever attempted suicide? • Why did you want to hurt yourself?

Suicide risk assessment It is a difﬁcult task to accurately predict an individual patient’s suicide risk. Factors that suggest increased risk include: • Psychiatric disorders (generally depression, alcoholism, and personality disorders). • Physical illness (terminal, painful or debilitating illness, AIDS). • Previous suicide attempts. • Family history of suicide, alcoholism, or other psychiatric disorders. • Divorced, widowed or single status. • Living alone (socially isolated). • Unemployed or retired. • Bereavement in childhood. • If the patient is under psychiatric treatment, the risk is higher in: ° those who have recently been discharged from hospital ° those who have made previous suicide attempts. • In addition, recent life stressors associated with increased risk of suicide include: ° marital separation ° bereavement ° family disturbances ° change in occupational or ﬁnancial status ° rejection by a signiﬁcant person ° shame and threat of being found guilty. The suicide assessment should include the assessment of: • current suicidal thoughts and plans • characteristics of any attempt, past or present • the presence of a severe mental disorder • the presence of substance intoxication or disorder • risk factors for suicide as noted above • available family and psychosocial supports and the patient’s capacity to cope with difﬁculty.

Assessing suicide risk through questions and observations 1. Assess whether the person has current suicidal thoughts • Questions ° Do you feel unhappy and hopeless? ° Do you feel unable to face each day? ° Do you feel life is a burden? ° Do you feel life is not worth living? ° Do you feel like committing suicide? • Further questions ° Have you made any plans to end your life? ° How are you planning to do it? ° Do you have the means in your possession to carry out suicide (pills, guns, poisonings, or other methods)? ° Have you considered when to do it? • Ask the patient or accompanying friends or family about self-harm. 2. Assess the characteristics of any attempt was made • Was the attempt planned or was it impulsive? • Did the person let anyone know or leave a suicide note? • Were steps taken to avoid discovery?

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• • • • •

Did the person attend the hospital or clinic of their own volition? What method was used? How does the patient feel now about the attempt? Look for signs of poisoning or intoxication or signs of self-injury. Medically treat as necessary. ° Ensure that the person is closely monitored to prevent further selfharm. ° Do not leave the patient alone or unsupervised.

3. Assess whether there is an imminent risk of self-harm or suicide • Ask the patient and carer about current thoughts or plans to commit suicide or self-harm • Ask about history of thoughts or plans of self-harm in the past month or acts of self-harm in the past year. • Ask about access to means for following through on those thoughts or plans. • Assess for current mental disorder, suicidal ideation, and intent. • Look for signs of emotional distress, hopelessness, agitation, uncommunicative behaviour, social isolation. 4. Assess coping resources and activate psychosocial support • What coping mechanisms does the person have? • What are the family and social supports? • What is the service support?

Management of the suicidal patient • If a suicide attempt has been made, observe for signs of self-injury and urgently treat associated medical complications. • Remove means of self-harm. • If a suicide attempt has been made or a plan or threat exists for imminent suicide: ° do not leave patient alone; ° talk gently with the patient; ° keep the patient in a secure and supportive environment in the facility – if possible, offer a separate quiet room while waiting; ° assign a named staff member or family member for continued monitoring to ensure patient safety; ° attend to the patient’s mental state and emotional distress. • Management of the medical consequences of an act of self-harm may require admission to a general (non-psychiatric) hospital. In these cases, when admission for medical management is done, close monitoring is necessary to prevent subsequent self-harm in the hospital. • Assess for underlying mental disorders and start appropriate treatment. • In situations where there is imminent risk of serious self-harm, urgent referral to a mental health service is recommended. However, if such a service is not available, activate psychosocial support. Family, friends, concerned individuals, and other available resources should be mobilized to ensure close monitoring of the individual as long as the imminent risk persists. • Consult a mental health specialist if available. Admit to a psychiatric hospital or mental health service (if possible) if needed to treat an underlying severe mental health disorder.

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• Assess for and begin treatment of co-morbid problems: ° physical (including chronic pain, epilepsy) ° mental disorders and substance use – follow this Section as well as Sections 16 and 17 ° emotional problems. • When the patient is well enough for conversation, follow good clinical practice – spend enough time, listen effectively, offer emotional support, and be sensitive to the patient’s distress. • Use counselling, psycho-education and psychotherapies. • Involve carer or family support as needed and as appropriate for the patient. ° Provide psycho-education and support for carers and family. ° As caring for a suicidal patient can be extremely stressful, provide support to the carers and family. Emphasize that they should avoid hostility or aggression, even if frustrated. • Work to understand and lessen suicidal feelings; explore reasons to stay alive. • Focus on positive strengths and build on coping resources. • A structured problem-solving approach should be considered as a treatment for persons with a history of acts of self-harm. • Provide information about community-based services and patient support or self-help groups and facilitate access to these services. • Ensure careful follow-up, including the involvement of carers and community health services. Regular contact with a non-specialized health worker is recommended. The contact should be more frequent initially and less frequent as the patient improves. • Continue to assess suicide risk until the patient is stable. • The individual, family, and relevant others should be advised to restrict access to the means for self-harm (e.g. pesticides and other toxic substances, medication, ﬁrearms) as long as the individual has thoughts or plans of selfharm. Advise the family and relevant others that asking about suicide will often lessen the anxiety of the patient and they may feel better understood. • Follow up patient over time with regular contact and ensure continuity of care.

Pharmacotherapy in patients with suicide risk • Treat underlying mental disorders and substance use disorders. • Special considerations in patients with suicide risk include the following: ° Medication may give access to a means of suicide or cause side-effects, such as restlessness, that may increase the risk of suicide. ° Choose drugs with fewer side-effects to ensure compliance. • Choose medications that are less dangerous in overdose (e.g. selective serotonin re-uptake inhibitors instead of tricyclic antidepressants). • Dispense small quantities of medicines (e.g. not more than 1 week’s worth while the patient is still suicidal). • As appropriate, involve relatives in the care and dispensing of medications. • Maintain close follow-up and monitoring of the patient.

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10.11.3 Abnormal behaviour or thinking Use this Section if the presenting symptoms include: • agitation, frightening or unusually impulsive behaviour; • unkempt appearance and odd ways of relating to others, or odd mannerisms; • disorganized or strange speech, thoughts, or behaviour; • distortions of thinking and perceptions; • reporting or responding to hallucinations (e.g. reacting to false or imagined perceptions, such as talking to imaginary people as a result of hearing voices); • reporting or responding to delusions (e.g. ﬁxed false beliefs, such as hiding from imaginary persecutors); • severe self-neglect; inability or disinterest in caring for self; • inappropriate or narrowed range of emotions; • impairment in cognition, memory, and attention.

Assessment of abnormal behaviour Accurate differentiation among the possible causes of abnormal behaviour, such as delirium, dementia, intellectual disability, or developmental disorders and psychosis is essential. Although these disorders can present with similar signs and symptoms, the management is different. Delirium is a period of acute confusion that is attributable to a medical condition, and treatment involves diagnosis and management of the underlying medical condition. Dementia is a chronic degenerative disease of the brain that typically worsens over time. Progression of some causes of dementia may be partially reversed with treatment (e.g. antiretroviral treatment may halt the progression of, or partially reverse, HIV dementia). Intellectual disability or developmental disorders have a childhood onset and will beneﬁt from the provision of family psycho-education and communitybased rehabilitation. Psychosis is a sign of a severe mental disorder in which contact with reality is lost or highly distorted, and may be found in schizophrenia, bipolar disorder, or brief reactive psychosis. Patients presenting with abnormal behaviour and fever likely have an underlying medical condition that must be identiﬁed and treated. In these patients, refer to Section 10.1. Some patients displaying these behaviours may be difﬁcult to assess. It may be necessary to get corroborative information from family, friends, or other informants. The table that follows presents a differential diagnosis of disorders in which patients display abnormal behaviours. See also Appendix 2.

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DDx: Behaviour that is strange, bizarre, agitated, or atypically impulsive: key symptoms and screening questions or observations Disorder Delirium see Section 3.4 Key differentiating symptoms Onset over hours to days Fluctuating level of consciousness within the day (e.g. confused one minute, clear-minded the next, occurring throughout the day and often worsening at night) Prominent difﬁculties in focusing, shifting, or maintaining attention Difﬁculty orienting to place, time, and sometimes person Evidence of underlying cause based on physical examination or abnormal laboratory investigations Fever may be present Symptoms of delirium (as above) Chronic use with sudden discontinuation of: • alcohol, substances, or medications with addiction potential (e.g. diazepam) Seizures Tremulousness Unstable vital signs Visual hallucinations Acute onset History of alcohol or substance use Screening questions and observations Patient appears confused, inattentive, incoherent. Patient appears to be agitated or withdrawn. Ask: Where are you? What day is this? Where possible, a complete screening mental status examination should be administered.

Delirium due to alcohol or sedative withdrawal see Sections 16 Alcohol, 17 Substance use

See delirium screening questions and observations above. Ask: Did you recently stop drinking or using any other substance or medication? Consider informant interview about substance use history. Ask: What did you drink or take today? Consider informant interview about substance use history. Interview informants. In moderate or severe disabilities, patients often look or behave atypically. This may include: • unusual physical features, expressions, or gestures. • unusual social behaviours.o • obvious cognitive impairments. Patient may be agitated, confused, or withdrawn. Level of consciousness does not show rapid ﬂuctuations. Forgetfulness is a prominent feature. Ask: Where are you? What day is it? What year is it? Mention 3 objects – e.g. shoe, dog, chair. Ask patient to repeat immediately and in 5 minutes. If possible, use a cognitive screening tool.

Intoxication from alcohol or other substance see Section 17 Substance use Intellectual disability (may also be called developmental disability, learning disability, or mental retardation)

Childhood onset Failure to achieve usual childhood milestones Problems developing normal social interactions Problems learning in school May be associated with abnormal faces, sensory disabilities, and physical or motor disorders Gradual onset Deﬁcits in intellectual domains, in the absence of an alteration in consciousness, with impairment of mental functioning including: • forgetfulness • misplacing things • difﬁculty in performing automatic tasks (such as carrying out daily routines) • impaired speech or word-ﬁnding difﬁculty • change in personality or behaviour • presence of neurological symptoms • unsteady gait, loss of balance • impaired hand–eye coordination • slowed response time • leg weakness • dropping things • tremors, poor handwriting • decline in motor skills • incontinence

Dementia

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Dementia due to HIV infection (HIV-associated dementia) see Section 13

Symptoms of dementia noted above Psychomotor slowing is often present Dementia onset at younger age than normally expected HIV-positive

If HIV status is unknown, test for HIV infection in accordance with local law. Look for signs of HIV-related medical illnesses. Dementia is more common with advanced HIV disease. May have excessive animation and inﬂated self-esteem, diminished comprehension, and hypersexuality.

HSV encephalitis see Sections 10.10b and 11.15

Fever Focal neurological deﬁcits Altered thinking Personality changes – hypomania, loss of emotional control Decreased comprehension and memory Hallucinations, most commonly auditory (hearing voices of people who are not there) Delusions: false ﬁxed beliefs that may be elaborate or bizarre Disorganized thinking or speech Disorganized behaviour, occasionally to the point of inability to care for self No ﬂuctuation of consciousness Physical examination and laboratory results do not suggest an underlying medical explanation of the symptoms History of previous episode or psychiatric hospitalization Poor social and occupational functioning Often long-standing history, usually at least 6 months for schizophrenia

Schizophrenia and other psychotic conditions not otherwise noted in this table

Patient may be agitated, suspicious, frightened ,or withdrawn. Conversation with patient often elicits implausible information. Ask for elaboration in a matter-offact manner. Ask: Do you hear voices when there is no one present or speaking to you? Ask: have you been troubled by unusual experiences lately? Have you felt threatened by events or people recently? Do you believe that people are trying to harm you? Tell me more? Mood is often restricted or out of keeping with content of conversation. Interview informants. Patient is often irritable, loud, or excited. Patient may be speaking very rapidly. Patient may make grandiose statements, such as having supernatural powers or being extremely successful and wealthy when this is not the case. Patient may have slept few hours yet appear alert and energetic. Ask: Do you feel you are unusually happy or excessively irritable? Is your energy unusually high? Do you feel that you do not need any sleep? Do you feel your thoughts are racing?

Bipolar disorder: Manic phase Manic episode

Distinct period ≥1 week characterized by: • abnormally elevated or irritable mood • decreased need for sleep • elevated energy • racing thoughts • rapid pressured speech • increased sense of self-importance • excessive pursuit of risk-taking behaviours • history of previous manic episode or psychiatric hospitalization • history of depression or currently taking antidepressant medication • family history of bipolar disorder

Other psychotic disorders

Brief psychotic disorders Delusional disorder

If the patient screens positive for a particular disorder, then proceed with assessment as appropriate for that speciﬁc disorder.

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In all cases, non-specialist health-care providers should ensure the protection of, and the respect for, the rights of people with mental, neurological, and substance use disorders and their families.3 This includes the following: • respecting the rights of patients and families within health-care facilities; • obtaining full and informed consent for all diagnostic and treatment interventions; • following local mental health regulations pertaining to the assessment and management of mental health conditions; • observing the conﬁdentiality of users and promoting their participation in all aspects of their treatment.

Delirium Delayed diagnosis and management of delirium can be fatal because it often occurs as a manifestation of an underlying severe medical condition. Risk factors and causes include: • high fever from any cause (refer to Section 10.1 Fever); • advanced stages of immunosuppression due to HIV, including associated infections and malignancies of the CNS; • other severe medical conditions, including hypoxia and metabolic abnormalities (see Appendix 2); • substance use or withdrawal (see Section 17 Substance use); • intoxication from any cause, including substances of misuse and ingestion of toxins (see Section 3.8 Poisoning); • drug overdose (accidental or deliberate); • head or brain injuries; • previous episodes of delirium; • dementia, including HIV dementia; • drug interactions in patients taking multiple medications (e.g. for HIV or tuberculosis). Diagnosis of delirium • The disturbance of consciousness with reduced ability to focus, sustain, or shift attention. • A change in cognition or the development of a perceptual disturbance. • The disturbance developed over hours to days and ﬂuctuates during the course of the day, and the disturbance is caused by the consequences of a general medical condition (including alcohol or drugs, medication, or acute head injury). • Often accompanied by alterations in sleep patterns, alterations in the level of activity, including underactivity or hyperactivity with arousal and agitation, emotional instability, and poor judgement. If delirium is suspected, refer to Section 3.4.2 Delirium.

3 Convention on the rights of persons with disabilities and optional protocol. Adopted by the United Nations General Assembly on 13 December 2006. http://www.un.org/disabilities/documents/convention/convoptprot-e. pdf

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Delirium is frequently overlooked Common misdiagnoses include the following: • When patients appear hypoactive, depression is a frequent misdiagnosis for delirium. • When patients appear agitated or restless, a primary psychotic disorder is a frequent misdiagnosis for delirium. • When patients have a history of dementia, acute changes in mental status due to delirium is often overlooked.

Intellectual disability in adolescents and adults Diagnosis of intellectual disability Intellectual disability is a lifelong condition characterized by limitations in mental functioning. A person with an intellectual disability may learn and develop more slowly and may require support to assist with full functioning. Some persons with intellectual disabilities may develop mental health problems, which further compounds their functional limitations. Typically, this presents with the onset of new behaviours that the family or community cannot manage. WHO classiﬁes intellectual disability into 4 levels on the basis of functioning: mild, moderate, severe, and profound. Common signs indicating a history of delayed development beginning in childhood include: • failure to achieve usual childhood developmental milestones • problems learning self-care • problems learning in school and developing occupational skills; • inappropriate social or sexual behaviour. Coexisting conditions and differential diagnoses include: • physical disabilities and motor disorders (e.g. cerebral palsy) • epilepsy • hypothyroidism • incontinence • depression • sensory disabilities, such as impaired vision and hearing • attention deﬁcit or hyperactivity disorder • autism spectrum disorders • other psychiatric and behavioural disorders • nutritional deﬁciencies. Management of intellectual disability When an adolescent or adult with intellectual disability presents with a marked change in function or a signiﬁcant alteration in behaviour, consider the possibility of a new onset mental health disorder and treat as indicated. Among adolescents, also consider developmental issues. In particular, growing physical strength and the increasing sexual drive that comes with the onset of puberty often present new challenges to caregivers. • Discuss prior management strategies and rehabilitation efforts.

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• Advise the family about handling the presenting problem, including enlisting additional support. • Assess and treat any co-morbid medical and mental disorders. • Avoid any unnecessary psychotropic medication. If medication is required, use caution as people with developmental disorders are often more sensitive to side-effects. • Refer to educational, and rehabilitation services that are age-appropriate. When possible, look for work opportunities that match the person’s strengths. • Avoid institutionalization. • Rewarding effort, not results, is the best overall approach to help the patient and family adapt to the patient’s functional limitations.

Dementia – a decline in cognitive function including memory, thinking, and new learning Dementia is a disorder of the brain causing a decline in cognitive function that is usually progressive and chronic. It may be classiﬁed based on symptom severity and impact of impairment on functioning, as follows: • mild – independent living is possible • moderate – some assistance is needed for activities of daily living • severe – close supervision is necessary. The symptoms associated with dementia can be wide-ranging. In the degenerative forms of dementia, forgetfulness, declining mental function, and apathy (little emotion) are the most prominent features. As the disorder progresses, patients can lose their capacity to independently manage many activities of daily living. Clinicians should be aware that dementia can be distressing to patients and families. Patients with HIV are at risk for HIV-associated dementia. This underscores the importance of determining patients HIV status when they present with signs and symptoms suggestive of dementia. At a population level, the rates of severe HIV dementia have fallen considerably with the early introduction of ART that results in full viral load suppression. Among HIV-positive individuals, the likelihood of HIV dementia increases with the progression of systemic HIV disease and immunological decline. Diagnosis of dementia The 3 most common causes of dementia are: 1. Alzheimer disease 2. Vascular dementia (formerly known as multi-infarct dementia) 3. HIV dementia. HIV dementia can occur at any age, whereas Alzheimer disease and vascular dementia occur primarily in the elderly. If there is a history of progressive cognitive impairment over a 6-month period that impairs function, a diagnosis of dementia is likely. Abrupt onset of acute cognitive impairment suggests a diagnosis of delirium or a delirium superimposed on a dementia rather than dementia alone. In all cases of cognitive impairment, it is essential to correct any ongoing medical problems that may be contributing to

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the impaired cognitive status. Common co-morbidities include hypothyroidism, cardiovascular disease, sexually transmitted infections, anaemia, poor dietary intake, malnutrition, and medication side-effects. Non-specialist health-care providers should seek to identify possible cases of dementia in the primary health-care setting and in the community. Patient examination, key informant interview, and cognitive tests should be used to assist in conﬁrming these cases. For a formal dementia diagnosis, a more detailed history, medical review, and mental state examination should be carried out to exclude other common causes of cognitive impairment and decline.

Non-pharmacologic management of dementia Convey the results of the assessment with sensitivity, and help the patient and family access support that will promote independence, mobility, and function. Always attend to the safety of the patient ﬁrst. • Ensure the patient’s safety with appropriate environment and level of supervision. • Ensure that the patient is taking medications as prescribed. • Protect wandering patients, and supervise any cigarette smoking that occurs. • Use strategies to prevent falls (e.g. reduce clutter on ﬂoors, re-evaluate medications that lead to orthostatic hypotension, encourage tailored physical activity to maintain mobility). Consider cognitive interventions applying principles of reality orientation, cognitive stimulation, or reminiscence therapy for the care of people with dementia. Healthcare providers should be trained to deliver these interventions and family members should be involved in their delivery. Examples include: • reorienting the patient; • encouraging the presence of familiar objects and people; • emphasizing routines; • providing lighting that corresponds with day and night; • providing a clock and calendar in the room to help keep patients oriented to time and to the day of the week; • using memory aids; • offering activities that keep the patient’s mind alert; • ensuring that individuals who require eyeglasses or hearing aids wear these to help lessen confusion and disorientation. Interventions for health-care workers should be provided as a part of the overall management of people with dementia. • Educate family members about the nature of dementia and methods for helping patients to maintain the activities of daily living. Inform about key adaptations in the home that might foster independence and functioning. • Information should be provided to people with dementia as well as to family members and other informal carers, keeping in mind the preferences of the patients and their families. • Training of health-care workers involving active carer participation (e.g. role playing of behavioural problem management) may be indicated later in the course of the illness for carers who are coping with behavioural symptoms.

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• The psychological strain of health-care workers should be addressed with support, counselling, or cognitive-behaviour interventions. • Depression in health-care workers should be managed according to the recommendations for depression. • Where feasible, home-based respite care may be encouraged for carers of people with dementia. Consider referral for psychiatric care when: • uncertainty remains about the diagnosis; • there is accompanying depression, psychosis, mania, or substance abuse; • there are behavioural disturbances; • a need exists for consultation regarding psychotropic medications, particularly when multiple psychotropic medications may be necessary, increasing the risk of drug–drug interactions and toxicity; • complex psychosocial strategies need to be implemented.

Pharmacologic management of dementia • All individuals with dementia should receive regular medical review (at least every 3–6 months) and appropriate care. • In persons with dementia presenting with behavioural symptoms, a complete physical assessment and medication review should be performed to identify any possible underlying precipitants for these symptoms. Appropriate management of these precipitants should be offered before considering the use of psychotropic medicines and non-pharmacological interventions. • When dementia is complicated by behavioural or psychological disturbances and non-pharmacological interventions are not effective in the management of these symptoms, antipsychotic medications may be useful in treating agitation, delusions, and hallucinations. • If behavioural symptoms persist or there is a clear and imminent risk of harm to the patient with severe and distressing symptoms, the short-term use of haloperidol or atypical antipsychotic medications can be considered, preferably with specialist inputs. To the extent possible, informed consent and agreement should be obtained from the patient or carer with regard to the balance of risk and beneﬁt. • Antipsychotics have been associated with increased risk of stroke; therefore, as much as possible, they should be avoided. • When using antipsychotic medication in patients with dementia, use the lowest possible dose and increase slowly as needed. For example, haloperidol should be initiated at 0.5 mg and titrated slowly with frequent review of impact and side-effects, particularly extrapyramidal side-effects. Thioridazine and chlorpromazine should not be used due to high potential for orthostatic hypotension and anticholinergic side-effects. • Patients with dementia are often sensitive to medication side-effects and at a population level, antipsychotic medications appear to increase the risk of death in elderly patients with dementia. • In people with dementia with symptoms or signs suggestive of moderate or severe depression, the use of ﬂuoxetine may be considered. • Benzodiazepines have been shown to increase confusion and decrease concentration. As such, it is recommended that diazepam be avoided.

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In the case of HIV-associated dementia, neurocognitive impairment may be partially reversible through the use of effective ART that fully suppresses viral replication. Fully suppressive ART is the treatment of choice for the prevention and treatment of HIV dementia.

10.11.4 Psychosis2 Psychosis is a state in which a person’s grasp of reality (or reality-testing) is diminished. This may be manifested by: • hallucinations (most often auditory); • delusions; • disorganized or strange speech; • bizarre behaviour or disorganized behaviour to the point that self-care is impaired; • lack of insight (e.g. patients may not see themselves as ill or in need of treatment, family or friends may bring them); • inappropriate or narrowed range of emotions; • social withdrawal.

Deﬁnitions of brief and persistent psychotic disorders Psychotic disorders that are not attributable to an underlying medical condition can be divided into 2 categories. 1. Brief (acute) and transient psychotic disorders Disorders characterized by the acute onset of psychotic symptoms and severe disruption of ordinary behaviour. The onset of symptoms is acute, often related to a signiﬁcant stressor. The time interval between the ﬁrst appearance of any psychotic symptoms and the presentation of the fully developed disorder should not exceed 2 weeks. Usually, there is full recovery, and no evidence of an organic cause. 2. Persistent or recurrent psychotic disorders Persistent or recurrent psychotic disorders can be further broken down based on whether or not a predominant mood or affective symptoms accompany the psychosis. Schizophrenia is the most common and severe non-affective chronic psychotic illness. These disorders often begin with non-speciﬁc symptoms, such as social withdrawal, loss of interest in usual activities, apathy, and diminished functioning. They generally have their onset in late adolescence and young adult life. The most common examples of recurrent or persistent psychotic disorders with prominent mood symptoms include mania with psychotic features (as one phase of bipolar mood disorder) and a severe depressive episode with psychotic features. Diagnosis of psychosis The diagnosis of a psychotic disorder is made by the identiﬁcation of the abnormal behaviour suggestive of psychotic symptoms described above. Important risk factors for the development of psychosis include: • prior psychiatric illness • family history of psychotic illness • substance misuse, including intoxication, abuse, dependence, and withdrawal • exposure to severe stressors or traumatic events.

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In addition, psychotic symptoms may be associated with a general medical condition or medications. Examples include patients with late-stage HIV disease who may develop psychosis more commonly than people in the general population. Examples of medications that may be associated with the development of psychotic symptoms include EFV and (anabolic) steroids.

Differential diagnosis The differential diagnosis of a patient presenting with psychotic symptoms includes the following. • Delirium and dementia (see Section 10.11.3 above). • Other medical causes. ° Even after excluding delirium and dementia, psychotic symptoms may be caused by an underlying medical condition, such as the conditions described in Appendix 2. ° Although a past history of a chronic or recurrent psychotic disorder strongly suggests an exacerbation or a relapse of that disorder, a relapse can also be precipitated by a serious medical problem, underscoring the importance of evaluation for an underlying or coexisting medical aetiology. • Primary psychotic disorders, including schizophrenia, mania, and depression with psychotic features. ° See the description for schizophrenia and other psychotic disorders in the table above, DDx: Behaviour that is strange, bizarre, agitated, or atypically impulsive: key symptoms and screening questions or observations. • Auditory hallucinations are the most common hallucinations in primary psychotic disorders. Other types of hallucinations should increase the index of suspicion that there is an underlying medical problem. • Schizophrenia may present with “negative” symptoms, such as lack of emotion, lack of motivation, and paucity of thought. These symptoms may, however, be confused with the side-effects of antipsychotic medications. • Patients with chronic psychotic disorders have decreased cognitive performance and may struggle with memory, concentration, complex thinking, and learning new tasks but not to the degree seen in dementia. • People with severe and persistent mental disorders are often at higher risk of being infected with HIV and other sexually transmitted infections due to elevated rates of unsafe sexual activities, including sexual victimization, and co-morbid substance use. Even if an individual has a conﬁrmed primary psychotic disorder, consideration should be given to HIV status. • Certain symptoms not typically classiﬁed as psychotic can nonetheless be bizarre or involve a loss of reality testing, such as the repeated rituals seen in obsessive compulsive disorder and the ﬂashbacks associated with posttraumatic stress disorder.

Investigations A parallel history from family members should be taken whenever possible. Psychotic patients may have poor insight into their symptoms and may fail to report them, or, in some instances, they may conceal them.

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Clinical management of psychosis not accompanied by mania or severe depression • Assessment for the safety of the patient and others should be performed as soon as possible. • Patients should be provided with the opportunity to seek support in making decisions about their treatment when they require it. Consult local mental health laws and guidelines. • Initial hospitalization often is required for acute stabilization, especially for patients who are at imminent risk of violence or self-harm. Also, hospitalization may be needed for those with new-onset psychosis. • Assessment for an underlying medical etiology and the initiation of appropriate medical treatment are essential. • Provide psycho-education that supports the patient’s recovery. Instil realistic hope and emphasize the importance of continuing regular activities. • Support the family and provide guidance in their interactions with the patient. • Antipsychotic medication is the mainstay of the acute management of psychotic symptoms. Emphasize the importance of medication adherence to reduce symptoms and suffering. • Encourage regular follow-up care, including the management of concurrent medical conditions. Patients with chronic psychotic disorders are at increased risk of co-occurring conditions, including substance use, HIV/AIDS, diabetes, heart disease, and smoking-related illnesses. These patients require a comprehensive approach to assessment and care over and above the management of psychotic symptoms. • Negative health-care worker attitudes have been documented as interfering with the delivery of medical care It is important that health-care facilities develop training resources for health-care workers to help overcome fear and stigma associated with working with patients with psychosis. • Facilitate rehabilitation in the community. Long-term treatment of chronic psychotic disorders such as schizophrenia often require interventions based on principles of psychosocial rehabilitation, including cognitive behavioural therapy (CBT), skills building, and family interventions. These interventions should be continued as long as needed by the user and their family, and therefore should be planned and developed in a sustainable way.

Use of antipsychotic medications: some basic principles and cautions • Haloperidol or chlorpromazine should be routinely considered in individuals with psychotic disorders. • The minimal effective dose of antipsychotics should be used, paying attention to minimizing adverse effects. • Trial medication at optimum dose for 4–6 weeks before considering it ineffective. Always check for treatment adherence. • Patients on long-term antipsychotic treatment should be given adequate information and encouraged to make a choice between oral and depot preparations, especially with the view to improve adherence. Depot antipsychotics should not be used for prompt control of acute psychotic symptoms.

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• Patients on antipsychotic medicines (oral and depot preparations) should be monitored regularly for symptom relief, functioning, and any adverse effects. • Women with psychotic disorders (including schizophrenia) who are planning a pregnancy, or are pregnant or breastfeeding and require antipsychotic treatment to manage symptoms, should be treated with low-dose oral haloperidol or chlorpromazine. • Depot antipsychotics should not be routinely prescribed to women with psychotic disorders (including schizophrenia) who are planning a pregnancy or who are pregnant or breastfeeding, because there is relatively little information on their safety. General principles for using antipsychotic medications: haloperidol, chlorpromazine, long-acting injectable ﬂuphenazine Contraindications and cautions: Do not use for alcohol withdrawal. Antipsychotic medications are associated with increased risk of death in elderly patients with dementia, and associated with increased risk for seizures and blood disorders. Serious acute side-effects: • acute dystonic reaction or severe muscle spasm (give biperiden- see Section 8.4) • neuroleptic malignant syndrome, a potentially life-threatening disorder characterized by muscular rigidity, elevated temperature, and high blood pressure. Serious long-term side-effects: • involuntary muscular movements that may not be reversible (tardive dyskinesia). Educate the patient and family: • Review medication facts as relevant. • Medications are not addictive. • Warn against the use of alcohol. Haloperidol as antipsychotic In healthy adults • Initiate treatment with 1.5–3 mg once daily. • Depending on symptom severity, symptom response, and tolerability, can be titrated up to 20 mg daily. • Typical effective dose: 3–20 mg daily. • Use lowest effective dose. In elderly or medically ill patients (Including those with HIV stage 3 or 4 – these patients are very sensitive to the side-effects of haloperidol.) • Initiate treatment with 0.5–1 mg once daily. • Depending on symptom severity, symptom response, and tolerability, can be titrated up to 5 mg daily. • Higher doses may be needed, but there is a signiﬁcant risk of toxicity. • Use the lowest effective dose. Chlorpromazine as antipsychotic In healthy adults • Initiate treatment with 75 mg at night. • Depending on symptom severity, symptom response, and tolerability, can be titrated up to 300 mg daily. • Typical effective dose is 75–300 mg daily, but up to 1000 mg may be necessary in severe cases. • Use the lowest effective dose. In elderly or medically ill patients (including those with HIV stage 3 or 4) • Haloperidol is preferred because even low doses of chlorpromazine may cause severe hypotension resulting in falls.

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Fluphenazine as antipsychotic – long-acting, injectable for long-term management Other contraindications and cautions: Neuromuscular side-effects can take a long time to clear after drug discontinuation. Avoid for acute treatment because it is difﬁcult to titrate the dose in accordance with symptom response and tolerability. In healthy adults • Start with 12.5 mg deep intramuscular injection in the gluteal region. • Typical effective dose is 12.5–100 mg IM every 2 to 5 weeks. • Repeat IM injections every 2 to 5 weeks as follows: ° if the initial dose was well-tolerated and effective, continue to use that dose; ° if the initial dose was tolerated but did not control the symptoms, the dose may be increased in increments of 12.5 mg. In elderly or medically ill patients (including those with HIV stage 3 or 4) • Oral haloperidol is preferred because severe extrapyramidal side-effects may take a long time to clear after medication discontinuation. • If using injectable ﬂuphenazine, start with 6.25 mg deep intramuscular injection. • Typical effective dose is 6.25–50 mg every 2 to 5 weeks. • Repeat the IM injections every 2 to 5 weeks as follows: ° if the initial dose was well-tolerated and effective, continue to use that dose; ° if the initial dose was tolerated but did not control the symptoms, the dose may be increased in increments of 6.25 mg IM; a maximum dose of 100 mg IM may be given although such a dose is rarely required. In all adults • The length of time between injections depends on how long the medication lasts in controlling symptoms and how well the patient tolerates the medication. • Use the lowest effective dose. • Long-acting medication is particularly useful in patients who have difﬁculty complying with treatment. • If severe side-effects occur, discontinue the injections, wait until the side-effects clear, and begin an oral antipsychotic.

Considerations for long-term antipsychotic treatment In patients with full and sustained remission following a ﬁrst psychotic episode, continue antipsychotic treatment for at least 12 months after the beginning of remission. Any further continuation of antipsychotic treatment should be based on a clinical review, preferably by a mental health specialist, and taking into account the preferences of the patient, and in consultation with the family. In patients with long-term or recurrent psychotic disorders (including schizophrenia) stable for several years on anti-psychotics, treatment withdrawal may be considered, keeping in mind the increased risk of relapse, the possible adverse effects of medicines, and patient preferences in consultation with the family. Preferably, this decision should be made in consultation with a mental health professional. If medicines are withdrawn, patients and family members need to be educated to detect early symptoms of relapse, and close clinical monitoring should be done.

10.11.5 Bipolar disorder2 Bipolar disorder is characterized by recurrent episodes of mood instability throughout a patient’s adult life, usually accompanied by signiﬁcant changes in activity and behaviour. The course of the disorder is characterized by 3 phases: (i) acute mania, involving elevations of mood; (ii) depressive phases, involving

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periods of low mood; and (iii) maintenance phase, where recovery and wellness is generally preserved. Pharmacologic interventions are speciﬁc to each phase. Patients with bipolar disorder can present with marked changes in behaviour and it is important to consider the diagnosis of bipolar disorder in patients presenting with abnormal behaviour as well as in patients presenting with disturbance of mood. Clinical management involves psychosocial and pharmacologic interventions.

Psychosocial interventions in bipolar disorders • Ensure patient safety and manage concurrent medical conditions. • Provide psycho-education. Patients and families need to understand the phases of mood disturbance and how to self-monitor for extreme mood states in order to best prevent severe relapses. • Encourage a regular sleep cycle. • Encourage patient to avoid alcohol and psychoactive substances. • Help patients reactivate social networks and to seek support from family and community-based resources. • Provide regular follow-up.

Pharmacologic management of bipolar disorder (i) Acute mania (with or without psychosis) in a patient with bipolar disorder The management of acute mania requires mood stabilizer medications and often also requires anti-psychotics. Psychiatric hospitalization often is required. If the patient is on an antidepressant, it should quickly be tapered and discontinued, balancing the risks of withdrawal syndrome against the impact of the antidepressant worsening the mania. The onset of effectiveness of haloperidol is more rapid than mood stabilizers and should be considered ﬁrst in individuals with severe symptoms of acute mania, for the management of agitation. Lithium4 or sodium valproate should be considered in individuals with acute mania for mood stabilization. Carbamazepine may also be helpful in the treatment of acute mania. Carbamazepine may negatively interact with antiretroviral medications and is best avoided in PLHIV taking ART. In women planning a pregnancy, pregnant or breastfeeding, lithium and sodium valproate should be avoided. In this group, low dose haloperidol should be considered with caution. In the elderly patient, start with lower doses of medications and increase slowly. Anticipate increased risk of drug interactions.

4 See Adaptation Guide – instructions on using lithium could be added from mhGAP guidelines if lithium laboratory monitoring is available.

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(ii) Acute depression (with or without psychosis) in a patient with bipolar disorder Treatment of the depressive phase of bipolar disorder is particularly challenging as antidepressant medication may precipitate a manic or hypomanic phase if the patient is not ﬁrst adequately treated with mood stabilizing medications. Consider the diagnosis of bipolar depression if the patient presenting with a depressive episode has a known or suspected history of mania (see Table: Mood stabilizers below). • The treatment of choice for bipolar depression is a mood stabilizer agent (sodium valproate, lithium4). • Once the patient is adequately treated with a mood stabilizer, an antidepressant agent can be added to help further alleviate depressive symptoms. Patients should be informed of the risk of switching to mania before starting antidepressant medication. • Antidepressant treatment should begin at a low dose and be increased gradually if necessary. Fluoxetine should be preferred to tricyclics. Patients should be monitored carefully for early symptoms or signs of mania. Antidepressant medication should be stopped soon after remission of depressive symptoms, while the mood stabilizer continued. • Behavioural activation, lifestyle modiﬁcation and cognitive behaviour therapy should be used to help alleviate depressive symptoms. Use of these interventions in combination with a mood stabilizer may help the patient avoid the use of an antidepressant medication.

Table: Mood stabilizers For Lithium see Adaptation guide Valproic acid (sodium valproate) for mood stabilization in bipolar disorder and acute mania Contraindications and cautions: Do not use for alcohol withdrawal. Serious side-effects include: • hepatotoxicity (can be fatal) • pancreatitis • hyponatraemia from drinking excess ﬂuid • blood dyscrasias • severe allergic reaction. Educate the patient and the family: • Review cautions and side-effects. • Mood stabilizers are not addictive. • Warn against use of alcohol. In healthy adults • Initiate treatment with 500 mg at night. • Depending on symptom severity, response, and tolerability, increase the dose by 200 mg every 7 days. • Typical effective dose is 1000–2000 mg daily. In elderly or medically ill patients (including those with HIV stage 3 or 4) • Initiate treatment with 200 mg in the morning and 200 mg at night. • Increase the dose by 200 mg every 7 days until there is a clinical response or the therapeutic blood level is reached. • The maximum dose can vary; assess tolerability and the clinical response.

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Carbamazepine – for mood stabilization in bipolar disorder, acute mania Contraindications and cautions: Avoid in pregnancy. Induces the metabolism of many other medications. Serious but uncommon side-effects include: • severe hypersensitivity or allergic reactions of skin or organs • arrhythmias, AV block, heart failure • blood dyscrasias • hepatitis or hepatic failure or pancreatits • hyponatraemia from drinking excess ﬂuid. Educate the patient and the family: • Review cautions and side-effects. • Mood stabilizers are not addictive. • Warn against use of alcohol. In healthy adults • Initiate treatment with 200 mg at night. • Increase the dose by 200 mg every 3–4 days until there is a clinical response. • Give in divided doses to reduce toxicity. • Typical effective dose is 400–600 mg daily, but in severe cases may need 1000 mg. In elderly or medically ill patients (including those with HIV stage 3 to 4) • Initiate treatment with 100 mg at night. • Increase the dose by 100 mg every 3–4 days until there is a clinical response. • Give in divided doses to reduce toxicity. • The maximum dose can vary; assess tolerability and the clinical response. • Be alert to possible virilogic failure in patients taking antiretroviral medications for HIV.

(iii) Maintenance treatment of bipolar disorder Treatment with a mood stabilizer, in combination with psychosocial interventions, is important to maintain wellness and avoid relapses of mania and depression in a patient with bipolar disorder. Lithium4 or sodium valproate should be considered in the maintenance treatment of bipolar disorder. Lithium can only be used when laboratory monitoring of blood levels is available. Carbamazepine can also be used but may negatively interact with antiretroviral medications and is best avoided in PLHIV taking ART. In women planning a pregnancy, or pregnant or breastfeeding, lithium and sodium valproate should be avoided. These patients should be referred to specialist mental health care, when possible. Maintenance treatment should continue for at least 2 years after the last episode of bipolar disorder. The decision to continue maintenance treatment after 2 years should preferably be done by a mental health specialist. If a patient has frequent relapses of mania or depression while on mood stabilizer therapy, consider switching or adding agents. These patients should be referred to specialist mental health care, when possible. Refer to specialty care guidelines for further information about the treatment of bipolar depression.

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10.11.6 Sad or low mood including depression2 Sadness and anxiety can be very common feelings in everyday life. The causes of sad or low mood, anxiety, nervousness, or excessive worry often can be attributed to mood disorders or anxiety disorders. Clinical assessment seeks to correctly identify those patients who are experiencing a depressive episode or an anxiety disorder, so that adequate treatment may be instituted. However, several other physical and psychiatric disorders may manifest with symptoms of sad or low mood, and must be considered by the clinician in the differential diagnosis. These disorders can include: • delirium with low mood (see Section 10.11.3) • intellectual disabilities (see Section 10.11.3) • dementia (see Section 10.11.3) • psychosis (see Section 10.11.4) • substance use disorders (see Section 17) • depression secondary to medical illnesses and medications. In this Section, a depressive episode refers to patients whose sadness is severe or persistent, who have a range of emotional and physical symptoms that characterize major depression, whose symptoms deviate from normal expected reactions to life stressors, traumas, and challenges, and who experience a signiﬁcant impairment in function or life quality due to the depressive episode. Sad or low mood and anxious states of mind often occur together. If there is prominent low mood, treat the depression ﬁrst. However, temporary relief from anxiety symptoms may be needed, particularly at the outset of treatment. At the start of treatment, always consider the possibility that medical causes may be contributing to depressive disorders. When patients do not respond to treatment for sad or anxious states of mind, see medical causes listed in Appendix 2. The lifetime risk of developing a depressive disorder is 10%–20% in women and somewhat less in men. It is estimated that 20% of patients presenting to general medical clinics have depressive episodes. Depression often presents concomitantly with physical health problems, and patients with chronic disease complicated by severe depression have signiﬁcantly worse health outcomes than patients with chronic disease without severe depression. Severe depression occurs more frequently in patients with HIV than in the general population, and can greatly affect their ability to adhere to antiretroviral treatment.

Assessment of patients with sad or low mood or depression Depressive disorders may present with both psychological and physical symptoms. Many patients with depression do not volunteer emotional complaints, presenting instead with somatic complaints, which typically include: • fatigue, which can be severe • insomnia and, less commonly, hypersomnia • somatic complaints, including changes in appetite and weight • bodily complaints, such as burning sensations in the head, unexplained aches, and pains.

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Psychological or emotional complaints are often elicited on inquiry. The symptoms cause signiﬁcant distress and may markedly impair function and quality of life. The table below, DDx: Sad or low mood or depression, lists the deﬁning characteristics of disorders associated with sad or low mood or depression. Common presenting symptoms that should alert the clinician to a possible depressive disorder and should trigger the use of this Section include the following: • sad or low mood • fatigue or loss of energy or tiredness • loss of interest or pleasure • guilt or loss of self conﬁdence • hopelessness and feelings of worthlessness • suicidal thoughts or acts or thoughts of death (Section 10.11.2 Suicide risk) • disturbed sleep • loss of libido • disturbed appetite (weight loss or gain) • feeling tense, anxious, excessively worried, or frightened • unexplained somatic symptoms ° tingling, numbness ° shortness of breath ° gastrointestinal distress ° palpitations ° aches and pains • reliving past traumas in thoughts, images, dreams or acts • persistent preoccupation with stressful life events or stressors. Patients presenting with these states of mind should receive an assessment for risk of suicide, self-harm, or the potential for violence or harm to others (see Section 10.11.2 Suicide risk). Investigations • Evaluation of the patient, including mental health history, review of medications, medical history, and mental status examination. • Consider medical conditions and laboratory investigations as appropriate. • History from family or friends if available and if the patient consents to these discussions. • Use the DDx tables below to identify the most suitable diagnoses to account for the patient’s symptoms, and to guide treatment initiation. • Consider the role of the following risk factors for depressive disorders in the patient’s presentation. ° past history of depressive episodes or family history of depressive episodes ° female gender ° major stressful life events including family conﬂict, loss, or separation ° chronic medical illness, including HIV infection ° absence of positive social support ° adverse social environment (poverty, homelessness, isolation, stigma, discrimination)

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° indications of the progression of HIV infection (notiﬁcation of positive test, progression of symptoms, drop in CD4 count) ° substance misuse ° side-effects of prescribed medications ° present or past exposure to physical and sexual abuse.

DDx: Sad or low mood or depression Psychiatric disorder Depressive episode Symptom constellation and treatment considerations Symptoms persist for at least 2 weeks and occur on most days for most of the day. Distinct period with deﬁned onset characterized by: • sad or low mood • fatigue or loss of energy or tiredness • loss of interest or pleasure • guilt or loss of self-conﬁdence • hopelessness and feelings of worthlessness • changes in appetite and sleep • loss of libido • suicidal thoughts or acts or thoughts of death. Antidepressants usually are helpful. A more persistent and chronic (>2 years) period of sadness and low mood; fewer and less severe symptoms than in severe depression, but associated with signiﬁcant impairment of quality of life and function. Antidepressant medication and psychotherapy often are indicated, but response to treatment may be more limited than seen with depressive episode. Current symptoms of depressive episode. Lifetime history of both depressive episode and mania or, its milder form, hypomania. Antidepressant medications can induce or precipitate manic episodes in patients with personal or family histories of bipolar disorder. Mood stabilizers are the treatment of choice for bipolar disorder. In the depressive phase, treat ﬁrst with mood stabilizer such as lithium. Consider adding antidepressants only if mood stabilizer is insufﬁcient to alleviate depressive symptoms. Use antidepressants to treat the depressive episode for the shortest possible period. Current symptoms of depressive episode. In addition to the symptoms of depression, the patient develops psychotic symptoms, e.g. delusions or hallucinations. Treatment necessitates the use of antipsychotic and antidepressant medications. Medical illness or medications used to treat medical conditions may contribute to depressive symptoms. Symptoms may be due to a depressive disorder, the general medical condition, or both. Treatment may involve addressing the underlying medical disorder or instituting antidepressant medication treatment. While memory loss is the hallmark symptom of dementia, many dementias, including HIV dementia, may present with symptoms of low mood, depression, and a slowing down or blunting of emotional responses. It is important to remember that many patients with dementia may also have a depressive episode. Both conditions will require targeted intervention.

Dysthymia

Bipolar disorder – depressive episode or depressive phase

Depressive episode with psychotic features

Depressive symptoms due to general medical condition

Depressive symptoms due to dementia

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Psychiatric disorder Uncomplicated bereavement

Symptom constellation and treatment considerations A period of sadness following the death of a close friend or relative; the passage of time and the support of friends and family are usually sufﬁcient to help people through a period of bereavement. If bereavement began in the prior 2 months, do not consider antidepressants as ﬁrst-line therapy. Use culturally appropriate mourning and support to facilitate adjustment. Although bereavement is not a mental disorder, some people may be at risk of developing the full constellation of persistent symptoms that meet the criteria of a major depressive episode and may require consideration of targeted antidepressant therapy. Time-limited mood symptoms may develop in response to a major stressful event without the full constellation of psychological and physical symptoms that are characteristic of severe depression. Treatment should focus on helping the patient to manage the adversity, by providing hope and reassurance, problem-solving, and facilitating connection with natural support systems. Physical activity should be encouraged and psychotherapies considered where available. Should the symptoms persist and their severity worsen, an adjustment disorder may develop into a depressive episode requiring antidepressant therapies.

Adjustment disorder (especially with depressive features)

Figure: Schematic illustration of common mood syndromes

The ﬁgure illustrates common mood syndromes. A patient with bipolar disorder will have distinct episodes of low mood and euphoria or high mood. A patient with depressive episodes will have episodes of low mood with a return to wellness, but episodes may be recurrent, and mild symptoms may persist between episodes. Some patients have persistently low mood; if this persists for at least 2 years without returning to wellness, they are considered to have dysthymic disorder. Severe depression and dysthymia may occur together, resulting in a baseline state of depression with periodic exacerbations.

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Depressive symptoms due to medical conditions Physical or somatic symptoms associated with depression, such as fatigue, weight loss, and insomnia, may be caused by physical illness alone or the medications used to treat physical illnesses. However, it is not uncommon for physical illness and depression to coexist. In these cases, there is a risk of diagnosing only one condition. When both disorders exist, it is important to identify and treat both, as each can contribute to worsening of the patient’s health status. • Physical illnesses may present with sad or low mood as a key symptom. The low mood is often accompanied by fatigue, lethargy, and loss of motivation. • Medications used to treat physical syndromes may cause low mood, loss of interest, and fatigue. Some medications used to treat HIV (e.g. EFV) have been associated with low-mood symptoms. Medical conditions and medications that can present with depression can be found in Appendix 2.

Depressive symptoms related to adverse life events Adverse life events can contribute to sad or low mood, but a depressive episode is not an expected outcome of such events. Depressive episodes often develop following an adverse or stressful life event but are distinguished from the conditions described in the table above, DDx: Sad or low mood or depression, by the symptom severity, the persistence, and pervasiveness of the mood symptoms and the functional impact. The DDx table also outlines other conditions to consider when making the differential diagnosis of sad or low mood. These conditions may be thought of as existing on a continuum of reactions to adverse life events. In general, with the help of natural support systems and the passage of time, most people will recover from the distress of adverse life events and circumstances. More targeted interventions, including antidepressant medications and psychotherapies, will be needed when symptom burden is greater and functional impact is more severe.

Acute management of depression When symptoms of a depressive episode are pervasive, persistent, and of moderate to severe intensity, medication treatment is usually necessary to reduce the symptoms. When symptoms are mild, psychotherapy and counselling without medications may be sufﬁcient to treat the episode. Physical activity and behavioural activation should be encouraged in all patients experiencing depressive episodes. However, in moderate and severe depression, this intervention should only be used as adjunct to antidepressants or brief structured psychological treatments. All patients should receive comprehensive clinical care including psycho-education, counselling and support, activation of social networks, structured physical activity programming, medication management, and regular follow up. Where human resources permit, referral for psychotherapy and additional psychiatric and mental health services should be considered.

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Health-care workers should perform the following for patients presenting with severe depression. • Assess for suicide risk (see Section 10.11.2) and ensure safety. • Initiate medication treatment. • Provide counselling. • Initiate management of any co-morbid conditions (e.g. treat substance use disorders, medical conditions, and pain).

Use of antidepressant medications: some basic principles and cautions • Antidepressant medications are the most effective treatment for a depressive episode of moderate to severe symptom intensity. • Counselling and psychotherapy often are sufﬁcient for the treatment of a depressive episode of mild intensity. Antidepressant medications should not be offered for the initial treatment of a mild depressive episode. • Fluoxetine5 or tricyclic antidepressants (TCAs) should be considered as treatment in individuals with moderate to severe depressive disorder. • If ﬂuoxetine is available, it may be better tolerated and equally effective as TCAs and may be initiated instead of a TCA. • If drug treatment is required in older people, ﬂuoxetine is preferable to tricyclics, which should be avoided due to side-effects. • In adolescents with depressive episodes, do not consider antidepressant medication as ﬁrst-line treatment. Psychosocial treatments, including psychotherapy, are preferable. If no response to psychosocial treatments, consider using the lowest effective dose of ﬂuoxetine (but not other SSRIs or TCAs). Adolescents on ﬂuoxetine should be monitored closely for suicidal ideations or behaviour. For all adolescents on ﬂuoxetine, support and supervision from a mental health specialist should be obtained. • Antidepressants should not be considered in the treatment of children younger than 12 years of age. • If drug treatment is required in women with a depressive episode or disorder who are planning a pregnancy, pregnant, or breastfeeding, avoid antidepressants as much as possible. Psychosocial treatments, including psychotherapy, are preferable. If no response to psychosocial treatments, consider using the lowest effective dose of antidepressant medication. • If antidepressant medication is required in patients with cardiovascular disease, SSRIs are the ﬁrst choice. Do not prescribe TCAs to people at risk of serious cardiac arrhythmias or recent myocardial infarction. • Antidepressant medications can precipitate mania in patients with a personal or family history of mania or bipolar disorder.

5 Other SSRIs are available. See Adaptation Guide.

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• With both SSRI and TCA medications, the early phase of acute antidepressant treatment may be a time of heightened risk for agitation, and harm to self or others. • When starting antidepressants, monitor patient for risk of harm to self or others at every contact. • All TCAs are highly lethal in overdose. To minimize the harm if overdose occurs, patients should have access to only a small supply at the initiation of treatment or at any points when suicide risk is high. • If severe anxiety is present or if marked and akathisia or agitation develops on SSRIs, consider short-term use of low-dose diazepam, i.e. 5–10 mg daily for 1 week. Diazepam does not treat depression and carries a risk of dependence. • Dosage adjustment of medication should be based on symptom response and tolerability. The treatment goal is full remission of symptoms and a full return to the level of function. • At each visit, assess medication tolerability and check adherence. • If the patient has a poor symptom response by week 12 despite good adherence to the maximum tolerated dose of a medication, switch to another antidepressant. • In adult individuals with depressive disorders who have beneﬁted from initial antidepressant treatment, do not consider ending the antidepressant treatment before 9–12 months after recovery. Treatment should be regularly monitored, with special attention to treatment adherence. Frequency of contact should be determined by the adherence, the severity of symptoms, and by local feasibility issues. • When terminating antidepressant medication treatment, remind the patient about the possibility of withdrawal symptoms. Counsel to taper the dose slowly and avoid abrupt discontinuation. • Advise patients to self-monitor for early signs of symptom relapse.

Use of antidepressant medication in the management of a depressive episode (moderate to severe) The 2 antidepressants available in the WHO formulary are fluoxetine and amitriptyline. Doses and titration are noted below.

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Fluoxetine for depression Contraindications and cautions: Watch for increased risk for agitation and suicidal ideation and behaviour (see Section 10.11.2). If there is a history of mania or bipolar disorder, use a mood stabilizer ﬁrst (see Section 10.11.5 on bipolar disorder for further details). Educate the patient and family: • about side-effects • that the medication is not addictiv • to avoid the use of alcohol • that it usually takes several weeks to get a response – do not be discouraged • that the patient may feel worse initially due to side-effects; most side-effects gradually diminish. In healthy adults • Initiate treatment with 20 mg of ﬂuoxetine daily. • May start at 10 mg daily to reduce the risk of side-effects that undermine adherence, and then increase to 20 mg as tolerated. • If 10 mg dosing is not available, give 20 mg every other day (ﬂuoxetine has a very long half-life) • If the patient has severe insomnia (caused by the psychiatric illness or ﬂuoxetine), consider adding diazepam 5 mg at bedtime. Gradually taper and discontinue diazepam as psychiatric symptoms improve. • If no response in 4–6 weeks or partial response at 6 weeks, the ﬂuoxetine dose may be increased to 40 mg. • The ﬂuoxetine dose may be gradually increased up to 60 mg as necessary and tolerable to achieve optimal response. • If the patient is being treated for depression and there is an inadequate symptom response by week 12 at the maximum tolerated dose, consider switching to amitriptyline. • When switching from ﬂuoxetine to amitriptyline, note that ﬂuoxetine may increase serum amitriptyline levels. Therefore, when switching, initially use the amitriptyline dosing schedule suggested for elderly or medically ill patients rather than for healthy adults. In elderly or medically ill patients or patients who cannot initially tolerate a 20 mg daily dose (including those with HIV stage 3 or 4): • Initiate treatment with 10 mg daily for 3 weeks. • If 10 mg doses are not available, give 20 mg every day (ﬂuoxetine has a very long half-life). • Bear in mind that ﬂuoxetine dosing can be increased as gradually as needed to manage uncomfortable sideeffects. Patients usually become accustomed to the side-effects in time. • If the patient has severe insomnia (caused by psychiatric illness or ﬂuoxetine), consider adding diazepam 2–5 mg at bedtime. Avoid diazepam in cognitively-impaired patients. Gradually taper and discontinue diazepam as psychiatric symptoms improve. • After 3 weeks, the dose can be raised to 20 mg daily, or raised more gradually, according to patient tolerability and symptom response. • The ﬂuoxetine dose may be gradually increased up to 60 mg as necessary and tolerable to achieve optimal response. • When switching from ﬂuoxetine to amitriptyline, note concerns mentioned above and start with lower doses of amitriptyline.

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Amitriptyline for depression Contraindications and cautions: In depressed patients, watch for increased risk for agitation and suicidal ideation and behaviour (see Section 10.11.2). If there is a history of mania or bipolar disorder, give only in combination with a mood stabilizer (see Section 10.11.5 Bipolar disorder for further details). Do not give if there is a history of arrhythmia or recent heart attack. If suicide risk is a concern, give only 1 week’s supply at a time, or have the caregiver dispense the drug. It may impair the ability to perform skilled tasks such as driving – take precautions until the patient is accustomed to the drug. Educate the patient and family: • about side-effects • that the medication is not addictive • to avoid the use of alcohol • that it usually takes several weeks to get a response in depression – do not be discouraged • that the effect on sleep or pain may be seen within 2–3 days • that the patient may feel worse initially due to the side-effects; most side-effects gradually diminish. In healthy adults • Initiate treatment with 50 mg of amitriptyline at bedtime. • Increase by 25–50 mg every 1–2 weeks, aiming for 100–150 mg by 4–6 weeks, depending on response and tolerability. • If no response in 4–6 weeks or partial response at 6 weeks, may increase to a maximum dose of 200 mg given in divided doses or a single dose at night. In elderly or medically ill patients (including those with HIV stage 3 or 4): • Initiate with 25 mg at bedtime. • Increase by 25 mg weekly, aiming for a target dose of 50–75 mg by 4–6 weeks. • If no response at 6–12 weeks or partial response at 12 weeks, may increase gradually to 100 mg in divided doses. • Monitor carefully for orthostatic hypotension.

Management of a severe depressive episode with psychotic symptoms • Patients with both severe depression and psychosis are at an increased risk of suicide compared to patients with severe depression alone (see Section 10.11.2). • Begin treatment with both an antipsychotic and an antidepressant, following dosages as described in the medication boxes above. Monitor carefully for side-effects, which are more common when 2 medications are given together. • Once stabilization has been achieved, the antipsychotic medication can be slowly tapered. The antidepressant should be continued for 9–12 months after symptom remission, as described below in the treatment of depressive episodes. • If psychosis re-emerges, restore the antipsychotic treatment. • If specialty care is available, referral for stabilization and management is desirable.

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10.11.7 Anxiety Anxiety often presents as apprehensiveness, fearfulness, nervousness, or excessive worry, accompanied by physical symptoms. Anxiety can be normal in stressful life situations. However, symptoms out of proportion to the severity of the stressful situation that persist after the stressor has gone, and that interfere with a person’s daily life, indicate an anxiety disorder. An anxiety disorder also can occur in the absence of any external stressor. Anxiety disorders are very common, often have a recurrent or chronic course, and may last for decades in the absence of effective treatment.

Assessment and diagnosis of anxiety In addition to assessment for suicide risk (see Section 10.11.2), patients who present with anxiety should be screened as follows. • Check for the following symptoms of anxiety: ° feeling tense, anxious, apprehensive or frightened ° being excessively worried. • Physical symptoms of anxiety: ° palpitations ° suffocation sensations ° dizziness ° trembling ° shaking ° pins and needles sensations. • Patients who complain of sadness frequently experience feelings of anxiety. • Check for the following symptoms of depression: ° low mood or sadness ° loss of interest or pleasure ° hopelessness ° decreased energy or increased fatigue. • If the diagnosis is positive for depression, see Section 10.11.6. • If negative for depression, follow the guidelines below for anxiety disorders. Diagnosis of anxiety A diagnosis of anxiety disorder should be made when the patient presents with the symptoms above, especially if the symptoms are severe and the patient’s daily functioning is impaired. Differential diagnosis for anxiety • If symptoms of abnormal behaviour are present, assess and treat for abnormal behaviour conditions. • If symptoms of sad or low mood are prominent, treat for depressive disorder. • If the patient does not respond to treatment for anxiety, see Appendix 2 for medical conditions associated with anxiety.

Management of anxiety Severe anxiety disorders should be treated. Patients with milder symptoms may beneﬁt from support, counselling, and relaxation training. Among people with milder symptoms and recent onset; ﬁrst provide support, address social issues ,and continue to monitor the symptoms. Treatment for severe symptoms often involves medication and counselling.

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• Address underlying medical conditions that could cause the anxiety symptoms, including possible modiﬁcation of prescribed medication (see Appendix 2). • Discuss health behaviours that may reduce anxiety, including eliminating caffeine, regulating sleep hygiene, and decreasing the use of alcohol and substances. • Benzodiazepines can be used for the short-term treatment of an acute episode of severe anxiety caused by a stressful life event. Longer-term treatment (beyond 2 weeks) with benzodiazepines is not indicated as it carries a risk of dependence and the potential for addiction and abuse. • SSRI medications are useful for the longer-term treatment of most anxiety disorders. • Amitriptyline and clomipramine can be useful for selected anxiety disorders. Before using these medications, see below, Making a speciﬁc anxiety disorder diagnosis. • Pharmacological interventions should not be offered to adolescents with anxiety disorders in non-specialist settings. In non-specialized care, relaxation training should be considered as treatment for anxiety symptoms of at least 2 weeks duration (in the absence of depressive disorder), for patients who are in distress or have some degree of impaired functioning. Cognitive behaviour therapy is an excellent treatment for anxiety disorders.

Psychotropic therapy for anxiety Diazepam – for short-term treatment only for acute anxiety Contraindications and cautions: Diazepam can be abused. Long-term treatment with diazepam can cause substance dependence. If a patient becomes dependent on diazepam, sudden discontinuation can cause withdrawal syndrome (this has similarities to alcohol withdrawal). It should not be given to patients using alcohol. Benzodiazepine use in patients with post-traumatic stress disorder may have a very high rate of development of dependence and should be used sparingly and with extreme caution. Educate the patient and family: • Review side-effects. • Be cautious about the addictive potential. • Warn against use of alcohol. In healthy adults • Initiate treatment with 2 mg of diazepam 1 to 3 times daily. • May increase gradually if needed to 5–10 mg twice daily. • Maximum dose is 20 mg during a 24-hour period. In elderly or medically ill patients (including those with HIV stage 3 or 4) • Initiate treatment of 2 mg of diazepam once daily (may repeat another dose in a day). • May increase gradually to 10–20 mg daily if necessary and tolerated. However, the preferred maximum dose in elderly patients is 10 mg daily after a gradual increase. In all adults • Taper medication slowly after symptoms have been controlled. • Wherever possible, do not exceed a 2-week duration of treatment. • If the symptoms return, consider SSRI treatment.

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Fluoxetine for chronic anxiety disorders – same dosing as for depression (see Section 10.11.6 for cautions and dosing)

Making a speciﬁc anxiety disorder diagnosis When there is a range of available treatments, it may be desirable to make a speciﬁc diagnosis of an anxiety disorder. There are several types of anxiety disorders with different symptoms, but the symptoms cluster around excessive, irrational fear and dread. The following table DDx: Speciﬁc anxiety disorders with screening questions and treatments, provides key features and speciﬁc screening questions related to each type of anxiety disorder: generalized anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and phobias (including social phobia). This Table also lists treatments with known effectiveness for each disorder.

DDx: Speciﬁc anxiety disorders with screening questions and treatments Anxiety disorder Generalized anxiety disorder (GAD) In favour Prominent worry Feeling tense or nervous Sense of foreboding Poor concentration Dizziness Sweating Fast or pounding heart Chest pain or constriction Dry mouth Stomach pains Restlessness, inability to relax Headaches Screening questions Have you been worrying a lot about many different things (for quite some time)? Have you been experiencing (tensionrelated symptoms) headache, pounding heart, complaint of “stress”, or insomnia? Treatments Counselling, support, relaxation training CBT Fluoxetine

Post-traumatic stress disorder (PTSD)

History of traumatic event. Re-experiencing symptoms, e.g. ﬂashbacks, nightmares. Avoidance symptoms, e.g. avoids stimuli associated with the trauma, has sense of detachment and numbness. Hyper-arousal symptoms, e.g. insomnia, irritability, difﬁculty in concentrating, hyper-vigilance, exaggerated startle response.

Do you often think or dream about something terrible that happened to you in the past? Can these thoughts or dreams be linked to a particular traumatic event? Do you avoid things that remind you of this event?

Access to psychological ﬁrst aid support for acute trauma exposure CBT including graded self-exposure Fluoxetine Amitriptyline

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Obsessivecompulsive disorder (OCD)

Obsessions: Recurrent and persistent thoughts, impulses, or images causing marked anxiety or distress. The patient may consider them “silly” but cannot escape them. Recognizes and attempts to ignore or suppress such thoughts, impulses or images or to neutralize them with some other thought or action. Compulsions: Repetitive and excessive behaviour or unrealistic mental acts that the person feels driven to perform in order to reduce anxiety from obsessions. These commonly include repetitive checking, washing or cleaning, rearranging and ordering objects to prevent or reduce distress or prevent some dreaded event or situation. Patients often have both obsessions and compulsive rituals. Recurrent and unexpected panic attacks (spontaneous episodes of severe anxiety that start suddenly, rise rapidly, and last from a few minutes to an hour). Physical sensations, such as palpitations, chest pain, sense of choking, churning stomach, dizziness, feelings of unreality, feelings of impending disaster (losing control, going mad, sudden death, heart attack). Worry about the implications of the attack or its consequences and about having more attacks. A signiﬁcant change in behaviour related to the attacks (e.g. avoiding places where they have occurred). Unreasonably strong fear or avoidance of people, places, or events such as: • leaving home • being alone at home • crowds or public places • open spaces • performing in public • social events • animals, darkness, heights, blood, or others. Person recognizes that the fear is excessive or unreasonable.

Do you have thoughts that disturb you but feel out of your control? Are there certain things that you must do over and over in order to feel better?

CBT (exposure and response prevention) Fluoxetine, often required in high doses Clomipramine

Panic disorder

Do you ever have periods of intense fear or anxiety with chest pain, pounding heart, shortness of breath, and sweating that occur out of the blue?

CBT Fluoxetine Amitriptyline

Phobias

Do you avoid certain places or situations or objects because they frighten you or make you feel anxious? Is there anything you tend to avoid or fear more than most people do?

CBT Fluoxetine improves social phobia (severe anxiety around people) but not speciﬁc phobias (e.g. animals, heights).

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Management of speciﬁc anxiety disorders When a speciﬁc anxiety diagnosis has been made, CBT is particularly effective for panic disorder, OCD, and social phobia. Exposure to traumatic life events is common and may be associated with the development of PTSD. Some important principles related to psychosocial therapies for PTSD and exposure to traumatic events. • Single session psychological debrieﬁng should not be used for people exposed recently to a traumatic event as an intervention to reduce the risk of post-traumatic stress, anxiety, or depressive symptoms. • Providing access to support, based on the principles of psychological ﬁrst aid, should be considered for people in acute distress exposed recently to a traumatic event. • If it is possible to continue to follow-up the patient, graded self-exposure based on the principles of CBT should be considered in patients with PTSD symptoms. • Psychotherapy for PTSD may be very effective, but it is essential that it is delivered by a therapist who is able to be attentive to establishing a sense of safety for the patient, who is able to guide the patient in reducing the intensity of overwhelming emotions, and who is able, over time, to help the patient to integrate the traumatic event psychologically. In addition to CBT, medication therapies are helpful for speciﬁc anxiety disorders. OCD usually requires higher doses of ﬂuoxetine, up to 80 mg, to achieve a therapeutic response in comparison with other anxiety disorders. OCD can also be treated with clomipramine.

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Clomipramine for treatment of obsessive compulsive disorder, depression, and anxiety. This is a tricyclic antidepressant, like amitriptyline. See 10.11.6 for side-effects, contraindications, cautions, and patient and family education. In healthy adults • Initiate a dose of 10–25 mg daily at bedtime. • Increase in divided doses by 25 mg every 4–7 days to a therapeutic dose of 150–200 mg in divided doses or a single dose at night. • When switching or discontinuing, taper the dose gradually to discontinue. In elderly or medically ill patients (including those with HIV stage 3 or 4) • Initiate a dose of 10 mg daily at bedtime. • Increase in divided doses by 10 mg every 4–7 days to 50–75 mg. • May continue to increase the dose as needed and tolerated up to the maximum dose for healthy adults. • When switching medication or discontinuing treatment, taper the dose gradually to discontinue. • Monitor carefully for hypotension. Somatoform disorder • Although not classiﬁed as an anxiety disorder, somatoform disorder can confer excessive worry, anxiety, and low mood. Patients with somatoform disorder present with multiple physical complaints that cannot be explained by either a known medical disorder after appropriate clinical investigations or by another mental disorder, such as depression or an anxiety disorder. Complaints can include, among other symptoms: ° persistent headache ° dizziness ° chronic fatigue or tiredness ° nausea ° chronic pain ° urinary or gynaecological complaints ° gastrointestinal complaints (e.g. ﬂatulence). Treatment based on CBT principles (e.g. re-attribution, graded activities) should be considered in repeat adult patients with medically unexplained somatic complaints who are in substantial distress, and who do not meet the criteria for a depressive disorder. Where a depressive or anxiety disorder coexists, speciﬁc treatment interventions should be initiated.

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Appendix 1. Psychotherapy and mental health counselling (i) Supportive psychotherapy and mental health counselling Psychosocial support and psycho-education are helpful interventions in mental health disorders. • An effective counsellor can provide tremendous help to a patient with mental health concerns, or a person facing adverse life events, by being empathetic, respectful, patient, compassionate, honest, and trustworthy. • An effective counsellor uses supportive psychotherapy and counselling skills to support a patient’s functioning through: ° the promotion of coping skills; ° the use of problem-solving techniques; ° helping patients with the containment and management of feelings and distress; ° the provision of support and the instillation of hope; ° reassurance and positive reinforcement; ° decreasing isolation; ° fostering connections with the patient’s natural support systems; ° focusing on short-term activities for pleasure and aiming to restore self conﬁdence; ° countering misconceptions, stigma, and discrimination; ° providing psycho-education about the nature of mental health disorders and their treatments; ° highlighting the patient’s efforts to cope, fostering hope, and recognizing that the patient is doing the best that they can. (ii) Cognitive behaviour therapy Cognitive behaviour therapy (CBT) is based on the idea that feelings are affected by thinking and behaviour. • CBT aims to improve a patient’s sense of well-being by identifying key patterns of thinking that are dysfunctional or distorted. These thoughts may contribute to unrealistic and overly negative appraisals of self and others, and may contribute to the patient’s mental health symptoms. • CBT has been shown to be helpful in managing a range of mood and anxiety disorders. Therapy approaches may include keeping a record of thought patterns and feelings related to speciﬁc events, examining automatic thoughts and assumptions, evaluating unhelpful or unrealistic belief systems that pertain to one’s view of self, others, or the world, graded exposure to settings or activities that may have been avoided, and trying out new ways of interacting with others. (iii) Interpersonal psychotherapy Interpersonal psychotherapy is an effective treatment for depression, including bipolar depression. • Therapy aims to improve a patient’s sense of well-being by identifying key areas involving interpersonal functioning, i.e. the interactions that one has with others and how depression may impact on and be impacted by these interactions.

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Common areas of focus in interpersonal psychotherapy include: • exploration of grief and loss • life changes and social role changes • social isolation and lack of meaningful relationships • disputes and disagreements with others. Interpersonal therapy may be delivered in individual or group settings, and has been shown to be effective when delivered in many situations including lowresource settings. (iv) Psycho-education • Review symptoms and give essential information: ° summarize the patient’s symptoms and explain the diagnosis or illness; ° explain the beneﬁts and risks of treatment; ° establish the patient’s coping practices and encourage their use; ° counter misconceptions, stigma and discrimination; ° empathize with the patient’s distress. • Explore ways to reduce stress with patients and family: ° provide supportive counselling (appropriate to circumstances); ° emphasize a problem-solving approach to help work towards solutions that will bring a greater sense of well-being; ° foster connections with the patient’s natural support systems, helping the patient to utilize family, friends, and community supports; ° explore activities that will enhance functioning and self-conﬁdence and give pleasure. • Help the patient and family to maintain hope: ° highlight the patient’s efforts to cope and recognize that she or he is doing the best that she or he can. • Remain an effective support: ° an effective counsellor can provide tremendous help to a patient by being empathic and respectful, patient and compassionate, and honest and trustworthy.

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Appendix 2. Medical conditions to consider before starting treatment for mental disorders and when patients do not respond to initial psychiatric therapy Many patients with mental health disorders have concurrent medical conditions that require treatment. Additionally, many medical conditions may present with mental health symptoms. Confusion, severe agitation, or bizarre behaviour

Medical conditions that may present with mental health symptoms Neurosyphilis HIV infection Systemic infections Liver failure Dehydration Fluid and electrolyte disturbance Renal failure Hypoglycaemia Diabetic ketoacidosis Hypoxia Prescribed medication side-effects, as well as drug-drug interactions and overlapping toxicities Withdrawal from alcohol and substances Endocrinopathy: hypothyroidism Endocrinopathy: hyperthyroidism Cushing’s syndrome Addison’s disease Pheochromocytoma Neurological disorders: Epilepsy Head trauma and intracranial lesion Parkinson’s Stroke

Sad or low mood

Anxiety

8 8 8 8 8 8 8 8 8 8 8 8 8 8 8

8 8 8

8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8

8 8 8 8

8 (postictal) 8 8 8 8

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Encephalitis Vitamin deﬁciencies (e.g. endemic neuritis) vitamin B12 vitamin B1 Under-nutrition Anaemia Cardiovascular conditions: Congestive heart failure Myocardial infarction Arrhythmias Pulmonary embolism Poisoning: Ingested poisons, such as pesticides and plants Accidental and intentional overdose

8 8 8 8

8 8 8 8 8 8 8 8 8

8 8 8 8

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10.12 Eye problems1 In this section: 10.12.1 Clinical approach to a patient with eye problems 10.12.2 Approach to red eye (with DDx table) • Manage red eye with no pain • Acute viral conjunctivitis • Bacterial conjunctivitis • Allergic conjunctivitis • Keratoconjuncitivis sicca • Manage red eye with pain • Acute angle closure glaucoma • Corneal ulcer or infective keratitis • Bacterial superinfection of the cornea • Fungal ulcers • Herpetic ulcers • Corneal erosions 10.12.3 Acute visual loss (with DDx table) 10.12.4 Progressive visual loss (with DDx table) • Cataract • Primary open-angle glaucoma • Refractive errors • Proliferative retinopathy 10.12.5 Geographically conﬁned eye diseases • Trachoma 10.12.6 Eye problems in patients with HIV (with DDx tables) • Anterior segment and adnexal eye problems • Herpes zoster ophthalmicus • Posterior segment eye problems 10.12.7 Neuro-ophthalmic involvement from mass lesions, TB, or cryptococcal meningitis

This Section covers an approach to eye problems, ranging from simple eye problems that can be managed at the district level to more serious conditions that will require identiﬁcation for urgent treatment or referral to prevent loss of vision. For more detailed instructions on the eye medicines, see Section 8.4. The anterior segment of the eye includes the cornea, conjunctiva, anterior sclera, anterior chamber, iris, ciliary body, and crystalline lens. The posterior segment includes the vitreous, retina, choroid, posterior sclera, and optic disc.

10.12.1 Clinical approach to a patient with eye problems Step 1: Perform Quick Check Exclude any serious or life-threatening conditions that might present with eye symptoms. Consider malignant hypertension and imminent eclampsia. Assess for sight-threatening conditions that require urgent intervention or an appropriate referral. Step 2: Take a history and examine the patient. Examine the eye and classify the eye problem. Step 3: Assess the patient’s HIV status. Step 4: Work through the appropriate differential diagnosis tables. Step 5: Perform investigations as necessary. Step 6: Treat and monitor the patient’s response to treatment, or refer as necessary.

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History Speciﬁc questions • What are the symptoms? ° pain ° light discomfort or photophobia ° red eye ° watering of the eyes ° discharge ° itching ° dryness ° sensation of foreign body. • Is there a history of trauma? • What are the visual symptoms? ° loss of or decreased vision ° diplopia (double vision) ° halos around lights ° ﬂoaters (black or grey specks in the ﬁeld of vision) ° ﬂashes of light. • What is the duration of symptoms? • What is the progression of symptoms? • Look at the patient’s past history of similar symptoms. • Are there any locally endemic conditions in the community (e.g. trachoma, onchocerciasis, conjunctivitis)? General questions • Systemic diseases – hypertension, diabetes mellitus, connective tissue disorders? • Co-morbidities – HIV, malignancies?

Examination Do a general physical examination Do a speciﬁc eye examination A basic ophthalmic examination may require the following: • a torch for gross examination of the eye structure and pupil response • blue light ﬁlter • Snellen chart or “E” chart for illiterate patients (or a LogMar chart) • ﬂuorescein drops or impregnated paper strips • short-acting mydriatric drops (e.g. 1% tropicamide) to dilate pupils – remember to assess visual acuity and pupil response ﬁrst • direct ophthalmoscope • topical anaesthetic drops (e.g. lidocaine) • cotton buds to remove foreign body • handheld applanation tonometer (Schiotz or Puff tonometer), if available.

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• Assess visual acuity ° Use a Snellen chart to measure distance acuity – this can be at any distance (e.g. 3 or 6 metres) as long as it is documented. ° Make sure the room is well lit. ° Have patient occlude one eye with palm (make sure patient is not peeking and is not putting pressure on the occluded eye). ° Ask patient to read aloud each letter in the ﬁrst row, or indicate with the hand what direction the E is pointing. Then proceed to the next smaller line until not able to distinguish all the letters on that line. ° Record the last line read accurately after the distance from the chart, for example 6/24 if the patient was 6 metres from the chart and the last line read was 24. ° If the patient is not able to read the top line, move forward a metre and retest up to 3 metres. If still not able to read top line, test whether the patient can count ﬁngers and record this. If not able to count ﬁngers, test whether the patient can detect hand motion. If not, test for light perception with a bright torch. ° Then test the other eye and record. ° Then test with glasses on. ° If acuity is less that 6/18 then assess again using pinhole and see if it improves; if yes, then a refractive error is likely. ° Assess near vision using speciﬁc near vision acuity chart, or assess ability to read newsprint or very crudely the ability to count ﬁngers or detect motion. ° Assess colour vision using Ishihara plates or test for red desaturation (a good indicator of optic nerve dysfunction). • Assess visual ﬁelds ° Use confrontation testing to detect gross defects (e.g. homonymous hemianopia – loss of half the visual ﬁeld). Confrontation testing compares the examiner's visual ﬁeld's with the patient’s, and may yield vital information that is often missed. ° Assessment of more discrete visual ﬁeld loss (e.g. from glaucoma) requires formal perimetry.

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• Examine the adnexa (attachments or structural components of the eye) ° Examine the eyebrows and eyelids. Look for ptosis (drooping), infection, congestion, hordeolum, warts, Molluscum contagiosum. ° Evert the eyelid to detect all foreign bodies. • Examine the conjunctiva ° Look for discharge, swelling, or congestion. • Examine the cornea ° Look for haziness, ulcers (herpetic or bacterial), and inﬂammation. ° Test for sensory loss with a wisp of cotton wool. ° The naked eye may not detect corneal defects due to ulcerations or abrasions. If there is trauma or a foreign body sensation in the eye, do ﬂuorescein staining as follows: ◊ Moisten a ﬂuorescein-impregnated strip with a drop of saline or artiﬁcial tears. ◊ Touch the strip to the inside of the lower lid. ◊ Illuminate the cornea with an ophthalmoscope with a blue ﬁlter if available (if not available, a strong white light may also reveal defects). ◊ Look for epithelial defects that stain bright green. • Examine both pupils ° Are they equal in size? ° Examine their reactivity to light. Shine a light alternately from one eye to the other. ◊ A normal response is equal constriction of both pupils, regardless of which eye the light is directed at. This indicates an intact direct and consensual pupillary light reﬂex. ◊ An abnormal response, or relative afferent pupillary defect (RAPD), will show that light directed in the affected eye will cause only mild constriction of both pupils (due to decreased response to light from the afferent defect), while light in the unaffected eye will cause a normal constriction of both pupils due to an intact afferent path and an intact consensual pupillary reﬂex. Thus, light shone in the affected eye will produce less pupillary constriction than light shone in the unaffected eye. • Examine the lens ° Look for any opacity (mature cataracts may be visible with torch examination. • Perform fundoscopy to visualize the fundus, optic disc, and vessels ° Fundoscopy is an examination of the posterior segment of the eye and is done using a direct ophthalmoscope. ° It should take place in a suitably darkened room. ° The patient's right eye should be examined with the examiner's right eye, and vice versa. ° The patient is asked to focus on an object in the distance, and the examiner's head is kept vertical to permit this. ° This approach with the patient ﬁxing on a distant straight-ahead target allows you to visualize the optic disc very easily. ° Turn to the +10DS lens in the lens wheel and observe the eye from 10 cm. Slowly move closer to the patient and at the same time gradually reduce the power of the lens in the wheel and focus on the crystalline lens, the vitreous, and ﬁnally the fundus. The power of lens necessary to focus on the fundus will depend on any uncorrected refractive error in the patient or in the observer. ° Once a blood vessel on the fundus has been located, move along it and

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locate the optic disc. While examining the disc, you will need to consider its colour, its margins, and the cup if there is one. Also, note the presence of optic atrophy and papilloedema. ° Retinal blood vessels should be examined in each quadrant after locating the disc. The veins are relatively large and dark red, while the arteries are relatively thin and brilliant red. ° Next, examine the retinal background, which is the normal retina between the blood vessels and other identiﬁable structures. ° To examine the macula and the fovea, instruct the patient to look into the ophthalmoscope light. ◊ This step will cause the pupil to constrict, dazzle the patient, and you will notice some troublesome corneal reﬂections. ◊ These factors make the macula a difﬁcult area to visualize. It may be useful to use a smaller aperture beam and slightly reduce the light intensity. ◊ The normal macula is the area between the superior and inferior temporal blood vessel arcades, and its centre is the fovea. • Assess ocular movements ° Ask the patient follow your ﬁnger with their eyes without moving the head; test the 6 cardinal points of gaze in an H pattern. ° Look for failure of movement and for nystagmus (pause to check it during upward and lateral gaze). • Assess ocular pressure ° If suspect glaucoma, press lightly on the globe with the ﬁngers. Does the eye feel hard? ° If handheld tonometer is available, measure intraocular pressure. • Additional examination usually performed by specialized eye-care professionals. ° Slit lamp examination. Classify the problem as red eye (with or without pain) or visual loss and consult the relevant DDx table below. For HIV-infected patients, see also these speciﬁc sections.

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10.12.2 Approach to red eye Red eye is commonly a sign of treatable conditions such as conjunctivitis. It is important to exclude more serious underlying conditions such as acute congestive glaucoma or iridocyclitis. Problems relating to the posterior chamber almost never present with a red eye. Ask whether there is pain with the red eye.

DDx: Red eye Condition Red eye with no pain Infectious conjunctivitis • bacterial • viral Painless red eye – little or no photophobia, no visual changes Mucopurulent discharge with matting of eyelids Conjunctival congestion Lid oedema if viral Itchy, burning with gritty feeling Local outbreaks in the community History of conjunctival exposure to water contaminated with urine of infected animals Red eyes (conjunctival suffusion) without purulent discharge involving both eyes – early phase of illness Fever and myalgias Bilateral Painless Itchy Watery or mucoid (stringy and ropy) discharge Cobblestoning or raised visible bumps (papillary hypertrophia of the palpebral conjunctiva) Conjunctival inﬂammation (chemosis) may occur Multiple creases in lower lid Seasonal Improves on antihistamines Bleeding beneath the conjunctiva Painless, harmless Associated with minor trauma, hypertension, increased venous pressure as in coughing, sneezing, vomiting, straining Triangular band of ﬁbrosis next to the cornea is a pinguecula; if encroaching on the cornea, a pterygium Present for weeks but may become acutely inﬂamed Painless although may feel gritty or dry Might decrease visual acuity if advanced and encroaches on the central part of the cornea (astigmatism) In favour

Leptospirosis see Section 11.22

Allergic conjunctivitis

Subconjunctival haemorrhage

Pinguecula or pterygium

Red eye with pain Keratoconjuncitivis sicca Burning or foreign body sensation Lack of tears or occasionally excessive tearing Common in children with HIV, Stevens Johnson syndrome, female hormonal diseases, other autoimmune diseases

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Condition Corneal inﬂammation or infection (keratitis)

In favour Severe eye pain Variable degree of decreased visual acuity (depending on location of ulcer) and photophobia Haziness or opaciﬁcation of the cornea (with or without ﬂuorescein uptake) Pupillary constriction (secondary to ciliary spasm and iritis) Presence of pus or white cells in anterior chamber (hypopyon) Foreign body sensation History of welding work or extended sunlight exposure Pain Photophobia Tearing History of splash or exposure to heat or chemicals Burns to eyelid or skin Singed eyelashes Flat thin haemorrhage or thicker collection of blood Intense pain localized to cornea after an injury Evidence of corneal abrasion with ﬂuorescein stain Foreign body may be seen directly or on eyelid eversion Round or oval sharply demarcated border with the base appearing ragged and gray Painful Blurred vision Blue/green mucopurulent discharge with ﬂuorescence in UV light in favour of P. aeruginosa Herpetic ulcer: dendritic branches on ﬂuorescein staining Varicella zoster virus (VZV) ulcer: loss of sensation with shingles on ophthalmic branch of trigeminal nerve typical for VZV Hypopyon (sterile pus in lower internal part of cornea) Sudden loss of vision Severe headache and eye pain Nausea and vomiting Halos around light Pupils mid-dilated, vertically oval non-reactive to light (sluggish) Very high intraocular pressure >30 mmHg – eye will feel hard on digital pressure Acute onset Unilateral, painful red eye, blurred vision, direct and consensual photophobia, tearing Ciliary (not only conjunctival) injection 360 degree perilimbal ﬂush Blurred vision with ﬂoaters Occasional pain Photophobia

Ultraviolet kerato-conjunctivitis (welder's arc, carbon arc, sunlight)

Thermal or chemical keratoconjunctivitis

Foreign body or corneal abrasion Corneal ulcer

Acute angle closure glaucoma (or closed angle)

Acute anterior uveitis (iritis or iridocyclitis)

Acute posterior uveitis (choroiditis or chorioretinitis)

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Manage red eye with no pain: Acute viral conjunctivitis Acute viral conjunctivitis is commonly caused by adenovirus. It is highly contagious and occurs in small epidemics in households, schools and the community. Key clinical features • Acute onset with painless red eye – little or no photophobia, no visual changes. • Discharge, matted eyelashes, redness and inﬂammation (chemosis). • Monitor for secondary bacterial infection – which is common. • Suspect herpetic conjunctivitis if there are skin ﬁndings, or if there is skin involvement (clusters of vesicles on an erythematous base on the face, eyelids. and mucous membranes typical of herpes simplex virus; shingles along ophthalmic nerve dermatome suggestive of herpes zoster virus). Follow management speciﬁc for these conditions (see below and Section 10.12.6). • Clinical diagnosis and culture or smears are not needed. Treatment • If suspect bacterial coinfection, use gentamicin2 or chloramphenicol eye drops or ointment (see Section 8.4). • Use cold compresses several times a day. • Give tears substitute such as carboxymethyl cellulose 0.5% drops or 1% geltears naturale. Prevention • Avoid contact between ﬁngers and eyes. • Meticulous hand washing. • Separate face and hand towels at home for the affected person.

Bacterial conjunctivitis Key clinical features • Mucopurulent discharge present. • May occur as a primary infection or is secondary to a viral infection. • Gram stain of the conjunctival smear will help to identify possible organism. • Hyper-acute gonococcal infection - sudden onset of extreme inﬂammation and purulent discharge from the eyes; there may be a history of urethral discharge or other signs of a sexually transmitted infection. This is an ophthalmic emergency. Refer urgently to an ophthalmology unit in case of gonococcal infection as it can rapidly infect the cornea and lead to a severe keratitis or perforation of the cornea. Initiate treatment below in the meantime. • Trachoma or chlamydial conjunctivitis in endemic areas – usually presents with a chronic red eye with stringy discharge. See Section 10.12.5.

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Treatment • Conjunctivitis due to Neisseria gonorrhoeae requires systemic antibiotics and urgent referral. ° ceftriaxone 1 gram IM OR ° spectinomycin 2 g by deep IM; OR ° ciproﬂoxacin 500 mg orally. • If suspect Chlamydia trachomatis, follow instructions in Section 10.12.5. • If neither of these, for other bacterial conjunctivitis give topical antibiotic drops such as gentamicin eye drops 4–6 times daily.2 Prevention When conjunctivitis is associated with an STI, treat sexual partners to minimize recurrence and spread of disease.

Allergic conjunctivitis Key clinical features • Itching is a cardinal sign. • Watery with minimal discharge. • Congestion and chemosis (swelling) with papillary reaction. • May be acute and periodic in seasonal allergic conjunctivitis. • Mild and chronic in atopic or perennial allergic conjunctivitis. Treatment • Allergen avoidance. • Topical sodium cromoglycate drops during the allergy season is the mainstay of treatment and is safe even if given for long periods.

Keratoconjunctivitis sicca This is also called dry eye syndrome. Key clinical features • Burning, foreign body sensation, lack of tears. • Occasionally excessive tears reacting to irritation. • Common in premenopausal and menopausal women and collagen vascular diseases. • In PLHIV,may be a consequence of previous Stevens Johnson syndrome. Common in HIV-positive children. Treatment • Give tear substitute such as carboxymethyl cellulose 0.5% drops or 1% geltears naturale. • Treat secondary bacterial infection, if present.

2 Gentamicin eye drops are on the WHO EML. An alternative is chloramphenicol eye drops. .

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Manage red eye with pain Acute angle-closure glaucoma This is due to increased intraocular pressure that leads to impairment of the functioning of the optic nerve and causes visual ﬁeld loss, ultimately leading to blindness. It is important to recognize and refer urgently for treatment to prevent visual loss. Key clinical features • More common among Asians. • Usually bilateral disease, but acute onset often unilateral. • Sudden loss of vision with halos around lights – often worse in the evenings. • Associated with severe headache, vomiting, eye pain. • Stage of primary angle closure glaucoma. • Evidence of ciliary congestion, lid oedema, hazy cornea, shallow anterior chamber. • A mid-dilated pupil (4 to 6 mm) that reacts poorly to light. • Intraocular pressure is very high – eye feels stony hard on digital pressure. • Fundoscopy – "cupping" of the optic nerve. Treatment • Urgent referral to specialist facility for further treatment. • Start the following medication until the patient reaches referral centre: • pilocarpine 1 drop (2% solution) every 10 minutes for 30–60 minutes, then 1 drop every 1–3 hours until intraocular pressure subsides, then 1 drop 4 times daily; PLUS • acetazolamide 250 mg orally stat, or IV if the patient is vomiting, then continue oral acetazolamide 500–750 mg per day.

Corneal ulcer or infective keratitis • Common cause of painful loss of vision with red eye. • Very often follows trauma that could be trivial. • Offending organisms include bacteria, fungi, virus (such as herpes or facilitated by HIV immunosuppression). Treatment • Urgent referral to specialist • Do not use steroids for a corneal ulcer as the infection may spread resulting in corneal perforation. • Start empirical broad spectrum antibiotic drops in all patients – chloramphenicol or gentamicin eye drops 6 times daily.

Bacterial superinfection of the cornea secondary to trauma • Diagnosis can be made by scraping margins of the ulcer and plating for bacterial and fungal cultures. This should be done by a trained ophthalmologist, using a microscope or loupe.

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Refer for specialist assistance. • P. aeruginosa infection causes a ground glass appearance of the cornea, and may lead to early perforation of the cornea. • Staphylococcal infections are less dramatic, but may cause loss of vision. Treatment • Urgent referral to specialist facility. • Initiate empirical antibiotic drops – chloramphenicol or gentamicin hourly or any other available broad spectrum antibiotic drop until the patient reaches the referral centre. • Give supportive treatment with a mydriatic (atropine eye drops) and timolol to reduce intraocular pressure. • If there is not copious discharge, give an eye patch to rest the eye.

Fungal ulcers • Fungal ulcers are commonly caused by ﬁlamentous fungi or yeasts (candida). • May occur in those who work in rural settings or those engaged in agricultural activity and in PLHIV. Key clinical features • Ulcers may follow trivial trauma. • Symptoms may be mild even with large ulcers. • Ulcers are dry, elevated, with feathery margins. Treatment • Urgent referral to tertiary level facility. • Treat as in bacterial ulcers.

Herpetic ulcers Herpes simplex virus (HSV) is a major cause of blindness worldwide from corneal scarring and opacity after cornea infection, inﬂammation (keratitis), and ulceration. See also Section 11.15. Key clinical features • Painful eye with blurred vision and discharge. • Dendritic ulcers are seen on ﬂuorescein staining of the cornea. • May coalesce to form geographic ulcers (ameboid shape, often with dendritic extensions at the edges). • Are usually unilateral. • Loss of corneal sensation if tested with wisp of cotton wool. Treatment • Refer urgently to tertiary level facility. • Treat with topical aciclovir ointment and do not use steroids. • If topical aciclovir ointment is not available, give oral aciclovir, 400 mg 5 times daily. • Administer supportive treatment with topical atropine.

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Corneal erosions Key clinical features • Areas of epithelial loss without inﬁltration. • Usually follows trivial trauma – may be a history of contact lens use or even ﬁngernail trauma. • Very painful. • If history of trauma is present, rule out penetrating ocular trauma. Treatment • Evert eyelids to look for foreign bodies. • Treat with antibiotic ointment (tetracycline) and rest with an eye patch. • Refer to specialist care if there is non-healing or delayed healing, or recurrent erosions. • Never use traditional medicines.

10.12.3 Acute visual loss • • • • Acute loss of vision is usually secondary to posterior segment diseases. All require urgent referral to a specialist facility. These conditions may or may not be associated with pain. They are usually not associated with “red eye”.

DDx: Acute visual loss Condition Central retinal artery occlusion In favour Sudden loss of vision Painless Fundoscopy – cherry red spot at fovea Visual loss less dramatic – painless loss of vision Older age Known hypertensive, sickle-cell disease or blood dyscrasias, or patient with high intraocular pressure Fundoscopy – retinal haemorrhages Photophobia, ﬂashing lights, ﬂoaters Recent blunt trauma or known sickle-cell disease High myopia, aphakia Poor or partial red reﬂex Visual loss mild to severe Following diabetic retinopathy or retinal vein occlusion Fever Signs of meningitis or pneumonitis Fundoscopy – haemorrhagic retinal necrosis (“pizza” pie appearance) Very low CD4 (<100) Visual loss may be slower in onset in early CMV disease and may not be noticed by the patients until advanced Unifocal in HIV-negative, multifocal in HIV-positive Blurred or hazy vision with ﬂoaters – erosions may look like headlights in the fog through the vitreous haze Occurs with vitritis

Central retinal vein occlusion

Retinal detachment

Vitreous haemorrhage CMV retinitis see Section 11.8

Ocular toxoplasmosis

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Condition Optic neuritis

In favour Females : Males = 2 : 1 Unilateral rapid visual loss Retro-orbital pain with eye movement Associated with viral illness, multiple sclerosis, systemic lupus erythematosis (SLE), post-meningitis – TB or cryptococcal Sudden loss of vision Severe headache and eye pain Nausea and vomiting Halos around light Pupils mid-dilated, vertically oval non-reactive to light (sluggish) Very high intraocular pressure >30 mmHg or eye feels hard on digital pressure Sudden painful visual loss following intraocular surgery or penetrating trauma or corneal ulcer Red eye Pus in the anterior chamber (hypopyon) Inﬂammation of all inner layers of the eye

Acute congestive glaucoma

Endophthalmitis

10.12.4 Progressive visual loss • Painless gradual loss of vision may be a result of various causes. • Diseases of the anterior chamber are usually amenable to treatment, while diseases of the posterior segment require urgent referral.

DDx: Progressive visual loss Condition Cataract In favour Old age, history of trauma or as part of a systemic condition May be unilateral or bilateral Opacities seen Fundoscopy – unable to see the fundus; red reﬂex obscured Common cause of visual loss in children Improvement of vision with pinhole technique conﬁrms refractive error Painless loss of vision Late-stage visual loss Cupping of optic disc on routine examination Intraocular pressure may be raised or normal Characteristic visual ﬁeld changes on manual or perimetry are diagnostic Painless central loss of vision Visual acuity decreased Longstanding DM poorly controlled or known sickle-cell disease Other risk factors: hypertensive, nephropathy, pregnancy Fundoscopy: presence of microaneurysms, hard exudates, retinal oedema, proliferative retinopathy

Refractive errors Corneal dystrophies Chronic open angle glaucoma

Hereditary macular degeneration Proliferative retinopathy e.g. diabetes mellitus, sicklecell disease

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Cataract Key clinical features • Opaciﬁcation of the lens with decreased vision. • Usually due to advancing age, but may also occur in younger population due to trauma or systemic disease, or may be present at birth or early years. • Clinically reduced clarity of lens, obscuring the view of the retina. Treatment • Referral to specialist for surgical extraction of the lens with intraocular lens implantation.

Primary open-angle glaucoma Key clinical features • Important cause for irreversible visual loss. • Early diagnosis of disease is important to prevent visual loss. • Visual loss in late stages. Treatment • Referral to specialist facility for detailed evaluation and treatment. • Start pilocarpine to lower intraocular pressure.

Refractive errors • A common cause of gradual progressive reduction of vision. • Improvement in vision with pinhole or spectacles likely indicates refractive error. • Regular and repeated screening, particularly in children and adolescents, to allow timely detection and treatment. • Short-sighted vision or myopia is the difﬁculty to see distant objects, while near objects are clear. • Far-sighted vision (hyperopia and presbyopia) is the difﬁculty to see near objects. In presbyopia, this is due to loss of accommodation, often after 40 years of age. • Uncorrected refractive errors are a common cause of headache. Treatment ° Corrective lenses ° Repeated examinations throughout growth to prevent poor vision, if left uncorrected.

Proliferative retinopathy • This is a disease of the pre-capillary arteriole and venules of the retina. • In diabetics, increasing duration of diabetes is the most important risk factor. Poor glycaemic control, concomitant HPT, nephropathy, and pregnancy are also signiﬁcant risk factors. • In sickle-cell disease, a history of multiple crises will increase the likelihood of retinopathy.

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Treatment • Stringent glycaemic control in diabetics. • Regular eye checks - annually if possible. • Referral to specialist centre for laser treatment if available; retinal photocoagulation can be vision-saving.

10.12.5 Geographically conﬁned eye diseases – onchocerciasis and trachoma Table: Geographically conﬁned eye diseases Condition Onchocerciasis see Section 11.28 Geographic area Onchocerciasis is found in 36 countries in Africa as well as in Guatemala, southern Mexico, some areas of Venezuela, small areas in Brazil, Colombia, and Ecuador; and in Yemen. In favour Inﬂammation of the eye Associated skin ﬁndings (itching), skin nodules ﬁne papular rash Lacrimation, photophobia and itching in eye Early – night blindness, narrowed visual ﬁeld Late – painful iritis or glaucoma Easily visible corneal opacity over the pupil Pupil margin blurred Substantial prevalence in the community – with severe visual loss and potentially disabling trachomatous lesions such as trichiasis and entropion (see trachoma grading system in text below).

Trachoma

Occurs globally. Speciﬁcally in Africa: Algeria, Burkina Faso, Chad, Djibouti, Ethiopia, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Malawi, Mali, Mauritania, Mozambique, Niger, Nigeria, Senegal, Togo, United Republic of Tanzania, Zambia. Eastern Mediterranean: Egypt, Morocco, Oman, Pakistan, Sudan, South Sudan, Yemen. South-East Asia: India, Myanmar, Nepal. Western Paciﬁc: Australia, Cambodia, China, Viet Nam. Americas: Brazil, Guatemala, Mexico.

Trachoma Trachoma is the result of infection of the eye with Chlamydia trachomatis. Infection spreads from person to person, and is frequently passed from child to child and from child to mother, especially where there are shortages of water, many ﬂies, and crowded living conditions. Infection often begins during childhood then becomes chronic. If left untreated, irreversible blindness typically occurs between 30 and 40 years of age, mainly in females. Key clinical features • Eversion of the eyelid shows red, swollen conjunctiva with follicles (whitish dots 0.2–2 mm) or papillae (visible red dots), scars, which can ultimately cause the in-turning of the upper eyelid (entropion trichiasis). • Damage to the cornea resulting in corneal opacities. • Other signs: limbal follicles (follicles at the upper edge of the cornea), herbert's pits (small round clear windows at the upper edge of the cornea), and pannus (gradual opaciﬁcation of the of the upper part of the cornea).

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Simpliﬁed grading of trachoma disease3 • Trachomatous inﬂammation (TF): 5 or more follicles (at least 0.5 mm in diameter) on the upper tarsal conjunctiva. • Trachomatous inﬂammation intense (TI) presents as inﬂammatory thickening of the upper tarsal conjunctiva that obscures more than half of the normal deep tarsal vessels. • Trachomatous scarring (TS): scarring (white ﬁbrosis) of the tarsal conjunctiva. • Trachomatous trichiasis (TT): at least one eyelash runs on the eyeball. • Corneal opacity (CO): central corneal opacity that is so dense that at least one of the pupil margins is blurred.

Treatment The WHO SAFE strategy4 to eliminate trachoma and prevent blindness includes: Surgery for trichiasis – corrective lid surgery Antibiotics to treat Chlamydia trachomatis infection in diagnosed patients Facial cleanliness and promotion of hygiene Environmental improvement to reduce transmission of Chlamydia trachomatis from one person to another. • The mainstay of treatment is tetracycline ointment. Apply 1% ointment directly to both eyes twice daily for 6 weeks • Give oral azithromycin, 20 mg/kg up to1 gm once a year as a family treatment or community intervention. • Refer patients with corneal opacity for specialist care.

10.12.6 Eye problems in patients with HIV infection Ocular manifestations of HIV infection are very common and varied. Simple infections and common eye diseases must be recognized, treated and differentiated from sight-threatening problems that may require referral or specialist management. These conditions are not speciﬁc to patients with HIV, but occur more commonly, with greater severity, and often with atypical features

Anterior segment and adnexal eye problems in patients with HIV infection DDx: Anterior segment and adnexal eye problems in patients with HIV infection Condition Molluscum contagiosum* In favour Pearly white papules, central umbilication Multiple lesions Unusually large in patients with HIV and do not resolve spontaneously Skin coloured – hyperpigmented papules or warty lesions Rough surface, on lids or conjunctiva Vesicular rash , dermatomal distribution – trigeminal nerve Acute pain, can involve tip of nose (Hutchinson sign) Can cause conjunctivitis, scleritis, keratitis, uveitis, glaucoma, nerve palsy

Papillomata* Herpes zoster ophthalmicus see Section 11.45

3 Trachoma simpliﬁed grading card with color illustrations. Available at http://www.who.int/blindness/causes/ trachoma_documents/en/index.html 4 Trachoma control: a guide for programme managers. WHO, LSHTM, and International Trachoma Initiative, 2006. Available at http://www.who.int/blindness/publications/tcm%20who_pbd_get_06_1.pdf

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Condition Conjunctival squamous cell carcinoma*

In favour Recent papular lesion with rapid increase in size, irregular surface and margins Grey/white rough foamy fungating appearance in interpalpebral zone Differs from pterygium with smooth shiny epithelium Tends to be very aggressive with recurrence if only simple excision used Red purplish cauliﬂower-like lesion on conjunctiva or eyelid – can be ﬂat or nodular Distinguish from subconjunctival haemorrhage Burning, dry, foreign body sensation Cornea lustreless Typical stain with Rose Bengal dye

Kaposi sarcoma*

Kerato conjunctivitis sicca

* Refer to a specialist if molluscum contagiosum, papillomata (warts), conjunctival tumours, or Kaposi sarcoma.

Herpes zoster ophthalmicus – see Section 11.45 Key clinical features • Unilateral vesicles and blisters involving the eye • More severe cases have corneal involvement • May have an atypical presentation and involve both eyes • May cause conjunctivitis, corneal lesions, keratitis, scleritis, uveitis, papillitis, and, in rare instances, retinal necrosis Treatment (all of the following as appropriate) • oral aciclovir 800 mg 5 times daily for 7 days • aciclovir 3% eye ointment applied into the eye every four hours • antibiotic eye ointment (chloramphenicol) • antibiotics for secondary skin infection if present • analgesia – paracetamol or stronger analgesics if necessary (see Section 20) • amitryptiline 25–50 mg before bed for neuropathic pain • assess for complicated disease and refer.

Posterior segment eye problems in patients with HIV infection • Most HIV-associated posterior segment diseases of the eye are associated with visual loss. • Loss of vision may be acute in onset and rapidly progressive. • Early recognition and treatment will help in preventing irreversible loss of vision. • All HIV-positive patients with any visual complaints require urgent referral to a specialist facility.

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DDx: Posterior segment eye problems in patients with HIV infection Condition Retinal microvasculopathy In favour Multiple cotton wool spots, haemorrhage Microaneurysm Asymptomatic No visual loss Painless loss of vision, large areas of retinal necrosis yellowish white, with areas of haemorrhage or necrosis ("pizza pie" appearance) No vitreous haze – fundi are clearly seen Vascular sheathing – “frosted branch” appearance Examine the other eye if this is diagnosed in one eye CD4 <100 – occurs less commonly if >100 (look for other cause of retinopathy) If bilateral with normal vision and reﬂex, then it is papilloedema If unilateral with decreased vision, then it is optic nerve disease Follows CMV of the eye most commonly, but also associated with other retinal opportunistic infections Decreased vision of gradual onset with ﬂoaters Recent initiation of ART Can result in cataract, epiretinal membrane, retinal neovascularisation that may threaten sight Poor prognosis – focus on protecting the sight of the other eye Posterior uveitis, may be focal, or diffuse mimicking CMV Serology for anti-CMV IgM if available to exclude CMV

CMV retinitis see Section 11.8

Optic disc swelling Immune recovery uveitis

Chorioretinitis from toxoplasmosis see Section 11.40

10.12.7 Neuro-ophthalmic involvement from mass lesions, TB, or cryptococcal meningitis • TB and cryptococcal meningitis in HIV-infected patients can result in papilloedema, papillitis, or ocular nerve palsies (see Section 10.10a) or may present with other neurological presentations. • As acute or progressive loss of vision can occur with TB and cryptococcal meningitis, examine the eyes routinely after diagnosis. • Papilloedema is not associated with early visual loss, but if long-standing, may cause progressive visual loss. • Papillitis is associated with acute visual loss.

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10.13 Painful joints1 In this section: 10.13.1 Clinical approach to a patient with painful joints 10.13.2 Diagnosis of single and multiple painful joints • DDx: Single painful joint – monoarthritis • DDx: Multiple painful joints • Table: Characteristics of synovial ﬂuid by diagnosis • Septic arthritis • Crystal deposition disease (gout, pseudo-gout) • Osteoarthritis • Rheumatoid arthritis • Gonococcal arthritis 10.13.3 Symptom management

Most joint pain may be a result of chronic conditions of varying duration. However, a substantial number of patients with joint problems require immediate and ongoing care. Prompt treatment can help limit symptoms, prevent disability, and improve outcomes. Follow a stepwise approach in the evaluation and management of painful joints. Both laboratory studies and diagnostic imaging can help to evaluate the joint and the joint pain. At the initial evaluation, and at each subsequent re-evaluation, there should be efforts to identify underlying conditions that may need disease-speciﬁc management.

10.13.1 Clinical approach to a patient with painful joints Step 1: Use Quick Check to identify severe conditions that require immediate medical or surgical care. Generally, an acute onset of joint pain with a prior trauma or appearance of warmth and swelling could indicate conditions such as dislocation, fracture, or a septic joint that requires more immediate attention. Other indicators of potential musculoskeletal emergency include constitutional symptoms (fever), numbness, or weakness. Step 2: Take a history and examine the patient. Step 3: Assess the patient’s HIV status. Step 4: Work through the differential diagnosis table. Step 5: Perform appropriate investigations. Step 6: Initiate treatment and monitor the patient’s response.

History • Is there any history of trauma or injury? • location of the pain: ° one or multiple joints ° true joint pain, pain from nearby bone, ligament, tendon, bursa, muscle, or referred pain. • character of the pain: ° quality – burning, sharp, constant, intermittent 1 See also the manual Surgical Care at the District Hospital, Section 19. WHO, 2003. Available at http://www.who. int/surgery/publications/scdh_manual/en/

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• • • • • • •

• • • •

° factors which worsen or improve pain ° diurnal rhythm – worse in the morning and eases at night, or worsens at the end of the day, unrelenting, or nocturnal. onset and progression, joints that were affected ﬁrst symmetry of joint involvement stiffness swelling limitation of motion constitutional symptoms, such as weight loss, unexplained fevers, chills, cough, night sweats. associated problems: ° weakness or numbness of affected limb ° gastrointestinal, genitourinary or eye problems. family history of joint disease and rheumatic conditions history of immunosuppression – HIV, immunosuppressive medicines drug history – particularly diuretics history of tick bite.

Examination Speciﬁc examination Assess for: • erythema (redness) or ecchymosis • warmth • evidence of any infective focus – e.g. a septic wound, an ulcer • crepitus, laxity, gross deformity, tendon, or muscle dysfunction (tested by resisted function) • joint swelling – hypertrophy or a joint effusion • sensory changes indicate possible neurological or vascular problems • range of motion (ROM) • ability to bear weight • contractures, bone deformities • weakness • pain that is out of proportion to the injury • limping, if lower extremities are involved • palpable, bony hypertrophy. General examination • extra-articular features of joint disease ° cutaneous nodules ° cutaneous vasculitis lesions. • lymphadenopathy • oedema • ocular inﬂammation • urethritis • tenosynovitis (tendon sheath effusions)

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• bursitis (swollen bursa) • diarrhoea • orogenital ulceration. Assess the patient’s HIV status HIV can cause either monoarthritis or polyarthritis at any CD4 count.

10.13.2 Diagnosis of single and multiple painful joints These tables are divided into conditions affecting single joints, and those affecting multiple joints.

DDx: Single painful joint – patient presenting with monoarthritis Condition Trauma In favour History of joint injury or trauma Pain, swelling, ecchymosis Bleeding into joint may be present Decreased range of motion Pain with motion and localized tenderness History of acute trauma or repetitive injury to the area Swelling over bursa Often involves knees or elbows If fever or recent bacterial infection, may be septic bursitis History of diabetes, IV drug use, sickle-cell disease Acute onset Large joint (knee most common, or also hip, shoulder, wrist, or ankle) May localize to joints with pre-existing arthritis or prior trauma Systemically ill with fever Hot tender swollen joint with decreased mobility More than one joint may be involved High WBC and ESR Joint ﬂuid WBC >50 000 (>90% neutrophils) Purulent arthritis, usually knees, wrists, or ankles (see septic arthritis) May have preceding skin lesions: papules and pustules, polyarthralgia, and tenosynovitis Sexually active, 25% have GU symptoms Synovial ﬂuid WBC >50 000 (>90% neutrophils) On diuretics Dietary and alcohol overindulgence Previous similar attacks Severe joint pain Redness, hot, tender, and swollen Typically affects the base of the big toe Gouty tophi Autoimmune Early morning stiffness lasting over 1 hour Early stages may present as monoarthritis Later symmetrical polyarthritis: often hand and wrist involvement Fixed deformities develop Extra-articular manifestations: fever, anorexia, malaise, weight loss Rheumatoid nodules: subcutaneous, usually extensor surfaces Elevated ESR, CRP, platelet count; low Hb; positive rheumatoid factor

Bursitis

Septic arthritis (usually Staphylococcus aureus or streptococcal species)

Gonococcal arthritis see Section 11.13

Gout

Rheumatoid arthritis

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Osteoarthritis (degenerative joint disease)

Gradual onset Usual age of onset over 40 Pain on weight-bearing or activity that is eased by rest Stiffness Crepitus Bony enlargement Tenderness to palpation Decreased range of motion Synovial ﬂuid – clear, WBC <2000/mm3, normal viscosity Gradual onset joint swelling Mildly inﬂamed, presentation may vary based on site Low-grade fever Night sweats Synovial ﬂuid: increased protein, increased WBC – predominantly lymphocytes Vertebral TB: X-ray of spine may show vertebral collapse

Tuberculous arthritis see Section 15

DDx: Multiple painful joints Condition Gonococcal arthritis see Section 11.13 In favour Sexually active Genitourinary symptoms Systemically ill Migratory polyarthralgia or polyarthritis (often asymmetric), tenosynovitis (asymmetric) involving ﬁngers, hands, or wrists Skin lesions – papules and pustules Septic arthritis may follow dermatitis if untreated Family history Back pain, uveitis, urethritis, gastrointestinal symptoms, and rashes Large joints of lower extremities Autoimmune Early morning stiffness lasting over 1 hour Symmetrical polyarthritis: often hand and wrist involvement Fixed deformities develop Rheumatoid nodules High ESR, CRP, platelet count; low Hb; positive rheumatoid factor Gradual onset Usual age of onset over 40 Pain on weight-bearing or activity that is eased by rest Stiffness Crepitus Bony enlargement Tenderness to palpation Decreased range of motion Fixed deformities Synovial ﬂuid: clear, WBC <2000/mm3, normal viscosity Viral illness spread by infected mosquito Severe joint pains Associated fever and rash Occurs in outbreaks or rarely in sporadic cases Diagnosed by serum antibody titres or PCR Usually of limited duration, <6 weeks Mono or polyarthritis Occurs predominantly in lower extremities Can occur at any CD4 count

Spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis) Rheumatoid arthritis

Osteoarthritis (degenerative joint disease)

Chikungunya

HIV-associated arthritis

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Perform investigations if required Consider investigations according to the suspected underlying cause. • erythrocyte sedimentation rate (ESR) • C-reactive protein (CRP) • rheumatoid factor • anti-nuclear antibody • uric acid. Arthrocentesis is urgently indicated when there is a warm, red joint with effusion, especially when there is no history of trauma. The aspirated synovial ﬂuid should be sent for cell count, chemistry, microscopy, Gram stain, culture, and crystals. Table: Characteristics of synovial ﬂuid by diagnosis Condition Normal Inﬂammatory Non-inﬂammatory Gout Pseudo-gout Septic arthritis Appearance Clear Turbid Clear Turbid Turbid Purulent/turbid WBC/mm <200 5000–50 000 <400 2000–5000 5000–50 000 >50 000

Diagnostic imaging • Plain X-rays remain the choice for the diagnosis of most joint abnormalities. • Computed tomography (CT) and magnetic resonance imaging (MRI) may be beneﬁcial when the diagnosis is not clear.

Septic arthritis Common presentations and features • most dangerous cause of acute arthritis; knee the most common site • usually of bacterial origin, but can be viral, fungal, or mycobacterial • resulting from bacteraemia, soft tissue infection, bite • much more likely in patients with pre-existing joint disease, especially rheumatoid arthritis • common organisms implicated are Staphylococcus aureus and streptococci • N. gonorrhoea in young adults • E. coli in the elderly, drug users, and very ill patients • S. aureus, M. tuberculosis, Salmonella spp. and Brucella spp. – may cause septic spinal (vertebral) arthritis or osteomyelitis.

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Diagnosis • commonly a single joint, associated fever • elevated WBC, ESR, CRP • synovial ﬂuid examination: turbid or purulent, gram stain or culture, cell count and differential. Treatment • Give pain control. • Give IV antibiotics for 2–4 weeks, depending on the clinical response and host factors: ° ceftriaxone 1–2 g once daily ° If Gram-positive cocci are seen on Gram stain or culture grows S. aureus, may switch to cloxacillin 2 g every 6 hours. ° In areas where MRSA is prevalent or diagnosis established, vancomycin 15 mg/kg every 12 hours, or cotrimoxazole (15–20 mg/kg per day of trimethoprim) every 8 hours. ° If N. gonorrhoea is presumed or conﬁrmed, see below. • Aspiration and joint washout to dryness.

Crystal deposition disease (gout, pseudo-gout) Common presentations and features • Can result from elevated levels of uric acid in the bloodstream where crystals of monosodium urate or uric acid are deposited on the articular cartilage of joints, tendons, and surrounding tissues. • Usually present as transient painful attacks of acute monoarticular arthritis. Eventually lead to chronic gouty arthritis, and the deposition of masses of urates in joints and other sites, creating tophi. • Can be difﬁcult to distinguish from septic arthritis. • Trauma, alcohol, and dietary overindulgence (meat and ﬁsh) increase the risk of gouty attacks. • Pseudo-gout – chondrocalcinosis is a very similar disease, caused by deposition of calcium pyrophosphate rather than uric acid. Diagnosis • The classic presentation of gout is podagra – sudden, unexplained swelling and pain at the base of the big toe on just one foot. • Gouty tophi, particularly when not located in a joint. • High uric acid levels support the diagnosis, but low or normal levels do not rule it out. • Deﬁnitive diagnosis is by arthrocentesis and polarized light microscopy of synovial ﬂuid for intracellular crystals; the latter is difﬁcult to perform and requires a trained microscopist: ° gout – negatively birefringent; needle shaped crystals ° pseudo-gout – weakly positively birefringent, linear or rhomboid shaped crystals. • If microscopy is unavailable, a combination of a history of episodic acute monoarticular arthritis, podagra, hyperuricaemia, and rapid relief with colchicine all strongly favour the diagnosis of gout.

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• A combination of episodic acute arthritis (especially of the knee), chronic arthritis resembling osteoarthritis, and cartilage or joint capsule calciﬁcations on X-ray favour the diagnosis of pseudo-gout. Treatment • Gout ° acute: NSAIDs, colchicine; may use corticosteroids if renal insufﬁciency ° chronic: urate-lowering agents, colchicine ° prevention: decreased meat and ﬁsh intake, weight loss, avoidance of alcohol • Pseudo-gout ° acute: NSAIDs, colchicine; may use corticosteroids if renal insufﬁciency ° chronic: NSAIDs, colchicine

Osteoarthritis This is a degenerative disease and is hereditary, mechanical, developmental, or metabolic. • It usually presents with joint pain, tenderness, stiffness, inﬂammation, creaking, and locking of joints. • Pain worse on weight-bearing, causing restriction in mobility resulting in regional muscle atrophy and lax ligaments. • Osteoarthritis is the most common form of arthritis and the leading cause of disability. Diagnosis • Usually a clinical diagnosis, but important to rule out other causes including rheumatoid arthritis and pseudo-gout. • X-rays can be used to conﬁrm, if diagnosis unclear. Typical ﬁndings include: ° joint space narrowing ° subchondral sclerosis and cysts ° marginal osteophytes. Treatment • Pain control: ° paracetamol ° NSAIDs are better than paracetamol for pain, but have a higher risk of GI symptoms. ° opioids only for acute ﬂares or when other treatments fail. • physical therapy • exercise • weight loss.

Rheumatoid arthritis Rheumatoid arthritis is a chronic inﬂammatory disease. • It usually begins in peripheral joints and proceeds inward. • It is more common in females.

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Diagnosis • Diagnostic criteria (any 4 for diagnosis – American College of Rheumatology): ° morning stiffness of more than 1 hour most mornings for at least 6 weeks; ° arthritis and soft-tissue swelling of more than 3 of 14 joints or groups of joints, present for at least 6 weeks; ° arthritis of hand joints, present for at least 6 weeks; ° symmetric arthritis, present for at least 6 weeks; ° subcutaneous nodules over bony prominences or extensor surfaces; ° rheumatoid factor at a level above the 95th percentile; ° radiological changes suggestive of joint erosion on posterior or anterior hand or wrist X-rays. • Systemic disease may involve: ° constitutional symptoms including fatigue, low-grade fever, malaise, morning stiffness (loss of appetite and loss of weight are common systemic manifestations seen in patients with active rheumatoid arthritis). • Skin, hepatic, renal, heart and blood vessels, eyes, anaemia, neurological. • Laboratory: ° Rheumatoid factor is diagnostic, but a negative result does not exclude rheumatoid arthritis. ° Other tests include anti-nuclear factor, ESR, CRP, FBC. • X-rays: ° no signiﬁcant changes in early disease – except for soft tissue swelling ° may be bony erosions and subluxation in chronic disease. Treatment • Pain control: ° paracetamol ° NSAIDs are better than paracetamol for pain but have a higher risk of GI symptoms. • Patients may require referral to a specialist for disease-modifying antirheumatic drugs (DMARDs). These drugs reduce the rate of damage to bone and cartilage. • DMARDs produce symptomatic remissions or delays, or halt progression. ° NSAIDs and analgesics may also be used to improve pain and stiffness, but they do not prevent joint damage or slow the disease progression. • physical therapy • lifestyle modiﬁcation.

Gonococcal arthritis Gonococcal arthritis is associated with the sexually transmitted disease, gonorrhoea. Gonococcal arthritis can present: • as dermatitis-arthritis syndrome with arthralgia, tenosynovitis, and painless non-pruritic dermatitis (papules, or pustules); OR • a septic arthritis. • Often there is a history of recent unprotected sexual activity or sexually transmitted infection.

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Diagnosis • Gram stain of synovial ﬂuid will show Gram-negative diplococci. Treatment • Dermatitis-arthritis syndrome ° ceftriaxone 1 g IV or IM for 24 hours after symptoms resolve then ceﬁxime 400 mg orally twice daily to complete total 7–10 days. • Septic arthritis ° ceftriaxone IV for 24 hours after symptoms resolve then ceﬁxime 400 mg orally twice daily to complete total 14–21 days. Note: add treatment for Chlamydia (doxycycline orally) and joint drainage for purulent arthritis. See also Section 11.13 Gonorrhoea.

10.13.3 Symptom management • Analgesia: ° paracetamol with or without codeine ° aspirin. • Anti-inﬂammatory: ° NSAIDs – ibuprofen, indomethacin. • Short-term steroid therapy can be used. • Topical analgesic: ° an ibuprofen or diclofenac-containing gel ° capsaicin also is used topically. • Physiotherapy – hot and cold modalities can be used.

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10.14 Female and male anorectal problems and genital ulcers1 In this section: 10.14.1 Clinical approach female and male anorectal problems and genital ulcers 10.14.2 Anorectal problems (with DDx table) 10.14.3 Genital ulcer disease (with DDx table) • Management of genital ulcers • Chancroid • Lymphogranuloma venereum • Donovaniasis (granuloma inguinale) • Management of persistent or non-healing genital ulcers 10.14.4 Special considerations in patients with HIV 10.14.5 Symptom management: rectal tenderness

This Section covers problems of the anorectal and genitourinary systems that affect both females and males. It is divided into: • 10.14.2 Anorectal problems (female and male) • 10.14.3 Genital ulcer disease (female and male) Problems that affect only females or only males are covered in the following Sections: • 10.15 Female genitourinary complaints • 10.16 Male genitourinary complaints Both men and women may feel uncomfortable talking about anorectal or genitourinary problems, or being examined. The health worker should reassure the patient and make him or her feel comfortable. It is particularly important to control genital ulcers and other STIs as they facilitate the spread of HIV.

10.14.1 Clinical approach to female and male anorectal problems and genital ulcers Step 1: Perform Quick Check. Use Quick Check to determine any life-threatening conditions. Step 2: Take a history and examine the patient. Step 3: Assess the patient’s HIV status. Step 4: Consider a differential diagnosis using the DDx tables. • DDx: Anorectal problem • DDx: Genital ulcer disease Step 5: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response. • Management of anal problems is included in the DDx table. • Use syndromic management for genital ulcer disease. • In persistent or non-responding ulcers, see management approach below. • Partner notiﬁcation and treatment is an essential step in treating STI-related anogenital problems. • Follow-up of patients and their partners is essential to monitor treatment success. It is particularly important if a syndromic approach is used, as it is possible that the treatment may not have worked.

1 Guidelines for the management of sexually transmitted Infections. WHO, 2003 (updated 2011 version in process). Available at: www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf Vol. 2 • 10. Acute and subacute by symptom: July 2011 Female & male anorectal problems 281

History • History of presenting complaint – duration, associated pain, discharge, or bleeding, history of previous episodes and treatments, similar symptoms in partner, associated constipation or diarrhoea. • Sexual history: number and sex of partners, change in sexual partner, recent unprotected sex, condom use, type of sexual activity: oral, vaginal, rectal, non-insertive. • History of recent trauma to area. • Relevant medical history (diabetes, bleeding disorders, inﬂammatory or ulcerative bowel conditions). • Previous surgery or surgical interventions. • Medications – including ART, antibiotics, traditional medicines, over-thecounter (OTC) medications, including creams and suppositories. • Any drug allergies. • Substance or alcohol use.

Examination • General examination • Look for fever, lymphadenopathy, rash. • Evidence of HIV. Speciﬁc examination • Examination of the anus ° Position the patient in the left lateral jack-knife (decubitus or fetal) position with the patient reaching behind with their right hand to lift the top buttock for visualization of the perianal area. ° An internal examination should be done digitally with a lubricated, gloved hand or with a lubricated anoscope. • Examination of the genitals ° See Section 10.15 for details for the female genitourinary examination. ° See Section 10.16 for details for the male genitourinary examination. • Assess size, number and characteristics of lesions (induration, exudate). • Ask whether there is tenderness.

Perform lab investigations Laboratory tests will depend on the ﬁndings of history and examination, and may include: • syphilis serology (see Section 11.37); • biopsy of an ulcer (should be considered in patients with a non-healing ulcer, especially if they are HIV-negative, as this may indicate malignancy); • swabs or urine specimens for bacteriology assessment in cases of failed syndromic treatment for suspected gonorrhoea and Chlamydia.

10.14.2 Anorectal problems Anorectal complaints are very common. Many people are uncomfortable talking about this part of their body and do not complain even if they are clearly experiencing problems. The stigmatization may be greatest for people who have

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anal sex even though most anorectal problems are not related to anal sex. Look to see if the patient has difﬁculty in sitting or walking, and try to put the patient at ease about discussing their symptoms. Common complaints may include: • bleeding (from rectum, on stool, from lesion on anus) • discharge (from rectum, on stool, from lesion on anus) • pain (localized or diffuse) or during anal sex • lesions (ulcers, masses, growths) • itch (internal or external).

Figure: Clinical approach algorithm for anorectal infections2 Due to its low sensitivity, microscopy is not recommended in the management of anorectal infections.

Patient with either passive anal sex in last 6 months or anal symptoms, or both

Take history* and do physical

No Anorectal ulcer? Yes Yes Treat for HSV-2 plus gonorrhoea plus Chlamydia*** * History of gastrointestinal conditions? Suggestive of gastrointestinal emergency? ** Risk: unprotected anal intercourse last 6 months, plus • partner with STI; or • multiple partners. *** If ulcer, consider adding treatment for syphilis. Also consider LGV treatment in MSM. Follow up after 1 week. If symptoms persist • Treat for lymphogranuloma venereum (LGV). • Treat for herpes simplex virus (HSV). • Refer. Yes Anal or perineal pain? No Treat for gonorrhoea and Chlamydia Yes Anal discharge?

Risk** assessment positive? No

Other management?

2 Reproduced from forthcoming revision of Guidelines for the management of sexually transmitted infections, WHO, 2011 as appears in the Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender people: recommendations for a public health approach. WHO, 2011. Available at http://www.who.int/hiv/pub/guidelines/msm_guidelines2011/en/ Vol. 2 • 10. Acute and subacute by symptom: July 2011 Female & male anorectal problems 283

DDx: Anorectal problems Condition Haemorrhoids In favour Constipation, prolonged sitting, pregnancy, heavy lifting, diets low in ﬁbre Bright red blood on stool or tissue Mucous discharge Pain or itch (especially external) Visible purple swelling History of constipation, diarrhoea, or trauma Pain on defecation Blood on tissue Small rocket-shaped superﬁcial cuts, usually in the midline Management Warm bath soaks Gradually increase ﬂuid and ﬁbre intake Anti-inﬂammatory creams Ligation, cautery, and haemorrhoidectomy if thrombosed, large, or prolapsed

Anal ﬁssures more common in PLHIV

Exclude syphilis, inﬂammatory bowel disease, TB, carcinoma Warm baths, analgesia, stool softeners (if constipated), high-ﬁbre diet, drink plenty of water Glyceryl trinitrate creams may be added Surgical internal anal sphincterotomy may improve ﬁssure healing Incision and drainage Excision under anaesthesia for ﬁstulae Antibiotic cover while awaiting surgery

Perianal abscess infection of anal crypt

Prior ﬁssures or inﬂammatory bowel disease Constant throbbing pain Erythema Fluctuant swelling Anal ﬁstula may develop History of receptive anal intercourse Sensation of rectal fullness Bleeding Pus on stool Constipation Pain on defecation (most severe with ulcerative proctitis like HSV or LGV) or during anal sex Cramping Bleeding Diarrhoea Fever Atypical presentation in PLHIV

Proctitis Gonorrhoea or Chlamydia, inclusive of variants causing lympho-granuloma venereum (LGV), internal HSV, internal syphilis chancre Proctocolitis

Treat for gonorrhoea, HSV, Chlamydia, or syphilis Note: Treat empirically as Gram stain difﬁcult to interpret due to presence of enteric bacteria.

Entamoeba histolytica, Shigella, Salmonella, Campylobacter, Cryptosporidium, CMV in HIV May be self-limiting, but treat if severe or in PLHIV External syphilitic chancre LGV HSV Consider anal carcinoma and anal amoebiasis in MSM

Anal ulcers see next Section 10.14.2

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Anal warts (HPV)

External or internal warts Flat or raised ﬂeshy growths Itch History of HPV elsewhere (HPV can migrate from genitals or transmit through contact; anal HPV can occur without anal sex)

For external warts, use podophyllin (risk of toxicity with systemic absorption if used internally)3 or cryotherapy. For internal warts, cryotherapy – use an anoscope to visualize. Warts that are too extensive, or progress despite topical therapies, should be managed with surgical excision. Note: Flat, brownish, mucopurulent warts may be condylomalata or secondary syphilis. Patients with warts must be counselled about the high transmissibility of HPV. If not caused by any of the above, then consider chronic diarrhoea, contact dermatitis, Candida infection, Staphylococcus infections, pinworms. Treat the underlying cause.

Perianal itch

Itch and discomfort in perianal area Associated dermatitis

10.14.3 Genital ulcer disease Genital ulcer disease (GUD) is common. In females, genital ulcers can occur: • on the pubic area • on the vulva • in the vagina • on the inner thigh • in the buttock cleft. In males, genital ulcers can occur: • on the shaft or head of the penis • at the urinary meatus • in the urethra • in the scrotum, inner thighs, or pubic area • in the buttock cleft.

3 Imiquimod ointment is an alternative that is easier to use but is costly and often not available.

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DDx: Genital ulcer disease Condition Herpes simplex virus (HSV) see Section 11.15 In favour Recurrent episodes Prodrome symptoms (tingling, itching, pain in area before lesions occur), episode begins with vesicles, which coalesce into ulcers. In settings where HIV is more frequent, there are often more severe outbreaks, especially with more advanced immunosuppression. Syphilis see Section 11.37 Primary syphilis – painless, indurated, single (in HIV-positive, may be multiple), clean ulcer Associated local lymphadenopathy Secondary syphilis – may have rash (involvement of palms and soles of feet classic, and unusual in other conditions), hair loss, and genital lesions (condylomalata) that are raised painless ﬂat lesions and may be mistaken for ulcers. Syphilis ulcers may be internal in patients who engage in receptive anal intercourse. Atypical manifestations may be seen with HIV. Single or multiple painful ulcers Well-demarcated with ragged undermined borders, not indurated Unilateral painful adenitis (bubo) that is often ﬂuctuant and suppurative Ulcers start as papule, then become pustular, and ﬁnally become an ulcer. Unilateral tender inguinal adenopathy (20% groove sign) Transient ulcer Associated proctocolitis, rectal ﬁstulas, or strictures Painless progressive ulcer – beefy red appearance Bleeds easily on contact No regional lymphadenopathy Painful extensive ulcers (Check for CMV at other sites, e.g. perform fundoscopy for retinal disease in HIV positive patients.) Associated with severe immunosuppression. Tuberculosis see Section 15 Neoplastic Crohn’s disease Behçet’s syndrome Trauma Drug reactions see Section 10.2 Systemic symptoms – fever, night sweats, loss of weight Regional lymphadenopathy Scraping may show AFB Non-healing after correct management Biopsy positive Ulcer accompanied by fever, diarrhoea, weight loss, abdominal pain Fistula formation, peri-rectal abscess Oral and genital ulcers Uveitis, arthritis, and vasculitis History of trauma Consider the possibility of sexual violence Well-demarcated red or purple lesions with lighter centres (target lesions) that can ulcerate Recently started ART (NVP or EFV), antibiotics (sulfonamides or tetracyclines), analgesics, or anticonvulsants

Chancroid

Lymphogranuloma venereum (LGV) Donovanosis (granuloma inguinale) Cytomegalovirus (CMV) see Section 11.8

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Hydradenitis suppurativa

Painful lesions involving the apocrine glands Foul-smelling discharge Evolving into multiple abscesses and sinuses Deep painful ulcers Advanced immunosuppression Coexistence with oro-oesophageal ulcers Associated ﬁstula This is a diagnosis of exclusion and other ulcer causes must be excluded. Genital irritation and ulcers (educate patient about increased risk of HIV transmission).

Aphthous genital ulcers

Frequent use of spermicides containing nonoxynol-9 In women

Traditional agents used for vaginal douching or dry sex Genital schistosomiasis see Section 11.34 Offensive discharge History of travel or resident in an endemic area for S. haematobium Dyspareunia, post coital bleeding Vaginal and cervical lesions Poor response to antibiotic therapy

Management of genital ulcers4 Establishing the cause of GUD is difﬁcult to do clinically. There is often more than one cause, and the manifestations and response to treatment may be altered in PLHIV. Treat all genital ulcers using national STI syndromic management protocols.

Chancroid Treatment • First-line: ° ciproﬂoxacin 500 mg oral twice daily for 3 days; OR ° erythromycin 500 mg oral 4 times daily for 7 days; OR ° azithromycin 1 gram oral single dose. • Second-line: ° cefriaxone 250 mg IM single dose. °

Lymphogranuloma venereum (LGV) Treatment • doxycycline 100 mg oral twice daily for 14 days; OR • erythromycin 500 mg oral 4 times daily for 14 days.

Donovaniasis (granuloma inguinale) Treatment • First-line: ° azithromycin 1 gram oral stat then 500 mg once daily until healed; OR ° doxycycline 100 mg oral twice daily until healed. 4 Guidelines for the management of sexually transmitted infections. WHO, 2011 – in process.

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• Second-line: ° erythromycin 500 mg oral 4 times daily; OR ° tetracycyline 500 mg oral 4 times daily; OR ° cotrimoxazole DS twice daily for 14 days minimum.

Management of persistent or non-healing genital ulcers Most non-healing genital ulcers are due to an STI, and are persistent because of poor adherence, re-infection, incorrect management, resistance to the drugs used, or sometimes incorrect diagnosis. In HIV patients, treatment is often needed for longer periods and in higher doses. • Conﬁrm that HIV testing has been done. • Review the initial management the patient received, including drugs prescribed, and patient adherence to treatment. • Consider syphilis serology if not previously performed or if previously nonreactive (test may be non-reactive with early primary syphilis – reactivity takes 2–3 weeks to develop). A non-reactive test with a persistent ulcer makes a syphilis diagnosis unlikely. • Consider that syphilitic ulcers can take some weeks to resolve. • Patients with reactive syphilis serology and neurologic signs or symptoms require a CSF examination and may need treatment for neurosyphilis. • If not yet treated for HSV and history is suggestive, give aciclovir according to national guidelines. • If treated for HSV with no response, or only slight response, repeat treatment using aciclovir (400–800 mg 3–5 times per day) until the ulcers resolve. In severe cases, IV aciclovir may be needed (5–10 mg/kg every 8 hours for 5–7 days). • If there have been frequent HSV episodes (i.e. 6 or more recurrences per year), the patient may beneﬁt from daily suppressive therapy – see Section 11.15. • Consider an alternate diagnosis – longer courses of treatment are needed for possible chancroid or LGV, and an aminoglycoside should be added to treat granuloma inguinale if improvement is not seen within a few days of starting oral therapy. • If exudate is present, consider secondary bacterial infection and treat with a broad spectrum antibiotic. • Consider schistosomiasis if from an endemic area (see Section 11.34 Schistosomiasis). • Continued non-healing requires a biopsy to rule out cancer and tuberculosis, and may need referral to a higher level of care.

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10.14.4 Special considerations in patients with HIV Table: Treatment considerations for HIV-positive patients Condition HSV Syphilis see Section 11.37 Diagnostic and treatment considerations May require longer treatment courses and higher doses. With frequent episodes, may beneﬁt from chronic suppressive therapy. Treatment of primary and secondary syphilis same for HIV-positive. If suspected treatment failure (titre increasing or not decreasing, clinical evidence of higher stage syphilis), re-treat with 1 dose every 3 weeks and check for neurosyphilis with CSF test. High index of suspicion for neurosyphilis if auditory, visual, or neurologic symptoms are present. If neurosyphilis diagnosed, treat as in Section 11.37 Syphilis. False-positive diagnoses are common in the context of HIV when using non-speciﬁc syphilis tests, e.g. RPR, and should be conﬁrmed with a more speciﬁc test, e.g. TPHA. Response to treatment may be reduced and risk of treatment failure is increased. Early treatment is important. Patient follow up at day 3-7 is important to assess healing. If healing is poor, treatment should be repeated or prolonged. May require longer treatment. Add aminoglycoside to standard treatment regimen if improvement is not seen within a few days of starting oral therapy. Standard treatment as for extrapulmonary TB. This is a WHO stage 4 diagnosis and ART-naïve patients should be started on or referred for ART 2 weeks after TB treatment is instituted. Consider with severe immunosuppression, particularly if clinical signs suggest CMV. Do fundoscopy to check for ocular CMV. See Section 11.8 for treatment. ART should be started in patients not yet on treatment. Consider with severe immunosuppression, particularly if associated with oral ulcers or ﬁstulas. Diagnosis of exclusion after treatment for other bacterial or viral causes. Treat with systemic steroids (prednisone 40–60 mg/day for 1–2 weeks, then taper). Consider TB before starting steroids. Squamous cell carcinoma is most common. Other possibilities: lymphoma or Kaposi sarcoma. Biopsy required for diagnosis. Refer to higher level of care for treatment.

Chancroid

LGV Granuloma inguinale Tuberculosis See Section 15 CMV see Section 11.8 Aphthous ulcer

Malignancy

Monitoring response to treatment and follow-up • First follow-up should be in 1 week. Treatment must be continued if symptoms are still present (even if they have improved). • If the ulcer is still persistent after all the above, consider referral to higher level. • For patients with presumed syphilis (ulcer and reactive syphilis serology), follow-up at 3, 6, and 12 months for serology and syphilis titre to ensure successful treatment. • If the ulcer is from an STI – notify and treat partners. • Counsel patients about sexual abstinence or condom use until both partners are treated; encourage condom use.

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10.14.5 Symptom management: rectal tenderness Hospital medication and clinical management • Make a thorough assessment for possible causes of rectal pain, e.g. haemorrhoids, perianal abscess, perianal ﬁstula, anal ﬁssure or tear, infectious proctitis, anorectal herpes simplex, anal or rectal cancer. • If there is an abscess, incise and drain. This can be very painful for the patient, so remember to premedicate with an appropriate pain medicine. • Use topical steroids, e.g. hydrocortisone enemas. • Give laxatives if constipated and if with anal ﬁssure. • Give speciﬁc treatment according to suspected cause (e.g. aciclovir for HSV; doxycycline for Chlamydia). • Control pain as per the analgesic ladder (see Section 20). Outpatient medication and clinical management • If there is local rectal tenderness – suggest petroleum jelly or local anaesthetic ointment. • If the patient is incontinent – use petroleum jelly to protect perianal skin. Home care • After the sick person has passed a stool: ° clean with soft tissue paper ° wash the rectal area when necessary with soap and water ° apply petroleum jelly around the rectal area. • The person should then sit in basin of water with a pinch of salt. If this is comfortable, suggest doing it twice daily.

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10.15 Female genitourinary complaints In this section: 10.15.1 Clinical approach to female genitourinary complaints 10.15.2 Abnormal vaginal bleeding or amenorrhoea, or lower abdominal or pelvic pain (with DDx tables) 10.15.3 Pelvic mass (with DDx table) 10.15.4 Abnormal vaginal discharge not responding to syndromic management (with DDx table) • Approach to management 10.15.5 Pelvic inﬂammatory disease 10.15.6 Septic abortion 10.15.7 Approach to urinary incontinence (with DDx table) • Symptom management: urinary incontinence 10.15.8 Cervical cancer 10.15.9 Schistosomiasis of female genitourinary tract

This Section provides an approach to the diagnosis and management of the most common genitourinary (GU) complaints in women. For diagnosis and management of anorectal problems and genital ulcers in women and men, see Section 10.14. It is important to remember to have a high index of suspicion for genitourinary complaints as both men and women may be reluctant to discuss these problems. Additionally, it may be considered culturally inappropriate to discuss such topics, especially with a clinician of the opposite sex. Use direct but sensitive questions to ask about genitourinary symptoms. Reproductive health is affected by traditional beliefs and practices, the status of women in the society, childbearing desires, family planning and reproductive choices, sexual partner behaviours and beliefs, the prevalence of domestic and sexual violence, fears, stigma, and other factors. It is important to always consider the possibility of sexual violence. Also, it is important for the health worker to be aware of the endemicity of schistosomiasis where the patient lives, or has lived in the past (see Sections 10.15.9 and 11.34). All patients from schistosomiasis endemic areas that present with genitourinary complaints should be treated empirically with a single dose of praziquantel at 40 mg/kg. Remember that patients may present with a combination of symptoms, e.g. pelvic pain with diarrhoea. It is important to distinguish the major symptom and to work through the approach for that symptom. It may also be necessary to work through multiple tables.

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10.15.1 Clinical approach to female genitourinary complaints Step 1: Perform Quick Check. Use the Quick Check to look for urgent and priority signs that may indicate the need for immediate intervention. Consider pregnancy in any women of childbearing age, particularly if presenting with missed or overdue menses, other abnormal bleeding, or pelvic pain. For the management of problems during pregnancy, refer to the IMPAC guidelines. Step 2: Take a history and examine the patient. Genitourinary complaints have a broad differential diagnosis, including primary problems in the gastrointestinal or urinary tract. Some systemic medical conditions (or therapies) may have gynaecological signs or symptoms. Vital signs (temperature, pulse, BP) are critical in determining the possible presence of an urgent or emergent problem requiring immediate intervention. Although the exam will focus on the abdomen and pelvis, the general examination is important to identify possible systemic disease or immunosuppression. Step 3: Assess HIV status. Step 4: Consult the relevant differential diagnosis table(s) and develop a differential diagnosis. Step 5: Perform investigations as needed. See individual diagnosis for speciﬁc investigations needed. Step 6: Initiate management and monitor response. Step 7: In confusing cases, rconsider the possibility of underlying malignancy or opportunistic infection related to HIV infection. Maintain a high index of suspicion for sexual violence as a cause or contributor to presenting complaints.

History Ask about the following in all women with GU complaints (the speciﬁcs for each presenting symptom are discussed above each table). • Reproductive tract: ° menstrual history – date of last menstrual period, missed or overdue periods, presence of abnormal bleeding (excessively heavy, bleeding between periods, irregular periods), note if postmenopausal; ° current sexual activity – number of partners or recent change in partners; ° contraceptive use – regular and reliable use, including condoms; ° pregnancy history – current gestational age, complications, history of recent delivery, miscarriage, abortion; ° history of infertility or other chronic gynaecologic conditions; ° previous history of STI/RTI in patient and partner – if recent, what treatment was prescribed and was it taken correctly. • Medical history – chronic or current other medical conditions: ° urinary problems – history of recurrent urinary tract infections or kidney stones, or current symptoms of dysuria, blood in urine; ° HIV status – if negative, when was the last test, if positive, last CD4 result, antiretroviral therapy status, presence of OI ; ° gastrointestinal problems – ulcers or inﬂammatory conditions, current symptoms (e.g. diarrhoea, rectal bleeding, melena); ° bleeding conditions – history of easy bruising, nose or gum bleeds, anaemia;

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° substance or alcohol abuse. • Surgical history – any abdominal or pelvic surgical intervention in the past. • Medications: ° long term treatments including ART; ° hormonal contraception; ° recent intake of medications – including prescribed and over-the-counter medications; ° treatment received at ﬁrst level, and adherence to prescriptions; ° traditional medicines.

Examination General examination • Ensure that vital signs are stable, paying particular attention to ﬁndings from the Quick Check, including heart rate, blood pressure. • Presence of a fever. • Perform a thorough general examination, paying particular attention to pallor, lymphadenopathy, skin and oral lesions, and looking for signs of systemic disease, and immunosuppression. Abdominal and pelvic examination • Assess for abdominal tenderness with the presence of rebound tenderness and guarding: ° palpate for costovertebral angle tenderness. • Assess for abnormal masses or hepatosplenomegaly: ° assess size, consistency, mobility, location. • Perform a visual inspection: ° look for lesions, warts, ulcers, discharge, presence of hyperpigmentation, erythema or induration, tenderness, evidence of trauma; ° associated inguinal or generalized lymphadenopathy. • Perform speculum and bimanual pelvic examination (see Section 7.2.8): ° presence of abnormal bleeding or discharge; ° lesions on the cervix or vagina; ° uterine, adnexal, or cervical motion tenderness; ° size of the uterus – if it is enlarged, check the consistency, tenderness, size; ° presence of an adnexal mass – if this is present, check the size, tenderness, consistency, mobility. If the woman with heavy vaginal bleeding is known to be pregnant assess the duration of her pregnancy. If it is late into the pregnancy (i.e. the late second or third trimester, or if the uterus is above the umbilicus), do NOT perform digital or bimanual examination because of risk of haemorrhage if placenta previa is present. (See IMPAC MCPC.1)

1 IMPAC Managing complications in pregnancy and childbirth: a guide for midwives and doctor. WHO, 2003. In revision. Available at http://www.who.int/making_pregnancy_safer/publications/archived_publications/mcpc. pdf

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Investigations The following investigations may be considered in the evaluation of GU complaints. Decisions about speciﬁc tests should be made based on the patient’s history, examination ﬁndings, and differential diagnoses. Considerations with individual investigations are listed below. Pregnancy test Qualitative urine pregnancy tests currently available can generally diagnose pregnancy within 2–4 weeks after conception, and can be performed at the point of care. Pregnancy testing should be strongly considered in the following situations: • when the pregnancy (intrauterine or ectopic) may be the cause of the presenting complaint(s), and it cannot be diagnosed on physical exam alone: ° consider in any woman with a missed or overdue period, or an abnormal bleeding pattern; ° consider in any woman with acute pelvic pain; • when the pregnancy will inﬂuence the treatment given for other conditions diagnosed or suspected. The possibility of pregnancy should be considered even in women using contraception. Pregnancy after tubal sterilization or with the use of an IUD is more likely to be ectopic. Wet mount with KOH preparation (see Section 7.2.15): consider this if the woman has abnormal vaginal discharge. Urine dipstick: consider this with either lower abdominal pelvic pain or urinary symptoms (burning, blood in urine), or both. Assess for the presence of leukocytes, nitrites, and blood. Urine microscopy (with filtration or concentration methods): check for S. haematobium ova. Haemoglobin: consider in patients with abnormal bleeding, pelvic pain, hypotension, tachycardia, dizziness, or pallor. Ultrasound: Consider a transabdominal ultrasound (see Section 7.2.21) for acute GU complaints in the following circumstances: • Positive pregnancy test (with acute pelvic pain or abnormal bleeding or missed menses). The aim is to identify the location of the pregnancy (intrauterine or ectopic): ° in almost all cases, identiﬁcation of an intrauterine gestation excludes the possibility of an ectopic pregnancy; ° ﬁndings suggestive of ectopic pregnancy: nothing in the uterus plus adnexal mass or free ﬂuid in pelvis; ° ﬁndings suggestive of missed or incomplete abortion: presence of intrauterine gestational sac but no fetal pole or fetal heart tones (after 7 weeks of pregnancy); ° in very early intrauterine pregnancy (before 5 weeks) there may be no ultrasound ﬁndings. • To characterize an intrauterine pregnancy, check: ° gestational age ° number of foetuses

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° location of placenta ° fetal presentation. • To identify the presence of gestational trophoblastic disease (molar pregnancy): ° “snowstorm” appearance on the ultrasound with a positive pregnancy test. • When a pelvic mass is identiﬁed or suspected based on the history and the exam, check: ° the location of the mass (uterine ﬁbroids, adnexal mass) ° the size of the mass(es) ° the characteristics of the mass (solid, cystic, complex vs. simple). • When there is postmenopausal bleeding, check to determine the thickness of the endometrium. Additional investigations will depend on the clinical picture.

10.15.2 Abnormal vaginal bleeding or amenorrhoea, or lower abdominal or pelvic pain In women with genitourinary complaints, abnormal vaginal bleeding or lack of menses often coexists with lower abdominal or pelvic pain, and there is signiﬁcant overlap in key questions, examination findings, and differential diagnoses. Therefore, these presenting complaints should be considered together. Exclude conditions needing urgent surgical or obstetrical interventions (ectopic pregnancy, appendicitis, abortion or labour, excessive bleeding), and also consider abdominal pathology with radiation of pain to lower abdomen (e.g. gastrointestinal problems).

History Ask speciﬁc questions relating to abnormal bleeding, amenorrhea, or pelvic pain (in addition to the history that should be asked of all women with GU complaints – see those questions above): • Do you have lower abdominal pain? • If yes: ° When and how did it start (gradual versus a sudden onset)? ° Is it continuous or does it come and go? ° Where is it located, and does it move around or radiate (pain may be localized or generalized)? ° What type of pain is it (cramp, colicky, sharp, dull)? ° How severe is the pain (on a scale of 1–10)? ° Is there anything that makes the pain worse or better? ° What has been used to treat the pain already, and how did it affect pain? ° Do you have any associated symptoms? (fever or chills, weight loss, nausea or vomiting, diarrhoea, constipation, loss of appetite, dysuria, abnormal vaginal discharge, urinary frequency or urgency, haematuria) • Have you gone through menopause? • If yes: • Details of bleeding are not as important – you should note the amount of bleeding, history of trauma, or use of traditional vaginal practises that may cause trauma to the vagina. • Have you missed a period or are you overdue? ° Do you have regular periods?

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° Describe the pattern of bleeding. What is longest and shortest time between periods? ° Do you have excessively heavy periods (some measure of the amount of ﬂow and the number and type of pads or cloths used in a 24-hour period, presence of clots)? ° Do you have bleeding between otherwise normal periods? ° Do you use any herbs or other agents in the vagina, and what are they? • Have you had any trauma in the genital area (rough sex, sexual assault)? • Do you have a history of a bleeding disorder (easy bruising, nose or gum bleeds)?

Examination Key ﬁndings on physical exam: (ﬁndings in BOLD may require urgent intervention) • Use the Quick Check for emergency signs suggesting shock: weak or fast pulse, prolonged capillary reﬁll, systolic BP <90. • Fever • Abdominal exam: ° soft or rigid ° localized vs. generalized tenderness, presence of rebound tenderness or guarding ° presence of masses, enlarged liver or spleen ° presence of costovertebral angle tenderness. • Pelvic exam: ° presence of abnormal discharge ° cervical motion tenderness ° uterine enlargement or tenderness ° adnexal mass or tenderness ° evidence of trauma. °

Investigations The laboratory tests to be performed will depend on the ﬁndings of the history and physical examination. Consider the following in all patients: • a pregnancy test – in all women of childbearing age (this is not needed in women who are clearly postmenopausal); • haemoglobin, white cell count, and differential – to look for signs of infection and bleeding.

Differential diagnosis of pelvic pain or abnormal vaginal bleeding, divided according to the presence of pregnancy.

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DDx: Abnormal vaginal bleeding or amenorrhoea or lower abdominal or pelvic pain, with a positive pregnancy test result (+) Abnormal bleeding or amenorrhoea Key features Uterus normal size or slightly enlarged; cervix closed; may palpate adnexal mass. Ultrasound shows adnexal mass, free intraperitoneal ﬂuid, empty uterus. IV access, surgical treatment. Possible blood transfusion. Patients with evidence of shock or rebound tenderness must be evaluated urgently for ruptured ectopic and need for immediate surgery. Refer to IMPAC MCPC1 Start IV antibiotics and stabilize (see Quick Check and Section 3.1.5 if septic shock). 12–14 weeks: vacuum aspiration is the recommended technique for surgical abortion. Dilatation and sharp curettage, where it is still practiced, should be replaced by vacuum aspiration. The procedure should not be routinely completed by sharp curettage. After 12–14 weeks: experienced provider for dilatation and evacuation under sono-guidance. If not available, use misoprostol. Management YES (usually missed period and abnormal bleeding or spotting)

Condition

Pelvic or lower abdominal pain

Ectopic pregnancy

YES (often unilateral, but may be more generalized with rebound tenderness if ruptured) YES (irregular, may be heavy) History of recent spontaneous or induced termination of pregnancy or recent delivery (pregnancy test may still be positive for an indeﬁnite period of time after termination of pregnancy or delivery); fever, elevated WBC; uterine tenderness, possible foul odour, or purulent discharge. Ultrasound may show retained products.

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Septic abortion or postpartum sepsis2

YES (usually midline, but may be generalized)

Female GU complaints

2 Safe abortion: technical and policy guidance for health systems. WHO, 2003 (updated version to be published in 2011). Available at http://www.who.int/reproductivehealth/ publications/unsafe_abortion/9241590343/en/

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298 Abnormal bleeding or amenorrhoea Key features Enlarged soft uterus Cervical os may be dilated Ultrasound shows enlarged uterus with or without products of conception. Signs of shock or excessive bleeding require urgent surgical intervention. Management YES (may be heavy with or without passage of tissue) Need to consider uterine perforation if previous legal or illegal procedure or incorrect diagnosis (e.g. ectopic). Refer to IMPAC MCPC. 1 Either vacuum aspiration or medical treatment can be recommended for women with incomplete abortion at any gestation whose uterine size at the time of treatment is 13 weeks or less. The recommended medical treatment is misoprostol (administered as a single dose either sublingually 400 mcg or orally 600 mcg). The decision for treatment should be based on the clinical condition and the patient’s preferences for treatment. Prophylactic antibiotics: single dose of nitromidazoles, tetracyclines, or penicillins. If this diagnosis is considered, patient needs urgent surgical intervention. Refer to IMPAC MCPC.1 +/- (although there may be some vaginal bleeding related to labour, the primary bleeding with ruptured uterus is within the peritoneal cavity and will not be visible) Abdominal distension Abnormal uterine contour Palpable fetal parts Often rapid pulse, hypotension YES (profuse, often heavy and continuous, typically without pain) Uterus palpable above umbilicus soft. Fetal heart tones normal. Abdominal ultrasound, see Section 7.2.21. Refer to IMPAC MCPC.1 Establish IV access – patient may require blood transfusion. Perform ultrasound to document diagnosis. May consider “double set-up” in the operating room, with preparation for surgery and examination to potentially rule out diagnosis of previa. Should be able to be managed at district level, but consider referral under the following circumstances: patient stable with minimal bleeding AND previous C-section (concern for placenta accreta or percreta) OR prematurity with need for neonatal intensive care and resources not available on site.

Condition

Pelvic or lower abdominal pain

Spontaneous miscarriage or abortion

YES (usually crampy, midline)

Female GU complaints

Ruptured uterus

YES (severe, may initially decrease after rupture takes place)

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Placenta previa see Quick Check page 24

DDx: Abnormal vaginal bleeding or amenorrhoea, or lower abdominal or pelvic pain, with a negative pregnancy test (-)

Condition NO Unilateral tenderness, possible palpable adnexal mass Nausea or vomiting May give history of pain being preceded by strenuous activity, sex. Ultrasound shows adnexal mass. Sudden onset, often preceded by strenuous activity or sex. Most common in functional cysts in late phase of menstrual cycle; can occur with cysts from endometriosis or a benign tumour (such as dermoid), with resulting chemical peritonitis. Clinical presentation similar to bacterial PID; patient generally has past history of TB OR contact with TB OR evidence of TB in other systems, often pulmonary. May have ascites with abdominal distension with ﬂuid thrill as well as infertility. Requires surgical intervention.

Pelvic/lower abdominal pain Key features Management

Abnormal vaginal bleeding or amenorrhoea

Ovarian torsion

YES (usually unilateral; may give history of recent episodes of similar pain) NO

Vol. 2 • 10. Acute and subacute by symptom: July 2011 Usually self-limited if minimal leakage; close observation needed. Speciﬁc management not required unless evidence of signiﬁcant haemorrhage. If evidence of shock or intractable pain, surgical intervention may be required. For pain management see Section 20. If suspect, refer where endometrial sampling for culture and stain is done. If treated for bacterial PID without improvement, consider this diagnosis. Also consider ovarian cancer, especially if ascites or pelvic mass present. Recommend HIV testing and counselling. YES (usually irregular spotting between menses)

Ruptured ovarian cyst

YES (usually unilateral, may be generalized if signiﬁcant intraperitoneal bleeding or leakage of cyst contents)

Tuberculosis see Section 15

YES

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300 Abnormal vaginal bleeding or amenorrhoea +/- (excessively heavy or long menses suggests that ﬁbroids may be located in uterine lining. Enlarged, irregular uterus, usually ﬁrm Localized tenderness if degenerated Ultrasound may show presence of ﬁbroids. Key features Management Heavy bleeding may require stabilization and, in some cases, may require transfusion or possible curettage for immediate control of bleeding. In some cases (e.g. patient without severe anaemia) attempt to manage bleeding with hormonal treatment, low dose COCs or progestin-only contraceptive methods (pills, injections, implants, LNG IUDs3). Menorrhagia with anaemia or shock may require surgical intervention (myomectomy or hysterectomy). Pain with degeneration usually self-limited; for pain management see Section 20 Biopsy for diagnosis, if possible (see Section 10.15.8). May need measures to control for persistent vaginal bleeding. Refer for surgical or radiation treatment. Biopsy for diagnosis, if possible. Refer for surgical or radiation treatment. YES (irregular, may be heavy or light, often bleeding after intercourse) Frequent history of abnormal foulsmelling discharge; cervical mass or ulcer. More common in HIV+ women. Uterus may be enlarged. More common in women with obesity, hypertension, diabetes, or if on unopposed oestrogen replacement. Ultrasound shows thickened endometrial lining. Chronic pain, often worse with menses; associated with infertility. May have tender adnexal mass (endometrioma). Evidence of trauma, such as bruising, tears, lacerations. YES (usually in postmenopausal women, may be light or spotting) NO May improve with LH agonists (recent evidence suggests greater efﬁcacy than continuous oral contraceptives). May require surgical intervention in severe cases or with infertility. Management of trauma. Psychosocial care. Pain control. Refer for counselling and supportive care. See Sections 4.4 and 10.11 YES (may be profuse if tears, lacerations)

Condition

Pelvic/lower abdominal pain

Uterine ﬁbroids (with or without degeneration)

YES (if degenerated, usually midline; no rebound)

Female GU complaints

Cervical cancer

+/- (generally without pain, except in later stages)

Uterine cancer

+/-

Endometriosis

YES

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Trauma or rape (similar picture may be seen with certain traditional vaginal practices)

YES (localized usually to vulvar or vaginal area)

3 Family planning: a global handbook for providers. WHO, (updated) 2011. Available at http://www.who.int/reproductivehealth/publications/family_planning/9780978856304/en/ index.html

Related to normal menstruation NO Symptomatic treatment (NSAIDs). Cyclic midline cramping pain with menses (dysmenorrhoea); mid-cycle unilateral pain associated with ovulation. May have evidence of cervical infection or PID; also seen with endometriosis, some pelvic masses. Treat underlying condition. May need psychological counselling. Exam generally normal, although ovaries may be somewhat enlarged on pelvic exam or ultrasound. May have history of infertility.

YES

Dyspareunia NO

YES (associated with intercourse) YES (usually history of periods of amenorrhoea followed by heavy and prolonged bleeding)

Vol. 2 • 10. Acute and subacute by symptom: July 2011 Rule out associated anaemia. If present, treat. Rule out uterine cancer or hyperplasia with biopsy if abnormal bleeding is prolonged. Treat with COCs or cyclic medroxyprogesterone acetate 10 mg orally daily for 10 to 14 days per month, if not trying to conceive (protective against uterine hyperplasia or cancer; COCs also provide effective contraception.) Refer if treatment needed for infertility. Requires urgent arrangement or referral for surgical intervention. NO Fever; right lower quadrant tenderness with or without rebound. FBC – high WBC. Treat with antibiotics. See Section 11.44. NO (in some cases haematuria may be mistaken for vaginal bleeding) Pain on urination. Urinary frequency and urgency, possible haematuria. Check for CVAT. Cloudy urine. Urine dipstick – blood, leucocytes, nitrites. Urine microscopy: leukocytes, RBC, bacteria. Gross or microscopic haematuria, with or without CVA tenderness. Ultrasound may show dilatation of ureter. Associated with chronic illness or signiﬁcant weight loss. NO YES (amenorrhoea for varying periods of time) Always rule out pregnancy. Treat underlying condition.

Polycystic ovarian disease

Appendicitis see Section 10.7a

YES (vague periumbilical pain that localizes to right lower quadrant, more generalized if ruptured)

Urinary tract infection, cystitis. pyelonephritis see Section 11.44

YES (if suprapubic – cystitis; if CVA tenderness – pyelonephritis)

Female GU complaints

Renal stone

YES (severe, colicky, may radiate into groin)

IV hydration, pain control (morphine) until stone passes. If pain continues without relief, refer for possible surgical intervention.

Hypothalamic amenorrhoea

301

10.15.3 Pelvic mass Pelvic masses may be due to a number of conditions. The patient may present with lower abdominal, pelvic pain, or abnormal bleeding or may have no symptoms. Serious conditions include abscesses, ectopic pregnancy, and cancers.

History Key questions (in addition to a history that should be taken for all women with GU complaints, see above). See key questions if the woman also has lower abdominal pain, abnormal vaginal bleeding, or amenorrhoea. In a woman who complains of or is found to have a pelvic mass on examination, and is without pain or abnormal bleeding, ask: • Do you have fever or chills, weight loss or gain? • Do you have gastrointestinal symptoms (nausea or vomiting, diarrhoea, constipation, rectal bleeding, bloating)? • Do you have urinary symptoms (dysuria, frequency, urgency, haematuria, urinary retention)? • Do you have abnormal vaginal discharge?

Examination Key ﬁndings on physical exam: • Constitutional ﬁndings: evidence of wasting, pallor, enlarged lymph nodes, fever. • Abdominal exam: evidence of ascites, liver or spleen enlargement, tenderness with or without rebound or guarding. • Pelvic exam: location, size, mobility, tenderness, characteristics of mass; abnormal vaginal discharge. In women of reproductive age, a normal ovary may be up to 5–6 cm in size. A palpable ovary in a postmenopausal woman should be considered abnormal and requires further evaluation.

Investigations Laboratory tests to be performed will depend on the ﬁndings of the history and physical examination. Consider the following in all patients: • Pregnancy test: if premenopausal. • Laboratory tests: FBC with differential. • Pelvic ultrasound. Ultrasound can determine whether the mass is solid or cystic, simple or complex, as well as the presence of ascites or free ﬂuid suggestive of blood. • Additional evaluations involving procedures such as laparoscopy or colonoscopy require referral.

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DDx: Pelvic mass Condition Ectopic pregnancy In favour Missed menstrual period and abnormal bleeding or spotting; unilateral abdominal pain (may be more generalized if ruptured) Adnexal mass – tender FBC – anaemia Pregnancy test positive Ultrasound – adnexal mass, free ﬂuid Fever, other features of PID (see above); generalized and rebound tenderness and shock suggests rupture Elevated WBC Can see similar presentation with postsurgical abscess Usually asymptomatic, but may have chronic pelvic pain or dyspareunia Often history of PID WBC normal Ultrasound – dilated cystic tubular structure Often asymptomatic Heavy or prolonged menses Urinary frequency Non-tender, unless degenerated Enlarged, irregular uterus, usually ﬁrm; localized tenderness if degenerated Ultrasound – ﬁbroids Possible known endometriosis Non-mobile masses Rupture or leaks cause sudden sharp abdominal pain and rebound tenderness. Often history of infertility and dyspareunia Ultrasound – complex cystic ovarian mass Often asymptomatic With cancer and some benign tumours, may have abdominal bloating and discomfort May be cystic, solid, or mixed Loss of weight, presence of ascites suggests malignancy Adnexal mass with great variation in size; with a solid consistency, irregular, and ﬁxed suggests cancer Ultrasound – multilocular complex cyst; presence of solid components, papillary projections, and ascites suggest cancer. Management IV access. Surgical treatment. If evidence of shock, see ETAT. Possible blood transfusion. Patients with evidence of shock or rebound tenderness must be evaluated urgently for ruptured ectopic and need for immediate surgery. IV access, IV antibiotics. Evidence of rupture with or without signs of septic shock requires urgent surgical intervention. No treatment needed if no symptoms. May require surgical intervention if chronic pain or if increasing in size.

Tubo-ovarian abscess or pyosalpinx

Hydrosalpinx

Fibroids

May try management with COCs or progestin-only contraception. Pain with degeneration usually self-limited; pain management. Menorrhagia with anaemia may require surgical intervention (myomectomy or hysterectomy). Refer for surgical management or hormonal treatment if early signs and if desires pregnancy.

Endometrioma, endometrial cyst

Benign or malignant ovarian tumour

Refer to specialist. Surgical intervention is required. Presence of adnexal mass in postmenopausal woman should be considered cancer until proven otherwise.

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Condition Functional ovarian cyst*

In favour Women of reproductive age Mostly asymptomatic, but may have unilateral pelvic pain If rupture, pain can be more generalized with signs of peritonitis Ultrasound – unilateral cyst <5–6 cm in size

Management Usually self-limited. After resolution, use of hormonal contraception can prevent new cysts from forming Does not require speciﬁc management unless evidence of signiﬁcant haemorrhage with rupture. If shock, arrange for possible surgical intervention. Pain management.

Ovarian torsion

Unilateral tenderness, possible palpable adnexal mass Nausea or vomiting May give history of pain being preceded by strenuous activity or sex Usually unilateral; may give history of recent episodes of similar pain Ultrasound – adnexal mass May present as pelvic mass; look for other constitutional signs (fever, weight loss, lymphadenopathy) DDx includes lymphoma, TB Change in bowel habits Gross or occult blood in the stool May have weight loss Signs of infection with abscess (fever, tenderness, elevated WBC) Inability to urinate; suprapubic tenderness

Requires urgent surgical intervention.

Retroperitoneal lymphadenopathy

Refer for appropriate diagnosis and treatment. Recommend HIV testing and counselling Refer for colonoscopy, possible surgical treatment if malignancy found. IV antibiotics for abscess. Consider Miegs syndrome. Urinary catheter, search for possible causes (e.g. infection; severe genital herpes; bladder, primary or secondary tumour).

Gastrointestinal mass (bowel malignancy, diverticular abscess)

Enlarged bladder due to urinary retention

* Ovarian functional cyst: functional cysts are the most common ovarian masses found among women of reproductive age, and are related to ovulation or corpus luteal cysts, although they are not usually clinically palpable unless >4 cm. Be careful of torsion in large pedunculated cysts. In cysts <4 cm resolution occurs spontaneously in 1 to 3 months. In a thin woman of reproductive age who is not guarding, palpating an ovarian cyst at mid-cycle or shortly before she is due for her period is consistent with an ovarian functional cyst. Re-examine her shortly after her next menses (i.e. at a different time in her cycle). If persistent, then an ultrasound is needed.

An ultrasound should be considered for any adnexal mass that is thought to be >5 cm in size or with a palpable adnexal mass of any size in a postmenopausal women. In reproductive-age women with smaller cysts (5 cm or less), an alternative is to re-examine them at a different time in their menstrual cycle. Small cysts can resolve with time. Larger masses are less likely to be functional, which is why they are less likely to resolve spontaneously, and torsion is a potential risk. Any patients with severe unexplained bleeding and anaemia, pelvic mass, ﬁndings suspicious for malignancy, or bleeding that is not resolved with conservative measures should be hospitalized. See the IMPAC MCPC.1

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10.15.4 Abnormal vaginal discharge not responding to syndromic management Patients may be referred to the second level of care because of abnormal vaginal discharge that does not respond to syndromic management. The primary care guidelines in IMAI Acute Care are based on the WHO STI syndromic guidelines and assume syndromic management without laboratory tests.

History Key questions (in addition to a history that should be taken from all women with GU complaints, see above): • How long has the discharge been present, and what does it look like (colour, consistency)? • Have you ever had water body contact in schistosomiasis endemic area? • Do you have any associated symptoms (e.g. pruritis, malodour, sores, lower abdominal or pelvic pain, fever, weight loss)? • Do you douche, or have you put any other substances into your vagina? • Have you taken any antibiotics recently? • How has the discharge been treated so far? Did it help?

Examination Key ﬁndings on exam: • constitutional: fever, lymphadenopathy, rash • abdomen: tender or non-tender. Pelvic exam: • characteristics, amount of discharge • associated signs: erythaema, oedema, cervical friability, sores • cervical motion, uterine, or adnexal tenderness. Ensure discharge is not from abscess or ﬁstula.

Investigations Laboratory tests to be performed will depend on the ﬁndings of the history and physical examination. Consider the following in all patients: • Saline wet mount with or without KOH preparation (see Section 7.2.15). Evaluate for the presence or absence of trichomonads, clue cells, white blood cells, or hyphae. • Swab test: a swab should be collected from the cervical canal (endocervix). If the swab appears yellow when held up against white paper (positive swab test), cervical infection is likely. • Gram stain (see Section 7.2.14) of vaginal secretions (this is helpful if saline wet mount and KOH are not available, or if they are unrevealing; highly speciﬁc for gonorrhoea if Gram-negative intracellular diplococci are seen). These tests, if available, can help in the etiological diagnosis of discharge related to vaginal infections. When cervicitis is suspected based on exam and with only WBC's on wet mount, speciﬁc gonorrhoea and Chlamydia testing can be helpful.

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DDx: Vaginal discharge using microscopic examination and KOH Condition Bacterial vaginosis In favour Homogenous, thin white or greyish discharge Little evidence of inﬂammation Saline or KOH – KOH odour, clue cells pH >4.5 Gram stain – decrease in lactobacilli; increase in other bacteria Vulvovaginal redness, oedema, swelling; excoriations; white, thick, curd-like discharge; itching, external dysuria Saline and Gram stain – hyphae, budding yeast pH normal Vulvar or vaginal inﬂammation and irritation Yellow-green, often frothy discharge Saline – motile trichomonads, WBC's inﬂammation pH >4.5 Purulent or mucopurulent discharge, cervical friability, (+) swab test Gram stain – Gram-negative intracellular diplococci, WBC's inﬂammation pH >4.5 Purulent or mucopurulent discharge, cervical friability, (+) swab test Gram stain or saline – inﬂammation, increased WBC, pH >4.5

Vulvovaginal candidiasis

Trichomoniasis

Gonorrhoea see Section 11.13

Chlamydia

Note: Above characteristics vary in sensitivity and speciﬁcity; when possible, a combination of ﬁndings and laboratory investigations should be used to optimize diagnosis. Other possibilities to consider with vaginal discharge not responding to syndromic management include: • Atrophic vaginitis: related to oestrogen deﬁciency; irritative symptoms, vaginal dryness, and dyspareunia; the vaginal epithelium appears thin and a watery discharge may be present; treat with either topical or oral oestrogens. • Foreign body. • Local irritants (e.g. spermicides, vaginal medications, soap, detergent, douches, traditional medicines and herbs used in vagina). • Fistula: foul smelling, discharge mixed with faeces or urine. • Cancer: cervical (suspect with cervical mass or ulceration). • Atypical infections (e.g. schistosomiasis, chronic endometritis, TB). In HIV-positive patients, clinical presentation may be altered including: • increased colonization, frequency, and persistence of candidiasis in association with immunosuppression; • increased frequency, persistence, and severity of bacterial vaginosis in association with immunosuppression, possible improvement with use of ART; • no change in clinical presentation of trichomoniasis, gonorrhoea, or Chlamydia; • increased risks of cervical cancer – carefully examine the cervix (refer to 10.15.8 below regarding cervical cancer screening in the presence of persistent vaginal discharge).

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Approach to management of abnormal vaginal discharge not responding to syndromic management • Review management at the ﬁrst level and consider possible non-adherence or reinfection. • Consider possible diagnosis of PID. If the condition meets the criteria, treat. • If laboratory tests suggest an etiological diagnosis, treat concordantly. If testing is negative or inconclusive, re-treat syndromically, but re-treat with a multi-day course, or consider using another drug. If yeast infection is suspected, may give single dose of ﬂuconazole (generally not recommended in pregnancy). • Consider local patterns of gonorrhoeal resistance. • Recommend HIV testing and counselling, if not done. • If patient is from a schistosomiasis endemic area, treat empirically with 1 dose of praziquantel at 40 mg/kg.

Bacterial vaginosis Treatment • metronidazole gel; OR • metronidazole 500 mg orally twice daily for 7 days; OR • clindamycin 2% cream, 1 full applicator (5 g) per vaginum daily for 7 days; OR • clindamycin 300 mg orally twice daily for 7 days. Metronidazole can be used in pregnancy, but avoid it in the ﬁrst trimester if topical agents are available. Treatment is the same both in HIV-positive and HIV-negative patients.

Trichomoniasis Treatment • metronidazole 2 g orally in a single dose; OR • metronidazole 400–500 mg orally twice daily for 7 days; OR • tinidazole 2 g orally in a single dose; OR • tinidazole 500 mg orally twice daily for 5 days. Avoid use of alcohol during treatment. Metronidazole can be used in pregnancy, but avoid use of tinidazole in the ﬁrst trimester. Treatment is same both in HIV-positive and HIV-negative patients.

Vulvovaginal candidiasis • Identify and manage underlying conditions: uncontrolled diabetes, corticosteroid use, topical or systemic antibiotics, spermicides (conﬂicting data), douching, immunosuppression, HIV-infection. • Pregnant women are also more likely to develop vulvovaginal candidiasis; treat appropriately. See Section 11.4.

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• Antifungal treatments include: ° miconazole 200 mg vaginal suppository, once daily for 3 days; OR ° clotrimazole 200 mg intravaginally daily for 4 days; OR ° clotrimazole 500 mg intravaginally in a single dose; OR ° ﬂuconazole 150 mg orally in a single dose (ﬂuconazole is not recommended in pregnancy); ° alternative (but less effective) is nystatin 100 000 unit vaginal table daily for 14 days. If this has already been treated topically, re-treat with oral drugs (consider more intensive dosing of ﬂuconazole 150 mg orally, repeated 3 days later). In severe cases (extensive vulvar erythema, oedema, excoriation, and ﬁssure formation), extend topical treatment to 7–14 days, or ﬂuconazole 150 mg, repeated after 3 days.

Recurrent vulvovaginal candidiasis • Usually deﬁned as 4 or more symptomatic episodes per year. In some cases, this may be related to non-albicans Candida species that do not respond as well to conventional therapies. • Consider topical therapy for 7–14 days or ﬂuconazole 100 mg, 150 mg or 200 mg orally every third day for a total of 3 doses. • Maintenance therapy for 6 months should be considered: ﬂuconazole 100 mg, 150 mg, or 200 mg orally weekly (preferred); alternatives: topical clotrimazole 200 mg twice weekly or clotrimazole 500 mg vaginal suppositories once weekly. • For persistent vulvovaginal candidiasis (failure or recurrence after the above regimens): consider boric acid 600 mg in a gelatine capsule inserted into vagina once daily for 2 weeks (clinical success rates of approximately 70%). Boric acid is contraindicated in pregnancy. Maintenance therapy: boric acid once daily for 2 weeks followed by twice weekly for 6 months. • Treatment in pregnancy: use topical agents only (ﬂuconazole is not recommended in pregnancy), for 7 days. • Treatment in HIV-positive patients: above treatment regimens are recommended irrespective of HIV status. In HIV-positive patients, assess for ART eligibility, and initiate if indicated. (See Section 13.) ° If the patient is referred after short-course treatment failure, and evaluation is consistent with vulvovaginal candidiasis, re-treat for 7–14 days. Continued recurrence or persistence should be managed promptly, as for recurrent or persistent vulvovaginal candidiasis above. Given higher colonization rates, which correlate with immunosuppression, consider the prophylactic use of topical antifungals when systemic antibiotics are given.

Gonorrhoea/Chlamydia cervicitis Treatment • Treat for both gonorrhoea and Chlamydia if the patient was previously treated only for vaginitis, or if they were diagnosed or treated for either infection alone. • Assess for possible PID and treat, if indicated. • Treatment for gonorrhoea (see Section 11.13): ° ceﬁxime 400 mg orally in a single dose; OR ° ceftriaxone 250 mg IM in a single dose (on complimentary drug list); OR

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° spectinomycin 2 g IM in a single dose (alternative); OR ° ciproﬂoxacin 500 mg orally as a single dose is also an alternative, but use of this drug should take into account local gonorrhoeal resistance patterns to ﬂuoroquinolones. Ciproﬂoxacin should not be used in pregnancy. • Treatment for Chlamydia: ° doxycycline 100 mg twice daily for 7 days; OR ° azithromycin 1 g orally in a single dose; OR ° erythromycin 500 mg orally twice daily for 7 days (alternative); OR ° tetracycline 500 mg orally 4 times daily for 7 days (alternative); OR ° oﬂoxacin 300 mg twice daily for 7 days (alternative). ° Note: Treatment with alternative agents may be less effective or less welltolerated; if possible, treat with a single dose of azithromycin to enable directly observed therapy. • Avoid use of quinolones and tetracyclines in pregnancy. Sex partners should be treated with the same regimen (for both gonorrhoea and Chlamydia, if their last sexual contact was within 60 days before the diagnosis or onset of symptoms). Intercourse should be avoided until therapy is complete, and the patient and her or his partner are asymptomatic. Ensure full adherence to antibiotic treatment to decrease development of resistant strains. If you suspect cervical cancer – see Section 10.15.8.

10.15.5 Pelvic inﬂammatory disease4 Pelvic inﬂammatory disease (PID) should always be considered in sexually active women presenting with lower abdominal pain. PID is an upper genital tract infection, including the uterus, fallopian tubes, and surrounding pelvic structures. It is usually polymicrobial in nature. Infection is commonly sexually transmitted, and follows infection with either Chlamydia trachomatis or Neisseria gonorrhoeae. It can also be caused by ascending infection with normal vaginal microbial ﬂora. This can occur following an abortion, postpartum, or post-operatively. The resultant infection, even when sexually transmitted, is usually polymicrobial, and thus should be treated with broad-spectrum antibiotics. PID rarely occurs in early pregnancy. A positive pregnancy test should always raise suspicion that the diagnosis of PID is in error, and alternative diagnoses (such as ectopic pregnancy) should be considered.

Diagnosis The most common presenting symptom of PID is lower abdominal pain. Other associated symptoms include: abnormal vaginal discharge, abnormal uterine bleeding, fever, nausea, vomiting, having pain with sexual intercourse (dyspareunia) or when passing urine. Although nausea and vomiting can occur with PID, if they are prominent symptoms with abdominal pain also consider other diagnoses, such as appendicitis. Examination: check for lower abdominal tenderness and pain on manipulation of the cervix. 4 Guidelines for the management of sexually transmitted Infections. WHO, 2003 (2011 updated version in process). Available at http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf

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Symptoms of PID may be virtually absent, or mild and non-speciﬁc. Therefore providers should maintain a high index of suspicion in women with lower abdominal pain or with other presenting genital tract complaints, including dyspareunia, postcoital bleeding, abnormal vaginal discharge, or abnormal bleeding (often between menstrual periods). Empirical treatment of PID can be considered in sexually active young women and others at risk of STIs if one of the following are present, and no other causes for the illness can be identiﬁed: • uterine tenderness; OR • adnexal tenderness; OR • cervical motion tenderness. Additional criteria that increase the speciﬁcity of a diagnosis of PID include: • fever >38.30C • abnormal cervical or vaginal mucopurulent discharge • increased WBCs on saline vaginal wet mount • evidence of infection with gonorrhoea or Chlamydia (e.g. culture, Gram stain) • elevated WBC count • thickened ﬂuid-ﬁlled tubes or evidence of abscess on a pelvic ultrasound. A pregnancy test should be done. Send endo-cervical swabs for a culture if it is available, but a negative result does not exclude the diagnosis.

Treatment Untreated PID can have serious complications and consequences, and treatment should be initiated without delay after a clinical diagnosis. Table: Broad-spectrum antibiotics5 for PID If on IV regimens (to be continued until at least 2 days after the patient has improved, and followed by oral therapy for up to 14 days) 1. ceftriaxone 250 mg IM single dose; OR ciproﬂoxacin 500 mg orally single dose*; OR spectinomycin 2 g IM PLUS doxycycline** 100 mg orally or IV twice daily PLUS metronidazole 400–500 mg orally or IV twice daily; OR chloramphenicol 500 mg 4 times daily OR 2. clindamycin 900 mg IV every 8 hours PLUS gentamicin 1.5 mg/kg IV every 8 hours daily; OR ciproﬂoxacin 500 mg orally twice daily*; OR spectinomycin 1 g IM, 4 times daily PLUS metronidazole 400–500 mg orally or IV twice daily Followed by chloramphenicol 500 mg orally 4 times daily or doxycycline 100 mg twice daily to complete 14 days. * Use only if local data on antimicrobial sensitivity supports its use ** Tetracycline can be substituted if doxycycline is not available.

Oral ambulatory therapy, if uncomplicated ceftriaxone 250 mg IM single dose PLUS doxycycline** 100 mg orally twice daily for 14 days PLUS metronidazole 400–500 mg orally twice daily for 14 days.

5 Guidelines for the management of sexually transmitted infections. WHO, 2003 (2011 updated version in process). Available at http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf

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In the following circumstances, consider admission for inpatient treatment of PID with IV antibiotics if: • a surgical emergency, such as an ectopic pregnancy or appendicitis, cannot be excluded • woman is pregnant • non-response to outpatient oral antibiotic therapy • the patient is unable to follow or tolerate an outpatient oral regimen • pelvic abscess is suspected • the patient is an adolescent • the patient has severe illness – high fever, nausea, or vomiting. If PID occurs with an IUD in place, treat using appropriate antibiotics. There is no evidence that removal of the IUD provides any additional beneﬁt. However, if the IUD remains in place, close clinical follow-up is critical, and removal should be considered if there is no improvement. If the woman does not want to continue IUD use, it should be removed after antibiotic therapy has been commenced. Offer appropriate contraceptive counselling and services for continued method use. Follow-up Outpatients with PID should be followed up no later than 72 hours after starting treatment (24 hours for women with fever), and admitted to the hospital if their condition fails to improve. Within 72 hours of initiating treatment, substantial clinical improvement (absence of fever, reduction in abdominal tenderness, and reduction in uterine, adnexal, and cervical motion tenderness) should be expected. Patients who do not improve within this period may require hospitalization, additional diagnostic tests, or surgical intervention. Perform an ultrasound. For all women diagnosed with PID, as well as their partners. • Offer counselling and testing for HIV, and counselling for risk-reduction and condom use. • Test for syphilis. • The patient’s partner(s) should be evaluated and treated presumptively for gonorrhoea and Chlamydia if they have had sexual contact within the 60 days preceding the onset of symptoms. Many and perhaps most of these male partners will have no symptoms, but this should not delay or discourage treatment. • The patient and her partner(s) should abstain from sexual intercourse until the treatment has been completed. Complications Immediate: • sepsis • abscess (may require surgical drainage). Long-term: • chronic pain, infertility, and ectopic pregnancy due to scarring of the fallopian tubes or other pelvic structures.

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10.15.6 Septic abortion2 Septic abortion is a miscarriage or surgical abortion complicated by fever and infection of the uterus. It most commonly occurs in countries where abortion is illegal or inaccessible, and it is a common cause of maternal mortality in these countries. It is usually associated with retained products of conception and, less commonly, associated with foreign bodies (e.g. IUDs), invasive procedures (e.g. amniocentesis), maternal blood stream infection, or spontaneous abortion. The bacteria associated with septic abortion are usually caused by multiple organisms, and may include normal vaginal ﬂora as well as sexually transmitted pathogens. An illegal abortion performed by insertion of rigid foreign objects increases the risk of perforation. The use of soap solution containing cresol and phenol is associated with a risk of uterine necrosis, renal failure, or central nervous system, cardiac, and respiratory toxicity.

Key clinical features • Consider this possibility in any woman of reproductive age who presents with vaginal bleeding or bloody discharge, lower abdominal pain, and fever. • Women may present late and may be moribund, as they are reluctant to reveal that they have had an abortion. A pregnancy test will usually be positive in this situation.

Examination • • • • lower abdominal tenderness boggy, tender uterus with a dilated cervix possibly a foul-smelling and bloody discharge Women may also present with a mild to moderate illness characterized by low-grade fever, abdominal pain, or moderate vaginal bleeding. This usually occurs in women who have had either an incomplete or failed abortion.

Investigations • A positive pregnancy test is useful if unable to conﬁrm a history of pregnancy and recent abortion. • If perforation of the uterus is suspected, a plain abdominal X-ray may show the presence of free gas in the abdominal cavity. • Blood, urine, and cervical specimens should be cultured if possible.

Treatment Evacuation of the uterus Patient should be stabilized prior to procedure. Start antibiotics prior to procedure. • Prompt evacuation of the uterus is important. Vacuum aspiration is the recommended technique for surgical abortion to 12–14 weeks. • Dilatation and curettage, where it is still practiced, should be replaced by vacuum aspiration. Vacuum aspiration should not be routinely completed by sharp curettage. • After 12–14 weeks, refer to an experienced provider for dilatation and evacuation. If not available, use misoprostol.

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• Vacuum aspiration can be performed under local anaesthesia with minimal sedation. • If none of these means are available, a Foley catheter with a 50 ml balloon attached can be placed in the lower uterus. One kilogram of traction from an orthopaedic weight at the foot of the bed is then applied to the catheter, which dilates the cervix and stimulates contractions. Indications for hospital admission for IV antibiotics include the following: • fever >38oC • pelvic peritonitis • tachycardia. Antibiotics • Treat with benzyl penicillin 5 million units IV every 6 hours OR ampicillin 2–3 g IV every 6 hours, combined with gentamicin 4–6 mg/kg IV daily and clindamycin 900 mg IV every 8 hours. • If clindamycin is not available, use metronidazole 500 mg IV every 8 hours. If gentamicin is not available or contraindicated, use ceftriaxone 1 gram IV daily as an alternative. • When the patient is ready for discharge, change to: ° doxycycline 100 mg orally every 12 hours plus amoxicillin-clavulanic acid 500 + 125 mg orally every 12 hours for a total of 14 days of treatment (or substitute metronidazole 500 mg every 8 hours in place of amoxicillinclavulanic acid). • For mild post-abortal infections, oral regimens suitable for treatment of pelvic inﬂammatory disease are appropriate. See Section 10.15.5 Pelvic inﬂammatory disease. Monitoring All women managed as outpatients should be reviewed after 48 hours of treatment and hospitalized if fever and pain persist. Complications Complications include uterine perforation, which may include injury to the bowel or pelvic abscess formation. This usually requires surgical management with a laparotomy with or without hysterectomy. Uncontrolled infection (ongoing sepsis, severe infection with gas-producing clostridium species) is also an indication for a total hysterectomy.

10.15.7 Approach to urinary incontinence Urinary incontinence generally is not life-threatening, but it causes signiﬁcant morbidity, and can result in social or cultural stigma that can have a major effect on quality of life. It is important to carry out a thorough assessment to establish the cause of incontinence and, whenever possible, to treat the underlying cause.

History Speciﬁc questions (in addition to a history that should be taken for all women with GU complaints, see above): • Pattern of incontinence, e.g. constant leakage, associated with cough, sneezing; associated with urgency.

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• How long have you been leaking urine? Is there any event that you can link to the occurrence of this problem (e.g. childbirth, surgery, other injury)? • Do you have any other symptoms related to urination (e.g. burning, urgency, frequency, haematuria)? • Do you have regular and normal bowel movements? • Do you have any medical problems such as diabetes, high blood pressure, or any psychiatric problems? • What medicines do you take (including traditional or over-the-counter)? This question should be part of the basic history in any woman with genital tract complaints, but should be re-reviewed with a complaint of urinary incontinence.

Examination • Constitutional: fever, cachexia or signiﬁcant weight loss, lymphadenopathy. • Abdominal exam: suprapubic or costovertebral angle tenderness. • Pelvic examination: prolapse of the bladder, uterus; genital sores; abnormal vaginal discharge; evidence or suspicion of ﬁstula.

Investigations Laboratory tests to be performed will depend on the ﬁndings of the history and the physical examination. Consider the following in all patients: • urinalysis • BUN, creatinine, glucose, electrolytes • FBC (if suspect underlying systemic infection) • urine dipstick, urinalysis or, if available, culture to rule out infection.

DDx: Urinary incontinence Condition Fistula In favour Total incontinence; recent childbirth after prolonged labour, history recent surgery; history of cervical cancer (or treatment with surgery or radiation for pelvic cancer). Dysuria, frequency, urgency, haematuria. Clean catch urine with increase in WBCs, bacteria or positive nitrites. Urine culture and sensitivity, if available. Management considerations Refer to surgeon with expertise in ﬁstula repair. At district level, a large bore urinary catheter to keep bladder dry may allow healing of a vesico-vaginal ﬁstula. Treatment with antibiotics. Consider or rule out upper tract infection (e.g. pyelonephritis). Consider antibiotic resistance if no improvement and obtain C&S, if not previously obtained. Pelvic ﬂoor muscle exercises. Possible surgical repair.

Urinary tract infection see Section 11.44 Stress urinary incontinence

Leakage associated with cough, sneeze, laugh, or other manoeuvre resulting in increased abdominal pressure; increased risk with increased parity. On exam, evidence of pelvic organ prolapse.

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Overactive bladder

More common in postmenopausal women; associated with urgency.

Frequent bladder emptying. Anticholinergic (antispasmodic) drugs to calm an overactive bladder and help with urge incontinence. Oxybutynin 5 mg orally every 8–12 hours (maximum 5 mg 4 times per day), might be of help. Teach patient to safely perform selfintermittent catheterization; address underlying cause. Teach proper catheter care, including cleaning of catheter and irrigation with saline, when necessary.

Overﬂow incontinence

Bladder never feels empty, frequent need to void at night; may have inability to void, even with urge; post-void dribbling. Bladder may be palpable; catheterization shows high post-void residual. Associated with some pharmacologic treatments (see below); certain disease conditions that result in neurogenic bladder (diabetes, polio, tumours compressing sacral nerves), urinary stones, stool impaction. On drug that is associated with urinary incontinence (see below). Frequent urination with large amounts of urine (polyuria). Associated with diabetes, CHF, diabetes insipidus, or renal disease, polydipsia (excessive thirst), alcohol or caffeine. Can be seen in women who are naturally or surgically postmenopausal; atrophic changes on exam (vaginal dryness, decreased rugae). Complaints of vaginal dryness. Often presents as overactive bladder symptoms. Acute or chronic psychiatric illness, possibly medication-related. Decreased awareness of the need to void. Unable to get to toilet as needed; may also have a neurogenic bladder with overﬂow. See next table.

Pharmacologic agents Excess urinary output

Adjust drug regimen, if feasible. Address underlying cause.

Atrophic urethritis, vaginitis

Topical oestrogen. See above treatment for overactive bladder.

Delirium see Section 10.11 Immobility

Address cause of delirium.

Perineal care to avoid pressure sores. Address cause of immobility; assistance as needed.

Drugs that can cause urinary incontinence

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Table: Drugs that may be associated with or lead to acute urinary incontinence Medication Diuretics (water pills) Effect on lower urinary tract Diuresis induced by diuretics may precipitate incontinence. This is particularly relevant in older persons or in those with already impaired continence. Benzodiazepines, especially long-acting agents such as ﬂurazepam and diazepam (valium), may build up in the bloodstream of an older person. This can cause confusion and alter the person’s ability to recognize the urge to void, leading to urinary incontinence. Alcohol can alter memory, impair mobility, and cause increased urine output resulting in incontinence. In addition, it has a sedative effect that may alter a person's awareness of the need to void. Prescription as well as over-the-counter drugs with anticholinergic properties are taken commonly by persons with insomnia, pruritis (itchy skin), vertigo (dizziness), and other symptoms or conditions. Side-effects include urinary retention with associated urinary frequency and overﬂow incontinence. Besides anticholinergic actions, antipsychotics, such as thioridazine and haloperidol, may cause sedation, rigidity (stiffness), and immobility.

Sedatives (sleeping pills), hypnotics, CNS depressants

Alcohol

Anticholinergic agents: antihistamines, antidepressants (TCA), phenothiazines, disopyramides, opiates, antispasmodics, Parkinson drugs

Alpha-adrenergic agents (high blood pressure drugs), sympathomimetics (decongestants), sympatholytics (e.g. prazosin, terazosin, and doxazosin) Calcium channel blockers (heart and blood pressure medications)

Alpha-adrenergic stimulation increases urethral tone and alpha-adrenergic block reduces it. Stress incontinence may become symptomatic in women treated with alpha-antagonists for antihypertensive therapy.

Calcium channel blockers can reduce smooth muscle contractility in the bladder and occasionally can cause urinary retention and overﬂow incontinence.

Source: http://www.seekwellness.com/incontinence/causes.htm

Symptom management: urinary incontinence Home care • Provide adequate support and reassurance about the situation. • Behavioural techniques and lifestyle changes work well for certain types of urinary incontinence. They may be the only treatment you need: ° pelvic ﬂoor muscle exercises – help strengthen urinary sphincter and pelvic ﬂoor muscles; ° scheduled toilet trips – going to the toilet according to the clock rather than waiting for the need to go, usually every 2–4 hours. • Pads and protective garments – absorbent pads may help manage urine loss. • Adult diapers are sometimes available. Where they are found they may be available in both disposable and reusable forms, and come in a variety of sizes. • Some people ﬁnd that wearing plastic underwear over their regular underwear helps keep them dry; others opt for washable underwear and briefs with waterproof panels.

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10.15.8 Cervical cancer6 Cervical cancer is a preventable disease, and is curable if diagnosed and treated early. If diagnosed late, cervical cancer is very difﬁcult to treat, and causes a great deal of morbidity. Human papilloma virus (HPV) infection plays a causative role in lower genital intraepithelial and invasive neoplasia. Invasive cervical cancer generally develops slowly over 10–20 years from the earliest pre-cancerous changes, which permits early detection (screening) and treatment. A vaccine is now available (see Section 19) that protects against infection by oncogenic strains. One of the two available vaccines also protects against strains responsible for genital warts. HIV-positive women have a higher risk of pre-cancer and invasive cervical cancer. The risk and persistence of HPV infection increases with decreasing CD4 count and increasing HIV viral load. Invasive cervical cancer is a WHO HIV Clinical Stage 4 condition. The role of ART in the management of cervical dysplasia The role of ART and immune reconstitution in the management of lower genital tract pre-cancerous lesions remains unclear, and study results are mixed in terms of regression or progression of cervical dysplasia or HPV persistence. HIV-positive women should continue to be followed closely for evidence of cervical cancer, regardless of antiretroviral therapy or CD4 count and viral load results.

General principles of screening for cervical cancer • Women should be screened according to national guidelines and all women should be offered the same cervical cancer screening options, irrespective of their HIV status. • Women should be notiﬁed when screening results are abnormal and counselled about further evaluation that is needed. • All positive or abnormal screening results require further evaluation and adequate treatment. • Recommendations are being reviewed as HIV-positive women may beneﬁt from an earlier age of ﬁrst screening and more frequent screening. Before embarking on a widespread screening programme, services need to be in place to adequately manage women screened positive or newly identiﬁed cancer cases. The district clinician can manage pre-cancer, while treating invasive cancer requires specialized care. Women whose disease is very advanced, or for whom treatment is impossible, need skilled palliative care, both symptom management and end-of-life care (see Section 20). The regular use of Pap smear screening has resulted in as much as an 80% reduction in incidence of, and mortality from, cervical cancer in high-resource settings. Quality assurance is crucial. • Pap smears require transporting specimens to a cytology laboratory where trained cryotechnicians (under the supervision of a pathologist) can read the slides. Quality assurance is crucial. Reliable transport of slides and test

6 Adapted from: Comprehensive cervical cancer control. WHO, 2006. Available at http://whqlibdoc.who.int/ publications/2006/9241547006_eng.pdf

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results to and from the laboratory is essential. Pap smear results are reported according to the Bethesda System (see Section 7.2.9 Procedures). Cytology programmes require adequate numbers of qualiﬁed and trained professionals to interpret the specimens. Pap smear screening is therefore not easily adapted for limited-resource settings. • Visual inspection of the cervix with acetic acid (VIA): VIA involves washing the cervix with a diluted solution (3–5%) of acetic acid, and viewing the cervix with the naked eye to look for abnormalities (see Section 7.2.10 Procedures). Pre-cancerous or cancerous lesions turn white after application of acetic acid. The supplies are inexpensive and locally available, and can be taught to health providers at different professional levels. In studies to date, VIA has sensitivity of 56–94% and speciﬁcity of 74–94% in detection of high-grade squamous intraepithelial lesions (HSIL) or cancer. With VIA, it is often possible to treat with cryotherapy on the same visit.

VIA screen and treat approach VIA techniques have been evaluated in several large cross-sectional and randomized studies, and are recommended where programme monitoring and quality assurance are possible. Because they have a low positive predictive value, this can result in unnecessary treatment or referral. They are less effective for use in postmenopausal women because the area at risk for dysplasia or neoplasia is more likely to be inside the cervical canal and not visible. Response to abnormal VIA screening test If the VIA test is positive and the lesion is eligible for cryotherapy, consider the eligibility and exclusion criteria. • Cryotherapy a) Eligibility criteria: positive screening test for precancerous changes; lesion covered by cryoprobe with no more than 2 mm beyond its edges; lesion fully visible with no extension into endocervix or onto vagina. b) Exclusion criteria: evidence or suspicion of invasion or glandular dysplasia; pregnancy; PID (until treated); lesion too large; menses. Before cryotherapy, discuss with the patient that abstinence is advisable for 4 weeks after the procedure until complete healing has occurred. The treatment may dramatically increase genital tract HIV shedding and may increase the risk of sexual transmission of HIV. Condom use should be advised and condoms offered if abstinence is not possible. If the VIA test is positive and the lesion is not suitable for cryotherapy, do colposcopy. If there is a visible cervical lesion (a cervical mass or non-healing cervical ulceration), do colposcopy. Histological evaluation on a biopsy is indicated without regard to cytological results, even if colposcopy is not available.

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Figure: The “screen-and-treat” approach, based on visual inspection with acetic acid VIA test

Negative

Positive

Suspicious for cancer

Suitable for cryotherapy

Not suitable for cryotherapy

Rescreen at any level health centre Treat with cryotherapy

Refer for colposcopy and biopsy Pre-cancer Cancer Normal

Treat with LEEP cold knife conization

Treat for invasive cancer

Post-treatment follow-up Rescreen in 3 years (or as per national policy)

Colposcopy • Do colposcopy or refer ° Do colposcopy if a health worker has the necessary training and the equipment is available (colposcope, biopsy forceps, and an endocervical curette). This procedure can be performed at the primary care level by trained and skilled physicians, nurses, and other health care providers. More commonly, colposcopy is performed as an outpatient procedure at a second level district hospital facility. See Section 7.2.11. ° Refer for colposcopy if the equipment or trained health worker is not available. • Indications for colposcopy ° Recommended for Pap smears showing atypia or a greater abnormality, and for abnormal VIA not eligible for cryotherapy. If an abnormality is seen with colposcopy, a biopsy should be obtained, with management dependent on the results of these tests. Colposcopy can help map the abnormality to better target loop electrosurgical excision procedure (LEEP) or cryotherapy. ° Essential to treat pre-cancerous lesions, depending on cervical intraepithelial neoplasia (CIN) level. Treat CIN 2 or greater; CIN 1 lesions often resolve spontaneously, but should be followed up. ° Outpatient treatments, including cryotherapy or LEEP, are preferable to more invasive treatments, such as cervical conization, which requires anaesthesia and has a higher rate of complications. ° See Table Comparison of cryotherapy, LEEP, and cold knife conization below, and WHO Comprehensive Cervical Cancer Control4 for further details on the criteria for choice of treatment. • Indications for referral to the third level of care ° Exam or pathology consistent with invasive cancer. ° The presence of large cervical lesions or lesions that extend beyond the cervix noted on evaluation. ° Evidence of cervical dysplasia requiring evaluation during pregnancy. ° The presence of extensive genital or cervical warts, or both.

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• Loop electrosurgical excision procedure (LEEP) ° Eligibility criteria: positive screening test for high-grade pre-cancerous changes; lesion extending less than 1 cm into endocervix. ° Exclusion criteria: evidence or suspicion of invasive or glandular dysplasia; lesion extending >1 cm into the endocervical canal, or whose upper extent is not visible; cervicitis or PID (until treated); pregnancy or childbirth within previous 12 weeks; bleeding disorders. • Cold knife conization is a surgical procedure done under anaesthesia that involves excision of a portion of the cervix. ° Eligibility criteria: positive screening test for micro-invasive cancer or endocervical glandular neoplasia; abnormal endocervical curettage; need for excision procedure and outpatient procedure (e.g. LEEP) is not feasible; no contraindications to anaesthesia. ° Exclusion criteria: untreated cervicitis or PID; pregnancy or childbirth within previous 2 weeks; obvious invasive cancer. Table: Comparison of cryotherapy, LEEP, and cold knife conization7 Cryotherapy Advantages • high cure rate (86–95%) for small lesions • equipment simple, relatively inexpensive • can be performed by trained physicians and non-physicians • can be performed as outpatient procedure in the primary care setting • takes only approximately 15 minutes for doublefreeze method • no anaesthesia required • no electricity required • complications and sideeffects rare • less effective for larger lesions (cure rates <80% at one year) • no tissue sample for pathologic evaluation • needs continuous supply of CO2 or nitrous oxide • causes profuse watery discharge LEEP • high cure rate (91–98%) • tissue specimen – can rule out invasive disease • few complications • can be performed as an outpatient procedure at the secondary level • takes only approximately 15 minutes and technically easy to perform • diagnosis and treatment can be offered at same time Cold knife conization • highly effective (91–94%) • allows best assessment of surgical margins to evaluate for complete excision

Disadvantages

• requires intensive training • post-operative bleeding in <2% • more sophisticated equipment needed • requires electricity • requires local anaesthesia

• requires operating room • requires spinal or general anaesthesia • requires highly skilled personnel • complications more common: bleeding, infection, cervical stenosis, cervical incompetence

Follow-up after treatment with cryotherapy, LEEP, or cervical cold knife conization The woman should be seen for follow-up within 6 weeks after the procedure to ensure good healing, and to give results if a histological examination was done. HIV-positive women have an increased incidence of recurrence after treatment, 7 320 For country adaptation. Female GU complaints Vol. 2 • 10. Acute and subacute by symptom: July 2011

correlated with the degree of immunosuppression. This may also be related to a higher incidence of positive surgical margins with excision treatment. If invasive cancer is identiﬁed on histology, referral to a tertiary centre for further management. After cryotherapy, LEEP, or conization, women should have follow-up screening every 6 months with prompt re-treatment if recurrence occurs. If results return to normal, annual screening is recommended after the ﬁrst year for at least 5 years. The most common complication after LEEP or conization is haemorrhage, which can occur up to 14 days after the procedure. There is no evidence that HIV-positive women are at increased risk for bleeding in general, but they are more likely to have platelet disorders predisposing to poor blood clotting. They are also more likely to be anaemic, making them more vulnerable to acute blood loss. Haemorrhage after the procedure is usually related to local infection, and treatment with antibiotics should be prescribed, with measures to stop the bleeding. Cervical incompetence may also be more likely in subsequent pregnancies after conization or extensive LEEP.

Treatment of invasive cancer A hysterectomy is NOT a primary treatment for a visible cervical lesion or an abnormal Pap smear until invasive cancer is ruled out, and should not be used unless there are other indications to remove the uterus. If there is invasive cancer, a hysterectomy alone is usually not sufﬁcient as treatment. Treatment for early stage cancer of the cervix may require radical hysterectomy with lymph node dissection (not total hysterectomy). The primary treatment of invasive cervical cancer is radiotherapy. In many settings, cervical cancer is diagnosed at an advanced stage and requires radical surgery or radiotherapy, or palliative care6. If smelly vaginal discharge from advanced cervical cancer, insert metronidazole 500 mg tablet as pessary, or crush tablet and apply powder intravaginally each night for 5 nights. If available, use metronidazole vaginal gel 37.5 mg at night for 5 nights. See Section 20 Palliative care.

10.15.9 Schistosomiasis of the female genitourinary tract (See Section 11.34.) Site Fallopian tubes Uterus Placenta Cervix Vagina Vulva Clinical manifestation Infection can simulate PID and lead to infertility and ectopic pregnancy Disturbed menstruation, fetal loss Second trimester abortion Ulceration, growths, sandy patches, cervicitis, discharge, post-coital bleeding, dyspareunia Growths, ulcers, sandy patches, rectovaginal and vesicovaginal ﬁstuale Swelling, ulceration, wart-like lesions, pruritis, clitoral hypertrophy

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10.16 Male genitourinary complaints1 In this section: 10.16.1 Clinical approach to male genitourinary complaints 10.16.2 Genital growths in men (with DDx table) 10.16.3 Dysuria and penile discharge (with DDx table) 10.16.4 Testicular and scrotal problems (with DDx table) • Epididymitis or epididymo-orchitis • Viral orchitis • Testicular cancers • Hydrocele • Inguinal hernia 10.16.5 Foreskin problems • Phimosis • Paraphimosis • Balanitis • Male circumcision 10.16.6 Prostate problems • Acute prostatitis • Chronic prostatitis • Benign prostatic hyperplasia 10.16.7 Schistosomiasis of the male genitourinary tract

This Section covers problems of the male urogenital system. See also treatment of genital ulcers in Section 10.14 Female and male anorectal problems and genital ulcers. Some men may feel uncomfortable talking about genitourinary symptoms or being examined. The health worker needs to reassure the patient under these circumstances. Men may present with: • genital ulcers (Section 10.14) • growths, ulcerations, itching, or skin changes (DDx: Genital growths) • burning on urination or urethral discharge (DDx: Dysuria and discharge) • pain or swelling in the testicles or scrotum (DDx: Testicular or scrotal pain and masses) • foreskin problems • prostate problems • blood in the urine (Sections 10.16.7 and 11.34)

1 Guidelines for the management of sexually transmitted Infections, WHO, 2003 (updated 2011 version in press). Available at http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf

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10.16.1 Clinical approach to male genitourinary complaints Step 1: Perform Quick Check. Patients may present with severe pain. Testicular pain may indicate torsion, which is a surgical emergency. Step 2: Take a history and examine the patient. Step 3: Assess the patient’s HIV status. Step 4: Perform investigations. Step 5: Consider differential diagnosis using the DDx tables and text below. • for genital ulcers see Section 10.14 • DDx: Genital growths in men • DDx: Dysuria and discharge • DDx: Testicular or scrotal pain and masses • Foreskin problems (text only) • Prostate problems (text only) • Schistosomiasis of the male genitourinary tract (text only) Step 6: Initiate management and monitor the patient’s response.

History When taking sexual histories, do not assume men’s sexual partners are exclusively female. Many men have sex with other men, even if they are married or in a relationship with a female and identify themselves as heterosexual. Ask about: • history of STIs in patient or partner • HIV status and status of sex partners if known • risk factors for STIs ° number and sex of sexual partners ° recent change of partner ° condom use ° type of sexual activity – oral, vaginal, anal or non-insertive • recent trauma, sexual violence • history of catheterization • relevant medical history (including diabetes) • history of travel to or residence in an endemic area for S. haemotobium • medications – including ART, antibiotics, over-the-counter medications, and traditional medicines • substance or alcohol use.

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Examination Do a general physical examination • Look for signs of HIV-associated conditions. • Look for signs of systemic disease – lymphadenopathy, skin and oral lesions, joint involvement, conjunctivitis. Do a genito-urinary examination • Undress the patient fully. • Inspect for retraction or elevation of testes with the patient standing up. • Make a visual inspection for rashes, ulcers, growths, discharge, and swelling. • Palpate inguinal region for hernias and lymph nodes, or undescended testes (may need to ask the patient to retract the foreskin if not circumcised). • Palpate testicles and epididymis for masses, tenderness, or swelling • Transilluminate the testis if swollen. • Do a rectal examination if indicated (see anorectal problems in Section 10.14). ° MSM ° men over 45 years to check prostate ° symptoms of prostatitis (see below) Note: Some men may get aroused by the physical examination. This is usually involuntary and the patient should be reassured.

Investigations Laboratory tests: • urine dipstick • Gram stain of discharge • rapid syphilis test or laboratory-based test • FBC – look at the WBC count • urine microscopy, culture, and sensitivity • recommend HIV testing • ultrasound of scrotum, if available and indicated

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10.16.2 Genital growths in men DDx: Genital growths in men Diagnosis Human papillomavirus (warts) see Section 10.14 Condyloma lata (secondary syphilis) see Section 11.37 Symptoms and signs Flat or raised ﬂeshy growths anywhere in the anogenital area including in the urinary meatus Flat, moist, malodorous, warty-like lesions Rapid syphilis test Dark-ﬁeld microscopy positive Dome shaped papules with central depression on genitals, thighs, (and elsewhere) Consider HIV-related illness if extensive Non-healing penile lesion May be red, indurated, and ulcerating Rarer in men circumcised at birth Increased in patients with HIV Round or oval red/purple plaques often with lighter centres (target lesions) Other lesions elsewhere on skin Pearly penile papules Blocked sebaceous glands or hair follicles Nevi Skin tags

Molluscum contagiosum virus see Section 10.2 Penile cancers: • squamous cell (majority) • Kaposi sarcoma • basal cell • melanoma Fixed drug reactions (often tetracyclines or sulfonamides) Benign lesions

10.16.3 Dysuria and penile discharge Dysuria and penile discharge must be treated syndromically according to national guidelines. Ensure that the treatment was taken correctly, the partners treated, and condoms used. In the event of non-response to treatment, it may be necessary to consider testing for speciﬁc etiological agents.

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DDx: Dysuria and penile discharge Diagnosis In favour Purulent green, yellow discharge (gently milk urethra if not evident) Burning on urination Red, irritated meatus Gram stain (after no urination for >1 hour): >5 PMNs per high power (HP) ﬁeld and gram-negative intracellular diplococci May also have minimal or no symptoms Mucopurulent, whitish, grey discharge Burning, tingle, or itch on urination Gram stain of urine (after no urination for >1 hour): >5 PMNs/high power ﬁeld and no diplococcic May also have minimal or no symptoms Pain unrelated to urination Recurrent self-limited episodes Prodromal symptoms Cluster of or coalesced, ulcerated vesicles or ulcers in urethral meatus or intra-urethra Men are usually asymptomatic Can be mild, transient discharge with dysuria or frequency Examine in saline solution under microscope Treat as a carrier if the female partner has been diagnosed Milder or intermittent dysuria No or sterile discharge Inﬂamed urinary meatus Mild and intermittent dysuria No or sterile discharge Symptoms persist despite antibiotics Frequent self-examination and worry Responds to dietary or psychological counselling, as appropriate

Neisseria gonorrhoeae urethritis see Section 11.13 Gonorrhoea

Chlamydia trachomatis urethritis see Section below

Herpes simplex virus lesions in urethra or meatus see Section 11.15 Herpes simplex virus

Trichomonas vaginalis

Other infectious causes: • adenovirus • Candida albicans balanitis Other non-infectious causes Anxiety over sexual activity (e.g. sex with sex workers, MSM, multiple partners)

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10.16.4 Testicular and scrotal problems DDx: Testicular or scrotal pain or swelling Diagnosis Testicular torsion This is an emergency! Refer urgently for surgery within 6 hours to prevent ischaemia and testicular atrophy Epididymitis or epididymo-orchitis see Section below Viral orchitis Other infectious orchitis: TB, Brucella, ﬁlariasis, fungi or syphlitic granulomas Blunt trauma In favour Sudden onset of unilateral severe pain, fever, nausea, and vomiting History of trauma or strenuous activity in adolescence or early adulthood Swelling that is tender to touch Testis high in scrotal sac Gradual onset, unilateral pain, or dull ache With or without symptoms of urethritis or prostatitis Epididymis boggy and tender on exam Pain relieved by lifting testis (Prehn’s sign) Urine dipstick (after prostate massage) – leucocytes Preceded by parotid swelling – mumps Usually resolves in 1–8 weeks, unless immunocompromised Abscess can complicate orchitis Initial presentation of HIV can be a testicular infection Haematoma and contusion Ultrasound Surgical plan or immediate referral if rupture or torsion suspected Age under 40 years Painless, palpable lump HIV positive Family history of breast or testicular cancer History of childhood undescended testis Marijuana use is a risk factor “Sac of worms” mass, usually non-tender Palpation with patient in upright position with valsalva Painless accumulation of ﬂuid around testes Illumination of the scrotum with visible shadowing of the testes Palpable bulge in groin accentuated by coughing, straining, or standing Disappears when lying down Usually painless

Testicular cancer

Varicocele (venous dilation in cord) Hydrocele Inguinal hernia

Epididymitis or epididymo-orchitis Age below 30: mainly due to gonorrhoea, Chlamydia, or enteric coliforms (in MSM having unprotected anal sex). Age above 30: mainly due to enteric coliforms or Pseudomonas from obstructive urinary disease, instrumentation, systemic disease, or immunosuppression. Treatment If sexual transmission is suspected: treat for uncomplicated gonorrhoea (see Section 11.13) and for Chlamydia.

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If coliforms are suspected: treat with ciproﬂoxacin 500 mg daily for 14 days2 or cotrimoxazole 2 SS tablets twice daily for 2 weeks. Supportive measures include: analgesia, ice, scrotal support.

Viral orchitis • Mumps, cocksackie, rubella, varicella, and others. CMV in immunosuppressed. Treatment • Supportive measures: analgesia, ice, rest, scrotal support.

Testicular cancers • Can be testicular tumour, metastases from other sites, lymphoma, or leukaemia. • Important to screen for cancer by teaching young men testicular selfexamination. Treatment • Consult a specialist – orchidectomy, radiation, or chemotherapy.

Hydrocele • Secondary to orchitis, injury, cancer or lymphatic ﬁlariasis. • Exclude cancer and other signs of lymphatic obstruction suggestive of ﬁlariasis.

Inguinal hernia This is a protrusion of the abdominal cavity contents through the inguinal canal, and can affect 25% of men in their lives. It is usually painless. If there is pain or inability to reduce the bulge, this suggests incarceration (strangulation), which is a surgical emergency.

10.16.5 Foreskin problems3 Phimosis Phimosis is a condition in which the foreskin of the penis is so tight that it cannot retracted from the head of the penis. It can occur at any age and may be present at birth. It may be caused by an infection (balanitis), or by scar tissue as a result of injury or chronic inﬂammation. A tight phimosis can interfere with urination, resulting in a thin urinary stream. In extreme cases, urine may collect between the foreskin and the glans, causing ballooning of the foreskin. In this situation an urgent circumcision is necessary, usually using the dorsal slit method. Treatment If seen at a peripheral health facility, patients with phimosis should be referred to a higher level of care for proper assessment and treatment; this will usually involve circumcision. 2 Alternatives include oﬂoxacin 300 mg 12 hourly or levoﬂoxacin 500 mg daily for 10 days. See Adaptation Guide. 3 Manual for male circumcision under local anaesthesia. WHO, 2008. Available at http://www.who.int/hiv/pub/ malecircumcision/local_anaesthesia/en/index.html

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• If balanitis is present: ° treat according to underlying cause and national guidelines (which may include topical antifungals or antibacterial medication)4; ° use hot compresses and gentle cleansing. • If there are retraction problems and no balanitis: ° topical steroids may help . • If the foreskin remains tight, circumcision is indicated.

Paraphimosis Paraphimosis occurs when the retracted foreskin cannot be put back in place because of swelling. This usually occurs when the penis is erect and during sexual intercourse. The retracted foreskin swells and tightens around the penis, which in turn causes more swelling. Treatment Treatment depends on how long the paraphimosis has been present. For acute paraphimosis: • Treat promptly as it can lead to serious complication, such as skin loss, infection, and in extreme cases loss of the penis. ° Reduce oedema by wrapping the swollen area in gauze and applying increasing pressure on the gauze to squeeze the tissue ﬂuid out. This may take 10–15 minutes. Once ﬂuid is out, it is usually possible to replace the foreskin over the glans. If the above is unsuccessful, surgical intervention is indicated (dorsal slit or circumcision). See Section 7.3.5 or circumcision instructions.3 Note: The least invasive treatment options should be tried ﬁrst unless ischaemia of the glans is present. If ischaemia is present, proceed to surgical interventions or involve an urologist for urgent management.

Balanitis Balanitis is an infection of the glans penis and can involve the foreskin (balanoposthitis). It often occurs in men and boys who have not been circumcised. It may be associated with diabetes, recent antibiotic use, or immunosuppression. Poor hygiene can also be a contributing factor. Key clinical features • Itching, redness, rash, pain, superﬁcial discharge, foul odour, and phimosis. • Commonly caused by Candida and other infections including bacteria, or may be caused by drug allergy, contact dermatitis, or secondary infection that complicates genital ulceration caused by an STI. Treatment Treatment depends on the underlying cause and may include: • Use topical or oral antifungal therapy. • Clean frequently (avoid strong soaps or chemicals). • Speciﬁc treatment needed if a bacterial or other etiology is suspected. • Circumcision is usually the best treatment in patients with severe or persistent inﬂammation or difﬁculty retracting the foreskin, 4 For country adaptation.

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Male circumcision Adolescent and adult male circumcision is increasingly becoming an important HIV-prevention strategy for heterosexual men as it has been shown to reduce risk of female-to-male sexual transmission of HIV by 60%. It is recommended particularly in settings with high HIV prevalence rates and low male circumcision rates. In such settings, recommending HIV testing and counselling and male circumcision to uncircumcised adolescents and adults should be supported within clinical services and in the context of broader sexual and reproductive health counselling for men. A minimum package of services should also include STI management and safer sex counselling. The effectiveness of circumcision as a prevention strategy is not as clear for MSM. However, MSM who practice exclusively penetrative anal sex (i.e. are not penetrated) and MSM who have both male and female partners may potentially beneﬁt. Male circumcision has other beneﬁts such as easier cleaning of the penis, reduced risk of UTIs in infants, prevention of balanitis, phimosis, and paraphimosis, reduced risk of some STIs, and reduced risk of penile cancer. Male circumcision is generally well-tolerated. For detailed information on preparation, the procedure, and post-operative care see the WHO Manual on male circumcision under local anaesthesia.3 • Short-term complications of male circumcision could include the following: ° Pain – can usually be controlled with analgesics. ° Bleeding – usually minor; dressing can be changed. ° Haematoma formation – are generally left alone and monitored. ° Wound disruption – can be re-sutured or left to heal by secondary intention. ° Infection indicated by pain or fever with or without purulent discharge from the wound – treat with antibiotics and do frequent dressing changes. Advise the patient to lie on his back to promote lymphatic drainage. ° Worsening infection and gangrene – rare but more likely in diabetics. Will require surgical debridement under anaesthesia. • Late complications include: ° decreased or increased sensitivity of the glans, particularly in the ﬁrst few months ° scarring and other cosmetic concerns ° adhesions ° inclusion cysts. • Counsel patients to: ° Refrain from sex and masturbation for 4–6 weeks to prevent wound breakdown. ° Use a condom for at least 6 months after circumcision to protect the wound and to prevent HIV transmission through the healing wound. Continue condom use thereafter to prevent HIV, STIs, and unwanted pregnancy.

10.16.6 Prostate problems Prostatitis refers to inﬂammation of the prostate gland. It can be acute or chronic.

Acute prostatitis Acute prostatitis is caused by a reﬂux of infected urine into the prostate or the migration of infection from the urinary meatus (usually during sexual intercourse). Causative organisms are usually coliform bacteria (e.g. E. coli, Klebsiela, Proteus)

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but may be staphyloccocal, streptococcal, Neisseria gonorrhoeae or Chlamydia trachomatis. In immunosuppressed patients, opportunistic bacterial, fungal, or viral prostatitis may occur. Key clinical features • fever • perineal pain • irritation on urination • tender prostate on digital examination • pain during anal sex (MSM). Investigations • Urine culture and Gram stain to help to narrow the diagnosis. Treatment • Usually give empirical treatment with ciproﬂoxacin for 21 days or cotrimoxazole. • Give supportive care (ﬂuids, analgesia, rest). • Avoid prostate massage as this may lead to sepsis. • Severe cases may require hospitalization and IV antibiotics.

Chronic prostatitis This is a poorly understood syndrome that presents with recurrent, variable symptoms, and can be caused by bacterial or non-bacterial causes. Key clinical features • dysuria, frequency, and hesitation • dull perineal, back, or testicular pain • low-grade fevers • urine culture and Gram stain (pre- and post-prostate massage) may aid diagnosis. Treatment • Treatment as for acute prostatitis above, but use lower doses for longer periods (4–6 weeks). • Use anti-inﬂammatory drugs. • Give sitz baths. • If the patient is sexually active, Ureaplasma, Mycoplasma or Chlamydia may be the cause and a 2 week course of doxycycline can be tried. • Alpha-blockers can be added to improve symptoms and quality of life.

Benign prostatic hyperplasia Benign prostatic hyperplasia occurs in men 50 years and older, and the incidence increases with age.

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Symptoms and signs include: • obstructive (urinary hesitancy, dribbling, inability to empty bladder) • irritative (frequency, nocturia, urgency) • enlarged, boggy prostate on digital rectal examination. Important differential diagnoses include: • bladder or prostate cancer • infection • prostate cancer. Progression may lead to urinary obstruction with stones, infections, overﬂow incontinence, or kidney damage. Treatment • Mild cases need symptomatic relief and advice to reduce alcohol and caffeine intake, timed voiding schedule, and reduced ﬂuid intake before bed. • Medications to reduce smooth muscle tone for symptom relief – not available in most centres. • If severe, or if medical management fails, surgery (trans-urethral prostatectomy) is indicated. Catheterization techniques – see Section 7.3.7.

10.16.7 Schistosomiasis of the male genitourinary tract – see Section 11.34 Table: Male GU clinical manifestations of schistosomiasis Site Semen Seminal vesicles Prostate, testes, epididymis Bladder Penis Clinical manifestation Lumpy semen, haemospermia Azospermia, leucocytospermia Caliciﬁcations Non-speciﬁc lesions Haematuria, calciﬁcation Ulcers (very rare)

See Section 11.34 for details on diagnosis and treatment of schistosomiasis.

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10.17 Disorders of the mouth and throat In this section: 10.17.1 Clinical approach to disorders of the mouth and throat 10.17.2 HIV and the mouth 10.17.3 Soft tissue lesions of the mouth (with DDx tables) • Oral candidiasis • Lichen planus or lichenoid drug reaction • Approach to persistent mouth ulcers 10.17.4 Oral cancer 10.17.5 Conditions related to the hard tissue of the mouth • Dental caries – tooth decay • Dental abscess • Tooth wear 10.17.6 Gum disease • Gingivitis • Periodontitis • Necrotizing conditions of the mouth 10.17.7 Noma disease 10.17.8 Dry mouth 10.17.9 Pharyngitis • Acute streptococcal pharyngitis • Peritonsillar abscess (quinsy)

This Section provides an approach to recognizing, diagnosing and managing common problems of the soft and hard tissues of the mouth (oral cavity), as well as the pharyngitis. Oral disorders may be due to disease processes localized to the mouth (teeth, gums, or mouth mucosa), or they may be signs of an underlying systemic disease, nutritional disorder, or bacterial or viral infection. An unhealthy diet rich in sugars and poor oral hygiene play major roles in localized oral diseases, affecting gums and teeth. People who use tobacco or drink alcohol in excess are particularly at risk of major oral disorders, particularly oral cancer and gum disease. Assessment of the mouth Assessment of the mouth is quick and easy and should be part of the routine health examination. The examination should be systematic and include all parts of the mouth, including the lips and face. Early management of mouth problems is especially important for HIV-infected patients who are at increased risk of both soft tissue lesions and salivary gland disorders, as well as accelerated gum disease. Rapid detection and referral for special care is important for oral cancer.

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10.17.1 Clinical approach to disorders of the mouth and throat Step 1: Use Quick Check. Facial asymmetry, or swelling of the lips with mucosal ulceration should be evaluated urgently as this may be a severe drug reaction (angio-neurotic oedema) needing urgent attention. Step 2: Take a history – both speciﬁc of the mouth and a general medical history. Step 3: Examine the oral cavity and lips, and also perform a general medical examination. Step 4: Assess the patient’s HIV status. Step 5: Classify the mouth problem and work through the relevant differential diagnosis (see DDx tables). Look for: • tooth decay or loss of tooth tissue • gingival bleeding or dental plaque • abscess • ulcerative soft tissue lesions • soft tissue swelling (lumps and bumps) • white lesions • red lesions • dry mouth • loosening of teeth. Step 6: Investigate if necessary. Step 7: Initiate treatment (or refer) and monitor the response. Note: Suspect mouth cancer if signs do not resolve with treatment and refer within 3 weeks.

History Speciﬁc history of the mouth • What is the duration of the symptoms? • Has there been a change in the condition? • Are there associated symptoms (e.g. pain, difﬁculty biting, chewing or swallowing, difﬁculty speaking, dryness of the mouth, or pain referred to the ear?) • Ask about use of dentures and appliances. • Ask about oral hygiene practices. • Discuss dietary habits (sugars, frequency of snacking). General history • Are there symptoms of systemic disease or co-morbidities? ° constitutional symptoms (fever, night sweats, malaise, lymphadenopathy); ° systems review for speciﬁc system involvement (central nervous system, cough, abdominal complaints); ° assess the patient’s HIV status; ° ask about autoimmune conditions and immunocompromising conditions like diabetes. • Is the patient using any medications (including those bought over-thecounter)? Remember to ask when medications were ﬁrst started.

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• Look for signs and symptoms suggestive of current or prior STIs. • Ask about tobacco (smoking, chewing), alcohol, and drug use. • Ask about the patient's diet.

Physical examination Assess the mouth (as below) and then perform a full general physical examination checking for signs of systemic disease. Speciﬁc oral examination Examination of the mouth is easy and non-invasive. Useful items include a tongue depressor or wooden spatula, gauze pads, and a light source. Use mouth mirrors if they are available. • Inspect the face and neck with the mouth closed – note skin changes, swellings, and blisters. Inspect the lips, paying particular attention to cracks and ﬁssures at the angles of the mouth. Note asymmetries of the face and neck that may indicate swollen salivary glands. • Palpate lymph nodes including the submandibular and cervical lymph nodes (are they enlarged, movable or ﬁxed, tender or non-tender?). See Section 10.5 Lymphadenopathy for more details. • Examine the oral cavity (remove dentures if present). A systematic oral examination is important so as to not overlook parts of the mouth that are likely to be missed. • Undertake a clinical examination of inside of the cheeks, tongue, gums, ﬂoor of the mouth, and palate. • Palpate any lumps visible during the clinical examination. • A two-ﬁnger palpation approach with one gloved ﬁnger inside the mouth and another on the corresponding facial structure is most useful for noting submucosal irregularities, swelling, or enlarged structures. • Examine the oropharyngeal area with the patient’s mouth open wide enough for the tonsillar tissue and upper pharynx to be visible. Gentle depression of the tongue may facilitate this. Remember to examine all sides of the tongue including the sides and ﬂoor. • Examine particularly teeth and gums.

Investigations • An X-ray may be useful in some mouth conditions, such as dental (apical) abscess, ulcerative gingivitis, advanced gum disease, and malignant oral cancers spreading to the jaw. Examining the mouth is important for: 1. detection of HIV-associated oral disorders that may help to identify the disease in the early stages and oral cancer, which, if not detected early, is lethal; 2. diagnosis and treatment of other common oral disorders, such as dental caries, loss of tooth tissue, gum disease, candidiasis, oral ulcers, and swelling of oral cavity. A differential diagnosis of white and red patches is presented, as some potentially malignant disorders (e.g. leukoplakia and erythroplakia) present as white or red lesions.

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10.17.2 HIV and the mouth The majority of people with untreated HIV develop oral manifestations at some time during the illness, and about 50% of PLHIV experience oral lesions. An examination of the oral cavity is particularly important: • when HIV is suspected; • for clinical staging of the disease; • when monitoring the response to ART; • as a marker of clinical treatment failure if HIV-associated lesions develop while the patient is on ART. Some conditions are particularly common in PLHIV, such as candidiasis, oral hairy leukoplakia, Kaposi sarcoma, necrotizing ulcerative gingivitis and advanced gum disease (periodontitis), atypical oral ulceration, and non-Hodgkin lymphoma. Oral candidiasis and oral hairy leukoplakia are HIV clinical stage 3 conditions.

10.17.3 Soft tissue lesions of the mouth Classify the lesion and consult the relevant differential diagnosis tables below. Sometimes, more than one differential diagnosis table may have to be used. • White lesions may be white patches on the tongue (dorsal, ventral or lateral surfaces), inside of the lips and cheek mucosa, palate, or tonsils. Attempt to wipe off the lesion with gauze. • Red lesions may be red patches or plaques. • Ulcerative lesions may be either small or large ulcers. • Soft tissue swellings are lumps.

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DDx: White lesions Diagnosis Oral candidiasis (pseudomembranous) See below and Section 11.4. Chronic hyperplastic candidiasis See Section 11.4. Oral hairy leukoplakia In favour Cheesy white lesion on mucosal surface Reveals red raw surface when wiped off Responds to topical antifungal agents; nystatin or amphotericin If recurrent, look for immunosuppressed status, e.g. HIV, diabetes, or cancer Painless white plaques close to the angle of the mouth on the inside of cheek (i.e. buccal mucosa); rarely, dorsal tongue No local trauma Responds to topical antifungal medication Painless, vertical corrugations along the sides of the tongue, bilaterally – washboard-like pattern Cannot be wiped off Responds to ART Lacy white striae or patches on the sides of the tongue or insides of the cheek Generally asymptomatic Note in history change of medication likely to cause a lichenoid reaction White patches on the buccal mucosa, lateral tongue, or lip due to accumulation of keratin Presence of friction or chronic irritation such as tissue chewing, broken or sharp teeth, or ill-ﬁtting dentures Cannot be wiped off White colouration of palate with red dots mostly on the hard palate History of heavy smoking – particularly pipes, asymptomatic Cannot be wiped off Responds to cessation of smoking Painless patches of keratosis on the mucous membranes including the tongue Cannot be wiped off Associated with tobacco use, alcohol, HPV Exclude trauma as a cause Considered potentially malignant; 4–15% of the lesions could progress to cancer

Lichen planus or lichenoid drug reaction Frictional keratosis

Nicotinic stomatitis

Leukoplakia

Oral candidiasis Candidiasis is common and is often a reﬂection of ill health due an underlying disorder, e.g. diabetes, anaemia, or immunodeﬁciency. It is the most common oral manifestation in PLHIV. It may interfere with taste and eating, which may compromise the general status of the affected person. Either topical or systemic antifungal medication may be used for treatment.

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Treatment • Early treatment is warranted as candidiasis causes discomfort and may spread to the pharynx and oesophagus. • Oral candidiasis in HIV patients usually responds to initial topical therapy (clotrimazole, nystatin, miconozole, see Section 11.4). • Recurrences are common, and if there is no response in 1 or 2 weeks, systemic agents for both treatment and maintenance therapy may be required. This includes giving ﬂuconazole 200 mg daily for 14 days. • Initiate ART. Prevention • Reduce tobacco consumption. • Reduce diet. • Maintain good oral hygiene. • Improve denture hygiene.

Lichen planus or lichenoid drug reaction Oral lichen planus is a chronic autoimmune inﬂammatory condition. It can result from an allergic reaction to food, food additives, fragrances, dyes, dental metals, or other substances. Treatment • Medical treatment focuses on symptom control and removing the offending substance if it can be identiﬁed. • Give pain control if necessary, and high-potency corticosteroid gels or ointments (triamcinolone) need to be applied to lesions.

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DDx: Red lesions in the mouth Diagnosis Erythematous candidiasis For treatment see oral candidiasis above and see Section 11.4 Angular cheilitis Signs and symptoms Red patches on palate or on dorsal surface of tongue No history of local trauma May co-exist with pseudomembranous candidiasis Usually asymptomatic – burning sensation may occur Responds to topical antifungal medication Painful erythaema associated with a crack or ﬁssure at angle of the mouth Presence of ill-ﬁtting dentures Dry mouth May be due to candidiasis or Staphylococcus aureus Single or multiple reddish-blue lesion on palate or gum Painless, but may progress May coexist with skin lesions Lymphadenopathy HIV-infected Generalized loss of papillae on dorsal tongue Burning sensation Dietary deﬁciencies Pallor Diffuse erythaema and sloughing Involvement of the gingiva Pain History of contact with, e.g. dentures, food colouring, toothpaste. Responds to withdrawal of allergen Red lesions with yellow/white border – migratory over time or may change size and shape Localized absence of papillae (small hairs on the surface of the tongue) Irregularly shaped smooth, red patches to form on parts of the tongue (gives the tongue a map-like, or geographic, appearance) Asymptomatic Red patches with well-demarcated borders Frequently found on the ﬂoor of the mouth, the tongue, the soft palate Precancerous – carcinoma is found in 50% of the lesions and severe dysplasia in the rest indicating potential for cancer development Associated with tobacco use

Kaposi sarcoma see Section 11.19

Atrophic glossitis – nutritional deﬁciency or anaemia Contact stomatitis

Geographic tongue

Erythroplakia

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DDx: Ulcerative lesions in the mouth Diagnosis Traumatic ulcer Signs and symptoms Isolated ulcer Obvious cause of irritation or trauma Resolve within 1–2 weeks after removal of the cause Painful ulcer with a whitish base surrounded by discrete red border May be small, large, or multiple ulcers Usually limiting – but may be large, deep, and longer-lasting in PLHIV Previous episodes Responds to topical steroids Painful recurrent oral and genital ulcerations Eye involvement and inﬂammation of other parts of the body Unknown cause Painful vesicles evolving to ulcers Palate or gingiva Constitutional symptoms Tender regional lymphadenopathy Starts as burning sensation or pain before onset of blister on lip Triggered by sun exposure, stress, or recent illness Previous episodes Very contagious Distribution of painful vesicles and ulcers on skin and mucosa Lesions do not cross the midline but are limited to: • one side of the anterior two-thirds of the tongue • one side of the mouth or face Large reddish ulcer with a white border Painful Immunocompromised Pain on swallowing Primary syphilis – painless ulcer that resolves spontaneously Secondary syphilis – painful superﬁcial ulcers or erosions Tertiary syphilis – painless, punched out ulcers – gumma Other features of syphilis on history and examination Positive syphilis serology Large, painful, deep ulcers – involvement of the tongue Constitutional symptoms of TB AFB present Coinfection with HIV

Aphthous ulcers

Behcet’s syndrome

Herpetic stomatitis or gingivitis

Herpes labialis

Herpes zoster

Cytomegalovirus (CMV) infection see Section 11.8 Syphilis see Section 11.37

Tuberculosis see Section 15

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Necrotizing conditions of the mouth see Section 10.17.6 below for management of acute necrotizing ulcerative gingivitis, acute necrotizing ulcerative periodontitis necrotizing stomatitis see also Section 10.17.7 Noma disease Adverse drug reaction

Very painful ulcers – sensitive to touch Swollen, red, bleeding gums Involvement of the bone with loose teeth or bone involvement, sequestration In some populations, may very rapidly lead to noma disease with an outbreak of the necrosis onto the face Foul mouth odour Advanced immunosuppression Consider drug reaction if drugs have recently been initiated – see below in HIV-associated disease

Recent initiation of new drug or long-term use of immunosuppressants Erosions, bullous lesions, or ulcers with crusting of the lips Involvement of skin and other mucosal surfaces (conjunctiva, vagina) Mostly over buccal mucosa and palate Sudden onset Persistent ulcer, with rolled margins Demonstrates induration at margins or base Rapidly increases in size High risk patient- tobacco or alcohol user

Squamous cell carcinoma

Approach to persistent mouth ulcers If mouth ulcers are not responding to empirical treatment, do not resolve in 2 weeks, and other causes are excluded consider other conditions such as: • neoplasms – squamous cell carcinoma • autoimmune conditions • inﬂammatory bowel disease • neutropenia. These conditions may need to be conﬁrmed by a biopsy and other appropriate investigations.

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DDx: Soft tissue swellings in the mouth Diagnosis Dental abscess see Section 10.17.5 Signs and symptoms Constant pain, history of toothache Localized swelling of the face or gums near a tooth Pointing or pus discharge Pain when tapping or biting on tooth Painless soft tissue swelling Ill-ﬁtting dentures Presence of local irritation or trauma Often in locations (e.g. sulcus) where the periphery of the denture is overextended Painless cystic swelling, generally blue colour Mostly on lip labial mucosa or buccal mucosa Painless White or pink often multiple irregular lesions Common during treatment with ART Reddish-blue swollen tissue on palate or gum (gingival) May accompany skin lesions Mostly asymptomatic unless ulcerating May complicate eating, swallowing, and talking Focal soft swelling that may be red and inﬂamed Painful Rapid enlargement Needs histological conﬁrmation (biopsy) Slow-growing mass on palate with normal colour Mostly on palate or upper lip Histological conﬁrmation Fibrous lump on gum (gingiva) Firm, may be single or lobulated, painless Overlying mucosa normal in colour In pregnancy, inﬂamed and vascular (pyogenic granuloma) Common benign disorder Pedunculated or sessile, over-growth of mucosa Painless Persistent lump, with central ulceration Demonstrates induration at margins or base Rapidly increases in size High risk subject (tobacco or alcohol user)

Denture-induced (reactive) hyperplasia

Mucocoele or ranula Oral warts or condylomas

Kaposi sarcoma see Section 11.19

Non-Hodgkin’s lymphoma

Minor salivary gland tumours

Epulis

Fibro epithelial polyp

Squamous cell carcinoma

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10.17.4 Oral cancer Oral cancer appears as a growth or an ulcer that does not go away. The most common sites are on the side of the tongue, buccal mucosa and sulci, and the ﬂoor of the mouth. Oral cancer can be life threatening if not diagnosed and treated early, and may spread to regional lymph nodes. Oral cancer is mostly caused by tobacco (smoking or chewing), areca nut (betel quid) and excessive consumption of alcohol. HPV infection is an emerging risk factor, particularly in the young. Common signs and symptoms of oral cancer include: • swellings, thickenings, lumps or bumps on the lips, cheeks, tongue, gums, or other areas inside the mouth; • a persistent ulcer that does not heal within 2 weeks; • development of white, red, or speckled (white and red) patches in the mouth; • unexplained bleeding in the mouth; • unexplained numbness, loss of feeling, and pain or tenderness in any area of the face, mouth, or neck; • soreness or a feeling that something is caught in the back of the throat; • difﬁculty chewing or swallowing, speaking, or moving the jaw or tongue; • hoarseness, chronic sore throat, or changes in the voice; • ear pain; • a change in the way teeth or dentures ﬁt together – a change in bite; • dramatic weight loss; • lumps in the neck due to spread of the disease. Deﬁnitive diagnosis requires a biopsy and referral to a specialist.

10.17.5 Conditions related to the hard tissue of the mouth Dental caries – tooth decay This condition is primarily caused by the combination of dietary sugars and oral bacteria in plaque, which is a sticky yellow-white coating on the tooth surface. The plaque bacteria (particularly Streptococcus mutans) ferment the sugars and produce acid, which eventually breaks down (decalciﬁes) the hard tooth tissue. Over time, this results in cavitations of the tooth and may cause increasing pain. Sensitivity related to hot or cold foods or drinks is common. If the progression is not stopped the bacterial invasion will ultimately involve the pulp of the tooth (central chamber of the tooth with nerve endings and blood vessels) causing excruciating pain. The infection can spread to the jaw bones and can cause an abscess or even cellulitis. Dental caries often impair dietary habits and affect nutritional status. Treatment Restorative treatment may be expensive or unavailable, and extraction of the tooth may be the only option for treatment. Where it is feasible to restore the tooth, minimally invasive techniques should be used.

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Prevention • Limit intake and frequency of sugars and increase intake of fruit and vegetables. • Oral hygiene measures, such as tooth brushing, ﬂossing, or use of traditional chew sticks. • Fluoride added to toothpaste, salt, or milk has a preventive effect. Be aware of dry mouth as a result of medication (including ART) as it increases the risk of tooth decay.

Dental abscess Dental abscesses are usually related to the spread of infection following the progression of dental caries to the pulp, or advanced gum (periodontal) disease. Treatment • Drain the abscess or, if extraction of the tooth is indicated, refer urgently to an oral health professional. • If the patient has fever, difﬁculty in opening the mouth, difﬁculty in breathing, or if the infection is spreading, give antibiotics: ° phenoxymethyl penicillin 250 mg 4 times a day OR amoxicillin 500 mg–1 g 3 times a day for 5–7 days PLUS metronidazole 500 mg 3 times a day for 5 days; OR ° amoxicillin-clavulanate 875 mg every 12 hours (or 500 mg 3 times daily) in adults. • Provide adequate pain relief (analgesics). Supportive measures • Advise the patient on oral hygiene. • Soft diet for a few days (soup, yoghurt, jelly, boiled eggs, porridge).

Tooth wear There are 3 types of tooth wear; attrition, erosion, and abrasion. Attrition Loss of enamel or dentine due to excessive masticatory forces, grinding, or bruxism. Flattening of cusps of teeth or loss of incisal edges may lead to shortening of the dentition. Erosion The irreversible progressive loss of hard tooth substance is caused by chemical factors, such as acids. Erosion is seen in persons suffering from bulimia due to the reﬂux of gastric juices into the mouth, in people exposed to an unhealthy environment, e.g. workers exposed to acids, and increasingly observed among people drinking large amounts of carbonated, sugar-containing soft drinks, and among alcoholics due to vomiting of gastric acids. Abrasion The irreversible progressive loss of hard tooth substances is caused by mechanical factors other than mastication or tooth-to-tooth contacts. Abrasion mostly is seen due to incorrect tooth brushing, which leads to notching at the junction of the crown and root of the teeth. It can be caused by environmental factors, such as exposure to quartz dust. 344 Disorders of the mouth Vol. 2 • 10. Acute and subacute by symptom: July 2011

Where there is tooth wear (due to any of above), the patient may complain of sensitivity of teeth to hot or cold drinks or food. This is transient but causes considerable discomfort. Use of ﬂuoride pastes and desensitizing toothpaste may help to control symptoms. Abraded cavities may need restoration.

10.17.6 Gum disease Gingivitis This is an inﬂammation of the tissues (gums) surrounding the teeth. It originates from plaque (yellow-white coating on the teeth – often along the gum margin) when toxins produced by plaque bacteria cause inﬂammation of the gums. Gums become inﬂamed and red and bleed upon touch. This common condition is reversible through oral hygiene measures, such as regular removal of plaque along the gums. If the plaque is not removed it can harden (calcify) into “calculus”.

Periodontitis If untreated, gingival inﬂammation might slowly develop into periodontitis – a breakdown of the tissues holding the teeth in place. A pocket develops between the gum and the tooth spreading toward the root of the tooth. Pain is rare but a bad-smelling breath develops, pus can accumulate, and an abscess could form. Eventually, teeth may loosen, move, and fall out. Treatment • Professional scaling and removing of plaque and calculus. • Adjunctive use of antiseptic mouthwash for a short period. • Extraction of mobile teeth. Prevention • Proper oral hygiene to remove the plaque along the gum (brushing, ﬂossing, use of chew stick) on a daily basis. Risk factors • tobacco use • inadequate oral hygiene (presence of plaque or calculus) • systemic health conditions, such as diabetes and HIV infection.

Necrotizing conditions of the mouth Under certain conditions, periodontitis may rapidly exacerbate into acute and severe situations. • Acute necrotizing ulcerative gingivitis (also known as ANUG): limited to the gums. • Acute necrotizing ulcerative periodontitis (also known as ANUP): destruction of bone supporting the teeth and oral mucosa. • Necrotizing stomatitis: destruction of cheek, sequestration of bone that can cause patients to be systemically unwell. These necrotizing conditions are caused by aggressive bacteria, stress, poor nutrition, and a decreased immune response, and may occur in PLHIV.

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Symptoms • ulcerated or necrotic gums • considerable pain • foul-smelling breath • fever and symptoms of common infection • intake of food and drink is painful. Treatment • In a patient with acute necrotizing ulcerative gingivitis or periodontitis, or necrotizing stomatitis, treat with metronidazole 200 mg 3 times daily for 7–10 days. • Hydrogen peroxide as a mouth wash, diluted 1:1, for 7 days.

10.17.7 Noma disease In non-HIV-infected persons, noma disease occurs mainly in young children living in poverty. Contributing factors are severe malnutrition, poor hygiene, aggressive necrotizing micro-organisms, and general infection (e.g. measles). Low immune status is also a factor, making it an HIV-related condition. The infection results in rapid, devastating destruction of soft and bony tissues spreading from the inside of the mouth, breaking down through the tissues of the cheek, lips, and nose. If untreated, this disease results in high mortality. In survivors, it results in severe facial defects often requiring plastic surgery, which is expensive and often not available. Treatment • Debridement of necrotic tissue or bony sequestrate. • Acute nutritional supplementation. • Instructing the patient in oral care – showing the patient and family how to clean the mouth with saline, peroxide, or sodium bicarbonate. • The acute stage responds readily to antibiotic treatment to control anaerobic organisms. Prevention Noma disease intervention should raise awareness of the disease. Prevention should focus on improved housing conditions, poverty reduction, improved nutrition, promotion of exclusive breastfeeding, optimum prenatal care, timely immunizations against the common childhood diseases, and access to clean water and sanitation facilities for optimal personal and oral hygiene.

10.17.8 Dry mouth Dry mouth is common in the elderly, in those taking regular medications that contribute to xerostomia, following radiation therapy to head and neck, and in association with connective tissue disorders (e.g. rheumatoid arthritis). Dry mouth is a common symptom in HIV infection. • Review medications – dry mouth can be a side-effect of hyoscine, morphine, atropine, amitriptyline, furosemide, and ART. • Check for signs of infection. • Breathing through the mouth can also contribute.

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• If there is a persistent problem with lack of saliva, pay close attention to preventive oral care and mouth hygiene. Intake of citrus juice or lemon may induce production of saliva. • If Candida, treat as suggested earlier and see Section 11.4 Advise the patient to: • Moisten the mouth with regular sips of water. • Maintain good oral hygiene. • Avoid sugary snacks. • Chew sugar-free gum.

10.17.9 Pharyngitis Pharyngitis is common worldwide and presents as an inﬂammation of the throat caused by various organisms from viruses to bacteria. Respiratory viruses causing the common cold are the most common causes, but herpes simplex virus, coxsackie virus, and Epstein-Barr virus (EBV) can cause acute pharyngitis. Cases caused by viruses usually resolve spontaneously. However, pharyngitis caused by Streptococcus pyogenes is a cause for concern. If untreated, this can progress to acute rheumatic fever or glomerulonephritis, both of which can cause signiﬁcant sequelae. Corynebacterium diphtheriae is a less frequent cause of bacterial pharyngitis in areas where there is insufﬁcient childhood vaccination coverage. It can be life-threatening through the formation of membranes in the throat. Pharyngitis can be complicated by tonsillitis and peritonsillar abscess (quinsy). Key clinical features • Pain on swallowing. • Red throat with enlarged tonsils. • White deposits (exudates) may be present on the pharyngeal surfaces in bacterial and in some viral cases. • Fever, headache, swollen and painful cervical lymph nodes, myalgias, and runny nose are associated in cases of respiratory virus infection, particularly adenovirus and inﬂuenza. • Vesicles and shallow ulcerations are present in herpes or Coxsackie virus infections. Treatment • For viral pharyngitis, supportive management with fever reducing agents (paracetamol) is adequate. • Antibiotic treatment should be reserved for cases of suspected streptococcal pharyngitis.

Acute streptococcal pharyngitis Group A beta-hemolytic streptococcus (GABHS) causes only approximately 10% of adult cases of pharyngitis. Antibiotic treatment of pharyngitis beneﬁts only those patients with GABHS infection.

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Key clinical features • high fever • very inﬂamed throat with many exudates • large, tender cervical lymph nodes • absence of cough. • other features of the common cold are usually absent (runny nose, sneezing). Complications • rheumatic fever (see Section 11.32) • post-infectious inﬂammation of the kidneys (glomerulonephritis, renal failure – see Section 11.31) • local extension: ear infection, sinusitis, pneumonia. Investigations If a streptococcal infection is suspected, use rapid antigen detection test or a culture to conﬁrm, if possible. A score has been developed that gives 1 point each for absence of a cough, swollen and tender cervical lymph nodes, temperature >38°C, tonsillar exudate or swelling, and age <15. A point should be subtracted if age >44. A score of 4 or more may justify empirical antibiotic treatment, although considerable overtreatment will still occur.1 Follow national guidelines. Treatment Antibiotic treatment should be reserved for cases of suspected streptococcal pharyngitis. This reduces the risk of rheumatic fever (Section 11.32).2 Give: • benzathine benzylpenicillin G 1.2 million units IM single dose (preferred); OR phenoxymethyl penicillin 500 mg PO twice daily for 10 days; OR • (if allergic to penicillin) erythromycin 250 mg 4 times daily for 10 days.

Peritonsillar abscess (quinsy) Peritonsillar abscess is usually a disease of older children, adolescents, and young adults. The infection can spread to the neck and chest, including the lungs. Swollen tissues may block the airway, which is a life-threatening medical emergency (see Section 3.1). Key clinical features • sore throat (may be severe and is usually on one side) • throat red and swollen on one or both sides • swollen palate (roof of mouth) • deviated uvula (shifted away from swelling) • difﬁculty and pain when opening the mouth • difﬁculty swallowing • drooling or inability to swallow saliva 1 B.A. Choby, Diagnosis and treatment of streptococcal pharyngitis. American Family Physician. 2009, 79:383–390. 2 Rheumatic fever and rheumatic heart disease. WHO, 2004. Chapter 8. Medical management of rheumatic fever. Available at http://whqlibdoc.who.int/trs/WHO_TRS_923.pdf

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• • • •

may have facial and neck swelling fever headache tender lymphadenopathy of the jaw and throat.

Treatment • Needle aspiration or incision and drainage. See instructions in the WHO manual Surgical care at the district hospital.3 • Antibiotics, for total 14 days duration: ° In areas where S. aureus remains susceptible to methicillin and patient able to take oral: ◊ amoxicillin 500 mg to 1 g 3 times daily for 5-7 days PLUS metronidazole 500 mg 3 times a day for 5 days; OR ◊ clindamycin 300 to 450 mg every 6 hours in adults; OR ◊ amoxicillin-clavulanate 875 mg every 12 hours (or 500 mg 3 times daily) in adults. ° In areas where S. aureus remains susceptible to methicillin and patient requires IV therapy: ◊ clindamycin IV 600 mg every 6 to 8 hours.

3 Surgical care at the district hospital. WHO, 2003. Available at http://www.who.int/surgery/publications/scdh_ manual/en/

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10.18 Pallor and anaemia1 In this section: 10.18. 1 Clinical approach to a patient with pallor and anaemia • Table: Focus history and examination according to the likely cause of the anaemia • Table: Normal ranges for haemoglobin by age and gender 10.18.2 Classiﬁcation of anaemia • DDx: Classiﬁcation of anaemia based on MCV and MCHC 10.18.3 Management of anaemia • Summary of initial laboratory investigations and management of anaemia • Blood transfusion therapy • Sickle-cell disease

This Section deals with the approach to pallor and anaemia. Anaemia is present when the haemoglobin concentration in the peripheral blood is lower than normal for age, sex, pregnancy, and environmental factors.

If a patient is found to be anaemic, always look for the cause. Anaemia is never the ﬁnal diagnosis.

A patient may present with symptoms of anaemia discovered during a routine examination or investigation of some other condition, or the patient may be symptomatic from the anaemia.

10.18.1 Clinical approach to a patient with pallor and anaemia Step 1: Use Quick Check to ensure that there are no serious or life-threatening conditions. Use the Quick Check and be aware that acute blood loss (e.g. trauma or pregnancy states, acute GI bleed) can present with shock. The chronically anaemic patient may decompensate and present with congestive cardiac failure. Step 2: Take a history and examine the patient. Examine the patient to identify key signs: • ask about associated symptoms and look for signs that reveal the underlying cause of the anaemia • ask about and look for any complications of the anaemia. Step 3: Assess HIV status. Step 4: Perform investigations. • FBC and peripheral blood smear. • Malaria smear or rapid diagnostic test (RDT) for malaria. • Other special investigations as indicated. Step 5: Classify anaemia and work through the differential diagnosis. • Classify the type of anaemia based on the shape and size of the red blood cells – mean corpuscular volume (MCV). • Classify the anaemia based on whether one cell line is involved or multiple. • Work through the differential diagnoses found in the attached tables. • Request special investigations or diagnostic tests to conﬁrm the diagnosis or refer to local referral hospital. Step 6: Initiate treatment and monitor response to treatment. Re-evaluate as necessary.

1 The Clinical Use of Blood Handbook. WHO, 2002, (in revision). Available at http://www.who.int/bloodsafety/ clinical_use/en/Handbook_EN.pdf

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History Non-speciﬁc symptoms of anaemia • tiredness, fatigue, or loss of energy • dizziness, light-headedness, syncope, or fainting • shortness of breath, especially on effort • ankle swelling • headache • worsening of any pre-existing symptoms, e.g. angina. Table: Focus history and examination according to the likely cause of the anaemia Cause of anaemia Increased loss of red blood cells • acute blood loss – haemorrhage from trauma, surgery, obstetric causes • chronic blood loss: from GI, urinary or reproductive tracts – like menorrhagia, parasitic infestations including hookworm and whipworm, malignancy, chronic autoimmune, or inﬂammatory disorders Decreased production of normal red blood cells • nutritional deﬁciencies: iron, B12, folate, malabsorption, malnutrition • viral infection: HIV, HBV, and HCV • bone marrow failure – aplastic anaemia, malignancies (leukaemia) • reduced erythropoietin production – renal failure • chronic illness • poisoning of the bone marrow: lead, drugs Increased destruction of the red blood cells • infections – bacterial, viral, protozoal, parasitic • drugs • autoimmune disorders: • inherited disorders – sickle-cell disease, thalassaemia, G6PD deﬁciency • haemolytic disease of the newborn • others: DIC, haemolytic uraemic syndrome, TTP Increased physiological demand for red blood cells • pregnancy • lactation • growth History • obstetric or gynaecological history, menorrhagia or other vaginal bleeding • bleeding from urinary tract • bleeding gums, epistaxis, purpura • GI bleed: melena, upper GI bleed, chronic diarrhoea, weight loss, indigestion • drug history • • • • • • history of high risk of exposure to HIV drug history nutritional history socio-economic status psychiatric disorders – anorexia, bulimia fever, night sweats, weight loss (malignancies, TB, HIV, and others)

• malaria episodes, travels or lives in malaria endemic area • fever, night sweats (malaria or other infections like TB) • family history, ethnic origins

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Examination Look for underlying diseases, signs of anaemia, and related complications. Signs of anaemia with clinical decompensation • pale mucous membranes, skin, and nail beds • rapid breathing • tachycardia • raised jugular venous pressure • heart murmurs • ankle oedema • postural hypotension – dizziness when the patient gets up from a sitting or sleeping position • pulmonary oedema • altered mental state.

Remember a patient may have several causes of anaemia – nutritional, HIV, malaria, parasitic infestation, or malignancy.

Signs of the underlying disorder • weight loss or underweight for their height or age • angular stomatitis, koilonychia (iron deﬁciency) • jaundice (haemolysis) • purpura and bruising (bone marrow failure, platelet disorders) • enlarged lymph nodes, hepatosplenomegaly, fever (infection, lymphoproliferative disease, HIV infection) • lower leg ulcers (sickle-cell disease) • skeletal deformities (thalassaemia) • neurological signs (vitamin B12 deﬁciency) • fever (malaria).

Investigations • Haemoglobin (Hb) – conﬁrm the presence of anaemia. Note that normal ranges for Hb are age- and sex-dependant (see table below). • FBC – look at the red blood cell (RBC) count, haemoglobin, haematocrit (HCT) and RBC indices, the white blood cell count, and differential leukocyte count and platelet count. • Perform a malaria smear or RDT for malaria. • Peripheral blood smear ° Assess RBC: size, shape, colour (Hb content), polychromasia, rouleaux formation, RBC aggregation, RBC inclusion bodies. ° Morphological abnormalities of other cells – WBC and platelets – are also reviewed and may show underlying pathologies (e.g. leukaemia, aplastic or megaloblastic anaemia, infections like malaria parasites, or bone marrow failure). ° If an automated blood-cell analyser is not available, the RBC size should be evaluated on the blood smear to detect microcytosis or macrocytosis.

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• Reticulocyte count ° Reticulocytes are newly produced red blood cells. A normal response to anaemia is for the marrow to produce reticulocytes, and therefore increase the RBC count. Therefore, the reticulocytes count is an indicator of the marrow response to anaemia. ° The reticulocyte count results (given as a proportion of total RBC) can be calculated manually or by an automated machine. The reticulocyte count represents the percentage of total erythrocytes and does not correct for anaemia. ° The corrected reticulocyte or reticulocyte index (RI) adjusts reticulocyte count for haematocrit, and reﬂects the bone marrow activity. It can be very useful when a bone marrow aspirate cannot be obtained. The formula for calculating RI is as follows: RI = reticulocyte count x (Hct/normal Hct) A normal reticulocyte count is 0.5-1.5%. A normal reticulocyte index is 1-3%.

Reticulocytes can also be identiﬁed by Wright Giemsa stains on a peripheral smear. Red blood cells indices using an automated blood cell analyser Use MCV to classify anaemia • Normocytic anaemia: MCV within the normal range 80–100 ﬂ. • Microcytic anaemia: MCV below 80 ﬂ. • Macrocytic anaemia: MCV above 100 ﬂ. Table: Normal ranges for haemoglobin by age and gender Normal Hb range 11.5–15.5 13.0–17.0 12.0–15.0 11.0–14.0 10.5–14.0 11.0–14.0 Anaemic if Hb (g/dl) < 11.5 13 12 11 10.5 11 Anaemic if Hct < (Hct 34%) (Hct 39%) (Hct 36%) (Hct 33%) (Hct 31%) (Hct 33%) Severe anaemia if Hb (g/dl) < 4 7 7 5 5 6

Age/gender Children 6–12 years Adult males Adult females: non-pregnant Adult females: pregnant(*) First trimester: 0–12 weeks Second trimester: 13–28 weeks Third trimester: 29 weeks – term

Additional tests • a faecal occult blood test; • iron studies tests: ° serum ferritin, which reﬂects total body iron stores and is the ﬁrst value to fall in iron-deﬁciency anaemia; ° total iron-binding capacity (TIBC), which measures the extent to which ironbinding sites in the serum can be saturated; ° serum total iron, which measures the serum iron that is bound to transferrin;

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• • • • •

° transferrin percent saturation, which measures the extent to which sites on transferrin molecules are ﬁlled by iron ions (serum Fe/TIBC). haemoglobin electrophoresis; sickling test – for sickle-cell disease; serum B12 level; direct antiglobulin test for autoimmune haemolytic anaemia; bone marrow sampling if it is indicated.

10.18.2 Classiﬁcation of anaemia Classify the anaemia according to the MCV and the MCHC work through the DDx table below.

DDx: Classiﬁcation of anaemia based on MCV and MCHC Blood ﬁlm Microcytic, hypochromic Low MCV, small RBC on smear Low MCHC Cause Acquired • iron deﬁciency • sideroblastic anaemia • anaemia of chronic disease In favour of Pallor of mucous membranes Smooth tongue Angular stomatitis (cracks on the sides of the mouth) Spoon-shaped nails (koilonychia) Brittle hair Pica α-Thalassaemia and β-Thalassaemia minor: Usually asymptomatic Mild pallor (low MCV) β-Thalassaemia intermedia: Moderate compensated anaemia (Hb 7–10) which may become symptomatic leading to heart failure, pulmonary hypertension Bony expansion when the patient is between 20 and 40 β-Thalassaemia major: Severe anaemia from infancy, poor growth, progressive bone marrow expansion (thalassaemic face, skeletal deformity), jaundice, leg ulcers, cholelithiasis, splenomegaly Pathological fractures common Often Hb <7 g/dl High unconjugated bilirubin Macrocytic, normochromic Increased MCV, large RBC on smear Normal MCHC With megaloblastic marrow • deﬁciency of vitamin B12 or • deﬁciency of folic acid Insidious onset Diarrhoea – known Crohn’s disease, tapeworms, autoimmune disease Sore, burning, red tongue Subacute combined degeneration in B12 deﬁciency – a neuropathy which presents with symmetric tingling in the hands and feet, loss of sensation in the legs, feet and hands, ataxia and, on examination, absent vibration sense, absent patellar reﬂexes with extensor plantar reﬂexes Note: The severity of neurologic ﬁndings does not correlate with the severity of anaemia. Diarrhoea Smooth tongue Cracks in mouth angles Darkening of the skin and mucous membranes, Modest temperature elevation (<38.9°C) is common in patients who are folate deﬁcient, despite the absence of any infection See vitamin B12 above as the same presentation Long-term ART use – see Section 13

Congenital • thalassaemia • sideroblastic anaemia

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Macrocytic, normochromic

With normoblastic marrow • alcohol excess • myelodysplasia • Haemolytic anaemia Patient may be severely ill – haemolytic crises with fever, chills, pain in the back and abdomen, prostration and shock In severe cases, jaundice, splenomegaly, red/dark urine Chronic haemolysis-pigment gallstones, normal MCV, normal MCHC High reticulocytes High unconjugated bilirubin High LDH Indirect hyperbilirubinaemia High urobilinogen in urine In an area of malaria transmission Fever, headache Patient maybe severely ill with signs of cerebral malaria including impaired consciousness or convulsions, respiratory or renal failure Generally mild, insidious onset Usually few or no symptoms Associated with HIV, chronic inﬂammation or autoimmune disorder, renal failure, hypothyroidism

Macrocytic Increased MCV

Normocytic, normochromic Normal MCV Normal MCHC

Chronic disorder • infection including malaria • malignancy • autoimmune disorders • renal failure • hypothyroidism • hypopituitarism • aplastic anaemia • red cell aplasia • marrow inﬁltration Various causes • leukaemia • metastatic cancer • myeloﬁbrosis • severe infections

Leucoerythroblastic Indices may be abnormal due to early and numerous forms of red and white cells

Metastatic carcinoma, lymphoma, or tuberculosis Disseminated fungal disease Symptoms of anaemia, low platelets and neutropaenia Splenomegaly, hepatomegaly, nucleated RBC, and tear drop forms Immature WBCs High reticulocytes, low platelets Bizarre-shaped giant platelets Lytic and blastic lesions on skeletal X-ray

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10.18.3 Management of anaemia Table: Approach to management of anaemia Type of anaemia Iron-deﬁciency anaemia Treatment • Seek bleeding site or intermittent loss, and treat • Consider bleeding from occult sites which may be due to malignancy • Stop NSAIDs or aspirin-containing drugs or other drug with anticoagulating properties • De-worm (consider hookworm; consider Schistosoma haematobium – see Section 11.34) • Provide iron through iron salts (sulphate, gluconate, fumarate) 60 mg of element iron daily for mild anaemia and 120 mg (plus folic acid 400 µg) for moderate or severe anaemia until Hb is normal and ceases to rise, then continue for 4–6 weeks (see algorithm below). Add ascorbic acid – 1 tablet daily to increase iron absorption. • Consider transfusion for patients with severe malaria and Hb<7 g/dl • Test for malaria and, if the result is positive, give antimalarials according to Section 11.25 • Watch for associated complications (dehydration, hypoglycaemia, avoid precipitating pulmonary oedema, anticonvulsants for convulsions) – see Section 11.25 • Monitor for haemolytic crisis – see Quick Check • Albendazole 400 mg orally once; OR • Mebendazole 500 mg orally once or 100 mg orally twice a day for 3 days • These usually occur within 4 to 12 weeks after ART initiation, but can occur as early as 2–4 weeks • AZT-related anaemia is either normocytic (early) or macrocytic (later) • Severe anaemia is a rare side-effect of AZT treatment • Risk of severe anaemia is enhanced by the patient having a low haemoglobin level before starting therapy • If drop of haemoglobin below 7 g/dl or at least 25% from the baseline, substitute another drug for AZT (see ART toxicity in Section 13 Chronic HIV care) • Vitamin B12 as 1 mg IM 2–4 times per week until haematological abnormalities are corrected, then once a month. Continue if high demands or malabsorption. • If neurological involvement, 1 mg IM on alternate days until no further improvement, then 1 mg every 2 months. Neurological improvement may take up to 6 months. • Folic acid 5 mg daily for 4 months (in pregnancy, continue to term) • Because it is impossible to differentiate anaemia due to folic acid deﬁciency and B12 deﬁciency based on FBC alone, always give B12 with folic acid. Folic acid given alone can precipitate neuropathy if there is underlying unrecognized vitamin B12 deﬁciency. • Try to establish cause of the macrocytic anaemia and treat. • Treat underlying cause, monitor Hb • Investigate the cause of anaemia in HIV-infected patients. Consider particularly OIs such as TB, disseminated infections, or malignancies, nutritional deﬁciencies associated with chronic diarrhoea, medications, e.g. AZT and cotrimoxazole. • If it is secondary to the infection with HIV itself, treatment with antiretrovirals will result in improvement in the Hb and Hct. Avoid the use of AZT if the Hb is below 8 g/dl.

Malaria-related

Hookworm-related AZT-related

Macrocytic anaemia (B12 or folate deﬁciency)

Anaemia of chronic disease

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Aplastic anaemia

• Pure RBC aplasia: immunosuppressants like prednisone • Cyclosporine or cyclophosphamide where available • Refer for specialist care • Transfuse as necessary • Vitamin C 500 mg daily with folic acid 1 tablet daily as this is occasionally associated with folic acid deﬁciency • Treat the cause of haemolysis, e.g. malaria • Iron replacement may be required because of haemoglobinuria and haemosiderinuria • Refer for splenectomy if there is hypersplenism • • • • • • • • • • • Drug withdrawal if drug-induced (plus corticosteroids in severe cases) Corticosteroids Intravenous immunoglobulin may be used when steroids are ineffective Transfuse if there is severe anaemia If corticosteroids fail or patient has a relapse, consider splenectomy Rehydrate Give oxygen if low SpO2 Pain relief If indicated, treat malaria Transfuse if there is severe anaemia or symptoms persist See Quick Check, Section 3, and below for haemolytic crisis

Myelodysplasia Vitamin C deﬁciency Haemolytic anaemia

Auto-immune haemolytic anaemia (AIHA)

Sickle-cell disease

Thalassaemia (major) (at referral centres)

• Planned blood transfusion to suppress erythropoeisis with target Hb 10–12 g/dl. • Iron chelation therapy and vitamin C 500 mg by mouth daily to promote excretion of iron the day of chelation, folic acid 5 mg per day • Consider referral for splenectomy • Long-term prophylactic penicillin • Vaccinate against hepatitis B and pneumococcus • Endocrine replacement (for hypopituitarism, hypothyroidism, parathyroid failure) • Anticoagulants if patient develops clots

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Figure: Summary of initial laboratory investigations and management of anaemia Anaemia

Further initial investigations • Full blood count (Hb, Hct, blood ﬁlm) plus white cell count and other relevant indices • Reticulocyte count • Thick and thin blood ﬁlm for malaria parasites or rapid diagnostic test • Faecal occult blood test

Diagnosis uncertain

Provisional diagnosis: iron-deﬁciency anaemia

Further investigations to identify cause and type of anaemia

Treat cause of anaemia

Give course of oral iron (ferrous sulphate), if indicated

Check haemoglobin at 4–8 weeks

Patient responding. Haemoglobin rising: reticulocytosis on blood ﬁlm. Diagnosis probably correct.

Patient not responding: review diagnosis

Reassess diagnosis to conﬁrm or identify cause and type of anaemia

Yes Continue iron (ferrous sulphate) treatment for at least 3 months. Is the patient taking oral iron?

No Reinforce advice to take oral iron.

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Blood transfusion therapy • Use the proper procedure for transfusing a patient with severe anaemia and congestive heart failure, under furosemide cover. Red cell concentrates, given at slow rate, are preferred over whole blood. Indications The only absolute indication for a blood transfusion is acute haemorrhage, leading to shock (see Quick Check). Anaemia in itself is not an indication for a transfusion. The goal of transfusion in haemorrhagic shock is to restore tissue oxygenation. There is no threshold of Hb or Hct value that indicates if transfusion is necessary and no "goal Hb" to attain. Therefore, the decision to administer blood must be based on the symptoms and functional status of the patient, such as: • clinical evidence of decompensation – heart failure, hypoxaemia (see Quick Check) • active haemorrhage associated with shock • haemorrhage that cannot be immediately controlled • surgical procedures.

Sickle-cell disease Sickle-cell disease (also known as sickle-cell disorder) is a genetic condition due to inheritance of abnormal haemoglobin genes from both parents. Adolescent and adult patients have long periods of well-being, with occasional acute crises. Acute crises include vaso-occlusive crises, and lead to pain and infarction. They present as acute bone pain and joint swelling, acute chest syndrome, neurological emergencies (stroke or seizure), arterial and venous thrombotic events (pulmonary embolus), and haematologic crisis (splenic sequestration crises, aplastic crises due to infections, folate deﬁciency, and rarely haemolytic crises). Chronic complications can occur as a result of prolonged or repeated ischaemia leading to infarction. They include skeletal abnormalities, neurological loss due to stroke, hyposplenism, chronic renal failure, impotence following priapism, loss of lung function, and visual loss. Laboratory investigations • Hb of 5–11 g/dl (Hb usually lower than expected relative to symptoms of anaemia) • Blood ﬁlm to detect sickle cells, target cells, and reticulocytosis Additional lab tests • Sickle solubility or slide test to identify sickle cells • Haemoglobin electrophoresis to identify abnormal haemoglobin patterns • HbF quantitation to detect elevation of HbF, which may modify the severity of the disease.

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Management The main aims are to prevent crises and minimize long-term damage when a crisis does occur. Prevention of sickle crisis • Avoid precipitating factors including dehydration, hypoxaemia, infection, cold, and slowed circulation. • Give long-term prophylaxis with folic acid 1 mg daily orally. • Vaccinate with 23-valent pneumococcal polysaccharide vaccine and hepatitis B if available (See national immunization guidelines). • Recognize and treat malaria promptly. Haemolysis due to malaria may precipitate a sickle crisis. • Treat other infections promptly. Adolescents and adults with sicklecell disease are usually functionally asplenic so have a lifelong risk of pneumococcal infection. • Consider whether regular transfusion is indicated to maintain a sufﬁcient proportion of normal HbA (about 30% or more) and reduce the frequency of crises and recurrent strokes. Consult with a specialist. Treatment of sickle crisis • Rehydrate with oral ﬂuids and, if necessary, intravenous normal saline. • Give oxygen if low SpO2. • Give effective pain relief: strong analgesics, including opiates (e.g. morphine) are likely to be needed. • Treat malaria, if infected. • Treat bacterial infection with the most appropriate antibiotic in full dose. • Give transfusion for crises and severe acute anaemia (haemoglobin concentration of <5 g/dl or >2 g/dl below the patient’s normal baseline). Aim for a haemoglobin level of 7–8 g/dl only.

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10.19 Abnormal bleeding and bruising1 In this section: 10.19.1 Clinical Approach to a patient with abnormal bleeding and bruising • Figure: Interpretation of initial coagulation investigations 10.19.2 Diagnostic approach to active bleeding • DDx: Bleeding with normal platelet count • DDx: Bleeding with low platelet count 10.19.3 Diagnostic approach to low platelets with no active bleeding (with DDx table) • DDx: Low platelet count with no bleeding • Table: Medicines affecting platelets • Figure: Diagnostic approach to low platelets • Thrombocytopaenia in an HIV-positive patient 10.19.4 Speciﬁc bleeding conditions in detail • Disseminated intravascular coagulation • Idiopathic thrombocytopenic purpura • Haemophilia • von Willebrand disease

This Section provides an approach to the patient presenting with symptoms or signs of abnormal bleeding and bruising. In addition, it outlines abnormalities seen in laboratory investigations in patients who may present with bleeding. It provides a simpliﬁed approach to identifying conditions that can be managed by the district hospital team and distinguishes those that need to be referred for more specialized care or managed in coordination with a specialist. Normal haemostasis involves the interaction of vessels, platelets, and coagulation factors. Bleeding disorders may be due to vascular defects, abnormality of platelets (low platelet count, excessive platelets or defective platelet function), or due to abnormalities of the coagulation or ﬁbrinolytic systems. Bleeding disorders can be inherited or acquired.

10.19.1 Clinical approach to a patient with abnormal bleeding and bruising Step 1: Perform Quick Check. Use the Quick Check to ensure that there are no serious or life-threatening conditions. Refer to Section 3.1 for management of the severely ill patient with haemorrhagic shock and Section 4 Trauma for the approach to the acutely injured patient. Also, look speciﬁcally for pregnancy or recent delivery, and signs of infection or sepsis. Step 2: Take a history and examine the patient. Step 3: Assess HIV status. Step 4: Consider the likely differential diagnosis using the differential diagnosis tables. Step 5: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response.

1 The clinical use of blood in general medicine, obstetrics, paediatrics, surgery and anaesthesia, trauma and burns. WHO, 2002. Available at http://www.who.int/bloodsafety/clinical_use/en/Manual_EN.pdf (in revision)

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History Focus on the following. • Symptoms of bleeding ° What is the duration of the bleeding? ° Is it the ﬁrst episode or is the bleeding recurrent? ° How many sites are involved? ° Is the bleeding spontaneous or following trauma? ° Obstetrical or gynaecological history (PPH, abnormal vaginal bleeding). • History of recent, large volume blood transfusions >10 units, or aggressive IV ﬂuid therapy (may result in dilutional clotting abnormalities) • History of exposure to drugs or chemicals ° harmful use of alcohol or illicit substances ° current or previous use of medications, e.g. warfarin, NSAIDs, aspirin, or traditional, herbal, or alternative medications ° exposure to chemicals at work or in the home. • Family history. ° relatives with a similar condition ° relatives with any history suggesting bleeding disorder. Other symptoms: • weight loss • anorexia • fever and night sweats • HIV status – CD4 count and treatment history. Symptoms suggestive of a bleeding disorder • easy bruising, purpura, and nosebleeds • excessive bleeding after circumcision, dental extraction or other surgery, or after giving a blood sample or blood donation • heavy menses with clots or perinatal haemorrhage • dark or bloody stools • red urine • episodes of swollen, painful joints or muscles • excessive bleeding after minor scratches • bleeding that recurs hours or days after the original trauma • poor wound healing. The source and type of bleeding usually suggest the most likely cause. Bleeding from mucous membranes or petechial bleeds suggests a low platelet count or platelet abnormalities, von Willebrand disease (vWD), or vascular defects. Muscle and joint bleeding or bruising may be suggestive of haemophilia A or B.

Examination Signs of bleeding or blood loss • pale mucous membranes • petechial haemorrhages • purpura or ecchymosis (bruising)

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• • • • •

bleeding from mucous membranes (conjunctiva, gums) muscle haematomas haemarthroses or deformed joints blood on rectal examination fundoscopy – retinal haemorrhages.

Note: Skin manifestations of bleeding disorders (e.g. petechial haemorrhages or ecchymoses) are sometimes difﬁcult to see in dark skinne patients. Examine the mucous membranes, including the conjunctivae, oral mucosa and optic fundi, for evidence of bleeding. Other signs that may point to underlying or co-morbid disease • splenomegaly • hepatomegaly • jaundice • fever • tenderness • lymphadenopathy.

Investigations For a patient with a suspected bleeding problem: • Perform FBC. • Assess whether abnormality is in a single cell line or multiple cell lines. ° single cell line (isolated low Hb, white cell count, or low platelets): ◊ low Hb – anaemia – may be as a result of bleeding, see Section 10.18 Anaemia; ◊ high WBC – sepsis or infection, leukaemia (blasts); ◊ low WBC count – leukopenia, may be result of an underlying preleukaemia or myelodysplastic syndrome; ◊ increased MCV – haemolysis, vitamin B12 and folate deﬁciencies, alcohol misuse or myelodysplastic syndrome – see Section 10.18 Anaemia; ◊ low platelets – ensure that not a false result due to platelet clumping on peripheral blood smear. Repeat the FBC – use citrate or blue tubes if available as this might provide a more reliable result. ° multiple cell lines (pancytopenia – low Hb, low WBC, and low platelets) indicating total marrow failure or involvement – leukaemia, HIV, marrow inﬁltration, myelodysplastic syndrome, drugs, aplastic anaemia. • Peripheral blood smear ° Platelets ◊ platelet clumping – platelet count incorrectly low on FBC ◊ large platelets. ° Red cells ◊ red cell fragments – haemolysis (DIC or TTP/HUS) ◊ macrocytic (large red cells; high MCV on FBC) – vitamin B12 and folate deﬁciency, chronic alcohol use – see Section 10.18 Anaemia ◊ nucleated red cells or a leucoerythroblastic ﬁlm – marrow inﬁltration (malignancy, leukaemia or lymphoma) ◊ parasitic inclusions (malaria). ° White cells

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◊ increased WBC – infection and sepsis – toxic granulation ◊ decrease WBC – leukopenia. aplastic anaemia or myelodysplasia ◊ blasts – leukaemia – refer for specialized care. • PT (prothrombin time) and the INR ° PT and INR screen for abnormalities in the extrinsic and common pathways of coagulation (factors I, II, V, VII and X). Its main use is for anticoagulant (warfarin) monitoring, and detection of acquired bleeding disorders – especially DIC, liver disease, and vitamin K deﬁciency. The PT is reported as the international normalized ratio (INR), which reﬂects the ratio of the patient's PT to the laboratory's control value. ° Normal range for the PT is between 10 and 13 seconds. An INR >1.5 or a PT ≥3 sec longer than a laboratory's normal control value is usually abnormal and requires further evaluation. ° Fill the citrate tube to the line for an accurate result. • aPTT (activated partial thromboplastin time) ° The aPTT screens for abnormalities in factors of the intrinsic and common pathways (II, V, VIII, IX, X, XI and XII). ° A typical normal range is 28 to 34 seconds. • Crude clotting time ° If aPTT or PT (INR) are not available, a crude clotting time will assist to exclude a coagulopathy. It is a crude screening test and not accurate. Conﬁrm abnormal tests with a repeat test and refer patients for further tests if the result is conﬁrmed abnormal. ° See Section 7.2.18 for details. ° Exclude medications, e.g. warfarin and heparin. Additional tests that may be requested depending on the clinical ﬁndings include: • rapid malaria test or malaria blood smear • occult blood in stool • pregnancy test • HIV test and CD4 count • liver function tests • renal function (urea, creatinine, and electrolytes) • ultrasound of the abdomen and pelvis • bone marrow aspirate or biopsy • further coagulation tests, such as ﬁbrinogen concentration, ﬁbrin degradation products such as d-dimers, factor assay, platelet function tests.

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Figure: Interpretation of initial coagulation investigations

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10.19.2 Diagnostic approach to active bleeding Patients who present with active bleeding may or may not have a history of prior episodes with a conﬁrmed diagnosis. Obtain an FBC and classify the bleeding according to whether the platelet count is decreased or normal. Consult with the relevant DDx table below.

DDx: Bleeding with normal platelet count Condition In favour

Primary inherited causes of bleeding von Willebrand disease (vWD) Haemophilia Family history of the disease Easy bruising, abnormal bleeding after surgical or dental procedures Normal or low platelet numbers, prolonged bleeding time Bleeding into tissues after minimal trauma, e.g. haemarthroses, muscle haematoma Arthropathy may be present Elevated aPTT and normal INR and platelets

Trauma or local injury Trauma or local injury see Section 4 History Bruising or bleeding at localized site Be aware of non-accidental injury patterns (physical abuse)

Underlying medical conditions or medication Renal failure see Section 11.31 History of renal disease Decreased urine output Uraemic ﬂapping tremor Raised urea and creatinine History of chronic liver disease , hepatitis or excessive alcohol use Weight loss Firm liver, jaundice, hepatomegaly and right upper quadrant pain, ascites Splenomegaly Decreased albumin Prolonged INR History of using warfarin or ingesting rat poison Easy bruising, epistaxis, GI bleeding Responds to vitamin K, but may need transfusion of FFP or prothrombin complex for rapid reversal Prolonged INR Normal aPTT and platelets Usually in patients on heparin infusion Prolonged aPTT Long-term steroid use can increase skin and vessel fragility, leading to bruising and bleeding

Liver disease or liver failure see Sections 10.9 and 11.14

Coumarin-based anticoagulants (warfarin, rat poison) see Section 3.8

Heparin overdose Corticosteroids

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DDx: Bleeding with low platelet count Conditions DIC (disseminated intravascular coagulation) In favour Severely ill patient with multi-organ failure Predisposing condition, e.g. shock, sepsis, malignancy, or obstetric complications, ABO incompatible blood transfusion Bleeding from puncture sites Gastrointestinal bleeding Prolonged INR and elevated aPTT, low platelet count, low ﬁbrinogen level, presence of ﬁbrin degradation products Peripheral smear – may have red cell fragments Signs of infection – fever, tachycardia, dehydration, shock Identiﬁable or suspected source of infection Endemic area or travel Fever, headache, malaise, maculopapular rash Bleeding tendencies with purpura, petechiae, haematemesis, melaena, or epistaxis Patients may be severely ill with shock and organ failure Prolonged INR Fever Confusion, seizures, intracranial haemorrhage, or coma Haemolytic anaemia (jaundice), renal failure Venous thromboses at unusual sites Abdominal pain Usually younger patients <60 years HIV-infected Drugs (e.g. quinine) Associated with haemolytic-uraemic syndrome (e.g. from enterohemorrhagic E. coli) FBC: Very low platelet numbers, anaemia Peripheral blood ﬁlm: evidence of haemolysis – RBC fragments on ﬁlm, high bilirubin, high LDH Proteinuria, haematuria, renal impairment Normal INR and aPTT Recent viral infection, History of chemotherapy or chloramphenicol, cotrimoxazole, NSAIDs, carbamazepine, or phenytoin Recurrent infections, anaemia HIV, hepatitis, and mycobacterial infections FBC: Persistent pancytopenia Low reticulocyte count Fatigue, fever, recurrent infections Lymphadenopathy, anaemia with or without hepatosplenomegaly FBC: Pancytopenia; or increased WBC Peripheral blood ﬁlm: blasts

Sepsis see Section 3.1.5 Viral haemorrhagic fever see Section 11.46

Thrombotic thrombocytopenic purpura (TTP)

Aplastic anaemia see Section 10.18

Leukaemia (ALL, AML) and deranged clotting/DIC – medical emergency seen in acute promyelocytic leukaemia

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Conditions Idiopathic thrombocytopenic purpura (ITP) (a diagnosis of exclusion)

In favour Incidental ﬁnding of low platelets in a well patient Easy bruising, petechiae, or nose bleeds Younger patients Women are more commonly affected than men No other cause of low platelets (autoimmune, HIV or other viral infection, drugs and alcohol) No splenomegaly FBC: isolated low platelet count Peripheral blood ﬁlm: large platelets Fatigue, anaemia, recurrent infections Older patient >60 years Platelet count does not respond to steroids FBC: pancytopenia Peripheral blood ﬁlm: dysplastic morphological features

Myelodysplastic syndromes (MDS)

10.19.3 Diagnostic approach to low platelets with no active bleeding Decide if only platelets or all cell lines are affected. Exclude artefactual decrease in automated count on FBC with platelet clumping. Look at a peripheral blood ﬁlm for platelet clumps, large platelets, blasts, increased WBC count (infection or sepsis), and RBC fragments. Exclude medical causes – consult the DDx table below. If a drug is suspected to be the cause of bleeding or low platelet counts, and other important causes have been excluded (HIV, infection and DIC), then the offending drug should be discontinued if possible. See table below for drugs known to affect platelets. The platelet count should return to normal within a short period of time. If recovery of the platelet count does not occur, a review of the list of other differential diagnoses must be considered.

DDx: Low platelet count with no bleeding Conditions Malaria see Section 11.25 In favour Fever, headache Splenomegaly Living in or travelled to an endemic area Malaria test positive (microscopy or RDT) Other causes excluded – may present as ITP Responds to ART Fever Loss of weight Evidence of cancer or known diagnosis of malignancy Long term alcohol use Parotomegaly Known diagnosis, e.g. rheumatoid arthritis, systemic lupus erythematosis Skin lesions Arthritis No other medical cause apparent Taking medication known to cause low platelets – see table below

HIV see Section 13 Metastatic malignancy

Alcohol see Section 16 Autoimmune conditions

Medicines Disseminated fungal infections

Generalized lymphadenopathy Unwell patient: fever, malaise, skin lesions with or without lung involvement Immunocompromised patient – CD4 <100 Abdominal bleeding and bruising

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Table: Medicines affecting platelets Drugs decreasing platelet count (drug-induced thrombocytopenia) Drugs affecting platelet function (normal platelet counts) • aspirin (up to 7 days); • heparin; • NSAIDs – diclofenac, ibuprofen (up to 48 hours); • clopidogrel (up to 7 days); • penicillins and cephalosporins in high dose; worse with renal failure or low albumin. Recommendations for elective surgery In most surgery, there is no need to stop aspirin or clopidogrel if they are used as monotherapy. If used together, stop the clopidogrel. For cardiac or neurosurgery, stop aspirin 7–10 days pre-surgery; stop clopidogrel 5 days pre-surgery. Commonly • heparin-induced thrombocytopaenia (HIT) – usually with IV heparin after 4–14 days of use if previous use; • anti-TB drugs – rifampin, isoniazid, ethambutol; • antibiotics – quinine and quinidine, cotrimoxazole, amphotericin B, nalidixic acid, cephalosporins (cephalothin, vancomycin); • psychotropic medications – diazepam, haloperidol; • analgesics and anti-inﬂammatories – paracetamol (acetaminophen), diclofenac; • cardiac drugs – methyldopa, digoxin, amiodarone, hydrochlorothiazide; • antiretrovirals – IDV, AZT; • cimetidine and ranitidine; • minoxidil; • chlorpromazine; • carbamazepine. Rarely or infrequently • • • • • • • ibuprofen phenytoin tetracycline glibenclamide ﬂuconazole captopril ampicillin

Figure: Diagnostic approach to low platelets Low platelets Initial investigations

Look at the blood ﬁlm for: Platelets clumps, large platelets, blasts Increase WCC (infection or sepsis) RBC fragments ?Malaria

Nutritional: Vitamin B12, folate and iron deﬁciency Alcohol

Other infections: HIV Hepatitis B & C EBV (monospot) Malaria

Other diseases: Liver disease Malignancy (metastatic) Autoimmune (SLE)

Exclude Drugs Medications

Supporting evidence: Malnutrition Gastric surgery GI malignancy Inﬂammatory bowel diseases

Commonly: cotrimoxazole, phenytoin, quinine, ceftriaxone, carbamazepine, etc See table Drugs affecting platelets

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Thrombocytopaenia in an HIV-positive patient This may be due to HIV itself, but it is important to ﬁrst exclude possible medical causes and drugs, such as TB treatment, cotrimoxazole. Look for lymph nodes, chest X-ray, skin lesions, sputum. Consider disseminated fungal infections, lymphoma, ITP, and TTP. Start ART.

10.19.4 Speciﬁc bleeding conditions in detail Disseminated intravascular coagulation (DIC) Disseminated intravascular coagulation is a pathological activation of coagulation mechanisms that occurs in response to a variety of underlying diseases. Fibrin clots form throughout the body and consume all the available coagulation factors, ﬁbrinogen, and platelets. Normal coagulation is disrupted, leading to widespread, uncontrolled bleeding from the skin (e.g. venepuncture sites), the digestive tract, the respiratory tract, and surgical wounds. This in turn stimulates an overproduction of ﬁbrinolytic enzymes to break down the clots formed and an increase in ﬁbrin degradation products. The microvascular thrombi also disrupt normal blood ﬂow to organs (such as the kidneys), leading to multi-organ failure. Red cell fragmentation occurs due to the passage of red cells in the narrowed and damaged microvasculature. DIC usually is a result of a serious underlying diagnosis (see below), but can in itself become life-threatening, by haemorrhage or thrombosis. DIC can occur in the following conditions: • infections: Gram-negative sepsis, Neisseria meningitidis, Streptococcus pneumoniae, malaria, TB, histoplasmosis, aspergillosis, Lassa fever; • obstetric: abruptio placentae (premature separation of the placenta from the uterus), retained dead fetus, pre-eclampsia, amniotic ﬂuid embolism, septic abortion or post-partum sepsis; • massive tissue injury: trauma, crush injury, burns, massive surgery; • severe hypoxia and acidosis; • cancers of the lung, pancreas, prostate, breast and stomach, acute myelogenous leukaemia, subtype acute promyelocytic leukaemia; • miscellaneous: liver disease, snake-bite (see Section 3.9), pancreatitis, shock, heat stroke, ruptured aortic aneurysm, malignant hypertension, pulmonary embolism, subarachnoid haemorrhage, acute haemolytic transfusion reaction. Key clinical features • often acutely ill • widespread low-grade haemorrhage or oozing (commonly from the mouth, nose, and venepuncture sites) • extensive bruising • shock • in severe cases, shock, gangrene, coma, and renal failure

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Treatment • Manage the patient carefully. Referral to a higher facility may be needed. • The only effective treatment is the reversal of the underlying causes, e.g. antibiotics for sepsis, removal of retained gestational products. • Give supportive treatment with ﬂuids to maintain renal perfusion and blood pressure. See Section 3.1. • Monitor the haemoglobin and consider transfusion when clinically indicated. See Section 10.18 Anaemia. • If the INR or aPTT is prolonged and the patient is bleeding, replace red cell losses with the freshest whole blood available, as it contains ﬁbrinogen and most other coagulation factors. Give FFP, as this contains labile coagulation factors. 1 pack/15 kg body weight (4–5 packs in adults). Repeat FFP according to the clinical response. • If ﬁbrinogen is low or the aPTT or thrombin time is prolonged, also give cryoprecipitate (to supply ﬁbrinogen and factor VIII). 1 pack/6 kg (8–10 packs in adults). • If the platelet count is less than 50 x 109/litre and the patient is bleeding, also give platelet concentrates, 4–6 packs (adult). • If the patient is stable enough for transfer to a higher level of care, this should be arranged immediately as intensive care usually is required.

Idiopathic thrombocytopenic purpura (ITP) ITP is the condition of having a low platelet count (thrombocytopaenia) of no known cause, i.e. idiopathic. It is a diagnosis of exclusion. Most causes appear to be related to antibodies against platelets, so ITP is known also as immune thrombocytopenic purpura or immune-mediated thrombocytopenic purpura. ITP usually is asymptomatic, however, a very low platelet count may present with: • bruises (purpura) and petechiae, especially on the extremities; • bleeding from the nostrils and bleeding at the gums; • haematomas in the mouth or on other mucous membranes; • possible fatal complications due to an extremely low count (less than 5000 per mm3), and may include: ° subarachnoid or intracerebral haemorrhage; ° lower gastrointestinal bleeding or other internal bleeding. Treatment A platelet count below 20 x 109/litre is generally an indication for treatment. Platelet counts between 20 x 109/litre and 50 x 109/litre are usually evaluated on a case-bycase basis. Admit patients with very low counts, and if the patient presents with signiﬁcant internal or mucocutaneous bleeding. A count below 10 x 109/litre is potentially a medical emergency as the patient is vulnerable to subarachnoid or intracerebral haemorrhage as a result of a mild to moderate head trauma. Consult with a specialized centre and consider the following treatments or refer for further management. • Steroids and intravenous immunoglobulin

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Treatment usually is initiated with IV steroids (methylprednisolone or prednisone), intravenous immunoglobulin (IVIg) or a combination of these drugs. After the platelet count has increased to a safe level, give an oral steroid, such as prednisone (1–2 mg/kg daily). Most cases respond during the ﬁrst week of treatment. Gradually reduce the dose of the oral steroid therapy over several weeks. Monitor regularly as 60%–90% of patients relapse after the dose is decreased below 0.25 mg/kg daily. • Platelet transfusion Platelets can be transfused in an emergency bleeding situation to raise the count quickly in order to start oral steroids. Platelet transfusion alone is not recommended, as platelets usually decrease afterwards due to autoimmune destruction. • Surgery Splenectomy may be performed although the procedure is potentially risky due to the increased possibility of signiﬁcant bleeding during surgery. Splenectomy is successful in 60% –65% of cases, but less so in older patients. Refer for specialized care if patient does not improve on steroids.

Haemophilia Haemophilia is a group of hereditary X-linked genetic disorders that impair the body's ability to control blood clotting or coagulation. It affects men more commonly than women. Haemophilia A has a deﬁciency of clotting factor VIII, and in haemophilia B, factor IX is deﬁcient. Refer to a specialized centre for diagnosis and management. The patient may be referred back to the district hospital with a supply of required clotting factor concentrates to be administered when needed. Treatment There is no cure for haemophilia. It can be controlled with regular infusions of the deﬁcient clotting factor, i.e. factor VIII in haemophilia A or factor IX in haemophilia B. • Avoid antiplatelet agents such as aspirin and NSAIDs • Do not give intramuscular injections. • Initial management of haemarthrosis includes strong analgesia, ice packs, immobilization, compression, and elevation. • Do not incise swellings and never incise a joint for haemarthrosis. • Give clotting factors before surgery, during an active bleed, or after injury, and, in some cases, on a regular basis to prevent bleeds. • In acute bleeding episodes give coagulation factor concentrates as quickly as possible. • Start physiotherapy as soon as possible after initial treatment to minimize loss of joint function. • Desmopressin may also be used as it releases stored endogenous factor VIII and von Willebrand factor, so may be useful in mild or moderate haemophilia A. It is not indicated in factor IX deﬁciency. • FFP and cryoprecipitate may be use if clotting factor concentrates are not available.

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Von Willebrand disease (vWD) Von Willebrand disease is the most common hereditary coagulation abnormality, although it can be acquired as a result of other medical conditions. There is a qualitative or quantitative deﬁciency of von Willebrand factor (vWF), required for platelet adhesion. Key clinical features • mucocutaneous bleeding, e.g. epistaxis, easy bruising • menorrhagia • bleeding after dental extractions • post-traumatic bleeding. Treatment • Patients will need to be referred to a specialized centre for diagnosis and management. They may be referred back to the district hospital for ongoing management with their speciﬁc medicines and blood products. • Bleeding episodes may be managed with desmopressin (although it may become ineffectual after repeated use), factor VIII, or cryoprecipitate, which also contains vWF.

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10.20 Splenomegaly In this section: 10.20.1 Clinical approach to a patient with splenomegaly 10.20.2 Use the DDx table to establish a likely differential diagnosis • DDx: Splenomegaly 10.20.3 Management of splenomegaly

This Section provides an approach to the patient with splenomegaly. Splenomegaly is only rarely symptomatic. In those cases, the patient may present with pain or a heavy sensation in the left upper quadrant. In most cases, splenomegaly is identiﬁed during either a focused or complete routine physical examination. Splenomegaly is not considered a diagnosis in and of itself. Rather, it is often a serious sign or indication of an underlying condition that requires identiﬁcation and treatment.

10.20.1 Clinical approach to a patient with splenomegaly Step 1: Perform Quick Check. Ensure that there are no serious or life-threatening conditions Step 2: Take a history and examine the patient. • conﬁrm that it is splenomegaly • look for underlying causes and associated conditions. Step 3: Assess the patient’s HIV status. Step 4: Consider the likely differential diagnosis using the DDx tables. Step 5: Perform investigations. Step 6: Initiate treatment and monitor the patient’s response. Always consider TB and parasitic infections.

History • What is the age of the patient? Is there sickle-cell or thalassaemia disease in the family? • Is the patient from a malaria endemic area or is it malaria season? • Is the area endemic for histoplasmosis, leishmaniasis, schistosomiasis, or trypanosomiasis? • What is the nutritional status of the patient? • Is there pain or heaviness in the left upper quadrant? For how long? • What is the HIV status of the patient? • Has the patient had prior TB or recent contact with TB? • Has the patient had travel or occupational exposure to any of the above infections? • Are there additional constitutional symptoms? • Is the patient on any hepatotoxic medications? • Does the patient drink alcohol? • Is there any shortness of breath on exertion? Ascites? Swelling of the legs?

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Examination Conﬁrm splenomegaly Examination techniques for the spleen: • Bimanual palpation. ° Position the patient supine with bent knees. ° Place the left hand on the lower rib cage and pull the skin upward and taut. ° As the patient inspires deeply and slowly, use the right hand to stroke upward, starting from the left lower quadrant. ° Record the number of centimetres below the costal margin at a ﬁxed point (e.g. umbilicus) at which the spleen tip is ﬁrst felt. • Percussion (Castell’s method). ° Position the patient supine. ° Percuss the lowest intercostal space in the anterior axillary line. ° If the percussion is resonant, the spleen is normal. If it is dull, the spleen is enlarged. Examine the rest of the body to advance the differential diagnosis • Skin: look for jaundice, pallor, ecchymoses, spider angiomata, caput medusae. • Neck and lymph nodes: look for the hepatojugular reﬂex (reﬂux) (abdominojugular test); feel for lymphadenopathy. • Heart and lungs: look for signs of heart failure (rales) or heart murmurs. • Abdomen: check liver for tenderness, enlargement, nodularity, bruits, ascites. • Extremities: look for joint swelling or tenderness, pedal oedema. • Neurological exam: check for encephalopathy, reﬂexes, sensation, proprioception. Investigations • FCB and smear: this may indicate infection, disseminated disease, or malignancy. Smear will show evidence of haemolysis. • Malaria thick smear; tests for other parasites. • Liver function tests; thyroid function tests if clinically indicated. • Sputum examination and chest X-ray for TB (see Section 15). • Ultrasound to conﬁrm splenomegaly, and assess for discrete lesions in the spleen. • Recommend HIV testing.

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10.20.2 Use the DDx table to establish a likely differential diagnosis DDx: Splenomegaly Condition In favour

Splenic enlargement due to increased demand for splenic function Sickle -cell disease, thalassaemia, or other haemoglobinopathies see Section 10.18 Nutritional anaemia see Section 10.18 Rheumatoid arthritis, systemic lupus erythematosus, drug reactions, thyrotoxicosis, ITP, other autoimmune and collagen vascular diseases see Sections 10.2, 10.13, 10.19 Signs and symptoms of anaemia (pallor, shortness of breath on exertion, fatigue, dizziness) Jaundice Family history Discoloured urine Signs and symptoms of anaemia (pallor, shortness of breath on exertion, fatigue, dizziness) Malnutrition Joint pain and swelling, rash, tachycardia, eye symptoms Abnormal bleeding or bruising Fever

Splenic enlargement due to response to infection HIV see Section 13 Viral hepatitis see Section 11.4 Cytomegalovirus see Section 11.8 Could manifest with any symptoms Nausea, vomiting, anorexia, fever Jaundice Large, tender liver Fever, fatigue, malaise Pharyngitis (exudative) Cervical lymphadenopathy Guillain-Barré syndrome (ﬂaccid ascending paralysis) Fever, fatigue, malaise Pharyngitis (exudative) Cervical lymphadenopathy Guillain-Barré syndrome (ﬂaccid ascending paralysis) Vision problems Neuropathy Heart murmur Fatigue Fever Signs of embolism (clotting) to distant areas, especially ﬁngers and toes High fever Relative bradycardia Non-speciﬁc symptoms (anorexia, cough, sore throat, constipation) Abdominal pain Cough Fever Weight loss Night sweats

Infectious mononucleosis see Section 10.5

Subacute bacterial endocarditis see Section 11.10

Typhoid fever see Section 11.43

Tuberculosis see Sections 10.6 and 15

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Malaria see Section 11.25

Regular cyclic fever Anaemia Hypoglycaemia Jaundice, pallor Pregnancy Mental status changes Tachypnea Malnutrition HIV-positive Irregular and prolonged fever Lymphadenopathy Cough Diarrhoea History of chancre Fever, headache, joint pain Lymphadenopathy Puffy face Enlarged liver, lymph nodes Cough or wheeze Weight loss Night sweats Fever without obvious focus Pain with palpation over spleen Sonogram with splenic lucency Fever Lymphadenopathy Eosinophilia Elevated WBC Depressed WBC

Visceral leishmaniasis see Section 11.20

Trypanosomiasis see Section 11.41

Histoplasmosis see Section 11.16

Splenic abscess

Other bacterial, viral, fungal, parasitic infections see sections 10.1, 10.5

Splenic enlargement due to abnormal splenic or portal blood ﬂow Non-speciﬁc cirrhosis see sections 10.7, 10.8, 10.9, 10.10a, 16 Hepatomegaly Liver tenderness Nodular liver edge Other stigmata of liver disease Chronic hepatitis B infection Look for hepatomegaly History of alcohol or hepatotoxic substances or medications (e.g. bush tea, INH) or chronic hepatitis B infection History of “swimmer’s itch” Fever, chills, cough, myalgia Bloody diarrhoea, abdominal pain No hepatomegaly. If splenic vein obstruction happens acutely, spleen will be tender.

Hepatic schistosomiasis see Section 11.34 Splenic artery aneurysm or splenic vein obstruction Splenic enlargement due to unknown etiology Berylliosis Idiopathic splenomegaly

Occupational exposure Shortness of breath No compelling evidence of another underlying condition

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10.20.3 Management of splenomegaly The management of splenomegaly requires the management of the underlying cause (see Sections cross-referenced in the DDx Table above). Splenectomy may be performed to correct cytopaenias when the cause is congestive destruction of blood cells. However, if the cause of cytopaenia is marrow failure, splenectomy is contraindicated as the hyperplastic spleen is the body’s only source of new blood cells.

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11. Multisystem communicable diseases, renal and HIV-related cancers (in alphabetical order) Table of contents 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9 11.10 11.11 11.12 11.13 11.14 11.15 11.16 11.17 11.18 11.19 11.20 11.21 11.22 11.23 11.24 11.25 11.26 11.27 11.28 11.29 11.30 11.31 11.32 11.33 11.34 11.35 11.36 11.37 11.38 11.39 11.40 11.41 11.42 11.43 11.44 11.45 11.46 11.47 Amoebiasis . . . . . . . . . . . . . Bartonellosis . . . . . . . . . . . . Brucellosis. . . . . . . . . . . . . . Candida . . . . . . . . . . . . . . . . Cryptococcosis . . . . . . . . . . . Cryptosporidiosis . . . . . . . . . . Cysticercosis . . . . . . . . . . . . Cytomegalovirus . . . . . . . . . . Dengue fever . . . . . . . . . . . . Endocarditis . . . . . . . . . . . . . Fascioliasis . . . . . . . . . . . . . Filariasis, lymphatic . . . . . . . . Gonorrhoea . . . . . . . . . . . . . Hepatitis – viral . . . . . . . . . . . Herpes simplex virus . . . . . . . Histoplasmosis . . . . . . . . . . . Inﬂuenza . . . . . . . . . . . . . . . Isosporiasis . . . . . . . . . . . . . Kaposi sarcoma . . . . . . . . . . . Leishmaniasis . . . . . . . . . . . . Leprosy . . . . . . . . . . . . . . . . Leptospirosis . . . . . . . . . . . . Liver abscess . . . . . . . . . . . . Loaisis . . . . . . . . . . . . . . . . Malaria . . . . . . . . . . . . . . . . Microsporidiosis . . . . . . . . . . Mycobacterium avium complex . Onchocerciasis . . . . . . . . . . . Penicilliosis . . . . . . . . . . . . . Rabies and animal bites . . . . . . Renal problems . . . . . . . . . . . Rheumatic fever. . . . . . . . . . . Rickettsial diseases . . . . . . . . Schistosomiasis . . . . . . . . . . Sinusitis . . . . . . . . . . . . . . . Strongyloidiasis. . . . . . . . . . . Syphilis . . . . . . . . . . . . . . . . Taeniasis . . . . . . . . . . . . . . . Tetanus . . . . . . . . . . . . . . . . Toxoplasmosis . . . . . . . . . . . Trypanosomiasis, human African Trypanosomiasis, American . . . Typhoid fever . . . . . . . . . . . . Urinary tract infection . . . . . . . Varicella/zoster . . . . . . . . . . . Viral haemorrhagic fever . . . . . Yellow fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

381 383 385 387 389 393 394 396 399 403 406 409 413 414 418 419 420 424 425 427 433 437 438 439 441 455 455 456 458 458 462 477 478 479 481 483 484 487 488 489 491 494 498 499 501 503 504

11. Multisystem diseases (in alphabetical order) This Section includes diseases that affect multiples organs and body systems, including opportunistic infections, an HIV-related cancer (Kaposi sarcoma), neglected tropical diseases, malaria, other infectious diseases, renal problems, and other common problems such as urinary tract infection and sinusitis.

11.1 Amoebiasis Amoebiasis results from infection with the non-invasive Entamoeba dispar or the invasive Entamoeba histolytica, and is the third most common cause of death from parasitic disease. It is most commonly contracted through ingestion of live cysts found with faecally contaminated water, food, or hands. Foodborne infection is caused by faecally contaminated soil or water used for growing vegetables. It is endemic in most developing countries. Some patients become chronic asymptomatic carriers who can excrete up to 15 million cysts a day, thereby enabling the spread of amoeba to new hosts. Acute amoebic colitis can be confused with bacterial diarrhoeas caused by Campylobacter, E. coli, Salmonella, Shigella, and cholera.

11.1.1 Intestinal amoebiasis Key clinical features • Gradual development of lower abdominal pain and mild diarrhoea. • Malaise, weight loss, and diffuse lower abdominal or back pain. • If caecum is involved, signs and symptoms will mimic those of appendicitis (right lower quadrant pain). • Full dysentery develops in some patients with passage of 10–12 stools per day. Stools are mostly blood and mucus. Severe gastrointestinal disease: • occurs mostly in children • characterized by high fever, profuse diarrhoea, and abdominal pain. Complications or unusual presentations: • amoebic liver abscess • amoebic colitis can be confused with inﬂammatory bowel disease • amoeboma (tender abdominal mass). Investigations Stool examination: • Fresh stools specimens must be examined for trophozoites typical of E. hemolytica. Cysts of both entamoeba species are very similar therefore trophozoites that have ingested red blood cells are diagnostic of E. hemolytica. If available, ultrasonography can establish the presence of a liver abscess (due to amoeba or bacteria).

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Treatment Supportive management of dysentery, as well as oral or intravenous rehydration, are both very important. Speciﬁc treatment is divided into two groups: To eradicate invasive disease: • metronidazole 750 mg 3 times daily for 7–10 days; OR • tinidazole 4 tablets (2 grams) by oral route once daily for 3 days. To eradicate cysts: • It is recommended to follow all treatment of conﬁrmed amoebiasis with eradication of cysts, although these agents may not be routinely available. If they are not available, relapse rates are high, and another course of a luminal agent may be warranted: ° diloxanide 500 mg orally 3 times daily for 5 days; OR ° iodoquinol 650 mg orally 3 times daily for 20 days; OR ° paromomycin 25–35 mg/kg/day orally divided in 3 daily doses for 7 days. Indications for aspiration are: • the need to rule out other causes of abscess • no clinical response after 3 to 5 days • threat of imminent rupture of the abscess • prevention of left lobe abscess rupture into pericardium. This relies on the availability of an ultrasound with an expert operator.

11.1.2 Amoebic liver abscess Amoebic liver abscess is caused by an often delayed extra-intestinal infection by E. histolytica. Amoebic infection is spread by ingestion of food or water contaminated with cysts. Ten to ﬁfteen percent of patients with amoebic liver abscess present with only fever. Key clinical features • Involves clinical tenderness of the liver. • Amoebic liver abscess is not usually associated with diarrhoea (although the source is always the colon). • In endemic areas, the course is often subacute with haepatomegaly and weight loss. • Fever is present in 30% of cases, and may be the only presenting symptom. • May be complicated by pleuro-pulmonary involvement when the abscess extends from the liver into the lung area. Investigations • An ultrasound of the liver can show abscesses. • Serology: positive serology means invasive amoebiasis and generally will revert to negative after 6–12 months. The presence of a liver abscess usually means that the etiology is amoeba rather than bacteria. • A negative stool examination for amoebic cysts or trophozoites does not exclude an amoebic liver abscess. • Aspiration of the abscess with Gram staining (and culture if available) may be useful to differentiate the amoebic abscess from a pyogenic abscess. Caution should be used in aspirating cysts, as an anaphylactic reaction can occur in

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cases of echinococcal cysts. The decision to perform a liver abscess aspiration should take into account this risk. Trophozoites are rare in liver aspirates (since they are in the capsule of the abscess and not in the aspirated necrotic centre). • Routine haematology and chemistry tests are rarely helpful, although about 75% of patients will have WBC more than 10 000 cells/µl. Liver enzymes are often normal or only mildly elevated. Alkaline phosphatase levels are often elevated and can remain so for months. Treatment • metronidazole 750 mg orally or IV 3 times daily for 5–10 days; OR • single dose tinidazole 2 g (should not be used in patients with HIV infection). Most patients will respond well to treatment with metronidazole, with a decrease in fever within 72 hours. The advantage of metronidazole is that if the etiology of the liver abscess is bacterial, this treatment will generally still work (if the bacteria is sensitive). Indications for aspiration (if possible under ultrasound guidance) are: • need to rule out other causes of abscess • no clinical response after 3–5 days • threat of imminent rupture of the abscess (superﬁcial abscess) • prevention of left lobe abscess rupture into pericardium (very rare).

11.2 Bartonellosis (Carrion’s disease, cat scratch disease, oroya fever, peliosis hepatis, trench fever, verruga peruana, bacilliary angiomatosis) Bartonella spp cause a wide variety of diseases that include trench fever, cat-scratch disease, peliosis hepatis, oroya fever, and verruga peruana. These clinical entities are not considered AIDS-deﬁning, but they are seen with increased frequency in PLHIV and patients with advanced immunosuppression. Bartonellosis is difﬁcult to diagnose and is largely a diagnosis of exclusion in patients with a fever of unknown origin, skin papules, lymphadenopathy, hepatosplenomegaly, maculopapular skin lesions fatigue, and malaise. (See fever table in Section 10.1)

11.2.1 Oroya fever and verruga peruana These entities are caused by B. bacilliformis, and are commonly encountered in the Andes mountains because the vector that transmits the disease is a sandﬂy. Both entities are a spectrum of the same illness. Oroya fever presents predominantly in patients who have never encountered the disease before and verruga peruana is the manifestation of the disease in patients who have been exposed in the past. Oroya fever is associated with profound anaemia that is usually the cause of death.

11.2.2 Cat scratch disease Cat scratch disease is a self-limited illness caused by B. henselae. It is associated with scratches from young domestic cats infested by ﬂeas. A majority of cases occur in children, but adults, particularly patients with immunosuppression due to AIDS or who are pregnant , are also affected. Enlargement of the lymph nodes can persist for several months, and therefore mimic a malignancy. Diagnosis is mostly clinical.

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Key clinical features • localized papule at the area of the cat scratch; • tender lymph nodes in the region draining the area of the cat scratch develop after 1 to 2 weeks; • nodes may become suppurative with bacterial superinfection common; • systemic symptoms are limited to malaise, anorexia, and weight loss. Complications • neurological: meningitis, encephalitis, seizures, transverse myelitis; • granulomatous hepatitis and splenitis; • endocarditis; • osteomyelitis. Investigations • serologic tests can be positive in 60–70% of patients; • biopsy of the affected lymph node, if available, will reveal stellate necrosis. Treatment This condition is usually self-limited, but systemic symptoms may be debilitating. Patients with complicated disease should be treated: • doxycycline 100 mg twice daily for 10–14 days; OR • azithromycin 500 mg orally daily for 5 days; OR • ciproﬂoxacin 500 mg daily for 10–14 days. Neurological disese and endocarditis need combined and/or longer treatment. Use caution with ciproﬂoxacin, as it may partially treat undiagnosed TB.

11.2.3 Trench fever Trench fever is caused by B. quintana, and is associated with infestation with body louse. It is therefore a disease of over-crowding and poverty. It occurs throughout the world. Key clinical features • sudden onset of headache, meningitis • persistent or relapsing fever • bacteraemia can persist for weeks • localized ﬁndings are uncommon. Complications Endocarditis may develop with prolonged bacteraemia. Investigations Blood culture may reveal the cause, but the organism grows very slowly. Treatment Antibiotic treatment needs to be prolonged to eradicate bacteria and to prevent relapse: • doxycycline 100 mg twice daily for 4 to 6 weeks; OR • eythromycin 2000 mg daily for 4 to 6 weeks; OR • azithromycin 500 mg daily for 4 to 6 weeks.

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11.2.4 Bacillary angiomatosis Bacillary angiomatosis can be caused by both B. henselae and B. quintana in persons who are immunocompromised. It was ﬁrst described in PLHIV, but has since been seen in other patients who do not seem to have a dysfunctional immune system. The disease classically involves the skin, but can spread to other areas including the liver (then it is called peliosis hepatis). Bacillary angiomatosis can easily be confused with Kaposi sarcoma, angiomas, and pyogenic granulomas. Key clinical features • Vascular nodules or papules or small tumours that are red or purple, and resemble Kaposi sarcoma. Complications • Dissemination: fever, abdominal pain, weight loss, malaise. • PLHIV can also have signs of central nervous system abnormalities such as brain lesions or psychiatric conditions. • Skin lesions are not always evident in disseminated disease. • Peliosis hepatis is associated with pain when palpating the liver. Investigations Diagnosis is mostly clinical, but in cases where there may be confusion with Kaposi sarcoma, one of the following may help differentiate the two: • a blood culture may yield organisms in disseminated disease; • a deﬁnitive diagnosis is done by examination of a biopsy that usually reveals tiny bacteria associated with new vessels (angiomas). Treatment Treatment needs to be prolonged, especially in cases where relapse has occurred. Patients with liver disease require intravenous treatment. Effective antibiotics include: • erythromycin 2000 mg per day orally for 3 weeks; OR • doxycycline 100 mg per day for 3 weeks. In patients with liver disease, intravenous antibiotics are recommended. Macrolides and tetracyclines are generally preferred to other antibiotics.

11.3 Brucellosis1,2,3 Brucellosis, also known as “Mediterranean fever” or “Malta fever”, is caused by infection with Brucella species. B. melitensis is the most virulent and invasive. Transmission to humans occurs through direct contact, through broken skin, with infected animal tissue, inhalation of infectious aerosols, or ingestion of infectious milk or dairy products. Brucellosis is predominantly an occupational disease. Sporadic cases and sometimes large outbreaks occur after consumption of raw milk and milk products. Animals involved are cows, sheep, goats, swine, and 1 Brucellosis in humans and animals. WHO, Food and Agriculture Organization of the United Nations, and World Organisation for Animal Health, 2005. Available at http://www.who.int/csr/resources/publications/Brucellosis.pdf 2 Excerpt from WHO recommended standards and strategies for surveillance, prevention and control of communicable diseases at http://www.who.int/zoonoses/diseases/Brucellosissurveillance.pdf 3 Heymann DL, ed. Control of communicable diseases manual, 19th ed. APHA and WHO, 2008.

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occasionally dogs. Human-to-human transmission occurs rarely, through blood transfusion or sexual contact. Brucellosis is endemic in the Mediterranean countries, North and East Africa, the Middle East, South and Central Asia, and South and Central America. Brucellosis is often unrecognized and frequently unreported. Key clinical features The patient has a history of recent exposure to known or probable source of brucellosis: • ingestion of unpasteurized milk or milk products • unprotected contact with potentially infected animal tissues, blood, or vaginal discharge • incubation period is variable from a few days to weeks and months. Brucellosis is a systemic disease with conﬁrmed intermittent or irregular fever (undulant fever of varying duration). Clinical manifestations are nonspeciﬁc. The term “localized” is used when symptoms related to a speciﬁc organ predominate. The disease has acute, subacute, and chronic presentations: • acute brucellosis: (50% of the cases); • untreated or unrecognized acute disease may become localized: ° may present as either: ◊ mild infection that resolves without treatment in 3 to 6 months; ◊ sudden onset fever, chills, sweating; ◊ gradual onset headaches, malaise, extreme fatigue with intermittent or absent fever; ° other clinical features include: ◊ myalgia and depression (common); ◊ anorexia, nausea, vomiting, diarrhoea, constipation, abdominal pain, haematuria, cough; ◊ enlarged liver spleen and lymph nodes; • subacute localized disease: ° localized disease (granulomas, vasculitis) can affect any organ: ◊ bone and joint involvement (most common) causing sacroiliitis, spondylitis, paraspinal abscesses, osteomyelitis, suppurative arthritis; ◊ genitourinary involvement – orchitis, epididymitis; ◊ CNS involvement – meningitis, encephalitis, depression; ◊ CVS involvement – endocarditis (commonest cause of death); ◊ respiratory involvement – bronchitis, lung abscess, effusions; ◊ abdominal involvement – liver granulomas; ◊ skin involvement – rashes, papules, erythema nodosum; ◊ ophthalmic involvement – uveitis, iridocyclitis (see Section 10.12). • chronic brucellosis: ° persistence of local or systemic disease; or ° relapses of local or systemic disease. Investigations To demonstrate the presence of Brucella, the following steps are necessary: • isolation of Brucella from blood, bone marrow, pus, or other tissues: ° blood culture – requires special technique and long incubation period, and is often negative in long-standing disease; ° PCR for Brucella;

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• serological tests for Brucella antibodies in blood or other tissue: combine Rose Bengal test for agglutinating antibodies (IgM, IgG, IgA) with a test for non-agglutinating antibodies (Coombs-IgG, ELISA-IgG); • X-rays to demonstrate joint disease (blurred joint margins, widened sacroiliac space, destruction of vertebrae). Do not forget to look for tuberculosis. Treatment Use two or more antibiotics in combination: • doxycycline 200 mg daily for 45 days PLUS streptomycin 1g IM daily (or gentamicin 5 mg/kg daily) for 15 days (preferred); OR • doxycycline 200 mg daily for 45 days PLUS rifampicin 15 mg/kg/day (600– 900 mg) for 45 days (alternative). Longer courses may be needed for endocarditis and CNS involvement. Surgical drainage of abscesses may be needed.

Buruli ulcer see Section 10.2 Skin problems 11.4 Candida Candidiasis is a fungal infection most commonly caused by Candida albicans. Candida is part of the normal human ﬂora and is found in the mouth, vagina, and gastrointestinal tract. Predisposing factors that can lead to infection are: • wide-spectrum antibiotic use • diabetes • HIV • pregnancy • skin maceration, or a break in the natural skin or mucosal barrier. Candidiasis can be limited to mucous membranes or can occasionally spread through the blood or be deeply invasive. Key clinical features Oral candida: • white deposits that adhere to the mucosa in the mouth and that can extend into the oesophagus; • difﬁculty with swallowing; • persistent oral candida is a WHO stage 3 condition indicating the need to initiate ART. (See Section 10.17 Mouth problems). Skin infection: • red macerated skin if infection occurs in skin folds under breasts or around the anus; • usually associated with itching. Vaginal candidiasis: • white itchy discharge; • sometimes associated with pain on urination.

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Oesophageal candidiasis: • can be asymptomatic; • often associated with chest pain and difﬁculty swallowing; • oesophageal candidiasis (and candida of trachea, bronchi, or lungs) is a WHO stage 4 condition, indicating the need to initiate ART. (See Section 10.7b Painful or difﬁcult swallowing). Candida can be a deeply invasive disease. Fungemia can occur mainly through infection of intravenous devices or urinary catheters and can spread throughout the whole body. There are a few organs that are very prone to be invaded after bloodstream infections. These are the eyes, causing blurred vision and showing white cotton ball lesions on fundoscopy, and the liver and spleen, particularly in patients recovering from very low WBC. These situations require speciﬁc treatment. Investigations • A wet smear can identify the fungus with pseudo-hyphae (branching structures). • A culture of the likely source will often yield a positive result. Treatment Approaches to management depend on the location and the severity of the infection. Topical agents are preferred for the skin, but invasive candidiasis needs to be treated with systemic antifungals. Patients with AIDS who have recurrent episodes of candidiasis beneﬁt from having each episode treated separately. Medications to be used depend on where the candidiasis is found: • Oral: ° clotrimazole troche (dissolving tablet) twice daily for 7 days; OR ° nystatin: one tablet 500 000 IU 4 times daily; tablets should be sucked and retained in the mouth for as long as possible; therapy should be continued for at least 48 hours after symptoms have resolved; OR ° miconazole gum patch once daily for 7 days; case reports also mention its efﬁcacy in treating oesophageal thrush; OR ° miconazole oral gel: 60 mg 4 times daily for 7 days. ° Recurrent oral candidiasis may require ﬂuconazole 100 to 200 mg for 7 to 14 days. • Skin: ° Use measures to reduce wetness or moisture and decrease friction. ° Topical application of an antifungal cream such as nystatin, cotrimazole, terbinaﬁne, or miconazole cream for 5 to 7 days. • Vaginal (see Section 10.15) • Oesophagus: ° ﬂuconazole tablet 100 mg or 200 mg daily for 14 to 21 days; OR ° itraconazole 200 mg daily, can be increased to a maximum of 400 mg daily, for 10–14 days; the capsules should be taken with food or an acid drink (such as a cola) to increase their bioavailability; OR ° ketoconazole: 200 to 400 mg daily if ﬂuconazole is not available, until remission is obtained. Ketoconazole is associated with hepatotoxicity. Ketoconazole should not be co-administered with nevirapine. When

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administered with lopinavir/r, the dose of ketoconazole should not exceed 200 mg daily. • Disseminated disease: ° Removal of prosthetic devices including catheters is recommended for the management of invasive candida infections. ° Give ﬂuconazole 400 mg daily (orally or IV if patient cannot swallow) for 14 days after the last fever. • Stopping ﬂuconazole ° Long-term administration of ﬂuconazole may result in the development of drug resistance. ° Patients stable on ART with immunological (CD4 count >100 cells/mm3) or clinical evidence of immune recovery and no evidence of candidiasis should stop ﬂuconazole.

11.5 Cryptococcosis4 This infection is most commonly caused by Cryptococcus neoformans, particularly in HIV-positive patients with advanced immunodeﬁciency (CD4 cell count generally <100/mm3). However, patients who have been on long-term steroid therapy, as well as other immunosuppressive drugs, are also at risk. Notably, other species of Cryptococcus (e.g. Cryptococcus gattii) are increasingly recognized as a cause of cryptococcosis in immunocompetent individuals. Typically, infection is acquired by inhalation of the fungus into the lungs. Cryptococcus is found in most areas with a relatively warm climate, and is not restricted to the tropics. Cryptococcal meningitis or meningo-encephalitis is the most common presentation in HIV-positive patients, and is associated with a universal mortality without treatment. Non-meningeal presentations of cryptococcosis include pneumonia, skin lesions, and lymphadenitis. Key clinical features • Sub-acute meningitis: headache increasing over days to weeks, fever, photophobia, nausea, seizures, confusion, irritability, blurred vision, sixth cranial nerve palsy, papilloedema on retinal exam are common. Nuchal rigidity is often not marked. • Coma, or a reduced level of consciousness are associated with a poor prognosis. • Lung infections: chest pain and cough in a minority of patients, but often no fever. • Skin lesions: disseminated disease is associated with papular lesions with an umbilicated, centrally depressed area (similar appearance to molluscum contagiosum), which can become ulcerated. Complications • Intracranial pressure can become raised (increasing headache, vomiting, cranial nerve palsy). 4 Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. WHO, 2011. Available at www.who.int/hiv/pub/cryptococcal_disease2011

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• Cryptococcomas can develop in the brain, more commonly in patients who are not immunocompromised. • Coma, cerebral oedema, and death follow if it is untreated, usually due to elevated intracranial pressure. • Hydrocephalus, blindness, dementia, and personality change can occur as permanent sequelae. Investigations • A lumbar puncture and CSF examination is the most useful investigation. • Presence of encapsulated yeast forms on an India ink stain of the CSF is the most widely available diagnostic test (sensitivity 82–85%, but may be negative if low fungal burden). • An alternative and highly sensitive and speciﬁc test is the CSF cryptococcal antigen (CrAg) latex agglutination test that examines for the presence of capsular antigen (sensitivity • 96–100%); serum CrAg may also be positive. • A positive CSF fungal culture is the deﬁnitive test, but is not widely available and may take some days. • Cryptococcus can be cultured in the blood in 70% of cases. • Other features of CSF: ° elevated opening pressure (more than 20 cm H2O in 70% of patients) ° low WBC (less than 50 cells/microlitre) with mononuclear predominance ° lowered glucose level ° slightly elevated protein. • Microscopy and culture from non-meningeal cryptococcal sites – visualization of encapsulated yeasts or positive culture from skin scraping or biopsy, sputum, urine, lymph node FNA, or biopsy. • Chest X-ray – similar to PCP (bilateral diffuse interstitial inﬁltrates). Anti-fungal treatment If the patient has meningitis or pneumonia, treatment with a regimen containing amphotericin is preferred. Given potential life-threatening adverse events (e.g. severe hypokalaemia) associated with amphotericin therapy, however, amphotericin-containing regimens should not be used without adequate laboratory monitoring (i.e., electrolytes and kidney function) and the use of pre-hydration and electrolyte replacement prior to amphotericin administration (see Box below for further details of safe administration of amphotericin B). The following therapies for cryptococcal meningitis are recommended: Option 1 (if amphotericin, lab monitoring, pre-hydration, and ﬂucytosine available): amphotericin B 0.7 to 1 mg/kg PLUS ﬂucytosine 100 mg/kg for 14 days, followed by oral ﬂuconazole 400 mg daily for 8 weeks. Option 2 (if amphotericin, lab monitoring, and pre-hydration available, but not ﬂucytosine): amphotericin B (as above) PLUS oral ﬂuconazole 800 mg for 14 days followed by ﬂuconazole 400 mg for 8 weeks. Option 3 (if lab monitoring unavailable): intravenous amphotericin B (as above) for 5-7 days PLUS oral ﬂuconazole 800 mg for 14 days followed by ﬂuconazole 800 mg for 8 weeks.

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Option 4 (if amphotericin, lab monitoring and pre-hydration NOT available): oral ﬂuconazole 800–1200 mg for 14 days followed by ﬂuconazole 400 mg for 10 weeks. Recommendations for safe administration of amphotericin B To reduce risk of thrombophlebitis, use large peripheral veins or a central venous catheter, changing venous access sites frequently and infusing over longer periods. Protect against life-threatening adverse events: • Monitor renal function and electrolytes (e.g., serum potassium, serum creatinine, ﬂuid intake and output, and daily weight) prior to initial treatment and then at least twice weekly. • One hour prior to administration of each amphotericin infusion, administer 1 litre of IV normal saline solution over 2–4 hours. • Consider addition of one ampoule (20 mmol) of potassium chloride with each litre of IV saline solution plus one to two 8 mEq KCL tablets orally twice daily. An additional one 8mEq KCL tablet twice daily may be added during the second week. If available, magnesium supplementation should also be provided (two 250 mg tablets of magnesium trisilicate twice daily). • Use with caution in renal impairment. If creatinine increases by ≥2 fold from baseline value, switch to liposomal amphotericin (3 mg/kg/day) if available. • If liposomal amphotericin not available, either skip an amphotericin B dose or increase pre-hydration to one litre 8 hourly. Once creatinine improved, restart at 0.7 mg/kg/day and consider alternate day amphotericin B. If creatinine remains elevated, discontinue amphotericin and continue with ﬂuconazole at 1200mg/day. Monitor creatinine daily. Minimize acute infusion reactions (e.g. fever, chills, headache, hypotension): • Infuse the initial dose slowly over 3–6 hours. • Prophylactic antipyretics or hydrocortisone should only be used in patients who have previously experienced acute infusion reactions (and in whom continued treatment with amphotericin is essential).

Control of raised intracranial pressure (ICP) Patients with increased intracranial pressure should have frequent (daily) lumbar punctures done to relieve the pressure and to avoid the development of blindness and other long-term complications. • Educate and inform the patient about the importance of baseline and followup lumbar punctures (i.e., improves treatment outcomes). • Measure the intracranial pressure (see Section 7.4.2). Treatment of raised intracranial pressure (ICP) in cryptococcal meningitis • • • • Raised ICP contributes to early mortality and residual morbidity. Raised ICP is present in >50% of patients. Repeated spinal taps lower ICP, reducing mortality and morbidity, as well as reducing severe headaches. If initial opening pressure is normal, repeat LP in 1–2 weeks or if worsening headache, visual, or hearing disturbances. • If initial opening pressure is >25 cm H20, tap up to 30 ml spinal ﬂuid to achieve pressure <20 cm H20. • Perform daily taps until the opening pressure is <25 cm H20.

Delay initiation of ART Due to the high risk of IRIS with CNS disease, which may be life-threatening, in HIVinfected adults, adolescents and children with a recent diagnosis of cryptococcal meningitis, ART initiation should be deferred until there is evidence of a sustained clinical response to antifungal therapy, and • after 2-4 weeks of induction and consolidation treatment with amphotericin B-containing regimens combined with ﬂucytosine or ﬂuconazole (two weeks with non-meningeal disease); OR

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• after 4-6 weeks of induction and consolidation treatment treatment with a high-dose oral ﬂuconazole regimen (four weeks with non-meningeal disease). Secondary prophylaxis • Give ﬂuconazole 200 mg by mouth daily until the patient is successfully on ART and the CD4 count is maintained above 200 cells/mm3 (two measurements 6 months apart). Drug interactions • Rifampicin and ﬂuconazole ° Rifampicin can reduce ﬂuconazole levels. ° Consider increasing ﬂuconazole by 50% if given with rifampicin. • Nevirapine and ﬂuconazole ° Available evidence is limited for co-administering nevirapine and ﬂuconazole. ° Studies have shown ﬂuconazole increases nevirapine levels. ° Nevirapine has not been shown to decrease ﬂuconazole levels signiﬁcantly. ° Monitor LFTs: ◊ If the baseline ALT is raised: monitor ALT at initiation, 1, 2, 3, 4, 6, and 8 weeks, and then according to the clinic’s usual standard for administering nevirapine. ◊ If the baseline ALT is normal: monitor ALT at initiation, 2 and 4 weeks, and then according to the clinic’s usual standard for administering nevirapine.

Cryptococcal IRIS Patients with advanced immune deﬁciency can develop IRIS after the initiation of ART as a result of partial immune restoration. Cryptococcal meningitis is a common infection implicated in IRIS. It occurs in patients with latent or recently treated cryptococcal meningitis who then develop an inﬂammatory meningitis, headache, or focal signs. Cryptococcal IRIS can develop between 1 week and 8 months after a patient starts ART, but typically within 1–6 weeks. It is usually accompanied by a signiﬁcant CD4 increase and a viral load (VL) decrease. Diagnosis In addition to the above history, look for: • recent initiation of ART • recent treatment for cryptococcal meningitis • history of long-standing mild headache prior to ART commencement. In addition to the above examination look for: • lymphadenopathy • increased intracranial pressure. Investigations CSF results can be difﬁcult to interpret, especially if the patient has recently been treated for cryptococcal meningitis. The CrAg and India ink test remain positive for many months after treatment and do not distinguish between live and dead organisms. Diagnosis will therefore often be based on the patient’s history and examination ﬁndings.

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• CSF: ° positive cryptococcal antigen (if recently treated will still be positive – does not indicate new infection) ° cryptococcal culture usually negative. • VL or CD4: ° signiﬁcant decrease in VL ° increased CD4. Treatment • continue ART • cryptococcal treatment (as above) • consider steroids if meningitis is life-threatening or focal neurology exists.

11.6 Cryptosporidiosis Diarrhoeal illness caused by Cryptosporidium parvum is acquired by ingesting oocysts from contaminated food or water. Oocysts are immediately infectious when excreted by infected persons; therefore, person-to-person transmission occurs in child care centres, medical centres, and among household contacts. The disease is self-limited in persons with normal immunity (including PLHIV with CD4 more than 200), but can be severe and debilitating in persons with immunosuppression. Key clinical features • watery, non-bloody diarrhoea • abdominal pain, nausea, fever, decreased appetite leading to weight loss. Severe disease (in patients with CD4 <100): • chronic profuse diarrhoea with severe dehydration • weight loss, wasting, and severe abdominal pain • fulminant disease – loss of more than 2 kg per day. Complications include: • Invasion of the biliary tree, occasionally leading to cholestatic disease with symptoms of right upper quadrant pain. Investigations Oocysts (4–6 micrometers diameter) can be found in stools using a modiﬁed acidfast stain. Since shedding can be intermittent, at least 3 stool specimens collected on separate days should be examined before considering stool examination to be negative. Treatment • Start ART. In PLHIV with fulminant disease, the most important thing to do is to start ART to increase the patient’s CD4 count. With improvement of the immune system, the cryptosporidia and the symptoms will disappear. • There are no good antiprotozoal treatment options for cryptosporidiosis. • If signs of dehydration, rehydrate. Give ORS if mild or moderate dehydration. If severe dehydration, give intravenous ﬂuids. See Section 10.7d on management of persistent diarrhoea.

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11.7 Cysticercosis see also Section 11.38 Taeniasis Taeniasis and cysticercosis are two different diseases caused by the same organism. Taeniasis is an intestinal infection caused by the large adult tapeworms Taenia solium (pork tapeworm) and Taenia saginata (beef tapeworm). Cysticercosis is caused by the larval stage of Taenia solium that can invade any tissue and produce a variety of clinical pictures ranging from asymptomatic to fatal disease. Morbidity and relevant clinical symptoms are almost exclusively caused by neurocysticercosis and less often by ocular infection.

T. solium and T. saginata are distributed worldwide where cattle and pigs are raised for human consumption. Higher prevalence is found in areas with poor sanitation and where untreated wastewater is used in agriculture. Cysticercosis is found where T. solium is found.

Key clinical features • Clinical manifestations vary greatly because the cysticerci can occur in any number, and in almost any organ: ° common sites: brain, muscles, subcutaneous tissue ° other sites: eye, orbit. • Cysticerci cause varying degrees of calciﬁcation, oedema, and granuloma formation. • Neurological symptoms are the most common reason for presentation, except in Asia where subcutaneous presentation is as common.

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• Neurocysticercosis presentations: ° can be asymptomatic ° adult onset seizures or epilepsy (most common presenting symptom) ° chronic headaches ° neurological deﬁcits (focal or non-focal) ° neuropsychiatric problems (altered mental status, behaviour changes) ° vomiting ° visual defects (due to neurological, meningeal, or ocular involvement) ° muscular pseudohypertrophy in massive, multicystic infection ° radiculopathy (due to spinal cysticerci) ° fever is uncommon (investigate for other causes if fever is present) ° other presentations include chronic stroke, febrile meningitis, hydrocephalus with raised intracranial pressure. • Presentations in other organ systems: ° muscle and subcutaneous tissue cysticerci: ◊ usually asymptomatic ◊ may have nodules that can be seen or felt ◊ can have pain. ° eye: retinal and vitreal involvement may affect vision ° orbital involvement. Investigations Diagnosis and staging of suspected neurocysticercosis requires CT or MRI imaging that is not available at most district hospitals. EEG is helpful for patients with seizures. • Demonstration of the parasite: ° larvae seen in biopsy of subcutaneous nodules (deﬁnitive diagnosis); ° fundoscopy for intraocular larvae (deﬁnitive diagnosis); ° stool examination is of limited use as not all patients with cysticercosis will have an intestinal infection; • Eye exam and fundoscopy to look for papilloedema and nystagmus (signs of neurocysticercosis); • X-ray to demonstrate muscle and subcutaneous cysts, which appear as small cigar-shaped opacities; • Serological tests: ° ELISA on CSF for anticysticercal antibodies or cysticercal antigens (antigen is only positive in active infections). Negative serology (including antibody or antigen testing in the CSF) does NOT rule out neurocysticercosis, especially in single lesions. Treatment Medical and surgical treatment generally depends on the location, number, and characteristics of the cysticerci which need to be determined with advanced imaging (MRI, CT). Imaging is also necessary to establish if there is a reason to withhold cysticidal treatment, for example in cysticercotic encephalitis (heavy intraparenchymal parasite burden), and to assess for stages of the disease where cysticidal treatment does not seem to be beneﬁcial (calciﬁed lesions). Patients with suspected neurocysticercosis should therefore be referred to a tertiary facility for further management. Empirical treatment of neurocysticercosis without imaging should be avoided. However, if no imaging is available at the referral hospital, the clinician has to be aware that there is a risk of exacerbating symptoms under cysticidal treatment

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due to increasing inﬂammation, which can be life-threatening. Steroids should be given in such circumstances. This is especially the case for cysticercotic encephalitis (heavy intraparenchymal parasite burden), when parasitic treatment is controversial and treatment of symptomatic disease usually consists of only steroids. A standard adult treatment regimen for uncomplicated cysticercosis would entail: • Antiparasitic treatment: ° albendazole 15 mg/kg daily for 8 days (preferred); OR ° praziquantel 50 mg/kg daily for 14 days (alternative second choice; is less effective and has more interactions with steroids and antiepileptics than albendazole; is contraindicated when antiepileptic drugs are given, or in the case of ocular cysticercosis). • Corticosteroids are usually added to antiparasitic treatment; a starting dose of dexamethasone 8–10 mg daily or prednisone 40 mg daily and titrated as inﬂammation changes. Length of treatment with corticosteroids is not welldeﬁned. Also recommended for symptom management: • Analgesics for headaches; • Antiepileptics (phenytoin, carbamazepine, valproate, phenobarbitol) for seizures (levels may be lowered when given concomitantly with praziquantel); • Mannitol may need to be given temporarily for raised intracranial pressure.

11.8 Cytomegalovirus (CMV) CMV is in the human herpes family of viruses, and as such is characterized by its potential for latency and disseminated infection. It causes a wide spectrum of diseases in older children and adults. It is distributed worldwide and, if acquired in utero, is associated with congenital malformations. Transmission is predominantly through repeated and prolonged contact, but it is most commonly transmitted through sexual contact. In addition, the virus has been found in breast milk, saliva, faeces, and urine. After acquisition, CMV persists for life, and can be reactivated if the immune system is weakened, such as by HIV or organ transplantation. CMV is difﬁcult to diagnose and requires pathological examination of specimens for deﬁnitive diagnosis. In areas where these examinations are not available, diagnosis relies on its typical clinical presentation (in case of CMV retinitis) that is not explained by other conditions. CMV also can cause a mononucleosis syndrome, more commonly caused by Epstein Barr virus. There are several syndromes caused by CMV.

CMV in persons with decreased immunity CMV causes retinitis and disseminated disease in HIV-infected patients whose CD4 counts are below 100. In the era of antiretroviral therapy, this is seen less often. However, it is important to note that CMV retinitis and colitis can occur in the ﬁrst few weeks after starting antiretroviral therapy, or can worsen as part of IRIS. If blindness has occurred in one eye due to CMV or other causes, the other eye should be examined carefully for signs of CMV infection before starting antiretroviral therapy. Relapses are uncommon if CD4 counts have increased due to treatment of HIV disease. Since disseminated CMV infection is only seen in patients who are

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severely immune deﬁcient, immune reconstitution through the prompt initiation of ART in HIV-positive individuals is key to managing this disease.

CMV retinitis – see Section 10.12 Eye problems Key clinical features • painless loss of vision • ﬂoaters, visual ﬁeld defects, or black spots • no vitreous haze – fundi clearly seen • vascular sheathing – “frosted branch” appearance • examine the other eye if this is diagnosed in one eye • CD4 <100 – occurs less commonly if >100, then look for other cause for retinopathy. Immune-recovery uveitis • Follows CMV of the eye most commonly, but also associated with other retinal opportunistic infections. • Decreased vision or gradual onset with ﬂoaters. • Follows recent initiation of ART. • Decreased vision, ﬂoaters, visual ﬁeld defects, or black spots. Investigations • Fundoscopic examination (by an ophthalmologist or trained clinician) shows typical yellow-white areas of peri-vascular inﬁltrates contrasting with red areas of intraretinal haemorrhage, typical yellow-white areas of retinal necrosis, peri-vascular inﬁltrates, with areas of haemorrhage or necrosis (“pizza pie” or cheese appearance). Other investigations are not helpful in this presentation. Complications • retinal detachment • immune reconstitution vitreitis is a vision-threatening complication of antiretroviral therapy initiation in the absence of effective anti-CMV treatment of active retinitis. Note: Although long-term anti-CMV treatment is costly, a strategy of having limited amounts of CMV drugs available for use while immune reconstitution takes place with ART in patients presenting with CMV end-organ disease may limit adverse consequences of CMV immune reconstitution syndromes. Treatment • Antiretroviral therapy plus: ° ganciclovir 5 mg/kg IV twice daily for 3 to 4 weeks, if available; OR ° oral valganciclovir 900 mg twice daily with food for 14 days, followed by 900 mg daily maintenance therapy until CD4 count is more than 100–150 for 6 months. • Co-administration of AZT with ganciclovir requires caution and careful monitoring because of additive bone marrow toxicity (anaemia and neutropaenia). • If vision is threatened, intraocular ganciclovir implants may be available from a specialist clinician; anaesthesia is required for insertion. Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

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• Relapses should be treated with a repeat of the induction dose of the same regimen.

Gastrointestinal CMV Suspect CMV gastrointestinal disease in patients with GI complaints that do not respond to common bacterial, antifungal therapy, and aciclovir (for suspected herpes simplex oesophagitis or proctitis), and for those who have a CD4 below 100. In case of simultaneous CMV retinitis, suspect other locations of CMV infection. Key clinical features • fever • oesophagitis: retrosternal pain and pain when swallowing • gastritis: substernal or burning epigastric pain • pancreatitis: epigastric pain radiating to the back • small bowel disease or colitis: abdominal pain, weight loss, and (bloody or non-bloody) diarrhoea. Complications • Perforation or bleeding are possible. • Initiation of antiretroviral therapy in the setting of untreated CMV end-organ disease can be associated with immune reconstitution syndromes that may rarely result in intestinal perforation. Treatment • Antiretroviral therapy PLUS ganciclovir 5 mg/kg IV twice daily for 3 to 4 weeks, if available. • Co-administration of AZT with ganciclovir – with caution and careful monitoring because of additive bone marrow toxicity (anaemia and neutropaenia). Oral valganciclovir 900 mg twice daily may be used if not contraindicated because of suspected malabsorption, ileus, or inability to swallow.

Neurological CMV – see Section 10.10a Neurologic problems Key clinical features • CMV polyradiculitis: ascending polyradiculopathy (affecting several nerve roots): progressive leg weakness, then bladder and bowel dysfunction. • CMV encephalitis: rapidly progressive delirium, cranial nerve dysfunction, nystagmus, and ataxia. Investigations A lumbar puncture reveals a raised protein, low glucose, and increased WBC, which can be monocytes or neutrophils. Note that these ﬁndings may be similar to those found in TB meningitis. The diagnosis should be suspected in patients with a CD4 count below 50 who present with the clinical features of encephalitis or polyradiculitis as described above. In resource-enhanced settings, the diagnosis can be conﬁrmed by CMV PCR of the spinal ﬂuid. Treatment • Antiretroviral therapy PLUS prompt initiation of ganciclovir, if available, 5 mg/ kg IV twice daily for 3 to 6 weeks.

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• Then maintenance with oral doses of valganciclovir 900 mg daily, can halt neurological progression, although established neurological deﬁcits are rarely reversible.

11.9 Dengue fever5 Dengue is the most rapidly spreading mosquito-borne viral disease in the world. In the last 50 years, incidence has increased 30-fold with increasing geographic expansion to new countries and, in the present decade, from urban to rural settings. Dengue virus is a small single-stranded RNA virus comprising four distinct serotypes. Infection by one serotype provides life-long immunity to that serotype, but only transient immunity to the others. Sequential infection with a different serotype increases the risk of serious disease. Dengue is transmitted in tropical and sub-tropical regions around the world, predominantly in urban and semi-urban areas. The past 25 years have seen an increase in outbreaks of dengue fever and cases of severe dengue. Dengue fever is now endemic in countries in Africa, the Americas, the Eastern Mediterranean, South-East Asia, and the Western Paciﬁc. The Americas, South-East Asia, and the Western Paciﬁc are the most seriously affected.

5 Dengue: guidelines for diagnosis, treatment, prevention and control: new edition. WHO, 2009. Available at http:// whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

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Figure: Revised dengue case classiﬁcation by severity Dengue ± warning signs Severe dengue

Without warning signs

With warning signs

1. Severe plasma leakage 2. Severe haemorrhage 3. Severe organ impairment

Criteria for dengue ± warning signs Probable dengue Live in or travel to dengue endemic area. Fever and two of the following criteria: • nausea, vomiting • rash • aches and pains • tourniquet test positive • leukopenia • any warning sign Laboratory conﬁrmed dengue (Important when no sign of plasma leakage.)

Criteria for severe dengue 1. Severe plasma leakage • shock (DSS) • ﬂuid accumulation with respiratory distress 2. Severe bleeding • as evaluated by clinician 3. Severe organ involvement • shock (DSS • liver: AST or ALT ≥1000 • CNS: impaired consciousness • heart and other organs

Warning signs* • abdominal pain or tenderness • persistent vomiting • clinical ﬂuid accumulation • mucosal bleed • lethargy, restlessness • liver enlargement >2cm Laboratory: increase in HCT concurrent with rapid decrease in platelet count *Requiring strict observation and medical intervention

Key clinical features Dengue fever clinical case deﬁnition: Criteria include the sudden onset of fever lasting 2 to 7 days, living in or travel to dengue endemic area, and two of the following: • anorexia, nausea, vomiting • rash • muscle and joint pains • tourniquet test positive • leukopenia • any of the warning signs listed immediately below. Dengue is difﬁcult to distinguish from other acute febrile illnesses, such as malaria or typhoid. Warning signs include: • abdominal pain or tenderness • persistent vomiting • clinical ﬂuid accumulation • mucosal bleed • lethargy, restlessness • liver enlargement more than 2 cm • laboratory: increase in haematocrit concurrent with rapid decrease in platelet count.

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Severe dengue fever: clinical case deﬁnition Criteria for dengue fever above, and: • severe plasma leakage leading to dengue shock syndrome and ﬂuid accumulation with respiratory distress; OR • severe bleeding as clinically evaluated; OR • severe organ involvement – liver: AST or ALT ≥1000; CNS – impaired consciousness; or heart and other organs. Investigations In areas endemic for malaria and dengue, dengue is often the next diagnosis to consider when the malaria test is negative. Blood investigations: • White cell count, platelets, haematocrit, other organ function tests as necessary: ° to conﬁrm dengue infection (see ﬁgure below): ◊ detection of NS1 antigen by rapid diagnostic test from day 1 to 6 of illness; ◊ detection of IgM by rapid diagnostic test or ELISA from day 5 onwards; ◊ some rapid diagnostic tests combine the detection of NS1 and IgM/IgG, which increases the chance of conﬁrming the diagnosis in the early stage of illness. Other imaging: • Chest X-ray (including right lateral decubitus) and abdominal ultrasound can be useful to detect plasma leakage.

Figure: Laboratory conﬁrmation for dengue virus infection6

6 Halstead SB. Dengue. Lancet, 2007; 370:1644–52, with permission to reproduce.

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Treatment Group A: dengue without warning signs – may be sent home • Group criteria: ° Patients do not have warning signs. AND ° Are able: ◊ to tolerate adequate volumes of oral ﬂuids ◊ to pass urine at least once every 6 hours. • Treatment: ° Advice for: ◊ adequate bed rest ◊ adequate ﬂuid intake ◊ paracetamol, 4 g maximum daily in adults ◊ patients with stable haematocrit can be sent home. Group B: dengue with warning signs – refer for inpatient hospital care • Group criteria: ° Patients with any of the following features: ◊ coexisting conditions such as pregnancy, old age, diabetes mellitus, renal failure; ◊ social circumstances such as living alone, living far from hospital. • Treatment: ° Encourage oral ﬂuids. If not tolerated, start intravenous ﬂuid therapy with NS or LR at maintenance rate. Patients with existing warning signs • Treatment: ° Obtain reference haematocrit before ﬂuid therapy. ° Give NS or LR. Start with 5–7 ml/kg/hour for 1 to 2 hours, then reduce to 3–5 ml/kg/hour for 2 to 4 hours, and then reduce to 2–3 ml/kg/hour or less according to clinical response. Group C: severe dengue – require emergency treatment • Group criteria: ° Patients with any of the following features: ◊ severe plasma leakage with shock or ﬂuid accumulation with respiratory distress; ◊ severe bleeding; ◊ severe organ impairment. • Treatment: ° Compensated shock: ◊ Start IV ﬂuid resuscitation with NS or LR at 5–10 ml/kg/hour over 1 hour. ◊ Reassess the patient’s condition. ◊ If the patient improves: • reduce IV ﬂuids gradually to 5–7 ml/kg/hour for 1 to 2 hours, then to 3–5 ml/kg/hour for 2 to 4 hours, then to 2–3 ml/kg/hour for 2 to 4 hours and then reduce further depending on haemodynamic status; • IV ﬂuids can be maintained for up to 24–48 hours. ◊ If the patient is still unstable: • check haematocrit after ﬁrst bolus; • if haematocrit increases or is still high (more than 50%), repeat a second bolus of crystalloid solution at 10–20 ml/kg/hour for 1 hour;

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• if there is improvement after second bolus, reduce rate to 7–10 ml/kg/ hour for 1 to 2 hours and continue to reduce as above; • if haematocrit decreases, this indicates bleeding and need to crossmatch and transfuse blood as soon as possible. ° Hypotensive shock: ◊ Initiate IV ﬂuid resuscitation with NS or LR or colloid solution at 20 ml/kg as a bolus for 15 minutes. ◊ If patient improves: • give NS or LR or colloid solution of 10 ml/kg/hour for 1 hour, and then reduce gradually as above. ◊ If patient is still unstable: • review the haematocrit taken before the ﬁrst bolus; • if haematocrit was low (more than 40% in females, more than 45% in males) this indicates bleeding (see above); • if haematocrit was high compared to baseline value, change to IV colloids at 10–20 ml/kg as a second bolus over 30 minutes to 1 hour, reassess after second bolus; • if patient is improving, reduce the rate to 7–10 ml/kg/hour for 1 to 2 hours, then back to IV NS or LR, and reduce rates as above; • if patient’s condition is still unstable, repeat haematocrit after second bolus; • if haematocrit decreases, this indicates bleeding and need to crossmatch and transfuse blood as soon as possible; • if haematocrit increases or remains high (more than 50%), continue colloid infusion at 10–20 ml/kg as a third bolus over 1 hour, then reduce to 7–10 ml/kg/hour 1 to 2 hours, then change back to NS or LR and reduce rate as above. ° Haemorrhagic complications: give 5–10 ml/kg of fresh packed red cells or 10–20 ml/kg of fresh whole blood.

11.10 Endocarditis Endocarditis is an infection of one or more of the heart valves. Risk factors include pre-existing heart valve disease that may be congenital or rheumatic heart disease. Conditions that are associated with bacteraemia, such as intravenous drug use or intravenous lines may also cause endocarditis. Endocarditis is always fatal without treatment, due to destruction of the heart valves and heart failure. Key clinical features • May present with a fever without a clinically evident focus. • New or changing cardiac murmur. • A precipitating event, such as a dental abscess or tooth extraction, can rarely be identiﬁed. • Can present with symptoms suggestive of embolization of the infection to distant sites, most commonly the vertebrae (presenting with back pain), brain (presenting with focal weakness or other neurological signs). Small emboli may also be seen in the ﬁngers or elsewhere on the skin. Complications of endocarditis are usually associated with a poor prognosis. Investigations • ECG is usually normal or shows non-speciﬁc ﬁndings such as tachycardia. Abscesses of the aortic ring may present as heart block.

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• Blood cultures are commonly positive. Common causative organisms include: Staphylococcus aureus and Streptococcus viridians. • Echocardiography may show valvular regurgitation (most commonly mitral and aortic) that may be visualized. If it is large, valvular vegetations may be visible. • Look for the possible source of bacteraemia, based on the type of bacteria isolated (e.g. dental abscess). Treatment • Treatment includes antimicrobial therapy, supportive care for complications (e.g. heart failure), and specialist advice, if available. • Referral for cardiac surgical consultation for complications of a destroyed heart valve (such as intractable heart failure, shock, progressive heart block, recurrent emboli, or persistent positive blood cultures) is recommended. • If blood culture results are available, treatment should be guided by the results of culture and antibiotic susceptibility tests. Empirical treatment options include: Native valve: • benzylpenicillin 12 to 18 million units in divided doses plus gentamicin 1 mg/ kg IV 3 times daily (preferred); OR • ceftriaxone IV/IM 2 g daily plus gentamicin 1 mg/kg IV 3 times daily (alternative if mild allergy to penicillin ); OR • vancomycin IV 30 mg/kg daily in 2 equally divided doses plus gentamicin 1 mg/kg IV 3 times daily (alternative if severe allergy to penicillin or if methicillin-resistant Staphylococcus aureus is suspected – recent admission to hospital, intravenous drug use). Prothetic valve: • vancomycin IV 30 mg/kg daily in 2 equally divided doses PLUS gentamicin 1 mg/kg IV 3 times daily PLUS rifampicine orally 600 mg daily. The duration of treatment depends on antibiotic susceptibility; generally courses of 2 to 6 weeks are required. Treat the source of bacteraemia if identiﬁed (e.g. removal of an infected tooth). If the patient has a non-anaphylactic allergy to penicillin (for example, skin rash only), then ceftriaxone can be used. Vancomycin is only recommended for patients allergic to penicillin and ceftriaxone, or for S. aureus resistant to cloxacillin (MRSA). Dosing of gentamicin and vancomycin should be guided by levels, especially in the presence of renal dysfunction. When these drugs are used in a district hospital for endocarditis, there should be collaboration with a referral hospital that provides specialist guidance and lab analysis of drug levels if possible. • For gentamicin, monitor creatinine and gentamicin levels at least once per week. Aim for peak serum concentrations 3-4 mcg/ml and trough <1 mcg/ ml when 2-3 divided doses are used; when given in a single daily dose, predose (trough) levels should be <1 mcg/ml and post-dose (peak, 1 hour after injection) levels should be approximately 10-12 mcg/ml. • For vancomycin, adjust dose to achieve peak serum concentrations (1 hour after infusion completed) of 30-45 mcg/ml and pre-dose (trough)

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concentration of 10-15 mcg/ml. The dose should not exceed 2 g per 24 hours unless levels are inappropriately low. Treatment options for native valve endocarditis where blood cultures are available are shown in the following table. Other regimens are required when blood cultures grow highly resistant viridans streptococci, S. pneumoniae, enterococci, or fastidious Gram-negative bacilli, or when blood cultures are negative but endocarditis is highly suspected (for example, based on echocardiography). Table: Treatment options for viridans streptococci and S. aureus7 Penicillin-susceptible viridans streptococci (minimum inhibitory concentration (MIC) ≤0.12 mcg/ml) 4-week regimen (for patients >65 years old or with impairment of the 8th cranial nerve or renal function) • benzylpenicillin 12–18 million units (7.2-10.8 g) per 24 hours IV in 4 or 6 equally divided doses OR • ceftriaxone 2 g per 24 hours IV/IM in 1 dose OR • vancomycin 30 mg/kg per 24 hours IV in 2 equally divided doses 2-week regimen (for non-complicated cases; not for patients with known cardiac or extracardiac abscess or for creatinine clearance <20 ml/min or impaired 8th cranial nerve function) • benzylpenicillin 12-18 million units (7.2–10.8 g) per 24 hours IV either continuously or in 6 equally divided doses OR ceftriaxone 2 g per 24 hours IV/IM in 1 dose AND • gentamicin 3 mg/kg per 24 hours IV/IM in 1 dose or in 2 to 3 equally divided doses Strains of viridans streptococci relatively resistant to penicillin G (MIC >0.12 mcg/ml and <0.5 mcg/ml) in patients with normal renal function • benzylpenicillin 24 million units (14.4 g) per 24 hours IV in 4 or 6 equally divided doses OR ceftriaxone 2 g per 24 hours IV/IM in 1 dose for 4 weeks AND • gentamicin 3 mg/kg per 24 hours IV/IM in 1 dose or in 2 to 3 equally divided doses for 2 weeks OR • vancomycin (alone) 30 mg/kg per 24 hours IV in 2 equally divided doses for 4 weeks

Staphylococcus aureus Sensitive to cloxacillin (MSSA) • cloxacillin 12 g per 24 hours IV in 4 or 6 equally divided doses for 6 weeks Resistant to cloxacillin (MRSA) • vancomycin 30 mg/kg per 24 hours IV in 2 equally divided doses for 6 weeks

7 Baddour LM et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005, 111:e394-e434.

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11.11 Fascioliasis8,9,10 Fascioliasis is caused by infection with the trematodes Fasciola hepatica and Fasciola gigantica. It is transmitted to humans through ingestion of contaminated water or food – usually uncooked vegetables to which the parasite’s larvae are attached. The lifespan of the adult worm in humans is about 9–13 years. Fascioliasis has been reported in more than 70 countries and is a major public health problem in several areas of the world, including the Andes range, the Nile valley, the Caspian Sea basin, and the Mekong valley. Key clinical features These vary by the phase of the infection. After the symptomless incubation period, fascioliasis can be roughly divided into acute (when immature worms migrate through liver) and chronic (when mature worms are lodged in bile ducts). Chronic fascioliasis can, however, be further divided into four phases, for a total of six phases. Re-infection and new infections can result in an overlap of phases. • Incubation phase ° Lasts from ingestion of metacercariae to appearance of the ﬁrst symptoms. ° Can last a few days to a few months. • Acute or invasive phase ° Lasts 2–4 months. ° Immature worms migrate through the liver and digest hepatic tissue. ° Worms may deviate and migrate through other organs causing ectopic fascioliasis. ° Worms cause haemorrhage and inﬂammation proportionate to the number of worms. Dying worms cause necrosis and scarring. ° Common symptoms: fever, abdominal pain, gastrointestinal disturbances, rashes, and respiratory symptoms. ° Less common symptoms: enlarged liver or spleen, ascites, anaemia, and jaundice. ° Complications: subcapsular haematoma, acute intra-abdominal bleeding, pneumothorax. ° Symptoms of acute phase usually disappear when the worms reach the bile ducts. • Latent phase ° Lasts months to years. ° Mature worms start laying eggs during this phase. ° Many patients are asymptomatic or have non-speciﬁc symptoms, such as gastrointestinal disturbance and intermittent biliary obstruction. ° Complications arise from worms living in the bile ducts for years causing ﬁbrosis, hyperplasia, and thickening of the duct walls.

8 Neglected tropical diseases, hidden successes, emerging opportunities. WHO, 2009. Available at http:// whqlibdoc.who.int/publications/2009/9789241598705_eng.pdf 9 Report of the WHO Expert Consultation on Foodborne Trematode Infections and Taeniasis/Cysticercosis. Vientiane, Lao People’s Democratic Republic, 12-16 October 2009. WHO, 2011. Available at http://www.who.int/ neglected_diseases/preventive_chemotherapy/WHO_HTM_NTD_PCT_2011.3.pdf 10 Control of foodborne trematode infections. Report of a WHO study group. WHO, 1995. (WHO Technical Report Series 849).

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• Chronic (obstructive) phase ° Common bile duct obstruction caused by parasites, parasite fragments, or debris in the common bile duct. ° Symptoms include biliary colic (from obstruction, spasm, or distension of the common bile duct), epigastric pain, fatty food intolerance, nausea, intermittent jaundice, pruritus, right upper-quadrant abdominal pain, fever. ° Complications: gallbladder swelling, pancreatitis, jaundice, cholestatic hepatitis, and secondary bacterial infection with cholangitis and cholecystitis. • Advanced chronic phase ° Characterized by stones in the gall bladder and common bile duct, bacteria in the bile (mainly E. coli, E. faecalis, Klebsiella pneumoniae), and chronic cholangitis and cholecystitis. ° Worms stop laying eggs during this phase. • Post-infection phase ° Characterized by complications such as cirrhosis and growth deﬁciencies. ° Stones cause chronic recurrent gallbladder obstruction, and eventually a dilated, atonic gallbladder. ° Ectopic worms die and form calciﬁcations or granulomas in ectopic sites, such as the gastrointestinal tract (most commonly), subcutaneous tissue, heart, blood vessels, lung and pleural cavity, brain, orbit, abdominal wall, dorsal spine, appendix, pancreas, spleen, lymph nodes (mostly inguinal and cervical), skeletal muscle, epididymis, uterus, ovaries, and breasts. ° Worms are no longer present in the liver during this phase. Note: Patients with fascioliasis often are coinfected with other parasites, and there is a signiﬁcant association between fascioliasis and giardiasis (Giardia intestinalis) due to the common transmission pathway (drinking of contaminated water). Investigations • Stool examination ° Detection of eggs or antigens in the stool ◊ detection of eggs • Kato-Katz or conic-cup sedimentation technique • speciﬁc but not sensitive, therefore more than one stool sample is needed • negative during incubation phase and acute phase • easy to miss early infections • negative in ectopic fascioliasis. ◊ Detection of speciﬁc worm antigens in stool (e.g. FES-Ag); is more sensitive than detection of eggs. It can only be used in chronic fascioliasis. • Serology (ELISA) ° Detects circulating antibodies to fasciola antigens (e.g. Fas2 and CL1) or uses monoclonal antibodies to detect circulating fasciola antigens. ° Can be used in incubation, acute, and chronic phases, as well as in ectopic fascioliasis. ° Highly sensitive and speciﬁc. • Haematological ° Eosinophilia is present in the acute phase, not always in the latent phase.

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° Anaemia due to blood loss in the bile (haemobilia), direct blood-sucking by the worm, as well as and possibly by increased destruction and decreased production of red blood cells. • Ultrasound ° Acute phase: migrating hypoechogenic liver foci and splenomegaly. ° Chronic phase: crescents, sludge, calculi, tender gall bladder, decreased contractility of the gallbladder. The sensitivity for diagnosis less than 15%. • Liver function tests may be abnormal during the acute phase. Staging Staging of the disease relies on interpretation of the clinical presentation, and the following criteria on stool examination (using Kato-Katz or conic-cup sedimentation) and serology. • stool (–) and serology (–): no infection or infection resolved • stool (–) and serology (+): acute or ectopic infection; infection resolved; biliary obstruction; intermittence of egg shedding • stool (+) and serology (+): chronic phase • stool (+) and serology (–): long term chronic phase (negativization of the Ab titre) Treatment11 • triclabendazole 10 mg/kg as a single dose • in case of treatment failure (see below for criteria), re-administer triclabendazole 10 mg/kg, followed by another dose 12–24 hours apart (giving a total dose of 20 mg/kg). Primary criteria of treatment failure This includes any of the following by day 60 after treatment: • detection of eggs in stools • persistence of FES-Ag in stools • crescents seen on ultrasound examination. Additional criteria of failure • persistence of nausea, pruritus, abdominal pain • increase of anti-fasciola antibodies • persistence of eosinophilia • persistence of IgE.

11 Report of the WHO informal meeting on use of triclabendazole in fascioliasis control. WHO, 2006. Available at http://www.who.int/neglected_diseases/preventive_chemotherapy/WHO_CDS_NTD_PCT_2007.1.pdf

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11.12 Filariasis, lymphatic (elephantiasis)8,12 The term ﬁlariasis refers generally to disease caused by the lymphatic-dwelling ﬁlarial worms Wucheria bancrofti, Brugia malayi, and Brugia timori. Wuchereria bancrofti is the most common, and Brugia malayi causes most of the remainder of infections. The infection is transmitted by mosquitoes. There are two principal forms of the infection: one, found in most areas of the world, where microﬁlariae circulate in the blood at night (the highest concentrations being between 10 pm to 2 am); the other, where microﬁlariae circulate continuously in the blood (but with the highest concentrations during the day), found mainly in the Paciﬁc region.

One third of people at risk live in India; one third in Africa; and the remaining third in Asia, the Paciﬁc and the Americas

12 Progress report 2000-2009 and strategic plan 2010-2020 of the global programme to eliminate lymphatic ﬁlariasis: halfway towards eliminating lymphatic ﬁlariasis. WHO, 2010. Available at http://whqlibdoc.who.int/ publications/2010/9789241500722_eng.pdf

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Progressive ﬁlariasis In progressive ﬁlariasis, the clinical features depend on the clinical stage. Key clinical features 1. Asymptomatic amicroﬁlariaemic stage • Some people living in endemic areas have no clinical signs and no detectable microﬁlaria in the blood despite signiﬁcant exposure to infective larvae. Some of these might be immune while others harbour adult parasites in their lymphatics. • Laboratory tests are not able to determine whether such individuals are immune or recently infected, but the circulating antigen test (ICT card test) can identify those with established infections but who are amicroﬁlariaemic. 2. Asymptomatic microﬁlariaemic stage • There may be no symptoms for months to years, despite circulating microﬁlariae. These people are an important reservoir of infection. • Blood surveys and other procedures will detect infection in these people. ° Blood must be taken at the correct time of day, depending on when the maximal microﬁlaramia is for the prevalent species. ° Use Giemsa-stained smears or haemolysed blood in a counting chamber for visualization of the microﬁlaria and species identiﬁcation. ° DEC provocative test (2 mg/kg). After taking DEC, microﬁlariae enter the peripheral blood within 15 minutes. ° Immuno-chromatographic test (ICT), also called the “card test”, to detect ﬁlarial antigen using ﬁnger-prick blood taken any time of day. ° Ultrasonography to visualize living adult worms in the lymphatics of the female breast or scrotum. Adult worms show constant thrashing movements, referred to as the “ﬁlarial dance”. 3. Stage of acute manifestations In the initial months and years following infection, patients may have recurrent episodes of acute inﬂammation in the lymph nodes or vessels of the limb and scrotum. These are generally related to bacterial and fungal superinfections of tissue compromised by reduced lymphatic function. Clinical manifestations: • Filarial fever (ADL-DLA) ° Acute adenolymphangitis (ADL): high fever, lymphatic enlargement in the area where the adult worm resides, transient local oedema, tenderness and redness of overlying skin. Ulceration can occur. ° Dermatolymphangioadenitis (DLA): high fever, chills, muscle aches, and headache with inﬂammatory skin changes in the area of infection. • Lymphangitis • Lymphadenitis • Epididimo-orchitis 4. Stage of obstructive (chronic) lesions • These take 5–15 years to develop. They result from permanent damage to lymph vessels by the adult worms. • Recurrent inﬂammatory reactions to the worms cause dilation of the lymph vessels, which results in oedema. The stages of lymphoedema are outlined below.

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Stages of lymphoedema Stage I • swelling reversible at night • skin folds: absent • appearance of skin: smooth, normal Stage II • swelling not reversible at night • skin folds: absent • appearance of skin: smooth, normal Stage III • swelling not reversible at night • skin folds: shallow • appearance of skin: smooth, normal Stage IV • swelling not reversible at night • skin folds: shallow • appearance of skin: irregular, occasional knobs or nodules Stage V • swelling not reversible at night • skin folds: deep • appearance of skin: smooth or irregular Stage VI • swelling not reversible at night • skin folds: absent, shallow, deep • appearance of skin: wart-like lesions on foot or toes Stage VII • swelling not reversible at night • skin folds: deep • appearance of skin: irregular • needs help with daily activities, dependent on family or health care system

Occult or cryptic ﬁlariasis, presenting as tropical pulmonary eosinophilic (TPE) syndrome Occult ﬁlariasis results from hyperresponsiveness to ﬁlarial antigens. Key clinical features • Classical manifestations: paroxysmal cough and wheeze, scanty sputum, occasional haemoptysis, adenopathy, chronic interstitial lung disease, recurrent low-grade fever, weight loss. • Occurs more commonly in males. Investigations In late disease, the diagnosis is often made clinically because the clinical signs are so suggestive. In early disease, when the differential diagnosis is broad and treatment would be most useful, the following tests may be used to help make a diagnosis. • Extreme elevations of the eosinophil count. • Rarely, demonstration of microﬁlariae in peripheral blood or lung biopsies.

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• Blood must be taken at the correct time of day, depending on when the maximal microﬁlariaemic is for the prevalent species. • Use Giemsa-stained smears or haemolysed blood in a counting chamber for visualization of the microﬁlaria and species identiﬁcation. • DEC provocative test (2 mg/kg). After taking DEC, microﬁlariae enter the peripheral blood within 15 minutes. • Immunochromatographic test (ICT), also called the “card test,” to detect ﬁlarial antigen using ﬁnger-prick blood taken any time of day. • Ultrasonography to visualize living adult worms in the lymphatics of the female breast or male scrotum. Adult worms show constant thrashing movements, referred to as the “ﬁlarial dance”. • Chest X-ray may show interstitial thickening and diffuse nodular mottling of tropical pulmonary eosinophilia. Treatment • Recommended regimen for lymphatic ﬁlariasis in clinical settings: ° Diethylcarbamazine citrate (DEC) 6 mg/kg daily for 12 days OR ° Diethylcarbamazine citrate (DEC) 6 mg/kg plus albendazole 400 mg, as single dose. NB: DEC should not be used in patients with onchocerciasis, due to possible severe adverse reactions. Patients should be examined for co-infection before using DEC. In co-infected patients, the following alternative regimen should be used: ° Ivermectin 200-400 micrograms/kg plus albendazole 400 mg, as single dose NB: ivermectin should not be used in patients with loiasis • Recommended regimen for lymphatic ﬁlariasis in public health interventions: ° Current public health strategies for lymphatic ﬁlariasis elimination rely on preventive chemotherapy with the aim of interrupting transmission of the infection. WHO currently recommends mass drug administration as an annual single dose of DEC 6 mg/kg plus albendazole 400 mg, yearly for 4-6 years in areas where onchocerciasis is not co-endemic with ﬁlariasis. In areas where onchocerciasis is present but loiasis is absent, an annual single dose of ivermectin 200-400 micrograms/kg plus albendazole 400 mg, yearly for 4-6 years, is recommended. • Supportive treatment and prevention of acute ADL attacks ° hydration and rest ° antipyretics and analgesics. • Treatment and prevention of lymphoedema ° Hygiene measures for the affected limb: ◊ wash twice daily with soap and clean water and dry well ◊ keep nails short and clean ◊ elevate the affected limb at night ◊ wear comfortable footwear ◊ prevent and treat entry lesions. ° Frequent exercise of the affected limb to promote lymph ﬂow: ◊ standing on toes, ﬂexing and circling ankles while sitting. ° Use of antibiotic or antifungal agents: ◊ antiseptic, antibiotic, and antifungal creams for small wounds and abrasions ◊ systemic antibiotics or antifungals in severe cases ◊ surgical treatment of hydrocele. Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

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Note: Current public health strategies for lymphatic ﬁlariasis control include interruption of transmission by population-based chemotherapy and vector control. WHO currently recommends mass drug administration as an annual single dose of DEC 6 mg/kg body weight, plus albendezole 400 mg, yearly for 4–6 years in areas where onchocerciasis is not co-endemic with ﬁlariasis. In areas where onchocerciasis is present but loiasis is absent, ivermectin plus albendazole is recommended.

11.13 Gonorrhoea13 Gonorrhoea is a sexually transmitted disease caused by Neisseria gonorrhoeae which can manifest itself in many different ways. The incidence of gonorrhoea is estimated to be very high in developing countries, and is an independent risk factor for the transmission of HIV. Key clinical features In men • Acute urethritis: purulent urethral discharge with pain on urination (dysuria). • Complications: epididymitis, prostatitis, and ﬁstula formation. In women • Mucopurulent discharge from the cervix with dysuria is the most frequent presentation. • Urethritis (inﬂammation of the urethra and often the bladder) causes “internal” dysuria. • Infection of the fallopian tubes (salpingitis), infection of the uterus (endometritis), and pelvic inﬂammatory disease (PID). Fever, abdominal pain, and cervical tenderness are common. • Pelvic peritonitis (with nausea and vomiting) and perihepatitis (jaundice and abdominal pain) are less common. • Infertility due to scarring can occur, and can lead to an ectopic pregnancy. In men or women • Rectum: acute pain, difﬁculty passing stools, purulent discharge. Can occur in women or men who have sex with men. See Section 10.14 Female and male anorectal problems and genital ulcers. • Pharynx: mild symptoms with cervical lymph node enlargement. • Eyes ° In adults, this results from contamination from a genital site. Characterized by swollen eyelids, severe redness, and swelling of the conjunctiva, which can lead to corneal ulcers. ° Complications include corneal ulcers and perforation, infection of the whole eye (panophthalmitis), and blindness. • Disseminated gonococcal infection ° This is the result of the bacteria passing into the blood and infecting distant sites. It is more common in women, and menstruation is a risk factor for dissemination of bacteria. 13 Guidelines for the management of sexually transmitted Infections. WHO, 2003 (updated 2011 version in press). Available at: http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

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° Fever, chills, and painful joints. ° Skin lesions: pustules and papules, often with some blood in them, located on the limbs. ° Septic arthritis: involves 1–2 medium joints (knees, wrists, ankles, elbows). Investigations • The diagnosis is usually clinical. • A Gram stain of urethral discharge in men reveals Gram-negative diplococci in the cells. • A culture can be done, but requires a special medium for inoculation, as well as immediate processing for a good yield. Treatment Resistance to antibiotics has emerged in many parts of the world, particularly to the ﬂuoroquinolone group of antibiotics (e.g. ciproﬂoxacin, oﬂoxacin). Check the latest information for the region in which the infection was acquired before choosing a regimen. Gonorrhoea without dissemination can be treated with: • ceﬁxime 400 mg orally – 1 dose; OR • ceftriaxone 250 mg IM – 1 dose; OR • spectinomycin 2 g IM – 1 dose (alternative); OR • ciproﬂoxacin 500 mg orally as a single dose is also an alternative, but use of this drug should take into account local gonorrhoeal resistance patterns to ﬂuoroquinolones. Ciproﬂoxacin should not be used in pregnancy.

Chlamydia is a common coinfecting agent, and additional treatment directed at Chlamydia is important in patients who receive treatment for gonorrhoea (doxycycline, or azithromycin in pregnant women). (See Section 10.14 Female and male anorectal problems and genital ulcers.)

Guinea worm see Section 10.2 Skin problems 11.14 Hepatitis – viral Acute viral hepatitis can be caused by ﬁve different viruses: hepatitis A, B, C, D, or E. All cause a wide range of symptoms, from asymptomatic infections to fulminant disease. In addition, the blood-borne viruses (B, C, and D) can cause chronic liver disease, leading to cirrhosis and liver cancer. Hepatitis A and E are the most common causes of acute hepatitis. Differential diagnosis Abdominal trauma or aneurysm, small bowel obstruction, cholecystitis, gastritis or peptic ulcer, pancreatitis, liver abscess, autoimmune hepatitis, drug-induced hepatitis including poisoning and alcohol, other viruses (e.g. cytomegalovirus), hepatocellular or pancreatic cancer.

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Transmission Hepatitis A and E Hepatitis B and C Faecally contaminated water Person-to-person Exposure to infected blood or body ﬂuids through sexual contact, blood transfusions, reuse of contaminated needles and syringes, and transmission from mother to child

Clinical features common to all causes of acute hepatitis The clinical features of acute hepatitis are similar for all types of viral hepatitis: • First: nausea, anorexia, vomiting, fatigue, malaise, headaches, muscle aches, sometimes fever • Clinical jaundice develops 1–2 weeks later (yellow skin and eyes and dark urine) • Enlarged, tender liver with right upper quadrant pain and discomfort • Complete recovery can take many months Investigations common to all causes of acute hepatitis Liver function tests • AST and ALT are elevated (at least 3 times higher than normal). The degree of elevation does not correlate well with the severity of disease. • Alkaline phosphatase is usually mildly elevated or remains normal. • Bilirubin levels are elevated ranging from 85–340 umol/litre. Blood count • Low WBC at ﬁrst, followed by an increase in lymphocytes. Coagulation studies • Elevated PT (prothrombin time). The degree of prolongation reﬂects the severity of the liver damage present. Speciﬁc investigations Hepatitis A Hepatitis B Anti-HAV IgM antibodies present within 10 days of the start of illness. Diagnosis of acute hepatitis B requires dosage of HBs Ag and anti-HBc IgM antibodies Screening of high risk groups for hepatitis B requires dosage of HBs Ag and anti-HBs HBs Ag (antigen) Acute infection Chronic infection (carriage) Past infection (cured) Vaccinated + + anti-HBc (total antibodies) +/+ + anti-HBs (antibodies) + +

Ag HBs (antigen) is a marker of carriage and thus contagiousness. Anti-HBc total antibodies is a marker of infection; speciﬁc dosage of IgM is helpful to distinguish between acute (IgM are positive) and chronic (IgM are negative) infection. Anti-HBs antibodies is a marker of recovery from a past infection or immunity due to vaccination. Hepatitis C Anti-HCV antibodies can be detected within 6–8 weeks of the onset of illness.

Treatment common to all causes of acute hepatitis Supportive care (ﬂuid management, and treatment of encephalopathy and coagulopathy in severe acute illness). No speciﬁc drug treatment is indicated.

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Speciﬁc treatment Hepatitis A Hepatitis B Nil Acute hepatitis B infection Ninety percent of cases spontaneously resolve and develop protective antibodies. It is not recommended to give speciﬁc antiviral therapy in acute hepatitis B. Provide supportive treatment: ﬂuid management, and treatment of encephalopathy and coagulopathy in severe acute illness. Chronic active hepatitis B infection There is no agreed deﬁnition of chronic active hepatitis B in resource-limited settings. In developed country settings, the decision to treat is based on the presence of active liver inﬂammation (elevated hepatic enzymes), the level of hepatitis B viral replication (HBV DNA), and evidence of histological active disease (cirrhosis on liver biopsy). The recommended treatment is tenofovir 300 mg daily. Lamivudine (3TC), 100 mg orally daily, may be the only drug available, but its use as monotherapy is associated with the rapid development of resistance. Adefovir 10 mg per day can also be used if it is available, but it is less active than tenofovir. Entecavir (see package insert for dosages) and telbivudine (600 mg/day) also are indicated for the treatment of chronic active hepatitis. In adults and adolescents with chronic active hepatitis B virus and HIV infection, triple combination antiretroviral therapy, with tenofovir plus lamivudine at a dose of 300 mg daily (or emtricitabine 200 mg daily) plus either efavirenz or nevirapine is recommended to avoid the development of HIV resistance. Adefovir, entecavir, and telbivudine should only be used in patients with HIV/HBV coinfection if combined with triple combination antiretroviral therapy for HIV infection. Hepatic ﬂares Hepatic ﬂares (worsening of hepatic enzymes with or without signs and symptoms of liver decompensation, which can be fatal) may occur on treatment (typically within 4–8 weeks of initiation) or if treatment is interrupted. Patient should be monitored more closely in the ﬁrst weeks of treatment and if treatment is stopped. Patients with HIV/HBV coinfection who fail ﬁrst line antiretroviral therapy and switch to second line therapy should retain hepatitis B active drugs (tenofovir and lamivudine) in the second line. Hepatitis C14 Acute hepatitis C infection Supportive care Most people will be asymptomatic 25–30% of people will clear the infection spontaneously Antiviral therapy may be indicated in certain situations, if available. Improved patient outcomes have been reported with early treatment in the ﬁrst 6 months, if the acute phase is not resolving within 3 months. Chronic hepatitis C infection See other sources for the management of chronic hepatitis C with (pegylated) interferon alpha coupled with ribavirin, if available. Treatment criteria include ﬁbrosis on a liver biopsy or other evidence of ﬁbrosis and detectable HCVRNA. Adults and adolescents with acute hepatitis C virus infection should be managed supportively. Patients with genotypes 2 and 3 experience the highest response, with rates in excess of 80%. In patients with genotype 1 response rates are up to 46%.

14 Management of hepatitis C and HIV coinfection. Clinical protocol for the WHO European Region. WHO, 2008. Available at http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hivaids/ publications/pre-2009/hivaids-treatment-and-care2.-clinical-protocols-for-the-european-region/protocol-06.management-of-hepatitis-c-and-hiv-coinfection

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Prevention Hepatitis A Primary prevention Active immunization with hepatitis A vaccine for persons at risk who are older than 12 months. Three vaccinations are required with several schedule options (see package insert). Secondary prevention (Post-exposure prophylaxis for exposed contacts.) Active immunization with hepatitis A vaccine (2 doses give life-long protection). The vaccine is safe in pregnant women and should be given in case of exposure to the disease. A combination hepatitis A and B vaccine is available. Other preventive measures Hand washing and other enteric precautions. Hepatitis B Primary prevention Active immunization with hepatitis B vaccine, anytime from birth. Three vaccinations required with several schedule options (see package insert). Secondary prevention Active immunization with hepatitis B vaccine; OR Passive immunization with immunoglobulin is indicated in two speciﬁc clinical situations: occupational post exposure prophylaxis, or infants born to mothers who are HBsAgpositive. Active and passive immunization have equivalent efﬁcacy in exposed individuals. Active immunization has the added advantage of providing extended protection. The vaccine is safe in pregnant women and should be given in case of exposure to the disease. A combination hepatitis A and B vaccine is available. Other preventive measures Condom use for sexual contact. No sharing of injecting drug equipment. Harm reduction interventions including opioid substitution therapy. Hepatitis C No vaccine is available. Injecting drug users are at highest risk. Men who have sex with men are at highest risk of sexual transmission. More common in areas with high prevalence of injecting drug users, tribal scarring, tattooing, and unscreened blood products Prevention interventions include condom use, harm reduction measures, and blood product safety.

Note on hepatitis E Transmitted through drinking contaminated water (faecal-oral route) and is a signiﬁcant cause of acute hepatitis, particularly in East Africa and Asia. Personto-person transmission is possible. Chronic hepatitis E is rare. Pregnant women are at high risk of acquiring the disease, and it is also more frequently fulminant in the third trimester of pregnancy. There is a high risk of mother-to-child transmission. Pregnant women and young children are at high risk for poor outcomes.

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11.15 Herpes simplex virus (HSV) This virus causes a variety of infections of the skin and mucous membranes, as well as the central nervous system, and occasionally of internal organs. Transmission happens through close contact with infected persons, even if they do not have any obvious lesions at the time, but are shedding the virus in their mucosa. There are two subtypes of HSV: HSV-1 and HSV-2. Both of these viruses cause similar illnesses, although HSV-1 is more often found in the mouth and face, and HSV-2 is associated with genital disease. Both viruses become latent in the nerve roots and can reactivate at any time. Therefore, infection with these viruses is life-long. Key clinical features • First episode: fever, malaise, muscle aches, swollen regional lymph nodes. Painful small vesicles that progress to ulcers in the affected regions. • Recurrent episodes: pain, groups of vesicles that can join to form small or large ulcers. • Herpes simplex oesophagitis can present with pain and difﬁculty swallowing. (See DDx tables in 10.7b.) Complications or severe disease • Eye infection: burning, blurring of vision, swelling of the conjunctiva leading to corneal scarring, and eventually blindness. (See Section 10.12.) • Nervous system: ° encephalitis – fever with focal neurological signs and symptoms; ° facial nerve palsy (drooping of one side of the face with inability to close the eye) can also occur during reactivation; ° autonomic dysfunction with hyperesthesia or anaesthesia of the perineal region and urinary retention can occur during primary genital HSV infection. • Visceral infections: stomatitis, oesophagitis, pneumonitis, and hepatitis can occur. Investigations • Diagnosis is most often clinical due to the typical, vesicular skin lesions involved. • WBC may be elevated. • Light microscopy with Tzanck’s preparation of the base of a lesion shows multinucleated cells with inclusion bodies. • In encephalitis, CSF shows predominantly lymphocytes; the red blood cell count and protein level are often elevated. The gold standard for establishing the diagnosis is the detection of herpes simplex virus DNA in the CSF by polymerase chain reaction (PCR), if available. Treatment Symptomatic management with pain control and a fever-reducing agent is recommended, as well as antiviral therapy, especially in early presentations or if it is disseminated disease. Sometimes, treatment for 2 weeks or longer is necessary in disseminated disease. Primary treatment for oral or genital herpes: • aciclovir 400 mg 3 times daily, or 200 mg 5 times daily for 7–10 days (longer if new lesions appear during treatment or if healing incomplete; this regimen applies to ﬁrst presentation and recurrent disease).

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Prophylaxis for recurrent herpes simplex (chronic suppression): • aciclovir 200 mg 3 to 5 times daily OR 400 mg 2 times daily • interrupt prophylaxis every 6–12 months for reassessment. For encephalitis or hepatitis: • aciclovir IV 10 mg/kg 3 times daily for 14-21 days. Note: Infuse aciclovir slowly and with ﬂuid bolus to avoid crystalluria and renal failure, and adjust dosages in case of renal impairment. • Start ART For oesophagitis: • In patients who are NOT immunocompromised: aciclovir 200 mg orally 5 times daily or 400 mg PO 3 times daily for 7 to 10 days (may be shortened if symptoms are improving). • In patients who are immunocompromised: aciclovir 400 mg orally 5 times daily for 14–21 days.

11.16 Histoplasmosis This is an infection caused by the fungus Histoplasma capsulatum that is found in moist surface soil containing bat or bird droppings. The infection is acquired through inhalation. Patients can become ill after acute infection, or due to reactivation of a latent infection. Histoplasmosis is endemic in many regions worldwide, and also in Africa and Asia. Histoplasmosis generally occurs late in the course of HIV infection when the CD4 count is <100. Key clinical features • In the immunocompetent host: mild symptoms in a majority of cases include cough, fever, and malaise. • In the chronic form: there is a gradual onset of productive cough, weight loss, and night sweats. • In the disseminated form: fever, weight loss, enlarged liver, spleen, and lymph nodes, anaemia, and papular skin lesions can also occur. Pulmonary involvement is observed in 50% of cases. It is important to differentiate histoplasmosis from PCP pneumonia (see Section 10.6.3 Pneumocystis jiroveci pneumonia), and TB (see Section 15). Investigations • Laboratory ﬁndings are non-speciﬁc. • A deﬁnitive diagnosis is by a culture of blood or affected tissue, but takes 4–6 months for a result. • Histoplasma antigen can be tested for in urine or blood and has high sensitivity, but the test is often unavailable in resource-limited settings. • Direct microscopy on Wright-stained smears is a cheap, easy to conduct method, but has a low sensitivity (less than 10%). If combined with blood cultures, it has sensitivity of up to 88%. • If there are pulmonary symptoms, the chest X-ray is abnormal in 50–70% of cases, showing mainly a diffuse interstitial image or reticulo-nodulair inﬁltrates. However, other abnormalities also are possible. Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011 Histoplasmosis

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Treatment • All PLHIV with histoplasmosis should be treated with ART. If there are mild clinical symptoms, and a single focus of disease other than the CNS: • initially, itraconazole 200 mg 3 times daily for 3 days; then itraconazole 200 mg twice daily with food for 6–12 months. • ﬂuconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. In severely ill patients with or without immunosuppression, the ﬁrst recommended option is: • amphotericin B 0.7 mg/kg IV until clinical improvement (usually at least 14 days), and then continue with itraconazole 200 mg twice daily for 6–12 months. • If there is CNS involvement: • same as severely ill patients, except that amphotericin B treatment should be continued for at least 4 to 6 weeks. Note: During treatment with amphotericin B, check the serum creatinine and electrolytes regularly. Also, be aware of a possible reaction during the infusion (fever, chills) which can be prevented by pre-treatment with paracetamol or corticosteroids. See advice on amphotericin administration in Section 11.5 and 8.4. Secondary prevention Itraconazole 200 mg daily needs to be administered for at least 1 year, and can be discontinued if the CD4 count rises above 150. If the CD4 count drops again, itraconazole therapy must be resumed. Note: Fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg IV given weekly as maintenance therapy to prevent relapse.

11.17 Inﬂuenza see Section 10.6 Chest symptoms Inﬂuenza infection is caused by one of three viruses – inﬂuenza A, B, or C – with inﬂuenza A and B being responsible for the vast majority of the 200 000 to 500 000 deaths attributed to annual inﬂuenza infections globally. In the temperate zones of the northern and southern hemispheres, inﬂuenza cases peak in the winter months, but in the tropical and subtropical zones, cases appear over much longer periods of time. There are three kinds of outbreaks in humans: • Seasonal inﬂuenza is caused by strains of inﬂuenza that circulate continuously in the human population. A portion of the population thus has pre-existing immunity due to prior exposure or exposure to similar inﬂuenza strains and is, therefore, protected from infection. Currently, there are two inﬂuenza A viruses (H1N1 and H3N2) and one inﬂuenza B virus that are responsible for annual epidemics.

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• An inﬂuenza pandemic occurs when an inﬂuenza A virus strain that is antigenically different from the seasonal virus strains enters the human population. There have been four documented pandemics in the past 100 years (1918, 1957, 1968, and 2009). The lack of pre-existing immunity to the pandemic strain in the human population leads to a substantial increase in the total number of inﬂuenza cases and, therefore, the number of inﬂuenzarelated deaths, even if the newly emerged virus does not cause more severe disease than seasonal inﬂuenza. • Outbreaks of inﬂuenza occur where limited numbers of humans in deﬁned geographical areas are exposed to novel inﬂuenza viruses. The ongoing outbreaks of avian (H5N1) inﬂuenza are an example. Key clinical features Human infection with inﬂuenza virus can vary from asymptomatic infection to uncomplicated upper respiratory tract disease to serious complicated illness that may include exacerbation of other underlying conditions and severe viral pneumonia with multi-organ failure.

Uncomplicated inﬂuenza: • Inﬂuenza-like illness (ILI) symptoms include: sudden onset of fever (often preceding respiratory symptoms) and cough, sometimes accompanied by sore throat, nasal congestion, or rhinorrhoea. Systemic symptoms such as headache, muscle or joint pain, and malaise may occur. Shortness of breath and dyspnoea are signs of severe inﬂuenza (see below). • Gastrointestinal illness may also be present, such as diarrhoea or vomiting, especially in children. Dehydration is a sign of severe inﬂuenza (see below). • Some patients may experience atypical symptoms and may not have fever (e.g. elderly or immunosuppressed patients).

Complicated or severe inﬂuenza • Shortness of breath, tachypnoea, hypoxia, or chest X-ray with evidence of pneumonia; central nervous system (CNS) involvement (e.g. encephalopathy, encephalitis), severe dehydration, or presenting secondary complications such as renal failure, multi-organ failure, and septic shock. May include rhabdomyolysis and myocarditis. • Exacerbation of underlying chronic disease, including asthma, COPD, chronic hepatic or renal insufﬁciency, diabetes, or other cardiovascular conditions (e.g. congestive cardiac failure). • Any other condition or clinical presentation requiring hospital admission for clinical management (including bacterial pneumonia with inﬂuenza). • Any of the signs and symptoms of progressive disease listed below. Signs and symptoms of progressive disease Patients who present initially with uncomplicated inﬂuenza may progress to more severe disease. Progression can be rapid (i.e. within 24 hours). The following are some of the indicators of progression that would necessitate an urgent review of patient management. • Symptoms and signs suggesting hypoxaemia (SpO2 <90%) or hypotension (SBP <90), such as shortness of breath (with activity or at rest), difﬁculty in breathing, tachypnoea, presence of cyanosis, other signs of respiratory distress, bloody or coloured sputum, chest pain.

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• Symptoms and signs suggesting CNS complications, such as altered mental status, unconsciousness, drowsiness, or difﬁculty waking, and recurring or persistent convulsions (seizures), confusion, severe weakness, or paralysis. • Clinical evidence of sustained virus replication or invasive secondary bacterial infection based on laboratory testing or clinical signs (e.g. persistent or recurrent high fever and other symptoms beyond 3 days without signs of resolution). • Symptoms and signs of severe dehydration, such as decreased activity, dizziness, decreased urine output, and lethargy. Risk factors for complicated or severe disease Certain patients with inﬂuenza virus infection are recognized to be at higher risk of developing severe or complicated illness. These include the following groups: • Pregnant women. • Persons of any age with chronic pulmonary disease (e.g. asthma, COPD), chronic cardiac disease (e.g. congestive cardiac failure), metabolic disorders (e.g. diabetes), chronic renal disease, chronic liver disease, certain neurological conditions (including neuromuscular, neurocognitive, and seizure disorders), haemoglobinopathies or immunosuppression, whether due to primary immunosuppressive conditions, such as HIV infection, or secondary conditions, such as immunosuppressive medication or malignancy. • Persons aged 65 years and older. • A higher risk of severe complications from pandemic (H1N1) 2009 virus infection was observed in individuals who were obese and from disadvantaged populations. Investigations • Treatment should be based on clinical diagnosis and suspicion of inﬂuenza infection based on local epidemiology and should not be delayed for results of laboratory investigations. • Point of care rapid diagnostic test results may have a high false negative rate.15 ° For individual patient management, because of low sensitivity, a negative result cannot exclude pandemic or seasonal inﬂuenza virus infection. Other information including surveillance data on circulating inﬂuenza viruses; symptoms and clinical ﬁndings; travel history or exposure to conﬁrmed or probable inﬂuenza cases is required to aid interpretation of a result to optimally inform patient management decisions. A true negative result is most likely when inﬂuenza is uncommon in the community (in the beginning and end of an outbreak) whereas as a false positive is most likely when inﬂuenza is common in the community (at the peak of an outbreak) or when the RIDT test is damaged. ° For outbreak management, rapid diagnostic tests can help to quickly identify inﬂuenza A cases in institutions, schools, or communities with reports of increasing incidence of inﬂuenza-like illness. They can also help to facilitate timely implementation of interventions for institutional control of outbreaks and inform public health guidance. Whenever possible, at least some of the positive specimens should be conﬁrmed by one of the more sensitive and speciﬁc methods in order to better characterize the virus and monitor viral evolution. 15 Use of inﬂuenza rapid diagnostic tests. WHO and TDR, 2010. Available at http://whqlibdoc.who.int/ publications/2010/9789241599283_eng.pdf

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• A markedly elevated white cell count may mean that the patient has a secondary bacterial infection. Treatment16 For the management of patients with severe respiratory distress or shock and suspected severe inﬂuenza infection, see Sections 3.1.4 and 3.2.1-3.2.3.

Seasonal or pandemic inﬂuenza infection For patient with mild (uncomplicated) illness AND NOT from high risk groups treat symptomatically: • rest and oral hydration • paracetamol as needed • avoid aspirin in patients less than 18 years due to risk of Reye syndrome Give antiviral treatment with oseltamivir 75 mg orally twice daily as soon as possible for patients with the following indications: • patients with mild (uncomplicated illness) AND in a group known to be at higher risk of developing severe or complicated illness; • patients who have severe or progressive clinical illness. Other considerations • When the clinical course remains severe or progressive, despite 5 or more days of antiviral treatment, antiviral treatment should be continued without a break until virus infection is resolved or there is satisfactory clinical improvement. • Consider higher dosing in patients with critical illness (e.g. severe pneumonia or shock) or with severe immunocompromising conditions: oseltamivir 150 mg orally twice daily. • If bacterial pneumonia is also suspected, give empirical antibiotic treatment as appropriate for community-acquired pneumonia as discussed in Section 10.6. Inﬂuenza pneumonia and bacterial pneumonia are difﬁcult to distinguish, so empirical treatment of both infections is a common practice until the clinical course and diagnostic tests allow a narrowing of antimicrobial coverage.

For patients with a (H5N1) virus infection17 Treat ALL patients with infection (this includes mild infection) because unlike seasonal inﬂuenza, H5N1 infection progresses rapidly and has a high case fatality rate. • Give oseltamivir 75 mg orally twice daily. • Monitor vitals signs for signs of clinical deterioration. Prevention • Inﬂuenza vaccine is recommended, especially for high risk groups. • Infection prevention and control – see Section 6.

16 WHO guidelines for pharmacological management of pandemic inﬂuenza A(H1N1) 2009 and other Inﬂuenza viruses. Revised February 2010. Part I Recommendations. Available at http://www.who.int/csr/resources/ publications/swineﬂu/h1n1_guidelines_pharmaceutical_mngt.pdf 17 Clinical management of human infection with avian inﬂuenza A (H5N1) virus. WHO Updated advice, 15 August 2007. Available at http://www.who.int/inﬂuenza/resources/documents/ClinicalManagement07.pdf

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Surveillance18,19 • Become familiar with the local and national inﬂuenza surveillance system. • If there are unusually clustered cases of disease (e.g. more cases of severe pneumonia or ILI), disease patterns (e.g.a shift in age group of severe inﬂuenza, or a change in the pattern of inﬂuenza-associated diseases) or unexpected deaths (e.g. an increase in apparent mortality from pneumonia), then report to the designated public health ofﬁcial. • Reporting these events is an important part of the early warning system of surveillance and should trigger an investigation.

11.18 Isosporiasis This is a diarrhoeal illness caused by Isospora belli. In immunocompetent hosts, it usually causes a self-limited, acute infection. In the immunocompromised hosts, it can cause severe, chronic or recurrent diarrhoea. Key clinical features • Sudden onset of fever, abdominal pain, vomiting. • Non-bloody, watery diarrhoea that can last for weeks or months. • Wasting if diarrhoea is persistent. Investigations • Large oocysts on stool examination with modiﬁed acid-fast stain. Treatment • Fluids for dehydration (see Section 10.7 Abdominal complaints). • Symptomatic relief (also see supportive measurement under cryptosporidium infection). • If immunosuppression, give antibiotic therapy: ° cotrimoxazole 1 DS (double strength) tablet (960 mg) orally twice daily for 10 days to 4 weeks; OR ° if contraindication to cotrimoxazole, ciproﬂoxacin 500 mg twice daily for 7 days (less efﬁcacious than cotrimoxazole). • Start ART. Prevention Cotrimoxazole prophylaxis reduces the risk of isosporiasis, in PLHIV, at 1 DS daily or 1 DS 3 times weekly until CD4 is higher than 200.

18 A practical guide to harmonizing virologic and epidemiological inﬂuenza surveillance. WHO Western Paciﬁc Region, November 2008. Available at http://www.wpro.who.int/NR/rdonlyres/55E9226F-C588-4618-87FC0D286C96DA8F/0/GuideToHarmonizingInﬂuenzaSurveillancerevised2302.pdf 19 Surveillance Recommendations for Member States in the Post Pandemic Period. WHO, 12 August 2010. Available at http://www.who.int/csr/resources/publications/swineﬂu/surveillance_post_pandemic.pdf

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11.19 Kaposi sarcoma Kaposi sarcoma (KS) is a tumour that can involve all organs, but is found mainly in skin, mucous membranes, and lymph nodes. In the case of visceral involvement, the lungs and the gastrointestinal tract are the most common locations. KS is a WHO clinical stage 4 condition. It is associated with human herpes virus 8 (HHV-8), or Kaposi sarcoma herpes virus (KSHV). Before the introduction of ART, KS was treated with chemotherapy for palliative purposes. The use of ART has brought about a decline in the incidence of KS. This decline is due to immune restoration and immunological control of KSHV. As such, AIDS-related KS can be considered an opportunistic infection. Visceral KS can be life-threatening due to GI and pulmonary blood loss. Key clinical features In general, KS is diagnosed clinically due to the presence of typical skin lesions. • Skin lesions ° Inspect the skin for macular and papular purple lesions or nodular tumours. KS presents as dark, patchy, painless swellings or non-pruritic nodules that are located mainly on lower limbs, face (nose), oral mucosa, and genitalia. ° The skin lesions are often preceded or accompanied by lymphoedema of the face, lower limbs, or genitalia. Inspect the face, genitals, and limbs for (painful) swelling. • Gastrointestinal KS lesions ° Can often be present without causing symptoms. ° In case of bleeding: haematemesis (vomiting of blood or coffee-ground like material) or melena (black, tarry stools). ° In case of ulceration: pain along the GI tract. ° Check oral cavity and anal region for lesions. In case of massive GI bleeding, a digital rectal examination can reveal blood or melena. • Pulmonary KS lesions ° Can often be present without causing symptoms. ° Dyspnoea, sometimes haemoptysis. Note: Always enquire about steroid use in the past. Steroids are frequently used in HIV-infected patients (e.g. for immune thrombocytopenic purpura and Pneumocystis jeroveci pneumonia). Corticosteroid therapy in HIV-infected persons can result in induction of KS or exacerbation of pre-existing KS. For differential diagnosis, see the table below and Section 10.2 Skin. Investigations • KS can be conﬁrmed by biopsy. • Perform a chest X-ray to exclude pulmonary KS lesions, as initially pulmonary KS lesions may be asymptomatic, but they are important in staging the patient. A chest X-ray may show reticulo-nodular inﬁltrates, enlargement of the mediastinal shadow, and sometimes a pleural effusion. Staging is based on whether lesions are conﬁned to the skin, or if there is mucosal and visceral involvement (T), and whether the patient has constitutional symptoms or not (S) (See Table: Staging of AIDS KS on next page). Staging helps to deﬁne the patient’s prognosis and the indication for chemotherapy. A more advanced stage has a worse prognosis. A patient with T0S0 or T0S1 disease in general can be

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treated with ART alone, while patients with T1S0 and T1S1 disease have an indication for chemotherapy. Staging of AIDS KS T0 = lesions conﬁned to the skin or lymph nodes, or minimal oral disease (non-nodular single KS conﬁned to the palate) S0 = No history of OI or oral thrush; no “B” symptoms (unexplained fever, night sweats, >10% involuntary weight loss, or diarrhoea >2 weeks); performance status ≥70 (Karnofsky) T1 = tumour-associated oedema or ulceration; extensive oral KS; gastrointestinal KS; KS in other non-nodal viscera S1 = history of OI or oral thrush; “B” symptoms; performance status <70; other HIV-related illness, (e.g. neurological disease, lymphoma)

Treatment Refer the patient with advanced disease (stage T1) to a centre with experience in KS treatment. Types of treatment include • ART alone: In patients who present with limited disease (T0S0), there is no indication to start chemotherapy, and they respond well to ART alone (complete remission of 80%). In patients with advanced disease, ART on its own can also be an effective treatment. It should not be withheld from patients in the absence of chemotherapy. Initiation of ART should occur regardless of the CD4 count. ART may be associated with an initial worsening of the KS lesions as part of IRIS. IRIS usually occurs in the ﬁrst 2 months after the introduction of ART. • Local therapy: Local treatment modalities are useful for managing symptomatic bulky KS lesions. Radiation therapy is effective as local therapy, and is useful to treat ulcerating or bleeding lesions, or solitary symptomatic lesions that are not responding to ART alone. Other options for local therapy are surgical excision, cryotherapy with liquid nitrogen, or intralesional injections with a chemotherapeutic agent. • Chemotherapy ° Chemotherapy must always be combined with ART. Continue prophylaxis with cotrimoxazole in patients on chemotherapy. ° Drugs with proven efﬁcacy include vinblastine, vincristine, dacarbazine, doxorubicin, and actinomycin D. Alkylating agents (e.g. cyclophosphamide, chlorambucil, bleomycin, doxorubicin, etoposide) also may be of value. Multiagent intravenous chemotherapy, rather than single-agent usage, is preferred for disseminated aggressive Kaposi sarcoma. ° Chemotherapy is indicated in patients with: ◊ rapidly progressive or extended cutaneous disease (more than 25 lesions) causing pain, oedema, or skin ulceration (T1 disease); ◊ visceral involvement (T1 disease); ◊ extensive disease refractory to ART alone. Timing of treatment The optimal moment to start ART in patients with KS who require chemotherapy is unknown. It is probably best to start ART soon after, or concurrently with the chemotherapy, especially in patients with advanced immune deﬁciency. Be aware, however, that patients may develop IRIS to the KS lesions, particularly patients with large lesions, and patients with lesions in the gastrointestinal or respiratory tract.

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Assessment of treatment response Once patients respond to therapy (partial or complete), the chemotherapy can be interrupted while immune restoration does the work, even in patients with pulmonary KS.

11.20 Leishmaniasis (kala-azar, black fever, dumdum fever, Aleppo boil)20 Leishmaniasis is a disease caused by infection with protozoa called Leishmania, and is transmitted to humans by infected sand ﬂy bites, and in some cases by contaminated blood transfusions. The two clinical types – cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) – are outlined below.

11.20.1 Cutaneous leishmaniasis (CL)

In the Eastern hemisphere CL is caused by L. infantum, L. major, L. tropica, and L. aethiopica. In the Western Hemisphere CL is caused by L. braziliensis, L. mexicana, and L. guyanensis complex. L. donovani, L. infantum, and L. chagasi usually cause visceral disease but can also cause cutaneous disease. Mucosal lesions are mainly due to L. braziliensis and L. panamensis.

20 Control of the leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22-26 March 2010.(WHO Technical Report Series 949). Available at http://whqlibdoc.who.int/trs/WHO_ TRS_949_eng.pdf

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Key clinical features Cutaneous leishmaniasis (CL) is a disease of the skin and mucous membranes. There are different clinical forms of CL: localized CL, diffuse CL, and mucosal leishmaniasis. The typical features of each are outlined below. Cutaneous lesions • Occur mainly on exposed body parts (face, neck, arms, legs). • May be single or multiple with regional lymph node enlargement. • Are usually painless. • If secondarily infected, they can be painful and itchy. Localized cutaneous leishmaniasis • Papule at the site of the bite (like an insect bite). • If papule persists, it develops into either: ° a small nodule ° an ulcer with a ﬂat base and raised border ° the nodulo-ulcerative form (broad-based ulcer with crust). • Leishmaniasis recidivans is localized CL that is characterized by a chronic solitary lesion that expands slowly and often reoccurs. The lesion can continue for many years, causing severe disﬁgurement. Diffuse cutaneous leishmaniasis • Coalescence of papules and nodules to form plaques. • Chronic and very difﬁcult to treat. Mucosal leishmaniasis • Is the most severe form of CL, causing severe disﬁgurement and mutilation of the face. • Nasal lesions cause discharge, bleeding, obstruction, deformity, and destruction of cartilage with collapse of the nose. • Oropharyngeal lesions: difﬁculty chewing and swallowing, bleeding gums, toothache, loose teeth, perforation of the hard palate. • Involvement of mucosa can follow: ° primary infection (with L. major or L. donovani); OR ° dissemination of cutaneous leishmaniasis; OR ° treatment for visceral leishmaniasis (post-kala-azar dermal leishmaniasis). Investigations Demonstration of the parasite: • microscopic identiﬁcation of intracellular amastigote in Giemsa-stained specimens from lesions; • culture of extracellular promastigote on specialized media; • Montenegro test (leishmanin skin test): ° intradermal injection of killed amastigotes, measure skin induration after 48–72 hours (more than 5 mm is positive); ° useful in established disease; • PCR on a skin biopsy; • serology tests are of little use because of very low antibody levels in CL.

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Treatment • Spontaneous healing is mainly observed in old world CL after several months (L.major: 40-70% after 3 months, 100% after 12 months; L. tropica: 1-10% after 3 months, 68% after 12 months, close to 100% after 3 years); • The decision to treat is based on the species, the potential for dissemination, as well as the location, number, and size of the lesions, and previous treatment used if any. With the exception of L.major, CL of the old World is commonly treated with local treatment (for exceptions see below). Because of the risk of developing mucocutaneous leishmaniasis, CL of the New World is commonly treated with systemic treatment. • Solitary lesions are common. • Small, localized lesions usually heal without treatment other than wound care. • Diffuse and mucosal lesions are usually severe and difﬁcult to treat. Arrange referral to designated leishmaniasis treatment centres if possible. • Local treatment This needs to be adapted according to species, national guidelines and the clinical characteristics – site, size, number of lesions, whether open or nodular, whether superinfected, and the immune status of patients. ° local inﬁltration (1 to 5 intralesional injections, every few days or weekly) with pentavalent antimonials, with or without cryotherapy (preferred); OR ° paromomycin ointment (15% paromomycin plus 12% methyl benzethonium chloride ointment twice daily for up to 20 days); OR ° thermotherapy (1 or 2 applications of localized heat (55°C during 5 minutes) using a thermal device), with or without cryotherapy with liquid nitrogen (-195°C) applied to the lesion once or twice weekly up to 6 weeks. • Systemic treatment ° pentavalent antimonials (meglumine antimoniate or sodium stibogluconate) 20 mg/kg daily IV/IM for 21 days; OR ° liposomal amphotericin B 3 mg/kg for 6 doses (up to 30 mg/kg total dose if needed); OR ° pentamidine – only recommended if no other treatment available, due to severe side-effects and toxicity (except for L. guyanensis for which it is the preferred choice); OR ° miltefosine 150 mg daily (or 2.5 mg/kg daily if weight less than 25 kg) for 28 days; OR ° ﬂuconazole 200 mg orally daily for 6 weeks; OR ° ketoconazole 600 mg orally daily for 28 days.

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11.20.2 Visceral leishmaniasis (kala-azar, VL)

VL is found in 98 countries or territories with 90% of the cases occurring in Bangladesh, Brazil, Ethiopia,India, Nepal, and Sudan.

Key clinical features Visceral leishmaniasis is a systemic disease, however infection is often not clinically apparent. Malnutrition and HIV infection predispose to the development of overt clinical disease (see Section 11.20.3 HIV/leishmaniasis coinfection below). Possible clinical presentations include: • fever – irregular and prolonged (more than 2 weeks) • weight loss which can be severe with wasting • enlarged spleen (often massive) and enlarged liver • cough, diarrhoea, right upper quadrant pain • generalized lymphadenopathy • anaemia, leukopenia, thrombocytopenia • skin lesions that occur after treatment – post-kala-azar dermal leishmaniasis – see above. Investigations • blood investigations: ° low platelets or pancytopenia (in advanced disease); ° low albumin; 430 Leishmaniasis Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

• demonstration of the parasite: ° microscopic identiﬁcation of parasite on Giemsa-stained smear from blood, bone marrow, lymph nodes, or spleen (splenic puncture requires training and a blood transfusion service); ° culture of organism from aspirated or biopsied material; • serology; • rk39 rapid diagnostic tests depending on the sensitivity of the test locally; • direct agglutination test (DAT) by a trained laboratory technician; • negative serology result does not rule out leishmaniasis in HIV patients due to low sensitivity. Treatment Mortality in untreated patients is very high (almost certain), so effective therapy is very important. The treatment of visceral leishmaniasis depends on geographic location, the species involved, and other conditions of the patient (e.g. age, pregnancy, HIV coinfection). Preferred treatment can change rapidly based on new combination drug regimens and sensitivity of the parasite. For detailed information refer to the WHO Technical Report Series 949, Control of the leishmaniases.20 Treatment options for visceral leishmaniasis and post-kala-azar dermal leishmaniasis Geographic area and disease form Indian subcontinent (Bangladesh, Bhutan India, Nepal) Anthroponotic visceral leishmaniasis caused by L. donovani 1st preference Liposomal amphotericin B: 3–5 mg/kg over 3–5 days up to a total dose of 15 mg/ kg by infusion or 10 mg/ kg as a single dose by infusion Alternative options by rank of preference 1. Combinations (co-administered) • liposomal amphotericin B (5 mg/kg by infusion, single dose) plus miltefosine (7 days, as below) • liposomal amphotericin B (5 mg/kg by infusion, single dose) plus paromomycin (10 days, as below) • miltefosine plus paromomycin, both for 10 days, as below • amphotericin B deoxycholate: 0.75–1.0 mg/kg per day by infusion, daily or on alternate days for 15–20 doses 2. Miltefosine; for people aged ≥12 years and <25 kg body weight, 50 mg/day; 25–50 kg body weight, 100 mg/day; >50 kg body weight, 150 mg/day; orally for 28 days; or paromomycin: 15 mg (11 mg base) per kg body weight per day IM for 21 days 3. Pentavalent antimonials: 20 mg Sb5+/kg per day IM or IV for 30 days in areas where they remain effective: Bangladesh, Nepal, and the Indian states of Jharkhand, West Bengal, and Uttar Pradesh.

East Africa (Eritrea, Ethiopia, Kenya, Somalia, Sudan, and Uganda) and Yemen Visceral leishmaniasis caused by L. donovani

Combination: pentavalent antimonials (20 mg Sb5+/ kg per day IM or IV) plus paromomycin (15 mg (11 mg base) per kg per day IM for 17 days)

1. Pentavalent antimonials: 20 mg Sb5+/kg per day 2. IM or IV for 30 days 3. Liposomal amphotericin B: 3–5 mg/kg per day by infusion over 6–10 days up to a total dose of 30 mg/kg 4. Amphotericin B deoxycholate: 0.75–1.0 mg/kg per day by infusion, daily or on alternate days, for 15–20 doses 5. Miltefosine orally for 28 days at dosage as above

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Mediterranean basin, Middle East, Central Asia, South America Visceral leishmaniasis caused by L. infantum Post-kala-azar dermal leishmaniasis in East Africa

Liposomal amphotericin B: 3–5 mg/kg per day in 3–6 infusions, up to a total dose of 18–21 mg/kg Pentavalent antimonials (meglumine antimoniate or sodium stibogluconate): 20 mg Sb5+/kg per day IM or IV for 30–60 days, when indicated Liposomal amphotericin B: 3–5 mg/kg per day in 3–6 infusions, up to a total dose of 18–21 mg/kg, or pentavalent antimonials: 20 mg Sb5+/kg per day IM or IV for 28 days

Pentavalent antimonials: 20 mg Sb5+/kg per day IM or IV for 28 days Amphotericin B deoxycholate: 0.75–1.0 mg/kg per day by infusion, daily or on alternate days for 20–30 doses, for a total dose of 2–3 g Liposomal amphotericin B: 2.5 mg/kg per day by infusion for 20 days, when indicated

Post-kala-azar dermal leishmaniasis in Bangladesh, India, and Nepal

Amphotericin B deoxycholate: 0.75–1.0 mg/kg per day by infusion, daily or on alternate days for 20–30 doses, for a total dose of 2–3 g

11.20.3 Leishmania/HIV coinfection The HIV pandemic has modiﬁed the natural history of leishmaniasis disease with a dramatic impact on its clinical course and response to treatment. Coinfection has been reported in 34 countries worldwide. Currently 2%–12% of all reported VL cases are in people coinfected with HIV. Impact of coinfection Both HIV and VL target similar immune cells, causing damage to the immune system and a drop in CD4 count. Coinfected patients often present late with low CD4 counts and high HIV viral loads. Coinfection increases the risk of developing overt VL disease, and reduces response to treatment. The risk of VL relapse is increased with a low CD4 count, and VL relapse inhibits CD4 recovery in a patient on ART. Key clinical features Coinfected patients often present atypically, especially those with lower CD4 counts. CL disseminates to the viscera, and VL manifests cutaneously more frequently in coinfected patients. VL causes progression to AIDS and is an AIDSdeﬁning illness that warrants ART. CL can present with more than one clinical form in the same patient (polymorphism). Investigations Serological or immune-based tests have limited use in coinfected patients due to low antibody levels. However, antigen detection tests are promising because of the high parasite burden in these patients. PCR on blood or bone marrow is highly sensitive, but not available in most resource-limited settings. Treatment All drugs are less effective, and most patients will relapse within 6 months. With each relapse, the patient responds less to treatment until eventually no drug will work. Coinfected patients are more likely to have side-effects from treatment, and there is overlapping toxicity with drugs used for treatment of VL, HIV, and TB. Amphotericin B deoxycholate or lipid formulations should be considered ﬁrst and pentavalent antimonials only in areas of no signiﬁcant resistance and when lipid

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formulations of amphotericin B are unavailable or unaffordable. Lipid formulations infused at a dose of 3–5 mg/kg daily or intermittently for 10 doses (days 1–5, 10, 17, 24, 31, and 38) up to a total dose of 40 mg/kg are recommended. Secondary prophylaxis is given to prevent relapses and prolong disease-free intervals. There is some concern about the development of drug resistance. Secondary prophylaxis: • is for patients coinfected with HIV to prolong disease-free intervals; • can be stopped if CD4 count is more than 200 for more than 6 months; • options for secondary prophylaxis include: ° liposomal amphotericin B 3–5 mg/kg per dose once every 3 weeks; OR ° liposomal amphotericin B 3–5 mg/kg per dose once every 3 to 4 weeks; OR ° pentavalent antimonials 20 mg/kg per day every 3 to 4 weeks; OR ° amphotericin B 0.75–1.0 mg/kg per day every 3 to 4 weeks; OR ° miltefosine in repeated 28-day courses (dosing in Table: Treatment options for visceral leishmaniasis and post-kala-azar dermal leishmaniasis) ; OR ° pentamidine 4 mg/kg per dose (300 mg) every 3 to 4 weeks. Prognosis Without ART, the prognosis is very poor, especially in patients with AIDS, other OIs, low CD4 counts, low platelets, or frequent relapses. The introduction of protease inhibitors has resulted in fewer symptoms, fewer relapses and improved survival.

11.21 Leprosy Leprosy is a chronic infection caused by Mycobacterium leprae. It most commonly manifests itself in the skin, peripheral nerves, eyes, and upper respiratory tract. This disease leads to signiﬁcant deformity that has historically resulted in social isolation and stigmatization of patients. The most effective way of preventing disabilities in leprosy, as well as reducing further transmission of the disease, lies in early diagnosis and treatment with multidrug therapy (MDT). Most previously highly-endemic countries have now reached elimination (deﬁned as a registered prevalence rate of less than 1 case per 10 000 population). The few countries where leprosy is still a problem are very close to eliminating the disease. However, pockets of high endemicity still remain in some areas of Angola, Brazil, Central African Republic, Democratic Republic of Congo, India, Madagascar, Mozambique, Nepal, and the United Republic of Tanzania. Transmission can occur through droplets and soil, although it is unclear which is the most common route. Skin-to-skin contact carries a very low risk of transmission; therefore, health workers caring for leprosy patients are usually not considered to be at high risk. The incubation period is very long, typically 5 to 7 years, and most individuals exposed to the bacteria do not develop the disease. Leprosy does not appear to be increased in persons living with HIV. Key clinical features Leprosy presents as a spectrum of disease from lepromatous to tuberculoid states, and passes through various borderline disease states in between. Tuberculoid leprosy (paucibacillary) There are few bacteria present in this form. The manifestations are due to an immune reaction to the bacilli. Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

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• Skin lesions: ° hypopigmented ﬂat macules or plaques with sharp edges; ° decreased sensation in the area; ° absence of hair follicles, sweat glands on the area affected. • Nerve lesions: ° enlargement of one or more of the peripheral nerves (most commonly ulnar, tibial, peroneal nerves); ° decreased sensation in the area innervated by the affected nerve; ° myopathy in the area affected. Lepromatous leprosy (multibacillary) This form of leprosy is characterized by an increased number of bacteria in skin lesions, blood, and nerves. • Skin lesions: ° nodules and raised plaques with dermal inﬁltration causing thickening of skin; ° diffuse lepromatosis: no visible lesions, but diffusely inﬁltrated and thickened skin. • Loss of eyebrows and eyelashes. • Symmetric enlargement of nerves with resulting neuropathy in ﬁngers, toes, and limbs. Variants Reactional states occur either as a result of the start of therapy or before diagnosis. Type 1 reactions: in borderline cases. This is called a reversal reaction if it occurs after starting therapy –the presentation changes to a more tuberculoid form. Or it is called a downgrading reaction in patients who have not yet started therapy – in this case the presentation becomes more lepromatous as a result of the reaction. Type 1 reaction symptoms include: • inﬂammation of macules, papules; • new skin lesions; • nerve inﬂammation with painful and enlarged nerves, resulting in damage within 24 hours if untreated (foot-drop for example); • low-grade fever. Type 2 reactions: (Erythema nodosum leproticum – ENL) seen in patients with more lepromatous forms of leprosy: • painful red papules which resolve spontaneously; • malaise and fever; • inﬂammation of nerves, lymph nodes, eyes, testes may occur; • episodes of ENL can be chronic, recurrent, and sometimes result in death. Lucio’s phenomenon Large ulcers and sharply demarcated plaques develop, usually in the lower limbs. Generalized eruptions can cause secondary infection by bacteria that may lead to sepsis and death.

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Complications • Limbs: neuropathy can lead to foot and wrist drop, and impairment of hand and foot function. Plantar ulcerations are also common and must be treated early. • Nose: chronic congestion and nose bleeding, destruction of cartilage. • Eyes: corneal ulcerations, cranial nerve palsies, inﬂammation of the anterior chamber of the eye (uveitis). • Testes: invasion of the testes leads to dysfunction resulting in infertility and impotence in many patients, particularly in those with lepromatous leprosy. • Nerve abscesses: seen mostly in patients with borderline tuberculoid leprosy: swollen, painful nerve, with signs of inﬂammation in overlying skin. Investigations Diagnosis usually is made by the presence of typical clinical features. Only for the ﬁrst exam – in daylight or a well-lit room: • examine the whole body (respecting patient’s privacy) • test 1 or 2 skin patches for sensory loss • count the number of skin patches. For all assessments Look for disabilities: • examine feet for ulcers, blisters on the sole or between toes, dry cracks or ﬁssures • examine hands for injury, dry cracks or ﬁssures • biopsy of a skin lesion will show granuloma formation around the dermal nerves • AFB are present in lesions of patients with lepromatous leprosy • sputum may be positive for AFB in lepromatous leprosy. Treatment21 Five simple steps to start MDT If in doubt about the diagnosis of leprosy, refer the patient to the nearest referral centre. Classify the type of leprosy. 1. If there are 1–5 patches, this is paucibacillary (PB) leprosy. • Treatment: 6 PB monthly blister packs If there are 6 or more patches, this is multibacillary (MB) leprosy. • Treatment: 12 MB monthly blister packs If in doubt, classify it as MB. If a visible disability is detected, manage the disability (see below). 2. Educate the patient and anyone accompanying her or him about the disease and its treatment. Encourage them to ask questions and clear up any doubts. 3. Give the patient the ﬁrst dose at the health facility. Show the patient which drugs from the MDT blister pack should be taken once monthly, and which should be taken every day. 4. Give the patient enough blister packs to last until the next visit. Arrange the time and place of the visit. If it is difﬁcult for the patient to come back to the hospital or to the health centre, give a the full course of treatment. 5. Fill out the patient card.

21 Guide to eliminate leprosy as a public health problem (1st ed.). Global Alliance for Elimination of Leprosy and WHO, 2000. Available at http://www.who.int/lep/resources/Guide_Int_E.pdf. The MDT regimens are available at http://www.who.int/lep/mdt/MDT_Regimens.pdf

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Paucibacillary leprosy (PB: <6 skin lesions; also called the tuberculoid form) – adult treatment. Once monthly: day 1 • 2 capsules of rifampicin (300 mg times 2) • 1 tablet of dapsone (100 mg) Once daily: days 2–28 • 1 tablet of dapsone (100 mg) Full course: 6 months – 6 blister packs (each blister pack lasts for 1 month). Multibacillary leprosy (MB: >6 skin lesions; also called the lepromatous form) – adult treatment. Once monthly: day 1 • 2 capsules of rifampicin (300 mg times 2) • 3 capsules of clofazimine (100 mg times 3) • 1 tablet of dapsone (100 mg) Once daily: days 2–28 • 1 capsule of clofazimine (50 mg) • 1 tablet of dapsone (100 mg) Full course: 12 months – 12 blister packs (each blister pack lasts for 1 month). Note: WHO supplies blister packs free of charge through national ministries of health (MOH). If patient has a side-effect Minor side-effects Red-coloured urine Then manage as follows Continue drug and Reassure the patient that this is normal for rifampicin. This is taken once monthly – it lasts for only a few hours after taking the drug. This is due to clofazimine. The darkening is harmless and will disappear within a few months of completing therapy. Encourage the patient to take the medicines regularly.

Darkening of skin

Minor side-effects Severe itching or new red or dark spots on the skin Stop drugs see Section 10.2 Skin

Response to leprosy reactions Patients can develop reactions that are part of the natural course of the disease. Reactions are not a side-effect of MDT. They are the body’s response to leprosy, and do not mean that the disease is becoming worse, or that the treatment is not working. Signs of reactions include: • existing skin lesions become reddish and swollen • painful reddish nodules appear • peripheral nerves become painful, tender, and swollen • signs of nerve damage such as loss of sensation and muscle weakness

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• fever and malaise • hands and feet may be swollen. Managing reactions: Reactions require urgent treatment to prevent irreversible deformities: • give aspirin or paracetamol to reduce pain and fever • advise the patient to rest • advise that the patient must continue to take MDT during a reaction. Give prednisolone: • 40 mg daily for weeks 1 and 2 • 30 mg daily for weeks 3 and 4 • 20 mg daily for weeks 5 and 6 • 15 mg daily for weeks 7 and 8 • 10 mg daily for weeks 9 and 10 • 5 mg daily for weeks 11 and 12. Examine the patient and reduce the dose of corticosteroids every 2 weeks. The maximum dose of prednisolone is 1 mg per kg of body weight. If inadequate response to prednisolone or if corticosteroids are contraindicated, give clofazamine 200-300 mg daily in 2 to 3 divided doses for maximum 3 months.

11.22 Leptospirosis22,23 Leptospirosis is a cosmopolitan bacterial (spirochetal) infection due to various species and serovars of Leptospira. Severe disease is most associated with Leptospira interrogans acquired from rodents or dogs in urban and rural settings, especially in ﬂood-prone areas and slums. Additionally, cattle, water buffalo, and pigs are important sources of other pathogenic Leptospira species in the agricultural setting. Leptospirosis is most commonly acquired percutaneously or by conjunctival exposure from environmental water sources contaminated with the urine of chronically infected animals. Leptospirosis is not known to be acquired by ingestion. Many areas where leptospirosis is endemic are also endemic areas for rickettsial diseases, malaria, and zoonotic viral infections, thus clinical differentiation may be difﬁcult. Key clinical features Leptospirosis may present with several distinct syndromes: • non-speciﬁc febrile illness – fever, myalgia (especially affecting the legs), headache; • conjunctival suffusion is a quite speciﬁc symptom; • aseptic meningitis – headache, fever, photophobia, neck stiffness; 22 Excerpt from WHO recommended standards and strategies for surveillance, prevention and control of communicable diseases. Available at http://www.who.int/zoonoses/diseases/Leptospirosissurveillance.pdf 23 Human leptospirosis: guidance for diagnosis, surveillance and control. WHO, 2003. Available at http://whqlibdoc. who.int/hq/2003/WHO_CDS_CSR_EPH_2002.23.pdf

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• Weil’s disease – complications of the non-speciﬁc febrile illness include jaundice, renal failure, and haemorrhage (pulmonary most common, but also gastrointestinal and cerebral). Additional, unusual features that vary by region include myocarditis, uveitis, and biphasic illness (a second episode of fever after the ﬁrst, which may occur despite antibiotic therapy, characteristically not responding to antibiotics). Investigations Diagnosis is primarily based on clinical features in a patient with risk factors (contact with fresh water, or farming, or contact with rodents or dogs). Reliable tests (such as the MATT serology) are rarely available outside of major cities and reference centers, and may not be sensitive early in the course of the disease. Other blood tests (urea and electrolytes, liver function tests, complete blood counts) may demonstrate organ dysfunction but are not speciﬁc. Direct observation of spirochetes in urine, blood, and cerebrospinal ﬂuid is not recommended because of frequent artifactual ﬁndings. Treatment Antibiotics are thought to be beneﬁcial in severe disease, but mild disease is selflimited. Suggested regimens (oral dosing for mild disease, parenteral for moderate to severe disease) for 7 days treatment include: • doxycycline 100 mg orally, twice daily (recommended in regions where rickettsial diseases such as scrub typhus are common); OR • benzylpenicillin 1.5 million units IV every 6 hours; OR • ceftriaxone 1 g IV daily; OR • cefotaxime 1 g IV every 6 hours; OR • ampicillin 500 mg to 1 gram IV every 6 hours.

11.23 Liver abscess Liver abscesses are usually due to bacteria or the parasite Entamoeba histolytica (see Section 11.1). Bacterial liver abscesses are usually caused by multiple species of bacteria. In Asia, Klebsiella is an increasingly recognized cause of liver abscesses, which may spread to other sites, including the eye. Key clinical features • Fever without an obvious focus. • Pain in the right upper quadrant may be present, but may only be elicited by percussion over the lower ribs on the right. • Jaundice is uncommon unless there is obstruction of the biliary tree. Tenderness in the right upper quadrant under the costal margin on inspiration (Murphy’s sign) is more suggestive of acute cholecystitis due to gall stones. Investigations • Positive serology for amoeba means invasive amoebiasis, which generally will revert to negative after 6–12 months. In the presence of a liver abscess, it thus usually means that the etiology is amoeba rather than bacteria.

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• A negative stool examination for amoebic cysts or trophozoites does not exclude an amoebic liver abscess. • Ultrasound may demonstrate an echolucent cavity in the liver. • Aspiration may be diagnostic; pink pus is suggestive of an amoebic abscess, while purulent, offensive smelling pus may be suggestive of a bacterial infection. Pus aspirated should be sent for microscopy and culture. Treatment If amoebic liver abscess is suspected: see Section 11.1. If bacterial liver abscess is suspected, use: • ampicillin 1 g IV 8 hourly plus metronidazole 400 mg orally; OR • ceftriaxone 1 g IV daily plus metronidazole 400 mg orally is another option, in penicillin-allergic patients; • minimum duration of treatment is 2 weeks with IV antibiotics followed by minimum of 4–6 weeks of oral antibiotics, depending on the clinical response. Patients who respond quickly can change to oral antibiotics (amoxicillinclavulanate) and metronidazole to complete therapy after 2 weeks. Aspiration of large abscesses (more than 5 cm) may be therapeutic, or necessary if the response to IV antibiotics is poor.

11.24 Loaisis (Calabar swellings) Loaisis is a disease caused by the ﬁlarial worm loa loa. It is transmitted to humans by day-biting ﬂies. Adult worms migrate through the body in the subcutaneous or deeper tissues releasing microﬁlariae into the peripheral blood for 6 months after infection. Loaisis is found in the African rain forest of West and central Africa; the Congo river basin is most severely affected. Key clinical features • Diagnosis is clinical. • Appropriate travel history or exposure is essential for diagnosis. • Symptoms are primarily due to adult worms migrating near the surface of the skin and eye and may take several years to develop. • In people living in endemic areas: ° transient swellings (lasting from a few hours to a few days): ◊ known as “calabar swellings” ◊ found anywhere on the body, most commonly the limbs ◊ painless, puffy and diffuse, located subcutaneously. ° generalized pruritis, fatigue, and joint pain ° ocular (in the conjunctiva) or skin passage of worm (lasting a few minutes) ° adult worms in the scrotum can cause hydrocoeles. • Travellers: ° swellings are more frequent ° allergic symptoms are more common. • Severe disease: ° severe allergic reactions with giant urticaria and fever ° meningoencephalitis with life-threatening encephalopathy following treatment in heavily infected individuals (see below).

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Investigations • Ocular passage of the worm is diagnostic. • Visualization of microﬁlaria in peripheral blood (taken during the day, if possible around midday): ° stained thick blood smear using 2 to 3 drops of blood from a ﬁnger prick ° stained blood sediment after separation of red cells and haemoglobin (laking) ° membrane ﬁltration: 1–2 ml of venous blood ﬁltered through a 3 µm pore size membrane ﬁlter. • Haematology: eosinophils are increased, especially in travellers. Treatment Treat the infection with one or other of the following drugs: • diethylcarbamizine (DEC): ° do not use if onchocerciasis ° dosing: ◊ day 1: 1 mg/kg single dose (can also dose according to height) ◊ days 2 to 3: 2 mg/kg single dose ◊ days 4 to 21: 2–3 mg/kg 3 times daily ° kills microﬁlaria and may kill the adult worm. ° hypersensitivity reactions following DEC administration are common and can be severe (see below); in case of high microﬁlaremia, treatment can be started at lower doses (6.25 mg on day 1, doubling the dose every day up to the daily total dose of 6 mg/kg) to reduce the risk of serious adverse event (see below). • ivermectin (Mectizan®): ° 200–400 mcg/kg (can dose according to height); ° reduces microﬁlaria in the blood; ° serious adverse reactions occur in patients coinfected with onchocerciasis, especially when the number of microﬁlaria in the blood is high; therefore, in areas endemic for both loasis and onchocerciasis, ivermectin should not be used.24 • hypersensitivity reactions with DEC or ivermectin: ° reaction to dying adult worms; ° treatment with either drug requires close medical supervision; ° those most at risk are heavily infected (microﬁlaria more than 2000/ml blood); ° can result in meningoencephalitis with life-threatening encephalopathy; ° cover with corticosteroids and antihistamines from 2 days before treatment and continue for 2 days afterwards. • If feasible, surgical removal of the adult worm from under the conjunctiva is indicated.

24 Recommendations for the treatment of Onchocerciasis with Mectizan® in areas co-endemic for onchocerciasis and loiasis. WHO, 2004. Available at http://www.who.int/apoc/publications/englishmectccloarecs-june04.pdf

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11.25 Malaria25,26 11.25.1 Suspicion of malaria The diagnosis of malaria is ﬁrst suspected on the basis of clinical criteria and then conﬁrmed by the detection of parasites in the blood by microscopy or of malaria antigens by a rapid diagnostic test (RDT). WHO recommends diagnostic testing in all cases of suspected malaria regardless of age or setting. The deﬁnition of a “suspected case” is variable from one country to another and it is essential to refer to the national guidelines. In general: • in settings where the risk of malaria is high, suspicion of malaria is based on either a recent history of fever or temperature ≥37.5°C or the presence of anaemia (Hb <8 g/dl), or both. • in settings where the risk of malaria is low, suspicion of malaria is generally based on a recent history of fever or temperature ≥37.5°C, and an additional criteria, such as the absence of an obvious cause of fever. In high malaria endemic areas, the differential diagnosis of an acute febrile episode should thus always include malaria, and the patient should be tested for malaria by microscopy or RDT. On the other hand, a febrile patient may have both malaria and another cause of fever. All patients, irrespective of the results of malaria testing, should therefore be fully assessed for other potential causes of fever (see Section 10.1 Fever). In settings where malaria incidence is very low, parasitological diagnosis for all fever cases may lead to considerable expenditure to detect only a few patients who are actually suffering from malaria. In such settings, malaria testing should be restricted to patients with a higher probability of having malaria, e.g. having no obvious cause of fever or having travelled to a high endemic area. HIV increases the risk of acquiring malaria, as well as progression to severe malaria, but it also leads to an increased incidence of febrile diseases not due to malaria, such as opportunistic diseases. This causes further difﬁculties in symptom-based diagnosis of malaria, and these patients should imperatively have a parasitological test (microscopy or RDT).

11.25.2 Parasitological diagnosis of malaria In all settings, suspicion of malaria should be conﬁrmed with a parasitological test. Parasitological diagnosis of malaria: • improves patient care in both parasite-positive patients (increasing certainty of the diagnosis), and parasite-negative patients (prompting a search for the actual diagnosis); • prevents unnecessary exposure to antimalarials, thereby reducing sideeffects, drug interactions, and drug pressure selecting for resistant parasites; • reduces cost by reducing unnecessary treatment with antimalarials; • improves malaria case detection and reporting; • conﬁrms treatment failures (by microscopy).

25 Guidelines for the treatment of malaria, 2nd ed. WHO, 2010. Note: The WHO Global Malaria Programme with its Technical Guideline Development Group will review the evidence on an annual basis and update these guidelines periodically. Available at http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf 26 Parasitological conﬁrmation of malaria diagnosis: Report of a WHO technical consultation, Geneva, 6-8 October 2009. WHO, 2010. Available at http://whqlibdoc.who.int/publications/2010/9789241599412_eng.pdf

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Parasitological diagnosis is particularly important to conﬁrm the diagnosis: • in settings with high HIV prevalence, because of the high incidence of febrile disease that is not malaria in a person living with HIV. Thus, PLHIV presenting with fever should always have a parasitological test. • in stable high-transmission settings in adults since malaria becomes progressively less likely as a cause of fever as immunity is acquired. • in pregnant women, parasitological diagnosis is very important in order to reduce unnecessary use of antimalarials in pregnancy. The distinction between severe and uncomplicated malaria is based on a set of clinical and non-malaria laboratory tests (such as blood glucose), and not on the basis of the parasite density. When a patient presents with a severe febrile illness (fever plus danger signs), antimalarials and antibiotics should be started immediately while waiting for the result of the malaria test. Note: If a patient fulﬁls the criteria for a suspected case of malaria and diagnostic tests are unavailable, he or she should be treated for malaria.

11.25.3 Management of uncomplicated (non-severe) malaria in adolescents and adults, except ﬁrst trimester pregnant women In uncomplicated malaria cases (with no symptoms or signs of severity), only patients with a positive diagnostic test for malaria (microscopy or RDT) should receive antimalarial treatment. If symptoms or signs of severity are present, see Section 11.25.5. If both an RDT and microscopy are performed in parallel to assess a new episode of fever, and one of the two tests (or both) is positive, the patient should be considered as having malaria. In addition, the patient should be assessed for other causes of fever, and speciﬁc treatment should be provided in addition to the antimalarial treatment if needed.

Artemisinin-based combination antimalarials To counter the threat of resistance of P. falciparum to monotherapies, and to improve treatment outcome, artemisinin-based combination therapies (ACTs) are now recommended by WHO. The treatment schedules for uncomplicated malaria comprise 3 days of artemisinin-based combination therapy. It is very important to ensure the patient receives 2 different drugs to treat malaria, whether in 1 coformulated tablet or in 2 separate tablets. Fixed-dose combinations are strongly preferred over blistered co-packaged or loose tablets, to promote adherence and to reduce the potential selective use of the medicines as monotherapy. Use one of the ﬁrst-line treatment options in the following table. Consult the national malaria guidelines. Note: All women of childbearing age should be asked about the possibility of their being pregnant. Treatment recommendations for pregnant women are different from those for non-pregnant women (see Table: First-line antimalarial treatment options, below)

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Table: First-line antimalarial treatment options for P. falciparum in all adolescent and adult patients except ﬁrst-trimester pregnant patients* Artesunate + amodiaquine daily dose, Artemether/ once daily lumefantrine twice for 3 days daily for 3 days* Dihydroartemisinin/ piperaquine once daily for 3 days Sulfadoxine/ pyrimethamine (SP) single dose in clinic + artesunate daily for 3 days** Separate tablets: SP tablet (sulfadoxine 500 mg + pyrimethamine 25 mg); artesunate tablet (Art) 50 mg Day SP 1+1 2 2 1 Art SP 2+2 3 3 2 Art SP 4+4 4 4 3 Art 4 4 4 Mef 4 2 2 3 2 2 Mef Art 4 2 4 1 4 1 2 1 1 Mef Art 2 1 2 2 1 1 2 3 Artesunate daily for 3 days + meﬂoquine split over the 2nd and 3rd days***

Age and weight 5–7 yrs (19–24 kg) 8–13 yrs or small or wasted adult (25–50 kg) 14 yrs + (>50 kg)

Separate tablets: artesunate Coformulated tablet: tablet 50 mg; artemether 20 mg + amodiaquine lumefantrine 120 mg table 153 mg base Morning Evening

Coformulated tablet: DHP 40 mg + PQP 320 mg

Separate tablets: artesunate table (Art) 50 mg; meﬂoquine tablet (Mef) 250 mg base Day Art 1 1 2 1 3 1

The second dose on the ﬁrst day should be given any time between 8 and 12 hours after the ﬁrst dose. Dosage on the second and third days is twice daily (morning and evening). Lumefantrine absorption is enhanced by co-administration with fat. It is essential that patients or caregivers are informed of the need to take this ACT immediately after a fatty meal or drink – particularly on the second and third days of treatment. ** Do not use sulfadoxine/pyrimethamine for treatment if patient is on cotrimoxazole prophylaxis. *** In case of clinical failure after a treatment with AS+MQ, do not give AS+MQ within 60 days, because of an increased risk of neuropsychiatric reactions. Second-line treatment should rather be given. For children under 5 years, see IMCI guidelines.

The choice of ACT in a country or region will be based on the level of resistance of the partner medicine in the combination: • In most areas of multidrug resistance (South-East Asia), artesunate plus meﬂoquine, or artemether plus lumefantrine, or dihydroartemisinin plus piperaquine are effective.27 • In most areas without multidrug resistance (mainly Africa), any of the ACTs including those containing amodiaquine or sulfadoxine-pyrimethamine are still effective.28 Consult the national malaria guidelines.

27 In limited areas, either artesunate plus meﬂoquine or artemether plus lumefantrine, or both, are no longer effective. 28 In some areas, either artesunate plus amodiaquine or artesunate plus SP, or both, are no longer effective.

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Antimalarial treatment in people living with HIV • Patients with HIV infection who develop malaria should receive prompt, effective antimalarial treatment regimens as recommended above. • Treatment or intermittent preventive treatment with sulfadoxinepyrimethamine should not be given to HIV-infected patients receiving cotrimoxazole (trimethoprim plus sulfamethoxazole) prophylaxis. • Treatment in HIV-infected patients on zidovudine or efavirenz should avoid, if possible, amodiaquine-containing ACT regimens.

Antimalarial treatment for uncomplicated malaria in travellers Travellers who acquire malaria are often non-immune persons who either reside in cities with little or no transmission within endemic countries, or are visitors from non-endemic countries who travel to areas of malaria transmission. Both are at higher risk for severe malaria. If the patient has taken chemoprophylaxis, then the same medicine should not be used for treatment. One of the oral treatments in the table below should be given. Table: Treatment options for P. falciparum in travellers Recommended treatment options Artemether + lumefantrine Atovaquone + proguanil Formulations currently available Treatment schedule in adolescents and adults Treatment schedule in adolescents and adults

See Table: First-line antimalarials, above Co-formulated tablets for adults containing 250 mg of atovaquone plus 100 mg of proguanil Separate blisters with tablets containing 50 mg of artesunate, and tablets containing 100 mg of doxycycline 1 g of atovaquone plus 400 mg of proguanil once daily for 3 days Plasma concentration of atovaquone is reduced when the drug is co-administered with rifampicin, rifabutin, metoclopramide or tetracycline. Doxycycline is contraindicated during pregnancy and breastfeeding, and should not be given to children <8 years of age. It should be taken with plenty of water to prevent oesophageal irritation. Contraindicated with liver dysfunction. Clindamycin is contraindicated in patients with liver or kidney dysfunction, and in patients with history of colitis.

Artesunate + doxycycline

200 mg of artesunate once daily for 3 days and 200 mg of doxycycline once daily for 7 days

Artesunate + clindamycin

Separate blisters with tablets containing 50 mg of artesunate and capsules containing 150 or 300 mg of clindamycin

200 mg of artesunate once daily for 3 days and 600 mg of clindamycin twice daily for 7 days

Dihydroartemisinin + piperaquine

See Table: First-line antimalarial treatment options for P. falciparum in non-pregnant patients

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Quinine + doxycycline

Separate blisters with tablets containing 150 or 300 mg of quinine salt, and tablets containing 100 mg of doxycycline

600 mg of quinine salt 3 times daily for 7 days and 200 mg of doxycycline once daily for 7 days

See contraindication and advice for doxycycline above. The use of antiarrhythmics, such as ﬂecainide and amiodarone, should be avoided. The risk of arrhythmias can be increased with antihistamines such as terfenadine, and antipsychotic drugs such as pimozide and thioridazine. Cimetidine can increase quinine levels, while rifampicin reduces the plasma concentration of quinine leading to increased treatment failures. See precautions with quinine and contraindications for clindamycin above.

Quinine + clindamycin

Separate blisters with tablets containing 150 or 300 mg of quinine salt, and capsules containing 150 or 300 mg of clindamycin base

600 mg of quinine salt given 3 times daily, every 8 hours for 7 days and 600 mg of clindamycin base 2 times daily for 7 days

Use chloroquine 10 mg/kg immediately and then 5 mg/kg at 6, 24, and 48 hours (total dose: 25 mg/kg over 2 days) for treatment for P. vivax, P. ovale, and P. malariae. Full anti-relapse treatment with primaquine (15 mg once daily, except for South-east Asia and Oceania where 30 mg once daily is necessary) for 14 days should be added to chloroquine in case of P. vivax and P. ovale infections, except during pregnancy and breastfeeding.

Antimalarial treatment for uncomplicated malaria if not able to tolerate oral treatment These patients require parenteral administration for 1 to 2 days until they can swallow and retain oral medication reliably. Although such patients may never show other signs of severity and thus do not fulﬁl the deﬁnition of severe malaria, they should receive the same initial antimalarial dose regimens as for severe malaria. Initial parenteral treatment must always be followed by a full 3-day course of an ACT.

Management of vomiting Vomiting is common in acute malaria and may be severe. Antiemetics are widely used (see Section 20 Palliative Care). There are no studies of their efﬁcacy in patients with malaria and no evidence that they are harmful, although they can mask severe malaria. Patients who vomit everything, including the medicines, should be managed as severe malaria.

Use of antipyretics Fever is a cardinal feature of malaria, and is associated with constitutional symptoms of lassitude, weakness, headache, anorexia, and often nausea. Treat with antipyretics and, if necessary, fanning and tepid sponging. Antipyretics should be used if core temperature is more than 38.5oC. Paracetamol 15 mg/kg every 4 hours is widely used; it is safe and well-tolerated, given orally or as a suppository.

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Ibuprofen (5 mg/kg) has been used successfully as an alternative in malaria, although there is less experience with this compound. Aspirin (acetylsalicylic acid) should not be used in children or young adolescents less than 16 years because of risk of Reye syndrome.

Complications • If untreated, uncomplicated malaria can progress to severe malaria. • Febrile patients without any danger signs and with a negative malaria test do not have malaria, and thus will not progress to severe malaria. Antimalarial treatment should not be given, but a malaria test should be repeated in cases of persisting fever, and other causes of fever should be considered (see Section 10.1 Fever). • Anaemia is the most common complication of repeated untreated episodes of malaria, especially in pregnant women.

11.25.4 Follow-up of malaria patients and suspected treatment failure No speciﬁc follow-up is needed for non-severe malaria in adults. Advise them to return if still having fever or feeling ill after 2 days or immediately if worse. Recurrence of P. falciparum malaria can be the result of a reinfection or a recrudescence (i.e. failure). In an individual patient, it is not possible to distinguish recrudescence due to treatment failure from recrudescence due to reinfection. If fever and parasitaemia fail to resolve or recur within 2 weeks of treatment, a failure of treatment is possible. Treatment failures may result from: • poor adherence, or • inadequate drug exposure (from under-dosing, vomiting, or unusual pharmacokinetic properties in an individual), or • substandard medicines, or • drug resistance. It is important to determine from the patient’s history whether he or she vomited the previous treatment or did not complete a full course. Indeed, if a full course of treatment has not been ingested, a full treatment with the ﬁrst-line medicine should be given before considering the possibility of treatment failure. When a full course of an efﬁcacious antimalarial medicine has been taken, treatment failure is possible and must be conﬁrmed parasitologically by microscopy (as RDTs may remain positive for days or weeks due to persistence of antigens after clearance of P. falciparum infection). This may require referring the patient to a facility with microscopy.

Suspected treatment failure within 14 days Treatment failure within 14 days of receiving an ACT is very unusual. Treatment failures within 14 days of initial full treatment should be treated with a second-line antimalarial. The following second-line treatments are recommended, in order of preference: • an alternative ACT known to be effective in the region; • artesunate plus doxycycline or clindamycin (see Table: Treatment options for P. falciparum in travellers); Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

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• quinine plus doxycycline or clindamycin (see Table: Treatment options for P. falciparum in travellers); • artesunate or quinine, plus tetracycline. The alternative ACT has the advantages of simplicity, and where available, a ﬁxeddose combination formulation improves adherence. The 7-day regimens using quinine are not well tolerated, and adherence is likely to be poor if treatment is not directly observed. It is essential that the patient and the caregiver understand the importance of completing the full 7-day course of treatment.

Suspected treatment failure after 14 days Recurrence of fever and parasitaemia more than 2 weeks after treatment could result either from recrudescence (rare at the moment with ACTs) or new infection, and this distinction can only be made through parasite genotyping by PCR. Therefore, persisting or recurrent fever after 2 weeks of initial antimalarial treatment should be considered as new infections, especially in areas of high transmission, and be treated with the ﬁrst-line ACT. However, reuse of meﬂoquine within 60 days of ﬁrst treatment is associated with an increased risk of neuropsychiatric reactions and, in cases where the initial treatment was AS+MQ, a combination not containing meﬂoquine should be given.

11.25.5 Management of severe malaria Severe malaria due to Plasmodium falciparum is a life-threatening condition. If a patient resides in or has travelled to a malaria endemic area and is found to have P. falciparum parasitaemia, consider severe malaria if he or she has the signs and symptoms below:

Key clinical features of severe malaria History: • irritability • change in behavior • altered consciousness (lethargy, confusion, coma) • convulsions. Examination – the main features are: • altered consciousness (lethargy, confusion, coma) • convulsions • shock • jaundice • marked pallor • fast and deep breathing – respiratory distress or acidosis • bi-basilar crackles and fast breathing – pulmonary oedema • abnormal bleeding • haemoglobinuria • decreased production of urine (urinary ﬂow less than 400 ml/24 hours).

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Investigations for severe malaria • A blood smear to determine parasite density – all patients with suspected severe malaria should have a blood smear done as soon as possible. It may be necessary to do more than one smear to follow response to treatment when the initial blood slide is positive; • A malaria RDT can be performed while waiting for the result of the blood slide to decide earlier on treatment. • Blood glucose. • Full blood count (or haemoglobin, if not available). • Lumbar puncture in patients with any alteration in consciousness or meningeal signs to exclude bacterial meningitis which, if left untreated, is invariably fatal. Cerebral malaria may present with neck retraction but is not associated with signs of meningeal irritation (neck stiffness, photophobia, or Kernig’s sign). • Renal function – BUN, creatinine, serum bicarbonate. • Blood culture. • Platelet count and clotting studies. • Electrolytes. • Type and cross-match for possible transfusion. Laboratory criteria of severe malaria – note that the Hb and glucose criteria to classify as severe malaria are lower than the criteria for initiating treatment in adolescents and adults: • severe anaemia – Hb less than 5 g/dl (but transfuse at 7 g/dl) • hypoglycaemia – glucose less than 2.2 mmol/l (but give glucose if 3 mmol/l or less) • acidosis (low bicarbonate in the blood) – less than 15 mmol/l) • renal failure – high serum creatinine more than 265 µmol/l (more than 3.0 mg/ dl) • hyperparasitaemia – more than 5% or more than 250 000/µl.

Treatment of severe malaria Severe malaria is a medical emergency. The mortality rate of untreated severe malaria is thought to approach 100%, but with antimalarial treatment, the rate falls to 15–20%. a) Emergency measures Emergency measures should be started within the ﬁrst hour. Do the Quick Check and provide emergency treatments. Repeat the Quick Check on a regular basis when caring for patients with severe malaria: • Assess airway, breathing, and circulation. • The airway should be secured in unconscious patients. • Perform a detailed clinical examination, with particular note of the level of consciousness. • Do a blood glucose test; if no blood glucose measurement is available or is low, give IV glucose (see Quick Check page 41, Vol. 1). • Treat convulsions with intravenous (or, if not possible, rectal) diazepam or intramuscular paraldehyde. Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011

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• Restore circulating blood volume and, if possible, treat severe anaemia (see ﬂuid balance disturbances and anaemia below). • The patient should be weighed or body weight estimated so that drugs, including antimalarials and ﬂuids, can be given on a body weight basis. • Start treatment with an effective parenteral antimalarial for P. falciparum. b) Antimalarial treatment • Intravenous artesunate should be used in preference to quinine for the treatment of severe P. falciparum malaria in adults. • If the malaria test result is likely to be a delayed for more than 1 hour, immediately start antimalarial treatment while waiting for the test result. • Give artesunate 2.4 mg/kg body weight IV or IM on admission (time = 0), then at 12 hours and 24 hours, then once daily. This is the recommended treatment. ° Artesunate is dispensed as a powder of artesunic acid with 60 mg/vial. ° This vial should be mixed with 1 ml of 5% sodium bicarbonate solution (provided) and shaken for 2 to 3 minutes for better dissolution. ° For intravenous infusion, then add 5 ml of 5% dextrose or normal saline to make the concentration of artesunate 10 mg/ml. This is administered by slow IV infusion. See Quick Check page 39, Vol. 1 for dosing table. ° For IM injection, then add 2 ml of 5% dextrose or normal saline to make the concentration of artesunate 20 mg/ml, for injection in the anterior thigh. ° The solution should be prepared freshly for each administration and should not be stored. • If parenteral artesunate is not available, give quinine 20 mg salt/kg body weight on admission (IV infusion or divided IM injection), then 10 mg/kg body weight every 8 hours. ° Quinine should preferably be given by IV infusion in normal saline or 5% glucose. ° Quinine dihydrochloride should be given by rate-controlled infusion with the IV infusion rate not exceeding 5 mg salt/kg body weight per hour. Quinine must never be given by intravenous bolus injection, as lethal hypotension may occur. ° If a safe rate-controlled IV infusion is not possible, quinine can be given by intramuscular injection to the anterior thigh (not the buttock, to avoid sciatic nerve injury). The ﬁrst dose should be split, 10 mg/kg body weight to each thigh. Undiluted quinine dihydrochloride at a concentration of 300 mg/ ml is acidic (pH 2) and painful when given by intramuscular injection, so it is best either formulated or diluted to concentrations of 60–100 mg/ml for intramuscular injection. ° Note that the ﬁrst administration is a double dose; this IV infusion is over a period of 4 hours. ° If the patient remains in acute renal failure or has hepatic dysfunction, then the dose should be reduced by one third after 48 hours. Dosage adjustments are not necessary if patients are receiving either haemodialysis or haemoﬁltration. • If parenteral artesunate or quinine are not available, give artemether 3.2 mg/ kg IM on admission, then 1.6 mg/kg per day. ° Artemether should only be given if none of the alternatives are available, as its absorption can be erratic. ° Parenteral artemether should be taken until the patient can take oral medication.

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° As soon as the patient can take medicines orally, complete the dose with a full dose of the recommended artemisinin-based combination therapy (ACT). ° Artemether is dispensed dissolved in oil and given IM in the anterior thigh. • Give parenteral antimalarials in the treatment of severe malaria for a minimum of 24 hours. Then, as soon as the patient can tolerate oral medication, complete treatment by giving a complete course of: ° artemether plus lumefantrine; OR ° artesunate plus amodiaquine; OR ° dihydroartemisinin plus piperaquine; OR ° artesunate plus sulfadoxine-pyrimethamine; OR ° artesunate plus clindamycin or doxycycline; OR ° quinine plus clindamycin or doxycycline. c) Supportive care of severe malaria • Patients with severe malaria require intensive nursing care and monitoring. • Following the initial assessment and the start of antimalarial treatment, clinical observations should be made as frequently as possible. These should include repeating the Quick Check assessment and measuring and recording of vital signs, with accurate assessments of respiratory rate and pattern, coma score, and urine output. Use the severely ill patient monitoring form (see Section 3.11). • Check blood glucose every 4 hours if possible, particularly in unconscious patients and pregnant women. Hypoglycaemia should be suspected in any patient who deteriorates suddenly. For management see Table: Speciﬁc management of complications of severe malaria, below. • Fluid requirements should be assessed individually. See Section 3.1.5. ° Adults with severe malaria are vulnerable to ﬂuid overload and there is a thin line between under-hydration (renal impairment) and over-hydration (pulmonary oedema). ° Monitor ﬂuid balance including ﬂuid given to infuse antimalarials. ° Clinical evaluation includes careful and frequent evaluation of the jugular venous pressure, peripheral perfusion, venous ﬁlling, skin turgor, and urine output. ° Monitor blood urea and creatinine. • There is also a considerable clinical overlap between septicemia, pneumonia, and severe malaria – and these conditions may coexist. See table below and Sections 3.1.4 and 3.2.4 for speciﬁcs on ﬂuid management, use of vasopressors, monitoring. Many of the principles of caring for severely ill patients with suspected septic shock and for severe respiratory distress with pneumonia and no shock are the same as for severe malaria. • There is increasing evidence for the beneﬁt of co-administration of antibiotics with antimalarials in the management of severe malaria patients, even in the absence of a positive blood culture. As soon as bacterial sepsis is suspected, antibiotics should be given.

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Table: Speciﬁc management of complications of severe malaria Manifestation/ complication Coma (cerebral malaria) Management Assess level of consciousness – use AVPU or the Glasgow Coma scale Maintain airway, place patient on his or her side Intubate if necessary (see Quick Check page 63, Vol. 1) Exclude other treatable causes of coma (e.g. hypoglycaemia, bacterial meningitis) Insert nasogastric tube to avoid aspiration Turn the patient twice hourly to prevent the development of bedsores Avoid harmful auxiliary treatment such as corticosteroids, heparin, and epinephrine (adrenaline) Tepid sponging, fanning, cooling blanket Give paracetamol Maintain airway Treat promptly with intravenous or rectal diazepam (see Quick Check page 21, Vol. 1 and Section 10.10c) or intramuscular paraldehyde Exclude other treatable causes of convulsions, e.g. hypoglycaemia Check blood glucose – especially in pregnant women, patients with hyperparasitaemia, and comatose patients Give glucose immediately to correct hypoglycaemia (D50 25 to 50 ml – see Quick Check page 41, Vol. 1) Maintain with glucose-containing infusion HIV coinfected and pregnant patients are at particularly high risk Transfuse with screened packed cells, if available. If not, use screened fresh whole blood.

Hyperpyrexia (temperature >40.5°C) see Section 10.1.4. Convulsions

Hypoglycaemia (blood glucose concentration of <3 mmol/l; <54 mg/100 ml (these are treatment thresholds; severe malaria criteria is 2.2 mmol/l) Severe anaemia (haemoglobin <7 g/dl or haematocrit <15%) (this is the transfusion threshold in adults; severe malaria criteria is 5 gm/dl) Acute pulmonary oedema/ ARDS (adult respiratory distress syndrome) see Section 3.2.5

Prop up patient at an angle of 45° Give oxygen Decrease ﬁlling pressures on the right side of the heart – give a dose of IV furosemide, opiates, venodilators Stop intravenous ﬂuids Intubate if not adequately ventilating (see Quick Check page 63, Vol. 1 for indications for intubation) Treat empirically with clindamycin or penicillin + metronidazole

Aspiration pneumonia see Sections 3.2.4 and 10.6 Acute renal failure see Section 11.31 Disseminated intravascular coagulation (DIC) – spontaneous bleeding and coagulopathy

Exclude pre-renal causes, check ﬂuid balance and urinary sodium If in established renal failure, add haemoﬁltration or haemodialysis, or if unavailable, peritoneal dialysis The beneﬁts of diuretics/dopamine in acute renal failure are not proven. Fewer than 5% of patients with severe malaria develop clinically signiﬁcant DIC Transfuse with screened fresh whole blood (cryoprecipitate, fresh frozen plasma, and platelets if available) Give a vitamin K injection

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Metabolic acidosis

Metabolic acidosis presents with deep laboured breathing while the chest is clear Correct reversible causes of acidosis, especially dehydration, severe anaemia, hypoglycaemia, hypovolaemia, and septicaemia If severe, add haemoﬁltration or haemodialysis, if available Hypotension Suspect septicaemia from non-malarial cause – shock seldom occurs in malaria if there is no septicaemia Take blood for cultures – usually Gram-negative bacteria Give parenteral antimicrobials as well as antimalarials Correct haemodynamic disturbances – give ﬂuids (NS or LR) – see ﬂuid recommendations in Section 3.1.5 Mortality is high Treat with parenteral artemisinin derivates, e.g. artesunate or artemether (or, if not available, quinine)

Shock see Section 3.1.5

Hyperparasitaemia

11.25.6 Malaria and HIV Increasing numbers of people in malaria endemic areas are living with HIV infection. In areas with stable malaria and a high prevalence of HIV infection, malaria diagnosed on clinical grounds (rather than on the basis of a parasitological test) may result in febrile illnesses caused by opportunistic infections being misdiagnosed as malaria, and thus left untreated. Conﬁrmatory parasitological testing for malaria should be applied with a high priority for patients at risk of HIV (in particular older children and adults). In addition, health providers should offer HIV testing and counselling.

Possible protective effect of cotrimoxazole Daily cotrimoxazole prophylaxis reduces morbidity in PLHIV in WHO stage 2 or 3, and mortality in persons with both HIV infection and tuberculosis, and may be protective against malaria. Cotrimoxazole prophylaxis is recommended for PLHIV in Africa who either are symptomatic or are asymptomatic with a CD4 count less than 500 (see Section 13). Medicines used in the management of opportunistic infections in people living with HIV may also interact with antimalarials. Interactions are possible between cotrimoxazole, which is used for prophylaxis of opportunistic infections, and sulfadoxine-pyrimethamine (SP), which is used for intermittent preventive treatment of malaria in pregnant women in some parts of Africa. Sulfadoxinepyrimethamine should not be given as malaria treatment in PLHIV receiving cotrimoxazole prophylaxis. Daily cotrimoxazole probably provides an equivalent antimalarial effect.

Possible increased risk of severe malaria and treatment failure in PLHIV In malaria endemic areas, PLHIV are at increased risk of asymptomatic parasitaemia, clinical malaria, or severe and complicated malaria. In areas with stable malaria, HIV infection increases the risk of malaria infection and clinical malaria in PLHIV. In settings with unstable malaria, patients with AIDS are at increased risk of severe malaria and death. There is insufﬁcient information at the present time on how HIV infection modiﬁes the therapeutic response to antimalarials. However, increasing parasite burdens

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and reduced host immunity, both of which occur with HIV infection, are associated with increased treatment failure rates. Antimalarial treatment failure may thus be more common in PLHIV with low CD4 cell counts than in those not infected with HIV.

Drug interactions between antimalarials and antiretrovirals There is limited information on drug interactions between ACTs and antiretrovirals. Based on limited studies, treatment of malaria in HIV-infected patients receiving zidovudine or efavirenz should, if possible, avoid amodiaquine-containing ACTs.

11.25.7 Malaria in pregnancy • Pregnant women with symptomatic acute malaria are a high-risk group, and must receive prompt, effective antimalarials. • Malaria in pregnancy is associated with anaemia in the mother, low birth weight, and, in low-transmission areas, an increased risk of severe malaria and death. • In high-transmission settings, despite the adverse effects on fetal growth, malaria is usually asymptomatic in pregnancy or associated with only mild, non-speciﬁc symptoms. • Preventive measures for malaria in pregnancy are very important.

Antimalarial treatment in pregnancy • There is insufﬁcient information on the safety and efﬁcacy of most antimalarials in pregnancy, particularly in the ﬁrst trimester, and treatment recommendations are different for the ﬁrst trimester from those for nonpregnant adults and second and third trimester pregnant women. • Inadvertent exposure to ACTs in the ﬁrst trimester is not an indication for the termination of the pregnancy. First trimester: • Give quinine plus clindamycin for 7 days (artesunate plus clindamycin for 7 days is indicated if this treatment fails). • An ACT is indicated only if this is the only treatment immediately available. Second and third trimesters: • Treat as for non-pregnant women (see Section 11.25.3). • There is an increased risk of hypoglycaemia associated with quinine usage in the second and third trimesters. Despite these restrictions in the ﬁrst trimester, effective treatment must not be delayed in pregnant women. In practice, if ﬁrst-line treatment with an artemisinin combination is all that is immediately available for symptomatic malaria in the ﬁrst trimester, then it should be given.

Antimalarial treatment in lactating women Lactating women should receive standard antimalarial treatment (including ACTs) except for primaquine and doxycycline, which should not be given during lactation.

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Malaria in HIV-positive pregnant women HIV infection impairs the ability of pregnant women to control P. falciparum infection. They are more likely to: • develop clinical and placental malaria (placental malaria is associated with increased mother-to-child transmission of HIV in utero); • have detectable malaria parasitaemia; • have higher malaria parasite densities in peripheral blood; • have anaemia; • have preterm birth and intrauterine growth retardation. Children born to women with dual malaria and HIV infection are at high risk of low birth weight and death during infancy. The presence of HIV may result in a poorer response to treatment with antimalarials, and in a decreased protective effect of intermittent preventive treatment for malaria during pregnancy. Malaria episodes in HIV-infected pregnant women who are receiving cotrimoxazole prophylaxis should be managed with non-sulfa antimalarials. Intermittent preventive treatment is not recommended for women already on cotrimoxaxole (see above).

11.25.8 Preventive measures for malaria Long-lasting insecticide-treated nets The use of long-lasting insecticide-treated nets should be strongly encouraged in all people living in an endemic area, especially pregnant women.

Intermittent preventive treatment in pregnancy (IPTp) IPTp is the administration of a full treatment dose of a drug at predetermined intervals during pregnancy. This preventive strategy protects pregnant women from malaria and reduces the related consequences, namely low birth weight and anaemia. Currently, sulfadoxine-pyrimethamine (SP) is the medicine of choice. All pregnant women in areas of stable transmission in Africa should receive at least 2 doses of treatment with sulfadoxine-pyrimethamine during the second and third trimesters (after quickening). Intermittent preventive treatments should be given at least 4 weeks apart under direct observation at visits to antenatal clinics. Women known to be HIV-positive should receive at least 3 doses of intermittent preventive treatment. If the prevalence of HIV among pregnant women is higher than 10%, the national policy should be to deliver 3 doses of preventive treatment during pregnancy. IPTp should not be given to HIV-positive pregnant women receiving daily cotrimoxazole. Treatment with sulfadoxine-pyrimethamine is contraindicated in cases of hypersensitivity to sulphonamides.

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11.26 Microsporidiosis Microsporidia are protozoa that can cause disease, most notably in immunocompromised patients. In patients with AIDS, they can cause chronic diarrhoea. Key clinical features • chronic, watery, non-bloody diarrhoea • sometimes abdominal pain and cramping, nausea, vomiting, and weight loss. Disseminated disease: • cholecystitis and biliary tract infections, hepatitis, and peritonitis • kerato-conjunctivitis • infections of the lungs, muscles, and brain. Investigations Modiﬁed trichrome stain identiﬁes spores in stool specimens. Treatment • At present, there is no effective treatment for microsporidia. In patients with AIDS, starting antiretroviral therapy as soon as possible is important. • Albendazole has been reported to decrease diarrhoea (but does not eradicate the organism) in patients with AIDS. • Give cotrimoxazole prophylaxis. • Supportive symptomatic treatment (hydration – see Section 10.7d for recommendations for rehydration and antidiarrhoeal drugs).

11.27 Mycobacterium avium complex (MAC) MAC is often a life-threatening disease in PLHIV, but can also occur as a more limited, pulmonary form in HIV-negative individuals. In patients with HIV infection, MAC is primarily of concern in those with very low CD4 counts (typically less than 50), or in WHO stage 4 disease, and is usually generalized. Localized manifestations, mainly in lymph nodes, can be seen, especially in IRIS. MAC shows important regional variations in infection rates. Key clinical features Disseminated disease: • prolonged fever and night sweats • wasting • enlarged liver and spleen • gastrointestinal symptoms such as diarrhoea, abdominal pain • symptoms of anaemia • localized disease • generalized lymphadenopathy, papulo-pustular eruption on trunk and extremities. Investigations The diagnosis of MAC is often made by exclusion in a patient with symptoms

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compatible with disseminated TB or MAC, who fails to respond to TB medicines, and when other causes of insufﬁcient treatment response, such as poor adherence, or multi-drug resistant TB have been ruled out. • FBC – severe anaemia, leukopenia and thrombocytopenia due to bone marrow inﬁltration. • LFTs – high alkaline phosphatase (more than 2 times ULN) and gamma GT levels (more than 3 times ULN). • Deﬁnitive diagnosis is made by either blood or bone marrow culture, or both, but this may not be possible in resource-limited settings. Treatment • Empirical TB treatment plus a macrolide, until conﬁrmation that the patient does not have TB. • Initiation of ART is the preferred treatment for MAC in many resourceconstrained settings. • Treatment of MAC may not be possible at the district level due to lack of access to the deﬁnitive treatment. ° At least 2 drugs should be used to avoid the emergence of resistance: ◊ ethambutol 15 mg/kg/day daily for 6 months PLUS either ◊ clarithromycin 500 mg twice daily for 6 months; OR ◊ azithromycin 600 mg daily for 6 months (this is the preferred option if the patient is on ART because of drug-drug interaction). • Emphasis on symptomatic treatment (hydration, antidiarrhoeal drugs). MAC and ART If the patient develops MAC when on ART, many experts recommend the continuation of ART, and close monitoring of the patient, including treatment with steroids if necessary.

11.28 Onchocerciasis (river blindness) Onchocerciasis is caused by a ﬁlarial worm and is transmitted from person to person by the bite of a black ﬂy. Microﬁlaria invades the eye, skin, and other organs. Severity depends on the number of bites and number of parasites in the skin. Infection affects multiple organ systems, but the greatest morbidity is due to cutaneous and ophthalmologic complications Key clinical features • Presumptive diagnosis is based on typical clinical ﬁndings and a history of travel to an endemic area. • Pruritus is the most common early symptom of infection. Itching can be severe. • Skin involvement can have several patterns (see Section 10.2): ° Nodules: subdermal, painless, hard, rolling easily over the bones underneath. Do not suppurate. ° Acute papular dermatitis, which is numerous small pruritic papules that may progress to vesicles or pustules. Papules tend to develop on limbs, shoulders, face, and trunk. ° Chronic papular dermatitis – larger, pruritic, ﬂat-topped papules distributed

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• • • •

symmetrically over the buttocks, waist, and shoulders. ° Licheniﬁed dermatitis is an intensely pruritic dermatitis with excoriations and hyperpigmented and hyperkeratotic papules and plaques. ° Later, skin atrophy – the skin appears wrinkled and thin, and atrophic changes are most often noted over the buttocks and limbs. ° Depigmentation is a common ﬁnding in advanced onchocerciasis. The patchy lesions resemble vitiligo and are commonly found on the shins. Photophobia, itching of eyes – can lead to iritis or glaucoma. Punctuate keratitis can lead to sclerosing keratitis. Slow progression over years. Night blindness and narrowing visual ﬁelds in early stages, to irreversible impairment in late stages.

Investigations • Demonstration of microﬁlariae on skin samples (skin snip, skin biopsy, see Section 7.2.3). • A positive skin snip biopsy result is 100% speciﬁc for onchocerciasis. In early or latent disease however, low microﬁlarial loads produce false-negative results, thus decreasing the sensitivity of the test. Treatment • Ivermectin should be given to patients with signs and symptoms of onchocerciasis. Ivermectin 150 mcg/kg once daily orally as a single dose every 6 or 12 months. (Because ivermectin is a microﬁlaricide and does not kill adult worms, the treatment does not cure the disease.) This is the only approach in hypoendemic areas. • Manage complications. • Serious adverse reactions occur in patients co-infected with loaisis and onchocerciasis, especially when the number of microﬁlaria in the blood is high.Therefore, in areas endemic for both loaisis and onchocerciasis, ivermectin should not be used.24 Prevention • Prevention involves using ivermectin as chemoprophylaxis against the parasite. In hyperendemic areas, ivermectin is given once or twice yearly as part of control and elimination programmes, as well as using larvicides against the vector.8 Everyone is treated with ivermectin tablets except the following: ° children who are younger than 5 years old, weigh <15 kg, or are shorter than 95 cm tall ° pregnant women ° mothers who are breastfeeding babies younger than 1 week old ° people with disease of the CNS ° severely ill people.

PCP [Pneumocystis jiroveci pneumonia] see Section 10.6.3 Chest complaints and Section 3.2.3 Manage severe respiratory distress

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11.29 Penicilliosis This disease is caused by the fungus Penicillium marneffei, and is an important cause of opportunistic infections in PLHIV with advanced HIV disease (CD4 <100). It is more commonly found in South-East Asia, particularly in Thailand and China. Transmission is suspected to be by inhalation of spores. Key clinical features • fever (for longer than 4 weeks), malaise, weight loss • lymphadenopathy or hepatosplenomegaly, or both • cough, dyspnoea, and chest pain (if lung involvement) • skin lesions: ° occur in face, upper trunk, and limbs; ° papules commonly umbilicated or ulcerated (can be confused with molluscum contagiosum, cryptococcosis, or TB); ° extension into the mouth and eyes can be seen in PLHIV. • lung lesions – can be cavitary and may cause haemoptysis. Investigations • Blood count – anaemia and increased WBC may be present. • Smears, skin biopsies, or aspirates (from bone marrow or lymph nodes) can identify the fungus on microscopic examination. • Culture – body tissues and ﬂuids can be cultured. • Chest X-ray – diffuse nodular pulmonary inﬁltrates or cavitary lesions. Treatment • Give amphotericin B 0.7 mg/kg per day IV for 14 days followed by itraconazole 200 mg orally twice daily for 10 weeks. • For mild disease, start itraconazole 400 mg/day for 8 weeks. • Start ART. Secondary prevention • Itraconazole 200 mg orally daily, for at least 6 months after the patient’s CD4 has increased to more than 200 on ART.

11.30 Rabies and animal bites29 11.30.1 Rabies Rabies is a fatal viral disease that can affect all mammals. The virus is transmitted through inoculation of saliva, usually from the bite of an infected animal. The distribution is worldwide but the human disease is more common in developing 29 WHO guide for rabies pre and post-exposure prophylaxis in humans. WHO, June 2010. Available at http://www. who.int/rabies/PEP_prophylaxis_guidelines_June10.pdf Human Rabies Symptoms & Pre-Exposure Immunization, WHO. Available at http://www.who.int/rabies/human/ sympt_pre_exp/en/index.html Weekly epidemiological record. Rabies vaccine: WHO position paper. WHO, August 2010. Available at http:// www.who.int/wer/2010/wer8532.pdf WHO Expert consultation on rabies: ﬁrst report. WHO, 2005. (WHO Technical Report Series, no. 931). Available at http://www.who.int/rabies/trs931_%2006_05.pdf

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countries. An estimated 55 000 people die from rabies per year in Africa and Asia. More than 95% of the deaths are due to exposure to dogs, which are the major reservoir and transmitter of rabies, but transmission by wild animals such as bats, foxes, and wolves is also possible. The incubation period is relatively long (ranging from 3 weeks to 3 months) but can be as long as several years in rare cases. The closer the inoculation site is to the central nervous system, the shorter is the incubation period. It is important to note that in cases of exposure to bats, often a bite cannot be identiﬁed and the patient may be unaware or unsure whether exposure at the time had occurred. Key clinical features • Prodrome: ° Paresthesias (pins and needles sensation) around bite area are very suggestive of rabies. ° Fever, headache, malaise, muscle pain, nausea, vomiting, and cough. • Acute neurologic phase: ° Confusion, delirium, altered mentation, agitation, hallucinations. ° Excitation predominates in many cases with hypersensitivity or spasms in response to touch, noise, visual, or olfactory stimuli. Hydrophobia (fear of water) and aerophobia (fear of air) may occur, and when they occur they are very suggestive of rabies. ° In paralytic rabies, phobic spasms occur in only half of patients. In early paralytic rabies, piloerection and myoedema may occur at percussion site on the chest, deltoid muscle, and thigh. ° Autonomic system dysfunction: enlarged pupils, increased production of saliva, tears, perspiration. • Coma: ° Occurs after several days to 1 week. ° Hypoventilation, loss of temperature control, heart dysfunction can lead to death. • Ascending paralysis: similar to Guillain-Barré syndrome, occurs in some cases and makes diagnosis more difﬁcult. • Atypical or non-classic rabies is increasingly being identiﬁed. Investigations In the early phase, most laboratory tests are non-speciﬁc. Diagnosis rests on history of exposure and typical neurological ﬁndings. • CSF: increased white cells (lymphocytes), mildly increased protein. • Laboratory conﬁrmation is usually postmortem (direct ﬂuorescent antibody test (FAT); or by ELISA in clinical specimens, preferably brain tissue; or FAT after inoculation of brain tissue, saliva, or CSF in cell culture; or after intracerebral inoculation in mice; or by PCR) although FAT or PCR on clinical specimens (e.g. skin from the nape of the neck) are possible antemortem. • Apparently healthy dogs and cats at the origin of the exposure should be kept under observation for 10 days. Dogs and cats that are suspected of being rabid, as well as wild animals, should be humanely killed and their tissues examined in the appropriate laboratory. Treatment There is no effective treatment against rabies. It is almost always fatal. Supportive management is important; recovery is exceedingly rare and has only occurred in cases where intensive respiratory and cardiac support were available.

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Palliative care The short clinical course of rabies entails much suffering, whether excitation or paralysis is predominant. Patients remain conscious, are often aware of the nature of their illness, and are often very agitated, especially when excitation is predominant. Patients with rabies should receive adequate sedation and comfort with emotional and physical support, preferably in a private room. Repeated IV morphine can relieve severe agitation and phobic spasms. Sedation with barbiturates can be added. Avoid intubation and other life support measures when the diagnosis is certain.

Health worker safety It is theoretically possible for person-to-person rabies transmission to occur since secretions may contain the virus; this has not been described. As a precaution, medical and nursing staff must wear mask, gloves, and goggles.

11.30.2 Rabies post-exposure vaccination after animal bites After an exposure the following measures should be undertaken: • Wound care for any scratches, abrasions, bites, or licks on broken skin: ° immediately scrub with alkaline soap and water, and ﬂush with water for 15 minutes; ° povidone-iodine or benzalkonium chloride 1–4% should be used on the wound, if available. • Decide on post-exposure vaccination and immunoglobulin use depending on type of contact.

Categorize the type of contact with the rabid animal The indication for post-exposure vaccination with or without rabies immunoglobulin depends on the type of contact with the rabid animal. Types of contact are: • Category I – touching or feeding animals, licks on the skin. • Category II – nibbling of uncovered skin, minor scratches or abrasions without bleeding. • Category III – single or multiple transdermal bites or scratches, licks on broken skin, contamination of mucous membrane with saliva from licks; exposure to bat bites or scratches. Treat according to category of contact: • Category I – no treatment is required • Category II – immediate vaccination • Category III – immediate vaccination and administration of rabies immunoglobulin Depending on vaccine type, the post-exposure schedule prescribes intramuscular doses of 1 ml or 0.5 ml given as 4 to 5 doses over 4 weeks. As for all vaccines, appropriate staff training is needed to ensure correct storage, reconstitution, and injection technique.

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If no prior rabies vaccination In category III exposure, and if available, rabies immunoglobulin should be used in addition to human rabies vaccine. In category II exposure, only vaccination is necessary. Immunoglobulin: Human rabies immune globulin 20 IU/kg or equine rabies immunoglobulin 40 IU/ kg (mostly injected at the site of the bite). If any is leftover, inject IM at a distant site. This can be given up to 7 days post-exposure if not available immediately. Vaccination: Tissue-culture or puriﬁed duck-embryo vaccines with a potency of at least 2.5 IU per single intramuscular immunizing dose, measured by the NIH test, should be applied according to the schedules below. Both regimens can be used in Category II and III exposures. Intramuscular schedules One dose of the vaccine should be administered on days 0, 3, 7, 14, and 30. In immunocompetent people, a regimen consisting on 4 doses on days 0, 3, 7, and 14 plus immunoglobulin may also be used. All intramuscular injections must be given into the deltoid region. The vaccine should never be administered in the gluteal region. Abbreviated multisite schedule In the abbreviated multisite schedule, the 2–1–1 regimen, 1 dose is given in the right arm and 1 dose in the left arm at day 0, and 1 dose applied in the deltoid muscle on days 7 and 21. Intradermal schedule In order to reduce the cost of post-exposure treatment, intradermal multisite regimens using a fraction of the intramuscular volume per intradermal inoculation site have been developed. Only the cell-derived vaccines that meet the WHO requirements regarding safety, potency, and efﬁcacy for this application may be considered for intradermal use. This regimen can be used in Category II and III exposures. WHO recommends the following intradermal regimen and vaccines for use by the intradermal route: 2-site intradermal method (2–2–2–0–1–1) for use with PVRV (Verorab TM, Imovax TM, Rabies vero TM, TRC Verorab TM) and PCECV (Rabipur TM). 2-site intradermal method (2–2–2–0–1–1). The volume per intradermal site is: • 0.1 ml for PVRV (Verorab TM, Imovax TM, Rabies vero TM, TRC Verorab TM) and PCECV (Rabipur TM).

If prior pre- or post-exposure vaccination For rabies-exposed patients who have previously undergone complete preexposure vaccination or post-exposure treatment with cell-derived rabies vaccines, 2 intramuscular doses of a cell-derived vaccine separated by 3 days are sufﬁcient. Rabies immunoglobulin treatment is not indicated in such cases. The same rules apply to persons vaccinated against rabies who have demonstrated neutralizing antibody titres of at least 0.5 IU/ml.

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11.30.3 Pre-exposure vaccination Pre-exposure vaccination is recommended for those in rabies diagnostic and research laboratories and veterinarians, individuals at high risk of exposure such as stray dog handlers, park ofﬁcials, or bat handlers. • Pre-exposure vaccination is administered as 1 full dose vaccine given 3 times, IM or 0.1 ml intradermal, on days 0, 7, and 21 or 28. A few days variation is acceptable. • Immunized individuals still need to get 2 post-exposure (after a bite) booster doses (see above). • Professional groups at high risk of exposure to live virus (laboratory researchers and technicians) should have their antibody level checked regularly every 6 months and receive a booster when the level is <0.5 IU/ml.

11.31 Renal problems (kidney disease) This Section focuses on renal problems, including acute kidney injury (AKI) (previously called acute renal failure), chronic kidney disease (CKD), haematuria, and proteinuria. Early diagnosis is imperative because focused management can improve or preserve kidney function and ultimately improve patient survival.

11.31.1 Clinical approach Step 1: Ensure that there are no serious or life-threatening conditions. AKI can present as a result of shock. AKI and CKD can cause volume overload, seizures, or altered consciousness from uraemia or electrolyte imbalance. Use the Quick Check and emergency treatments found in Section 2 to rapidly assess and treat patients with these problems. If the patient continues to have problems that are acute complications of kidney disease, use the table below, DDx: Acute kidney injury, to provide the appropriate treatment. Take a history and examine the patient. Examine the patient to identify key signs: Look for clues that reveal the underlying cause of kidney disease. Check urine output. Assess HIV status. Undertake investigations. Determine the time course of kidney disease and work through the differential diagnosis. Request special investigations or diagnostic tests to conﬁrm the diagnosis; or refer to a local referral hospital. Initiate treatment and monitor response. Re-evaluate as necessary. AKI can present as a result of shock. AKI and CKD can cause volume.

Step 2:

Step 3: Step 4: Step 5:

Step 6:

Use the Quick Check to look for serious or life-threatening conditions and respond using the following Sections: • • • • • • Volume overload: . . Hyperkalaemia: . . . . Metabolic acidosis: . Uraemic pericarditis: Seizures: . . . . . . . . . Drug overdose: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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History and examination A good history and physical examination provides important information about the possible causes of kidney disease. Non-speciﬁc symptoms and signs of kidney disease • hypertension • oedema • shortness of breath • nausea or vomiting • decreased appetite or weight loss • pulmonary problems and arthralgias – suggest vasculitis • weakness (from anaemia). Signs and symptoms that might hint at underlying causes • ﬂank pain – suggests kidney stone or pyelonephritis • fever, anuria – suggest shock or malaria • anuria, abdominal pain, or distended bladder – suggest obstruction • abdominal distension can occur from chronic bladder obstruction or ascites. Signs and symptoms of uraemia, severe CKD • pericarditis • altered consciousness • neuropathy • bleeding • uraemic frost (white calciﬁcations on the skin) • uraemic foetor (odour of stale urine) • uraemic ﬂap. Check urine output • oliguria – less than 400 ml urine output in 24 hours • anuria – less than 100 ml urine output in 24 hours (most commonly due to shock or bilateral obstruction).

Assess the patient’s HIV status HIV infection is associated with several kinds of kidney disease, including HIVassociated nephropathy (HIVAN). However, patients with HIV may also develop kidney problems due to opportunistic infections, sepsis, medications, and autoimmune causes. Moreover, HIVAN is an indication to start antiretroviral therapy irrespective of the CD4 count. Investigations Many symptoms often do not manifest until kidney disease is severe, making it difﬁcult to diagnose. Kidney disease often is discovered as an abnormality on a routine laboratory test, including an abnormal urinalysis or elevated serum creatinine.

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If kidney disease is suspected, the following investigations can be useful in determining the cause: • urine dipsticks for haematuria, protein, glucose, nitrites, pH, bilirubin, urobilinogen, and speciﬁc gravity; • urine microscopy for leucocytes more than 10/ml, red cell more than 2/ml, casts and crystals • serum electrolytes: K, Na, HCO3, Cl; • serum creatinine, urea (BUN); • full blood count; • urine electrolytes including urine sodium and urine creatinine ; • ECG if patient has hyperkalaemia – look for peaked T-waves indicating dangerously high levels of potassium (for more on the management of hyperkalaemia, see Section 5.2); • Renal ultrasound: ° Large kidneys suggest hydronephrosis due to obstruction, but may also be caused by HIV, diabetes, amyloidosis, or inﬁltrative malignancy. Hydronephrosis is easily detected by ultrasound. ° Small kidneys suggest CKD (although CKD can present with large kidneys – from the causes mentioned above). Common laboratory abnormalities may include hyperkalaemia and metabolic acidosis. If the creatinine is rising too fast in a patient with haematuria, haemoptysis, or high blood pressure, this patient may be having rapidly progressive glomerular nephritis and will need prompt referral for further management.

11.31.2 Acute kidney injury (AKI) It is important to determine the time course of kidney disease and work through the differential diagnosis. AKI is a sudden loss of kidney function as evidenced by oliguria and an increase in serum creatinine of ≥0.3 mg/dl above baseline within 48 hours, or a doubling of the serum creatinine.

Differential diagnosis of acute kidney injury Factors that may be used to differentiate the causes of AKI include history, physical examination, and lab ﬁndings including the BUN: creatinine ratio and urinalysis. Use the DDx table that follows.

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Table: DDx: Acute kidney injury (AKI) Condition In favour of

PRERENAL (decreased effective arterial volume) Hypovolaemia, hypotension due to sepsis or any other cause Congestive heart failure, arrhythmias Renal vasoconstriction due to NSAIDs, ACE inhibitors, iodinated contrast, amphotericin B Hypercalcaemia Hepatorenal syndrome INTRARENAL Malignant hypertension Rhabdomyolysis Acute tubular necrosis Very high blood pressure, history of hypertension, poor adherence to drugs Recent trauma Prolonged pre-renal state; hypotension; very dark urine – malaria (blackwater fever); AKI, jaundice, bleeding – leptospirosis (Weil’s disease) Recent streptococcal infection (scarlet fever, pharyngitis, cellulitis), haematuria, or haemoptysis History of rheumatic disease (lupus, vasculitis), hepatitis B or C; arthritis Both – low platelets, anaemia, renal failure HUS – preceding episode of bloody diarrhoea (Shigella, E. coli) TTP – neurologic abnormalities, fever Recently received cephalosporins, ciproﬂoxacin, NSAIDs, penicillins, or phenytoin; fever, drug rash Vomiting, diarrhoea, severe burns, orthostasis, low blood pressure, tachycardia, reduced skin turgor, fever, infection Oedema, dyspnoea, increased JVP Recent use of any of these medicines

Polyuria, kidney stones, confusion History of liver disease, hepatitis, alcohol use

Acute glomerulonephritis: rapidly progressive, poststreptococcal Vasculitis HUS, TTP

Acute interstitial nephritis

POSTRENAL (obstruction). Can be oliguric or non-oliguric, may have distended bladder on examination, hydronephrosis on ultrasound Prostate hypertrophy or cancer Neurogenic bladder Ureters – kidney stones, tumour, retroperitoneal ﬁbrosis Nocturia, hesitancy, urgency History of spinal trauma, stroke; urgency, incontinence Flank pain if kidney stones, stones visible on abdominal X-ray

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Management of AKI that is prerenal • Is usually treated with volume repletion with the goal of improving renal perfusion. • Sepsis and volume depletion are common risk factors for AKI. Use the Quick Check to respond rapidly to signs of sepsis. • Congestive heart failure is treated with diuresis to correct the haemodynamic imbalance leading to renal insufﬁciency. ° In patients with pulmonary edema, AKI, and oliguria, a high dose of diuretics may be required; for example, furosemide up to 250 mg IV (1 dose); may be repeated to daily maximum of 1 g. Lack of response to furosemide 250 mg likely means that even higher doses will not be effective; consider referral for dialysis, if available. • Appropriate non-nephrotoxic antibiotics, antifungals, and antivirals should be started as soon as possible. Avoiding nephrotoxins is imperative. • Many drugs need dose adaptation in function of GFR (see annexes 1 and 2 at the end of this Section).

Management of AKI that is postrenal Treatment requires removal of the obstruction, and is dependent on the site of obstruction. • Patients with a bladder outlet obstruction or neurogenic bladder should immediately have a urinary catheter placed. • A suprapubic catheter may be required if a urinary catheter cannot be passed through the urethra. • Post-obstructive diuresis may exceed 500–1000 ml/hour and may lead to hypotension and hypokalaemia. • Urinary output, vital signs, and electrolytes should be closely monitored. Some ﬂuid therapy is required due to initial concentration problems, but usually 75 ml/hour of normal or hypotonic saline is sufﬁcient. • Referral to higher centres is necessary for obstructions in the ureters or renal pelvis. A surgical consultation for stent or nephrostomy placement may be required. • All patients with suspected kidney stones should be treated with IV ﬂuids for hydration and pain medications as needed.

Management of AKI that is intrarenal • Recognize AKI and the need for referral to higher centres for further management if kidney function does not improve after initial steps. • Improve renal perfusion. • Remove offending drugs or agents. • Treatment of sepsis. • Manage malignant hypertension using local guidelines (avoid using sublingual nifedipine because it lowers BP too fast). If attempts at medical management fail, refer to a higher centre for dialysis. If not available, continue to treat and manage symptoms as they arise.

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11.31.3 Chronic kidney disease (CKD) Chronic kidney disease means abnormal investigations have been present for greater than 2 months, including abnormal urea, creatinine, urine analysis, ultrasound, or GFR less than 60. Some patients may require referral to a tertiary centre or nephrologist for renal biopsy and deﬁnitive diagnosis and management, which might include dialysis. Table: DDx: Chronic kidney disease (CKD) Category Glomerular (requires referral for diagnosis) Condition Diabetes mellitus HIV nephropathy Sickle-cell disease glomerulopathy Glomerulonephritis (may also be acute) In favour of Long-standing diabetes, diabetic retinopathy Uncontrolled HIV, nephrotic syndrome, normal size kidney on ultrasound Proteinuria Increasingly severe anaemia Proteinuria variable UA shows RBCs, WBCs, granular casts, RBC casts Underlying etiology: tuberculosis, streptococcal infection, hepatitis B, hepatitis C, HIV, malaria, ﬁlariasis, schistosomiasis Nephrotic range proteinuria, low albumin UA with no (or few) casts, cells Long-standing hypertension, hypertensive retinopathy, heaving apex beat or evidence of left ventricular hypertrophy on ECG Mild proteinuria, haematuria, WBCs, WBC casts, eosinophils Underlying etiology: visceral leishmaniasis/kala-azar, analgesics Underlying etiology: urolithiasis, BPH, schistosomiasis, nephrolithiasis, malignancy Haematuria, proteinuria, RBC casts, WBCs History of rheumatic disease (lupus, vasculitis), hepatitis C; arthritis Severe hypertension, abdominal bruit, ﬂash pulmonary oedema, unequal kidney sizes >2 cm on ultrasound, common in young females Family history, renal cysts on ultrasound, haematuria, ﬂank pain, hypertension

Nephrotic pattern (may also be acute) Nonglomerular Hypertension Interstitial nephritis Obstructive nephropathy Vasculitis Renal artery stenosis Polycystic kidney disease

Screen all patients with CKD for the major risk factors • diabetes mellitus • hypertension • HIV and related therapies. It is important that all patients with suspected renal disease have their blood sugar measured, BP taken and their HIV status established. If negative for the above, consider referral to a higher centre for speciﬁc diagnosis and management.

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Risk factors for kidney disease in PLHIV • race: black persons of African descent • family history of kidney disease • co-morbidities: diabetes mellitus, hypertension, cardiovascular disease, hepatitis C coinfection • low CD4 count (less than 200) • high HIV RNA levels (more than 4000 copies/ml).

Stage the patient with chronic kidney disease If possible, the patient should be staged by determining the glomerular ﬁltration rate (GFR), a measure of kidney function, by estimating the creatinine clearance. Using the Cockcroft-Gault formula is one way to estimate GFR: Creatinine clearance = [140 - age (years)] x weight (kg) x (0.85 for females) 72 x serum creatinine (mg/dl) Table: Stages of CKD Stage 1 2 3 4 5 GFR >90 (but persistent albuminuria) 60–89 30–59 15–29 <15 (or dialysis) Goals Evaluate for any underlying conditions and complications and treat. Consider cardiovascular risk. Follow and estimate progression. Watch for complications and provide treatment.

Prepare for dialysis if available, counsel regarding prognosis and palliative care if unavailable. Refer for dialysis if uraemic, and dialysis available. If not, supportive care and symptom control.

Management of CKD Look for and treat reversible causes: • infectious and autoimmune causes; • treat hypovolaemia; • stop the administration of potentially nephrotoxic drugs: ° these include NSAIDs, aminoglycoside antibiotics, and IV contrast media; ° look for and treat urinary tract obstruction; renal ultrasound may assist with the identiﬁcation of the obstruction. Intervene to slow disease progression: • reduce sodium intake (<2.4 g/day or <100 mmol/day, which is equivalent to <6 g of salt) • careful blood sugar control, diabetics should be treated with ACE inhibitors to slow the progression of diabetic nephropathy; • aggressive BP control to lower than 130/80; ACE inhibitors are preferred, especially in patients with proteinuria;

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• treat hyperlipidaemia with a statin;30 • encourage smoking cessation. Volume management: • Assuming that the patient is not hypovolemic, treat oliguria and edema (especially pulmonary edema) with furosemide (higher dose, such as 40 mg to 160 mg daily may be needed, depending on the degree of renal impairment). Care for end-stage patients: • Refer for peritoneal or haemodialysis to higher centres. • If dialysis is unavailable, treat and prevent complications along with symptom control (see Section 20 Palliative care).

11.31.4 Proteinuria Diagnosis and evaluation Almost all kidney diseases result in proteinuria. The urine dipstick for proteinuria is an excellent screening test for kidney disease, and although it is semi-quantitative, the gradations of 1+ to 4+ reﬂect increasing protein concentration. Table: DDx: Proteinuria Category Glomerular Etiologies Glomerulonephritis Nephrotic syndrome Medicines (heroin, captopril, lithium, NSAIDs) Allergic Infectious (bacterial, viral, parasitic, fungal) Pre-eclampsia Sickle-cell disease Functional (fever, exercise, CHF) Orthostatic (positional) Idiopathic (transient or persistent) Tubular ATN AIN Medicines (e.g. out-dated tetracycline) Multiple myeloma In favour of May have >3 g/d proteinuria

Asymptomatic No history of renal disease Normal renal function, urinalysis, and imaging Not apparent on urine dipstick Typically <1–2 g/d proteinuria Not apparent on urine dipstick

Overﬂow

30 See Adaptation Guide.

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Figure: Evaluation of the patient with proteinuria Proteinuria

History and physical Normal Repeat urine dipstick Positive Serum creatinine

Suggestive

Treat underlying condition, consider referral

Negative

Transient proteinuria

High creatinine Proteinuria 4+

Nephrotic range proteinuria Workup: FBC total protein albumin renal ultrasound Consider referral

Creatinine normal Proteinuria <4+

Overnight proteinuria negative Split urine test Overnight urine protein elevated Orthostatic proteinuria

Workup: Renal ultrasound Consider referral

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11.31.5 Haematuria Diagnosis and evaluation Haematuria can be clearly visible, red to brown coloured urine, or may only be detectable on urinalysis. Menstruating women should be asked to cleanse the perineum prior to collection of a urine sample. Microscopic haematuria is not grossly visible, but can be detected by urine dipstick or microscopic examination of the urine. It is deﬁned by the presence of more than 2 RBCs per high-powered ﬁeld. Urine dipsticks are sensitive enough to detect this small amount. Consider the differential diagnosis and possible etiologies of haematuria using the following table. Table: DDx: Haematuria Category Glomerular Etiologies Neoplasm Trauma Vascular: renal infarct, renal vein thrombosis Glomerulonephritis Sickle-cell disease Nephrolithiasis Neoplasm: prostate, bladder Infection: UTI, prostatitis Traumatic urinary catheter placement In favour of May have smoky brown appearance Dysmorphic appearing RBCs Proteinuria >1 g/d or ≥2+ May have cellular casts, including RBC casts (diagnostic of glomerulonephritis) May have clots Normal appearing RBCs No proteinuria or ≤2+

Nonglomerular/ extrarenal

A patient with a clear glomerular etiology for haematuria will likely require referral to a nephrologist for renal biopsy. If the history and physical are not suggestive of a particular cause: • The patient should be tested for schistosomiasis, and treated if positive. • If these tests are negative, 3 samples of urine should be sent for AFB smear, and if positive, the patient should be treated for TB. • Sterile pyuria with haematuria should raise the index of suspicion for TB. If the AFB smear is negative, check for other symptoms suggestive of TB (weight loss, cough, night sweats). When positive, perform a sputum exam and a chest X-ray (and an abdominal ultrasound) to evaluate for tuberculosis.

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Figure: Evaluation of the patient with haematuria Haematuria Suggestive

History and physical

Treat underlying condition Consider referral Praziquantel 40 mg/kg orally twice daily at least 6 hours apart

Indeterminate Urine microscopy for schistosomiasis eggs Serum schistosomiasis antigen, if available Negative Urine for 3 AFB smears Negative Any positive Consider referral Positive Treat TB Positive

<40

Repeat UA twice, every 6 months

All negative

Isolated haematuria, repeat in 1 year See evaluation of the patient with proteinuria

Proteinuria develops Age? Positive >40 Repeat UA in 1 month Negative

Consider referral

Repeat twice, every 6 months

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11.31.6 HIV-associated nephropathy (HIVAN) Renal disease in HIV-positive patients occurs commonly. It is often due to a glomerular pathology. However, there are several other causes that should be considered. Given the underlying disease, the tendency to acquire opportunistic infections, and problems associated with treatment with multiple drugs, HIVpositive patients are at risk for acute kidney injury, most often from prerenal causes or acute tubular necrosis. HIVAN usually presents with: • nephrotic syndrome and oedema • nephrotic range proteinuria (more than 3 g/d) • no RBC casts in the urine • varying degrees of renal dysfunction • hypoalbuminaemia. Renal ultrasound will often demonstrate echogenic kidneys. Blood pressure is typically within normal limits. Investigations • Urinalysis, followed by creatinine and quantitation of urine protein • Additional tests should include an FBC, total protein, albumin, and renal ultrasound. Treatment • The diagnosis of HIVAN is an indication to start antiretroviral therapy. • Early diagnosis of HIVAN can stabilize renal function or at least slow the progression to end-stage renal disease. • However, if diagnosed late when the renal functions is already at CKD stage 3 or worse, rapid progression to end-stage renal disease usually occurs even with ART.

Nephrotic syndrome or nephrotic range proteinuria and HIV-infected and not on ART • Start ART (do NOT include tenofovir) and ACE-I; • To start ACE inhibitor – see Figure: Algorithm for HIV-associated nephropathy: ACE inhibitor, below. Give ﬁrst dose ACE at night and consider suspending diuretics for 1 day or 2 when starting. • Follow random urine protein to creatinine ratio, serum electrolytes and serum creatinine: ° if worsening or not better in 3 months, refer to nephrology; ° if unable to refer to nephrology soon, and proteinuria is not better after 3 months on ART plus ACE-I or ARB, then consider adding prednisone 40 mg oral daily for 2 to 4 weeks and recheck proteinuria and serum creatinine. ◊ If better, consider continuing therapy for another 4 weeks, and recheck proteinuria. If the proteinuria resolves, taper prednisone gradually over 4 weeks. ◊ If the proteinuria is not better after 4 weeks, taper the prednisone. Note: Do not start prednisone if active tuberculosis or other uncontrolled systemic infection is present or highly suspected.

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Figure: Algorithm for HIV-associated nephropathy: proteinuria evaluation HIV+ patient >12 years-old with new diagnosis or no prior urine dipstick Follow-up in 6 months Follow-up in 1 year

Check urine dipstick and serum creatinine

Cr >2.3 mg/dl? Yes 1. Urine microscopy 2. Kidney ultrasound 3. Refer to nephrologist (if available) Yes And Proteinuria present? No CD4 >500? No

Yes <4+ proteinuria Repeat urine dipstick in 2 weeks

No Proteinuria present?

Yes

4+ proteinuria = NEPHROTIC SYNDROME

PERSISTENT PROTEINURIA

Hospitalize patient

Yes

Severe oedema?

Start ART (regardless of CD4) And 1. Start ACE-inhibitor (see next Figure) 2. Urine microscopy 3. Kidney ultrasound 4. Consult specialist 5. Consider renal biopsy

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Figure: Algorithm for HIV-associated nephropathy: proteinuria evaluation

How to increase enalapril dose Current dose Enalapril 2.5 mg Enalapril 5 mg Enalapril 10 mg Enalapril 20 mg Enalapril 40 mg Enalapril 40 mg and hydrochlorthiazide 12.5 mg daily Dose to give Enalapril 5 mg Enalapril 10 mg Enalapril 20 mg Enalapril 40 mg Enalapril 40 mg and hydrochlorthiazide 12.5 mg daily Continue medication and consult specialist

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Annex 1: Dose adjustments of common medications in HIV infection based on kidney function Drugs Ciproﬂoxacin Isoniazid Ethambutol Pyrazinamide Rifampicin Streptomycin Usual dose 750–1000 mg daily 300 mg daily 15 mg/kg daily 25–30 mg/kg daily 600 mg daily 15 mg/kg daily >50 ml/min 100% 100% 100% 100% 100% 100% 10 to 50 ml/min 75% 100% 15 mg/kg every 36 hours 100% 100% 15 mg/kg every 48 hours <10 ml/min 50% 100% 15 mg/kg every 48 hours 60 mg/kg twice a week 50–100% 15 mg/kg every 72 hours Follow serum creatinine closely and stop if creatinine rises Comments

Cotrimoxazole for treatment Cotrimoxazole for prevention

1 double-strength tablet (800/160 mg) twice daily 1 double-strength tablet (800/160 mg) once daily

100%

50%

Full daily dose every 48 hours One half singlestrength tablet (400/80 mg) daily

100%

One half singlestrength tablet (400/80 mg) daily

Annex 2: Antiretroviral agent dose adjustment based on kidney function Drug Abacavir Didanosine Usual dose 600 mg daily 400–250 mg daily (depends on weight) 300 mg daily 20–30 mg twice daily (depends on weight) 300 mg twice daily 300 mg daily 30–59 ml/min No adjustment 60 kg–200 mg/d <60 kg–125 mg/d 150 mg/d >60 kg–20 mg q12h <60 kg–15 mg q12h 300 mg twice daily 300 mg every 48 hours 10–29 ml/min No adjustment >60 kg–125 mg/d <60 kg–100 mg/d 100 mg/d >60 kg–20 mg/d <60 kg–15 mg/d <10 ml/min No adjustment >60 kg–125 mg/d <60 kg–75 mg/d 50 mg/d >60 kg–20 mg/d <60 kg–15 mg/d Comments

Lamivudine Stavudine

Zidovudine Tenofovir

300 mg twice daily 300 mg twice a week

300 mg/d Replace TDF with another NRTI Try to avoid if kidney function less than 50 ml/ minute. FDCs like truvada should be avoided in CKD

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11.32 Rheumatic fever31 Rheumatic fever (RF) occurs as a complication of group A streptococcal infection (pharyngitis). It is currently rare in industrialized countries, but is still an important cause of disease in the developing world. About 3% of patients who have acute streptococcal infection will go on to develop RF. Acute rheumatic fever usually occurs between the ages of 5 and 15, although it is also seen in adults up to the age of 40. Key clinical features The diagnosis of RF is mostly clinical, based on the Jones criteria. Jones criteria: This involves either 2 major criteria, or 1 major and 2 minor criteria, plus evidence of previous streptococcal infection. • Major criteria ° Carditis: sinus tachycardia, mitral valve disease, pericardial rub, enlarged heart. ° Migratory polyarthritis: extremely painful inﬂammation of medium joints (ankles, wrists, elbows, knees) over a few days. ° Sydenham’s chorea: uncoordinated jerky movements affecting the face and limbs with loss of ﬁne motor skills and problems with walking. ° Subcutaneous nodules: a rare manifestation, nodules are found over the extensor surfaces of joints, mostly in patients with long-standing disease. ° Erythema marginatum: also rare, a vanishing macular rash with rounded borders, usually found on the trunk. • Minor criteria ° Clinical: fever, arthralgias. ° Laboratory: elevated ESR, prolonged PR interval on ECG. Investigations • ECG can show increased PR interval. • Echocardiography for valvular heart disease is helpful, if available. • Throat culture can yield streptococci in up to 40% of patients. • Anti-streptolysin (ASO) titres are elevated in 80% of patients. Treatment Antibiotics are effective in primary prevention (see Section 10.17), treatment of acute rheumatic fever, and for secondary prophylaxis. For all three situations, benzathine benzyl penicillin is recommended as the preferred ﬁrst-line therapy. Evidence shows that this antibiotic can reduce recurrences and that IM therapy is better than oral therapy for this outcome. However, oral phenoxymethyl penicillin is an alternative if injections are unacceptable or not possible. In patients with hypersensitivity to penicillins, erythromycin is the recommended antibiotic. • Anti-streptococcal antibiotic treatment ° benzathine benzylpenicillin G 1.2 million units single dose (preferred); ° phenoxymethyl penicillin 500 mg twice daily for 10 days; OR ° erythromycin 250 mg 4 times daily for 10 days, if allergic to penicillin. • Symptomatic therapy ° salicylates escalating to a maximum dose of 2 grams 4 times daily for 4–6 weeks with a tapered dose at the end. Note: Gastric protection required. 31 Rheumatic fever and rheumatic heart disease. Chapter 8. In: Medical management of rheumatic fever. WHO, 2004. Available at http://whqlibdoc.who.int/trs/WHO_TRS_923.pdf

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° steroids may be useful for patients with severe carditis complicated by congestive heart failure.

Secondary prophylaxis • With carditis – prophylaxis for 10 years or until age 25: ° benzathine penicillin G 1.2 million units every 4 weeks; OR ° phenoxymethyl penicillin 250 mg orally twice daily; OR ° sulfadiazine 1 g orally once daily; OR ° erythromycin 250 mg twice daily, if penicillin allergy. • In valvular disease, prophylaxis is given up until 40 years of age or lifelong. • Without carditis ° As above for a minimum of 5 years or until age 21.

11.33 Rickettsial diseases (scrub typhus, typhus) Rickettsia are a group of bacteria that are intracellular, and thus are resistant to the action of many antibiotics. Individual species are mostly endemic to a speciﬁc region. Signiﬁcant species include Rickettsia africae (African tick typhus; found primarily in southern Africa), R. conorii (Mediterranean tick typhus; found around the Mediterranean sea and in subSaharan Africa), R. prowazekii (epidemic typhus; found in several regions in Africa and the Americas) and Orientia tsutsugamushi (scrub typhus; found in Asia, India, and Pakistan). Most are transmitted by ticks or mites, and an eschar may be evident at the bite site. Key clinical features • non-speciﬁc illness of fever and myalgia • maculopapular rash, sometimes petechial, may be present depending on which species • eschar: a dark scab (also called black spot) at the site of the tick bite may be present • central neurological signs, such as severe headache or stupor are sometimes found • a history of tick bit is often lacking • in some rickettsial infections, non-speciﬁc signs of severe illness and septic shock can occur. Investigations No laboratory test to diagnose rickettsiosis in the acute phase is available (except PCR on a biopsy of a skin lesion). This disease is thus suspected in a patient living in or having travelled to an endemic area, with fever and an eschar, or with fever and a rash, or with fever and a history of tick bite. As rickettsiosis does not respond to usual antibiotics and is potentially rapidly fatal, presumptive treatment should be given as soon as the diagnosis is suspected. Treatment • antibiotics with regimens active against rickettsial disease include: ° doxycycline 100 mg orally twice daily for 5 to 7 days; OR ° chloramphenicol 500 mg orally every 6 hours, in pregnancy.

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Scabies see Section 10.5.2 Skin problems 11.34 Schistosomiasis (Bilharziasis)8,32,33,34 Schistosomiasis or “bilharziasis” is a disease caused by blood ﬂukes. There are ﬁve main species of schistosome that cause disease in humans: Schistosoma haematobium, S. mansoni, S. japonicum, S. intercalatum, and S. mekongi. Larvae (cercariae) enter the body via intact skin in contact with infested water, usually while swimming, washing, wading, or working. Adult worms develop in the liver, live in the veins around the gastrointestinal and genitourinary tracts, and produce eggs that are deposited around the body. Genitourinary disease is caused by S. haematobium and intestinal disease by S. mansoni, S. japonicum, S. intercalatum, and S. mekongi.

Schistosomiasis affects about 200 million people worldwide, and 650 million people live in endemic areas in Africa, South America, the Caribbean, the Eastern Mediterranean, South-East Asia, and the Western Paciﬁc. The number of deaths, considered to be at least 20,000 per year, is likely to be underestimated due to delayed morbidity.

32 Preventive chemotherapy in human helminthiasis. WHO, 2006. Available at http://whqlibdoc.who.int/ publications/2006/9241547103_eng.pdf 33 Schistosomiasis website: http://www.who.int/schistosomiasis/en/ 34 Schistosomiasis. Weekly epidemiological record. WHO, February 2011. Available at http://www.who.int/ wer/2011/wer8609.pdf

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Key clinical features: Deposited and trapped eggs result in granulomas and scarring in the surrounding tissues. Symptoms are related to the number and location of the eggs. The clinical features of the four disease stages are: 1. Stage of invasion: • Cercarial dermatitis (“swimmers itch”): ° an itchy maculopapular rash that occurs when cercariae invade the skin (cercaria from non-human schistosomes may also cause a dermatitis, but do not go on to cause disease). 2. Stage of maturation: • Acute schistosomiasis (“Katayama fever”): ° usually occurs 4–8 weeks after infection; ° more common in travellers to endemic areas; ° usually mild, self-limited but can be severe manifestations, including neurological (CNS); ° symptoms and signs: fever, chills, cough, muscle aches, prostration, abdominal pain, vomiting, diarrhoea, generalized lymphadenopathy, weight loss, enlarged liver and spleen, confusion, decreased level of consciousness, and spinal cord involvement (myelopathy). 3. Stage of established infection: • It may be asymptomatic or have symptoms related to granuloma formation around deposited eggs, leading to organ dysfunction. Symptoms include: ° abdominal pain, diarrhoea with blood, tender enlarged liver, enlarged spleen (S. mansoni); ° supra-pubic pain, urinary frequency, dysuria, terminal haematuria (S. haematobium). • Lesions of this stage may resolve spontaneously or after anti-schistosomal treatment. 4. Stage of late infection: • Chronic schistosomiasis occurs if granulomas do not resolve and there is progression to ﬁbrosis. Chemotherapy might no longer be effective at this stage. ° intestinal disease: ◊ liver: portal hypertension, periportal hepatic ﬁbrosis, worsening liver function, liver failure, oesophageal varices with bleeding; ◊ intestine: chronic diarrhoea, polyps, protein-losing enteropathy, colorectal malignancy. ° urogenital disease: ◊ renal: kidney stones, hydronephrosis, hydroureter, recurrent infections, bladder calciﬁcation and ulceration, bladder papillomas, bladder cancer, kidney failure; ◊ genital tract: pain on ejaculation, blood in semen, absent sperm (men); painful intercourse, contact bleeding, lower back pain, infertility (females), entry point lesions for sexually transmitted infections. ◊ Other manifestations: • lungs: acute necrotizing arteriolitis, pulmonary hypertension, or pulmonale; • CNS: egg deposit in the brain and spinal cord can cause epilepsy and transverse myelitis.

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Investigations • inspection of urine for visible blood • urine dipstick for microscopic haematuria • markedly raised eosinophil count (rarely present in people living in endemic areas); • demonstration of schistosoma eggs: ° in stool: direct microscopy (qualitative) or Kato-Katz thick smear (quantitative); ° in urine: microscopic examination of urine sediment (qualitative) or ﬁltration through plastic or paper ﬁlters (quantitative); ° in biopsy samples – especially the rectum (rectal snip); ° on speculum examination – eggs appear as “sandy patches” on the cervix, often with associated contact bleeding. Treatment • Acute schistosomiasis: ° Is potentially dangerous and difﬁcult to diagnose (before egg laying); ° Treatment should be started if infection is clinically suspected: ◊ praziquantel 40 mg/kg as a single dose. ° If CNS involvement is suspected, refer patient to tertiary level for further investigation and treatment. • Patients with eggs on microscopy of urine, stool, or tissue specimens: ° Antischistosomal therapy is required: ◊ praziquantel 40 mg/kg as a single dose; ◊ dose may need to be repeated if there is still evidence of infection at follow-up microscopy after 4 weeks. Mild and transient adverse events following treatment may occur: abdominal pain or discomfort, nausea, and headache are the most frequent. To minimize their occurrence and severity, treatment should be administered between meals. Note: Current public health strategies for the control of schistosomiasis include large-scale population-based preventive chemotherapy interventions in endemic areas where the prevalence of infection is estimated at more than 10%.

11.35 Sinusitis Sinusitis is deﬁned as inﬂammation of one or more of the paranasal sinuses. Sinusitis is acute if it has lasted less than four weeks, subacute if it has lasted four to eight weeks, and chronic if it has lasted more than eight weeks. The most common pathogens associated with acute bacteria sinusitis are Streptococcus pneumonia, Haemophilus inﬂuenza, and Moraxella catarrhalis. In some regions of the world, these organisms may be resistant to penicillin. Chronic sinusitis may also be associated with Pseudomonas aeruginosa and anaerobe bacteria. Key clinical features • Acute sinusitis: ° nasal congestion, purulent nasal discharge, facial pain, headache, postnasal drainage, and cough; ° fever, malaise, and sore throat;

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° oedema and erythaema of the nasal mucosa, and purulent secretions. • Chronic sinusitis: ° more subtle presentation; ° nasal congestion, postnasal drainage, slight headache, and fatigue. Sinusitis commonly follows an upper respiratory tract infection with nasal congestion and the blocking of the sinus drainage passageway or underlying allergic rhinitis. Recurrent bacterial sinusitis in PLHIV is a WHO clinical stage 2 condition. An anatomical predisposing factor may be present, e.g. nasal polyposis or deviated nasal septum; surgery may need to be considered in these instances. Complications • facial or periorbital swelling; • visual changes or neurologic signs that could suggest intracranial involvement (mainly intracranial infections). Investigations • The diagnosis of acute sinusitis is usually made clinically. • Sinus X-rays may have signiﬁcant false positives and false negatives, and thus are not recommended. • If available, in case of chronic or complicated sinusitis a CT scan limited to the sinuses might be useful to look for an underlying cause. Treatment For acute uncomplicated sinusitis: • Normal saline irrigation (1/4 spoon of salt in a cup of water) and washout using a syringe without needle or neti pot (frequently sterilized and using sterilized water). • Short-term use (3–5 days) of topical decongestants (e.g. phenylephrine and oxymetazoline). • Oral NSAID. For sinusitis lasting for more than 7 days in spite of these local measures: • amoxicillin 1000 mg 3 times daily for 7 days; OR • amoxicillin-clavulanate 875 mg twice daily for 7 days; OR • oral cephalosporin for 7 days, in particular if the patient has mild allergy to penicillin; • if the patient is severely allergic to penicillin: cotrimoxazole double strength tablets orally twice daily for 7 days. For chronic sinusitis or sinusitis not responding fully to a 10–14 day course of antibiotics: • check if local measures to drain sinuses are applied correctly; • nasal or oral corticosteroids might be beneﬁcial in chronic sinusitis, especially in case of concomitant nasal polyps or mucosal swelling, or in sinusitis due to allergy.

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11.36 Strongyloidiasis Strongyloidiasis is caused by the intestinal parasite Strongyloides stercoralis or Strongyloides fuelleborni (found sporadically in Africa and Papua New Guinea), which has the ability to replicate in the human body and cause overwhelming infection. The worm is acquired through contact with contaminated soil or water containing larvae. The larvae penetrate the skin or mucous membranes. The majority of patients with strongyloidiasis have uncomplicated disease. As many as 50% of patients remain asymptomatic and can survive decades undiagnosed. Symptomatic infections typically manifest in gastrointestinal, pulmonary, and dermatologic systems. Severe symptoms may develop and death may ensue, especially in individuals who are immunocompromised. Strongyloides hyperinfection syndrome usually occurs in immunocompromised hosts and may require hospitalization and intensive care in disseminated infection. Patients with hyperinfection syndrome often have complications of sepsis, shock, and acute respiratory distress syndrome (ARDS). Any patient suspected of disseminated disease should receive care in a facility properly equipped for intensive management. Key clinical features • Skin: ° transient dermatitis when larvae penetrate the skin; ° intensely itchy dermatitis (larva currens) radiating from the anus; ° stationary wheal lasting 1 to 2 days; ° migrating larvae under the skin produce a red, serpiginous rash that moves across the trunk at several centimetres per hour. • Lungs: ° cough and wheeze as larvae migrate through the lungs. • Gastrointestinal: ° symptoms result from the adult worm in the intestinal mucosa; ° epigastric pain aggravated by food; ° nausea, vomiting, diarrhoea, constipation; ° GI bleeding, weight loss. Complications • Small-bowel obstruction with heavy infestation. • Strongyloides hyperinfection syndrome: ° severe wasting; ° secondary peritonitis; ° secondary Gram-negative sepsis with acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC); ° diffuse pulmonary inﬁltrates on chest X-ray; ° coma and death. Disseminated strongyloidiasis, heavy worm loads and hyperinfection syndrome can occur in immunocompromised patients with HIV. There is also a risk of developing hyperinfection syndrome in patients taking high-dose steroids. All patients starting high-dose steroids for a period of more than 1 month should receive treatment for strongyloidiasis before starting the steroids. Pregnant women with suggestive symptoms should be screened and treated if infected.

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Investigations • Eosinophilia • Identiﬁcation of the parasite (larvae): ° stool microscopy or wet mount ° sputum examination in patients with pulmonary symptoms ° duodenal aspirate. • Serology tests for larval stage antigens are sensitive (positive in 80–85%) but not speciﬁc, and may indicate past infection or cross reaction with other nematode antigens not routinely available in limited-resource settings. Treatment • Drug of choice: ° ivermectin 200 micrograms/kg stat or 200 micrograms/kg daily for 2 days. • Less effective: ° thiabendazole 25 mg/kg twice daily for 3–7 days; OR ° albendazole 400 mg twice daily for 3 days. Empirical therapy may be considered in patients with signs and symptoms suggestive of strongyloidiasis infection. THEN: Maintenance therapy once monthly is necessary to suppress symptomatic infection (albendazole 400 mg or ivermectin 6 mg once monthly).

11.37 Syphilis35 Syphilis is caused by Treponema pallidum. Patients with HIV and syphilis may have accelerated or atypical disease. Key clinical features Primary syphilis • Usually presents as a single painless chancre often with regional lymphadenopathy. • Chancres are usually on the genitals but may be found in the anal canal or mouth. Secondary syphilis • Presents weeks to months after the initial infection. • Papulosquamous (papular and scaly) rash which is generalized, and involves palms and soles. • Mucous patches. • Condylomata lata. • Constitutional symptoms of secondary syphilis include malaise, sore throat, headache, fever, and anorexia. Tertiary syphilis • This may progress within a year of initial infection or after latent infection for up to 30 years.

35 Guidelines for the management of sexually transmitted Infections. WHO, 2003 (updated 2011 version in press). Available at: http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf

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• It usually involves skin (cutaneous gummas), heart (aortitis), and neurologic systems. • Neurosyphilis can occur at any stage and is tertiary when it follows on secondary syphilis: ° early neurosyphilis is meningeal or meningovascular, and may present with symptomatic meningitis or meningitis with stroke; ° late neurosyphilis presents with general paresis (dementia) and tabes dorsalis (ataxia, incontinence, pain, and optic atrophy with Argyll-Robertson pupils). Investigations • Dark ﬁeld microscopy is deﬁnitive, but difﬁcult to perform. • Serology becomes positive 2–3 weeks after the appearance of a chancre. • Non-treponemal (diagnostic) tests (RPR and VDRL) correlate with disease activity and are used to follow response to treatment as the titre decreases and the test becomes non-reactive: • Treponemal (conﬁrmatory) tests (FTA-ABS, MHA-TP, and TPHA), as well as the new rapid tests, usually remain reactive for life. Rapid treponemal tests are becoming increasingly available. • Histology of skin may show classic ﬁndings. • Neurosyphilis is difﬁcult to diagnose particularly in HIV-infected patients: ° positive CSF VDRL ° increased CSF protein ° CSF pleocytosis (>5 WBC/µl and probably >20 WBC in PLHIV). Treatment For primary, secondary, and early latent syphilis (<2 years duration) • Give a single dose of benzathine benzylpenicillin G, 2.4 million U IM: ° add 5 ml sterile water to a vial containing 1.2 million units = 1.2 million units/6 ml total volume. Give 12 ml (6 ml in each buttock); OR ° azithromycin 2 g stat. Do not use azithromycin if the patient is HIV-infected. Alternative treatment only for non-pregnant, penicillin-allergic patients: • doxycycline 100 mg orally twice daily or tetracycline 500 mg orally 4 times daily for 14 days.. Alternative treatment only for pregnant, penicillin-allergic patients: • 2 week course of erythromycin 500 mg orally 4 times daily. If the patient is pregnant, plan to treat the newborn. Remember to treat the partner. For late latent syphilis (>2 years duration), syphilis of undetermined duration, and late syphilis: • benzathine benzyl penicillin G, 2.4 million U IM once weekly for 3 consecutive weeks; OR • doxycycline 100 mg orally twice daily, OR tetracycline 500 mg 4 times daily for 30 days; OR • erythromycin 500 mg orally 4 times daily for 30 days.

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For neurosyphilis: • aqueous benzyl penicillin G, 2–4 million U IV q 4h for 14 days; OR • procaine benzyl penicillin, 2.4 million U IM once daily, PLUS probenecid 500 mg orally 4 times daily for 10–14 days. Monitoring treatment • VDRL titres should decline fourfold over the 6–12 months after treatment. • If titres do not decline, rule out neurosyphilis with a CSF examination.

Figure: Treatment of syphilis Positive syphilis screening test Perform treponemal-specific test

Positive treponemal-specific test Establish stage of infection: obtain quantitative nontreponemal test titres

Negative treponemal-specific test

Primary syphilis suspected Obtain quantitative nontreponemal test titres Penicillin G benzathine, 2.4 million units IM (single dose)

False-positive test result Consider other causes

Signs or symptoms of primary or secondary syphilis

No clinical signs or symptoms (latent syphilis)

Signs or symptoms of tertiary (late) syphilis, or patient is HIV-positive or otherwise immunocompromised Lumbar puncture

Early latent syphilis

Late latent syphilis

Penicillin G benzathine, 2.4 million units IM (single dose)

Penicillin G benzathine, 2.4 million units IM once a week for 3 weeks (3 doses

Signs, symptoms, or CSF findings consistent with neurosyphilis

Yes

No penicillin allergy

Penicillin allergy Desensitization

Involve appropriate subspecialists, penicillin G benzathine, 2.4 million units IM once a week for 3 weeks (3 doses)

Aqueous crystalline penicillin G, 3 to 4 million units IV every 4 hours for 10 to 14 days; or Penicillin G procaine, 2.4 million units IM once daily; plus 500 mg of probenecid orally 4 times daily for 10 to 14 days

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11.38 Taeniasis (See also Section 11.7 Cysticercosis – a different disease by same organism.) Taeniasis and cysticercosis are two different diseases caused by the same organism. Taeniasis is an intestinal infection caused by the large adult tapeworms Taenia solium (pork tapeworm) and Taenia saginata (beef tapeworm). Cysticercosis, caused by the larval stage of Taenia solium, involves the tissues, and manifestations in the brain and eye are the main reasons for morbidity. On the other hand, taeniasis in an intestinal form plays an important role as a reservoir for direct transmission to other humans. Humans become infected after ingesting raw beef or pork containing larvae. The larvae develop into adult worms in the gut and cause the intestinal infection (taeniasis). In T. solium infection, the eggs produced by the adult worm are passed out in the stool and faeco-oral auto-infection can occur. The eggs develop into cysts in different parts of the body (cysticercosis) including the muscles and the central nervous system (neurocysticercosis). Neurocysticercosis causes serious morbidity in endemic areas. The diagnosis and treatment of taeniasis and cysticercosis are markedly different, and thus are considered separately. Key clinical features • The majority of intestinal infections with adult worms are asymptomatic. • Suggestive symptoms include: ° early morning abdominal pain, nausea, and vomiting ° history of passing proglottids (motile segments of the worm) in the stool. Investigations • Stool examination: ° observation of proglottids or other tapeworm fragments ° observation of eggs in stool or on anal swabs. Treatment Tapeworm carriers, identiﬁed by positive stool examination, should always be treated even when asymptomatic (epidemiologic indication). Treatment of patients living in an endemic area with suggestive symptoms or history of eating raw pork or beef should be considered even if stool examination is negative. • Both praziquantel and niclosamide are effective: ° praziquantel: ◊ contraindication: presence of ocular cysticercosis; ◊ adults more than 60 kg: 5–10 mg/kg as a single dose; ◊ patients 30–60 kg: 300 mg as a single dose; ° niclosamide: ◊ no contraindications, avoid alcohol during therapy; ◊ adults: 2 g in a single dose; ◊ children less than 35 kg: 1 g as a single dose.

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11.39 Tetanus36 Tetanus is a neurological disease caused by a powerful toxin that is produced by Clostridium tetani growing in necrotic tissue under anaerobic conditions. This organism is found in the soil and animal dung, and is introduced through wounds or injuries. Tetanus can also occur after abortions, childbirth, surgery, injections (both medicinal and injecting drug use – see Section 17 Substance use), burns, chronic wounds and infections, ulcers, and frost-bite. The disease is preventable by adequate vaccination, and clean delivery and aseptic cord care practices, but there are still many cases reported every year, particularly in resource-limited settings where neonatal tetanus cases constitute the bulk of the cases being reported. Key clinical features Generalized tetanus • The incubation period is usually 3–21 days (median 8 days) after injury. • Increased tone in muscles, often starting in the jaw (commonly called «lockjaw»), with difﬁculty swallowing, stiffness and pain in the neck, shoulder, back, or abdominal muscles. • Painful muscle spasms; in severe tetanus, arched back (opisthotonus) and generalized spasms can cause difﬁculty breathing. • Fever is usually absent or low-grade, or may develop if frequent spasms occur. • Mental status is preserved. • Autonomic dysfunction: hypertension or hypotension, tachycardia, dysrhythmias, high temperature, sweating may be seen. Local tetanus • Occurs only in muscles around the site of the wound. • No further CNS involvement occurs and mortality rates are very low, around 1%. Cephalic tetanus • Local tetanus of the head, usually after a middle-ear infection or head injury. This form of tetanus is very uncommon and carries a high mortality rate. Investigations • Diagnosis is only clinical. There is no diagnostic test. • A high WBC may be present. Treatment Tetanus can be fatal if not treated. • Antibiotics reduce the amount of bacteria, hence stopping toxin production. ° metronidazole 500 mg 4 times daily (every 6 hours) for 10 days; OR ° benzylpenicillin 2–4 million units every 6 hours for 10 days. ° tetracyclines, macrolides, clindamycin, cephalosporins, and chloramphenicol are also effective.

36 Current recommendations for treatment of tetanus during humanitarian emergencies. WHO, 2010. Available at http://whqlibdoc.who.int/hq/2010/WHO_HSE_GAR_DCE_2010.2_eng.pdf

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• Antitoxin lowers mortality, but only binds to the toxin that is still circulating. ° human tetanus immunoglobulin (TIG) 500 units IM; OR ° equine tetanus immunoglobulin (not preferred, can produce serum sickness and hypersensitivity reactions). • Management of spasms: ° diazepam titrated to control spasms – large doses (up to 500 mg per day) may be required initially; OR ° phenobarbital to a maximum of 1000–1500 mg in adults; ° chlorpromazine 50–150 mg IM every 4–8 hours (adults), or magnesium sulfate can be used alone (or with diazepam) 5 g IM or 75 mg/kg IV loading dose, then 2–3 g per hour until spasm control is achieved (monitor for toxicity). See Quick Check page 21, Vol. 1. • For severe autonomic dysfunction: ° labetalol (alpha and beta blocker), clonidine, magnesium sulfate, or morphine may be tried. • Intensive care ° Ventilatory support is crucial, and severe cases need to be referred for intensive care. ° With good supportive care (including nutritional support and good nursing care), patients whose spasms can be controlled usually survive with few or no long-term effects. Prevention • See tetanus toxoid dosing schedule in Section 19. • Ensure high coverage with the primary vaccination series with DTP in infancy. • Ensure high coverage with the booster doses at 4-7 years, in adolescence and in pregnancy (see Section 19). • Ensure skilled attendants at birth with aseptic cord care practices. • After acute injury in non-vaccinated persons: ° wash wound with soap and water; THEN ° tetanus immune globulin 250 units IM once; AND ° initiate an age-appropriate primary vaccination series. • All previously vaccinated persons need a booster dose every 10 years. ° For children >7 years, adolescents, and non-vaccinated adults: Td vaccine 0.5 ml IM at 0, 4–8 weeks, and 6–12 months.

11.40 Toxoplasmosis Toxoplasma gondii is a parasite that can cause a variety of illnesses in humans. It is acquired from the ingestion of oocysts, from stools of household pets, or cysts present in undercooked meat. It can be transmitted through blood transfusions and transplacentally from an infected mother to the fetus. The parasites invade the blood stream and form cystic aggregates in tissues. Usually, the patient’s immune system can control the acute infection and dormant cysts develop mainly in the retina and CNS, but also in the heart and lungs. In PLHIV and in fetuses, the poorly functioning immune system leads to a more aggressive primary infection. Dormant cysts are reactivated when CD4 counts drop below 100. Acquired infection in a pregnant woman can be transmitted to the unborn child and cause serious disease and possibly the death of the child.

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Key clinical features In patients who have normal immunity: • many cases do not have any symptoms • cervical lymph node enlargement may occur • fatigue, muscle pain, rash, and sore throat may be present. In PLHIV (usually subacute) • focal ﬁndings – cranial nerve deﬁcits, motor deﬁcits, visual ﬁeld loss, and aphasia are common; • altered mental status, fever, seizures, headaches; • meningeal irritation is infrequent. See Section 10.12 on chorioretinitis. Investigations • Serology: simultaneous presence of IgG and IgM denotes acute infection. The absence of IgG makes infection unlikely (negative predictive value 94–97%). • Encephalitis: CSF ﬁndings are usually normal; a slight increase in the white cell count or protein may be seen. Glucose remains normal. • Multiple or single ring-enhancing lesions may be seen on computed tomography (CT) of the brain, although this form of imaging is rarely available in non-specialized centres. In HIV-infected patients with a suggestive clinical picture and a positive toxoplasmosis serology OR normal CSF ﬁndings, toxoplasmosis treatment should be started. Treatment Option 1 Because of its wide availability in resource-limited settings, cotrimoxazole should be the ﬁrst option treatment for CNS toxoplasmosis. • Give cotrimoxazole 2 double-strength tablets 3 times daily for 6 weeks. • If severely ill and not able to take oral medication, cotrimoxazole IV can be used. Option 2 Pyrimethamine and sulfadiazine: • pyrimethamine 100–200 mg loading dose once, then 50 mg once daily for 6 weeks, PLUS sulfadiazine 4 to 6 grams 4 times daily for 6 weeks, PLUS folinic acid 10-25 mg daily for 6 weeks (not folate, even though folinic acid is often not available). Supportive management If intracranial pressure is elevated (papilloedema, vomiting), prednisolone (40 mg 4 times daily) or dexamethasone (4 mg 4 times daily) can be administered. Use of prednisone 40 mg 4 times daily to manage cerebral oedema can be used at the discretion of the provider, if TB is excluded. In the case of empirical treatment, a response can be expected after 7 days of treatment in about 3/4 of patients or after 14 days in almost all patients. If no improvement occurs, reconsider the diagnosis.

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Secondary prevention • cotrimoxazole, 1 double-strength tablet daily until CD4 >200 for at least 6 months. Primary prevention • All HIV-positive patients with a CD4 <200 should receive cotrimoxazole, 1 double-strength tablet daily until their CD4 count is >200 for at least 6 months. This will protect them from both toxoplasmosis and PCP.

Trachoma see Section 10.12 Eye problems 11.41 Trypanosomiasis, human African (sleeping sickness)8 Human African trypanosomiasis or sleeping sickness is caused by infection with parasites called trypanosomes. It is transmitted to humans by tsetse ﬂy bites, as well as congenitally from mother to child. There are two types of African trypanosomiasis, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense.

T. b. gambiense causes 95% of infections and is found in central and western Africa.

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T. b. rhodesiense causes 5% of infections and is found in eastern and southern Africa.

Key clinical features Human African trypanosomiasis infection is divided into two clinical stages. First stage: haemo-lymphatic involvement Trypanosomes multiply in subcutaneous tissue, blood and lymph. T. b. rhodesiense infection has a pronounced ﬁrst stage, whereas in T. b. gambiense the ﬁrst stage may go unnoticed. The ﬁrst stage is characterized by: • A painful chancre at the site of the tsetse ﬂy bite ° usually develops 5 days after the bite ° heals without treatment in 2–4 weeks, leaving a hyperpigmented area ° found in about half of all T. b. rhodesiense infections, but is rare in T. b. gambiense infection. • Fever, headache, joint pain, anaemia, patchy rash, itching, local oedema. • Lymphadenopathy in the posterior triangle of the neck (“Winterbottom’s sign”). • Myxoedematous inﬁltration of connective tissue (“puffy face syndrome”). • Cardiovascular disorders possibly resulting in death (in T. b. rhodesiense). • Endocrinological disorders leading to amenorrhoea and abortion.

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Second stage: neurological involvement Trypanosomes cross the blood-brain barrier and infect the CNS. In T. b. rhodesiense, progression to the second stage occurs rapidly within weeks, whereas in T. b. gambiense, this usually takes months. Because of the long asymptomatic incubation period in T. b. gambiense infection, patients usually present in advanced disease with CNS involvement. The second stage is characterized by: • Worsening headache and weakness. • Disturbance of the sleep cycle (somnolence, insomnia). • Neurological signs (convulsions, sensory, coordination, speech, gait, and tone disturbances). • Psychiatric disorders (behaviour changes, confusion, apathy, psychotic reactions, depression). Without treatment the disease is always fatal. Investigations • Serological tests are useful in the asymptomatic ﬁrst stage of T. b. gambiense infection only, and therefore are used for population screening. ° Direct haemagglutination with card agglutination trypanosomiasis test (CATT). Since CATT has a low sensitivity, a negative result does not deﬁnitively mean the disease is absent. Since it is not 100% sensitive, a positive result needs conﬁrmation with parasitological tests. • Parasitological tests are used for conﬁrmation of the diagnosis and staging of disease. Parasites are usually detectable 7–10 days after the bite of the ﬂy. In T. b. gambiense infection, the number of parasites can be too low for the test to recognize. A negative parasitological test in the presence of a positive serological test does not necessarily indicate the absence of infection. The test may need to be repeated to conﬁrm the diagnosis. • For diagnosis: ° Microscopy of body ﬂuids (blood, lymph node aspirate, chancre aspirate, CSF to look for trypanosomes). Haemoconcentration of the blood (capillary tube centrifugation or mini anion exchange centrifugation technique) is usually needed to observe T. b. gambiense in blood specimens. • For staging: ° First stage: ◊ parasites seen in the either the blood or lymph nodes, or both, but not in the CSF ◊ CSF leukocyte count ≤5/µl. ° Second stage: ◊ CSF with trypanosomes; OR ◊ CSF leukocyte count >5/µl. Treatment 37 Treatment varies according to the stage of infection and the sub-species. Early diagnosis is essential, as the drugs used in the ﬁrst stage are less toxic, easier to administer, and more effective.

37 Report of the 17th expert committee on the selection and use of essential medicine. WHO, 2010. http://www.who. int/selection_medicines/committees/expert/17/WEB_TRS_DEC_2009.pdf

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Treatment of T. b. rhodesiense infection First stage: • suramin IV – 5 mg/kg intravenously as a test dose, followed by 20 mg/kg on day 3, 10, 17, 24, and 31. Second stage: • melarsoprol IV – 2.2 mg/kg per day for 10 consecutive days given in hospital by slow IV injection to prevent thrombophlebitis and necrosis at the injection site. Treatment of T. b. gambiense infection First stage: • pentamidine deep IM – 4 mg/kg/day for 7 consecutive days. Second stage: • combined treatment of nifurtimox and eﬂornithine: ° nifurtimox 15 mg/kg daily orally, divide into 3 doses per day for 10 days; PLUS ° eﬂornithine IV – 400 mg/kg daily given as a slow infusion of 200 mg/kg every 12 hours for 7 days; • if combination treatment is not available, eﬂornithine can be used as monotherapy: ° eﬂornithine IV – 400 mg/kg daily, divided into 4 doses (infusions of 100 mg/ kg are given every 6 hours) for 14 days; given as a slow infusion over 2 hours. • alternative treatment: ° melarsoprol IV – 2.2 mg/kg per day for 10 consecutive days given in hospital by slow IV injection to prevent thrombophlebitis and necrosis at the injection site. Note: Melarsoprol causes reactive encephalopathy in 5% to10% of patients, of which 50% will have a fatal outcome. Increasing rates of resistance to melarsoprol (as high as 25%) have been reported in some areas in the Democratic Republic of the Congo, southern Sudan, and northern Uganda. The drug must be administered in a hospital, in an intensive care unit if possible. Eﬂornithine needs to be administrated in slow IV every 6 hours (in monotherapy) or every 12 hours (in combination therapy). This drug may thus be difﬁcult to administer in health facilities in rural Africa where human African trypanosomiasis is endemic.

11.42 Trypanosomiasis, American – Chagas disease8,38 Chagas disease (also called American trypanosomiasis) is caused by infection with the parasite Trypanosoma cruzi. T. cruzi infection is transmitted to humans by contact with the faeces of infected blood-sucking insects, called triatomine bugs (Chagas disease vector), with the insect bite, any other skin break, or mucosa membranes (mouth, eyes). Alternatively, transmission can occur through blood transfusion from an infected donor, through mother-to-child transmission, and

38 Control of Chagas disease: second report of the WHO expert committee. WHO, 2000 (WHO Technical Report Series, No. 905). Available at http://whqlibdoc.who.int/trs/WHO_TRS_905.pdf

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through ingestion of contaminated food, typically producing oral outbreaks of acute Chagas disease. Far less frequently, transmission occurs through organ transplantation or laboratory accident.

Around 10 million people are estimated to be infected by T. cruzi in the world. For thousands of years Chagas disease was conﬁned to the region of the Americas, mostly in the 21 Latin American countries, where it has been endemic. Due mainly to population mobility, in past decades it has been increasingly detected in other non-endemic countries in the region of the Americas (United States of America and Canada), some countries of the Western Paciﬁc Region, and many countries of the European Region.

Key clinical features Chagas disease has two successive phases: an acute phase and a chronic phase. Most acute cases are asymptomatic or have non-speciﬁc symptoms. Also, during the chronic phase most patients are symptom-free, but up to 40% may progress to clinical forms of the disease that can be life-threatening. Initially, there is an acute phase that commonly lasts for about two months during which a high number of parasites circulate in the blood. Most acute cases are asymptomatic or show non-speciﬁc symptoms. Depending on where T. cruzi entered the body, the ﬁrst sign may be a skin lesion (chagoma) or purplish swelling of both lids of one eye (Romaña sign) accompanied by local enlarged lymph glands and fever lasting for several weeks. Other symptoms of the acute phase may include (in order of frequency): headache, pallor, myalgia, dyspnoea, oedema of the legs or face, abdominal pain, cough, hepatomegaly, rash, painful nodules, splenomegaly, generalized oedema,

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diarrhoea, multiple lymphoadenopathies, myocarditis (with chest pain and even heart failure) and, less frequently, meningoencephalitis (with seizures and even paralysis). The acute phase may occur at any age, but is frequently more severe in children aged less than ﬁve years, the elderly, those who are immunosuppressed, or in individuals infected with a high number of parasites (what is supposed to occur during outbreaks of foodborne disease). Meningoencephalitis is the most frequent manifestation in people suffering from AIDS (differential diagnosis with toxoplasmosis). The acute phase is followed by the chronic phase, during which parasites hide in target tissues, especially in the heart. Different clinical forms may be observed: • The asymptomatic or indeterminate form, the most frequent form, is typically found immediately after the acute phase and is life-long in most patients. • The cardiac form occurs in ≤30% of patients, affecting the heart’s electrical conduction system, and causing arrhythmia (that may lead to sudden death), cardiomyopathy, heart failure, and secondary thromboembolisms. Consequent symptoms are fatigue, dyspnoea, palpitations, oedema of the lower limbs, among others. • The digestive form or a mixed form, that affects the heart and the digestive system, occurs in ≤10% of patients. The digestive form, generally presenting enlargement of the oesophagus (involvement varies from minor peristaltic disturbances to mega-oesophagus), or the colon (mostly in the sigmoid colon), is found South of the Amazon basin. It is normally accompanied with alterations of the autonomic nervous system. Consequent symptoms are difﬁcult or painful swallowing and constipation, among others. Investigations during the acute phase or during reactivation because of immunosuppression Diagnosis is made by the direct detection of parasites circulating in the bloodstream by: • a blood wet smear, or • a blood concentration technique such as microhaematocrit or Strout technique, or • a stained blood smear such as malaria ﬁlm, when parasitemia is high. In the Amazon basin, microscopy technicians who diagnose malaria have been trained to detect acute individual cases of Chagas disease and, through them, identify possible foodborne outbreaks. Investigations during the chronic phase When the parasites are hidden in the target tissues, diagnosis is made via the detection of antibodies against T. cruzi (serological techniques). • Some of the most frequently used techniques are: conventional or recombinant enzyme-linked immunosorbent assay (ELISA), indirect haemagglutination assay, indirect immunoﬂuorescence assay, western blot, and rapid diagnostic test (such as immunochromatography). • When available or for research purposes, the following tests may also be used: molecular tests (qualitative and quantitative polymerase chain reaction – PCR) and parasitological tests (haemoculture and xenodiagnosis – with examination of the faeces of uninfected triatomine bugs that have fed from an infected patient’s blood).

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Diagnosis of congenital transmission is done through the direct parasite detection in the blood of the cord of the newborn or through serology after 8 months of age (because before the serology might be positive due to maternal antibodies only, and not to an infection of the child). Clinical evaluations during the acute and chronic phase • Physical examination. • Electrocardiography (ECG): ° ECG alterations suggestive of Chagas disease are atrioventricular blocks, right bundle branch block, left anterior hemiblock, low voltage, primary T-wave changes, and frequent multifocal ventricular extrasystoles. ° Holter ECG may record arryhthmias. • Echocardiography may detect morphological (apical aneurism, enlargement of heart cavities) and functional alterations (hypokinesis or akinesis of the heart infero-posterior region) • Digestive radiography ° Barium swallow to detect mega-oesophagus. ° Barium enema to detect mega-colon. Treatment There are two available drugs to treat the T. cruzi infection: benznidazole and nifurtimox. They are most effective in the acute phase or at a younger age, but have also shown to be beneﬁcial at the early chronic phase (decrease or slowing the development of organ lesions). Patients who develop manifestations of the late chronic phase may require expensive life-long treatment and surgery. Treatment is urgently indicated for anyone during the acute phase (including in case of laboratory accident) and for those in whom the infection has been reactivated (immunosuppression). In these situations, drug treatment is almost 100% effective, and the infection can be completely cured. However, efﬁcacy decreases as the duration of the infection lengthens. Different treatment responses have been found in different geographical areas. Infants are less likely to have adverse events from treatment; this risk increases with age. Treatment is also indicated for infants with congenital infection and for patients during the early chronic phase. Adults, especially those with the indeterminate form of the disease, should be offered treatment, but its potential beneﬁts in preventing or delaying the development of Chagas disease should be weighed against the frequent adverse events. During the late chronic phase, when cardiac or digestive manifestations may occur, additional life-long medical treatment and surgery are usually indicated. The main contraindications to treatment are pregnancy and kidney or liver failure. Nifurtimox is contraindicated in patients with a history of psychiatric or neurological disorders (such as seizures).

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Table: Dosage and main adverse events of benznidazole and nifurtimox Benznidazole Adult 5 mg/kg/day, divided in 2 or 3 daily doses (PO) over 60 consecutive days. Preferably after meals. Up to 10 mg/kg/day Dermatitis with cutaneous eruptions (rash and rash erythematous), generalized oedema, fever, mialgias, artralgias, gastrointestinal disorders; depression of bone marrow; polyneuropathy, paraesthesia and neuropathy peripheral, among others. Nifurtimox 10 mg/kg/day divided in 2 or 3 daily doses (PO) over 60 consecutive days. Preferably after meals. Up to 15 mg/kg/day Nauseas, vomiting, diarrhoea, abdominal pain, anorexia, central nervous system alterations (sleep disturbances, excitatory states, seizures, psychotic behaviour), tremors, muscle weakness, paraesthesia, and polyneuritis, among others.

Paediatric Adverse events

Important notes: 6. In laboratory accidents it is important to begin treatment immediately and it should be continued for 10 to 15 days. 7. For benznidazole it is recommended not to exceed the 300 mg maximum daily dose. It is better to calculate the total dose for the patient and distribute it over more than 60 days. Source: WHO/NTD/IDM/Chagas disease programme 2009.

11.43 Typhoid fever Typhoid fever is caused by systemic infection with Salmonella typhi or paratyphi and is most commonly contracted through consumption of food or water contaminated with faeces. It is endemic in many areas, but cluster epidemics may occur from a source of contaminated food or water. Typhoid fever is often difﬁcult to diagnose because symptoms and signs are not speciﬁc even though the patient may be very sick, and laboratory ﬁndings are not conclusive unless cultures are performed. If untreated, the disease may be selflimited. Three percent of these untreated cases become asymptomatic carriers who continue to shed Salmonella (para)typhi and may contaminate food and water sources. History and examination ﬁndings are usually non-speciﬁc. It is therefore important to have a high index of suspicion of typhoid in the patient who looks ill but does not have an obvious focus of infection. Also always consider malaria and disseminated TB in these cases. Key clinical features • (para)typhoid has an incubation period of 3 to 60 days; • prolonged fever; • a maculopapular rash lasting 2 to 3 days (in only 30% of cases and rarely seen if the patient has dark skin); • abdominal pain and tenderness; • jaundice; • enlarged liver and spleen; • non-speciﬁc symptoms include anorexia, mild cough, sore throat, and constipation.

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In late or severe disease: • ﬂorid diarrhoea; • coma or decreased conscious state; • fulminant sepsis. Complications • focal salmonella infection in bone, meninges, heart valves, soft tissue, genitourinary tract; • bowel perforation; • gastrointestinal haemorrhage. Investigations • culture of blood, urine, stool – growth of salmonella (para)typhi species occur in 24 to 48 hours and is diagnostic; • the last generation of good quality rapid diagnostic tests have shown to be 80% sensitive on average and highly speciﬁc; • in the absence of cultures, laboratory results, including the white cell count, are non-speciﬁc and typhoid fever is an empirical diagnosis; • the Widal test has both low sensitivity and speciﬁcity and is thus not helpful. Treatment In countries where drug resistance to ampicillin, cotrimoxazole, or chloramphenicol among Salmonella typhi isolates is known to be a problem, follow national guidelines. In many cases, preferred treatment will include: • ciproﬂoxacin 500 mg orally twice daily for 10 days; OR • ceftriaxone 1–2 g IV or IM daily for 10–14 days. If there is known antibiotic sensitivity to chloramphenicol, it can be used. Supportive care • Depending on the severity of the illness, IV ﬂuids may be required.

11.44 Urinary tract infection Urinary tract infections can be limited to the lower urinary tract causing cystitis or can spread to the upper urinary tract or kidney and cause pyelonephritis. Risk factors include female sex, sexual intercourse, diabetes, pregnancy, menopause, instrumentation, and anatomical or functional abnormalities of the urinary tract including obstruction. The most common organisms include Gram-negative bacteria (Escherichia coli, Proteus, Klebsiella) and some Gram-positive organisms. Key clinical features Of lower urinary tract infection: • suprapubic abdominal discomfort and tenderness • pain on urination • urinary frequency • urinary urgency • haematuria (blood in urine).

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Of upper urinary tract infection: • fever >38°C • loin pain and tenderness • associated systemic symptoms: nausea, vomiting. Investigations • Microscopy of a clean, fresh, uncentrifuged specimen of urine. Cases of UTI will usually show more than 10 white cells per high-powered ﬁeld, or a dipstick will show a positive result for leucocytes or nitrites. • If possible, obtain a midstream urine sample for culture. Treatment Uncomplicated lower urinary tract infections: • Treat with oral antibiotics for 3 to 5 days. Options include: ° trimethoprim 300 mg daily for 3 days, amoxicillin with clavulanic acid 500 mg plus 125 mg twice daily for 5 days; OR ° nitrofurantoin 100 mg twice daily for 5 days. • If an organism is resistant to these antibiotics on culture, then it may be appropriate to use: ° ciproﬂoxacin 500 mg twice daily for 3 days, if available. • If treatment fails or a relapse occurs, treat as for a pyelonephritis or upper urinary tract infection. • If the patient is pregnant, use either: ° nitrofurantoin 100 mg twice daily for 5 days; OR ° amoxicillin with clavulanic acid 500 mg 3 times daily for 3 to 7 days. Upper urinary tract infection: • Mild: can be treated with ciproﬂoxacin or trimethoprim as above for lower tract infection, but continue treatment for 7–10 days. • Severe: as in high temperature, pain, debility, and inability to maintain oral hydration, and in pregnancy. Options include: ° ciproﬂoxacin 500 mg orally twice daily (if no vomiting); OR ° ceftriaxone 1 g daily; OR ° if these 2 options are not available: ampicillin 1 gm IV, 8 hourly plus gentamicin 4–6 mg/kg IV daily; Avoid quinolones in pregnancy. Patients treated initially with intravenous therapy can be changed to oral antibiotics once afebrile for 24 hours and improvement has been noted. Treatment should be for 10–14 days in total. Monitoring of upper urinary tract infection (pyelonephritis) Patients should improve within 2 to 3 days with effective treatment. Failure to improve within 48–72 hours of antibiotics may suggest a complication such as renal abscess or obstruction or infection with a resistant organism. If available, a renal ultrasound may be beneﬁcial to assess for complications. Complications of upper urinary tract infection (pyelonephritis) Infection of the upper urinary tract with obstruction of the kidney (e.g. renal calculi) requires insertion of a nephrostomy to relieve the obstruction. A renal abscess may require surgical drainage.

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11.45 Varicella/zoster The varicella virus causes two distinct syndromes in humans: a primary illness called chicken pox, which most often occurs in children and is relatively benign, and a second distinct syndrome called herpes zoster, which occurs in older adults and is due to reactivation of the dormant virus in the nerves. Herpes zoster causes signiﬁcant morbidity due to the intense and sometimes long-standing pain that it causes. It has become more signiﬁcant in recent years due to its propensity to affect patients with HIV infection. Herpes zoster in a young person is highly predictive of HIV infection and is a WHO clinical stage 2 condition.

11.45.1 Chickenpox Key clinical features • Prodrome of fever, malaise, nausea, “ﬂu-like” illness. • 2–5 days later a generalized, itchy rash appears. • Crops of papules-vesicles, then crusted lesions appear all over, sparing the palms and soles. • Lesions co-exist in different stages of progression, i.e. new papules appear when older lesions are already crusted. • Intense itching occurs. Complications are more often seen in patients who acquire the infection as adults, and particularly in pregnant women. • Pneumonia can be severe: difﬁculty breathing, low SpO2 and inﬁltrates on chest X-ray, occurs in 10% of pregnant women (see Sections 10.6 and 3.2.4). • Encephalitis is due to a necrotizing vasculitis that is seen in HIV-positive patients. • Hepatitis with increased liver function tests can also be seen. • Hemorrhagic syndromes can also accompany varicella in adults. These range from mild to life-threatening. Varicella in pregnancy carries a high risk of complications. • If acquired before 28 weeks gestation, it will cause congenital abnormalities in the child (also called congenital varicella syndrome). • If acquired around the time of birth, it can cause neonatal varicella, which carries a high rate of pneumonia and other complications. Treatment Antiviral therapy depends on age, pregnancy, and immune status. • In children without immune deﬁciency <12 years: ° aciclovir is not recommended. • In “high-risk” children >12 years with chronic pulmonary or cutaneous disorders or on corticosteroid treatment: ° oral aciclovir 20 mg/kg. • In HIV-positive children and children with disseminated disease: ° IV aciclovir 10 mg/kg 3 times daily for 7 days. • In adults including pregnant women: ° oral aciclovir 800 mg 5 times daily for 7 days. • In immunocompromised adults or those with disseminated disease: ° IV aciclovir 10 mg/kg 3 times daily for 7 days; OR ° high-dose oral aciclovir, if no IV available. Vol. 2 • 11. Multisystem communicable diseases, renal problems and HIV-related cancers: July 2011 Varicella/zoster 501

Treatment should be started as early as possible, ideally less than 24 hours after the start of symptoms. For oral treatment, the value of starting after 24 hours is not well established. Follow infection control precautions – see Section 6.

11.45.2 Herpes zoster Key clinical features • Painful vesicular rash in a dermatomal distribution of a nerve supply that does not cross the midline. • Pain sometimes comes before the appearance of the rash. • Vesicles form in groups and progress to crusted lesions after a few days. • Most common areas: trunk, particularly the ﬂanks, and forehead. • Can involve the eye and cause corneal scarring and blindness. • HIV patients have more frequent multidermal involvement, involvement of the trigeminal nerve, presence of systemic symptoms, and have a higher risk of disseminated disease. • Myelitis, meningitis, and encephalitis with headache, fever, neck stiffness, altered motor and sensory function. • Guillain-Barre syndrome. Complications • Blindness due to corneal involvement. • Post-herpetic neuralgia: chronic pain in the area where the lesions occurred that can last for months to years after the acute episode. Treatment • Local lesion care including treatment of secondary bacterial infections. • Chlorhexidine. • Calamine or topical or oral antihistamine preparations to reduce itching (no topical steroid creams). See Section 20 Palliative care. • Good hygiene is the key, and daily bathing with soap and clean water is recommended. • Isolation of the patient to avoid spreading the virus. Contact should be avoided until all lesions are crusted over. • Paracetamol if there is fever. Herpes zoster infection: • Aciclovir 800 mg 5 times daily for 7 days can be considered for all adults, and is recommended for all HIV-positive adults. Start aciclovir within 72 hours from the onset of symptoms. Ophthalmic involvement: • oral aciclovir 800 mg 5 times daily for 7 days and aciclovir 3% eye ointment applied into the eye every 4 hours. Pain management (zoster): • paracetamol or stronger analgesics if necessary;

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• amitriptyline 25–50 mg before bed for neuropathic pain and post-herpetic neuralgia. Prevention or post-exposure prophylaxis: If available, varicella immune globulin should be administered to pregnant women or persons at high risk of severe disease after exposure. Varicella vaccine is available for prevention in some areas.

Yaws see Section 10.2 Skin problems 11.46 Viral haemorrhagic fevers A viral haemorrhagic fever (VHF) is a syndrome caused by four taxonomic virus families: arenaviridae, bunyaviridae, ﬁloviridae, and ﬂaviviridae, and characterized by fever, malaise, hypotension that can lead to shock, and to coagulation defects that manifest as a tendency to bleed. Although commonly grouped together by their similar presentation, the pathogens that cause VHF syndromes are very diverse. Except for dengue fever (dealt with separately in this Section), all the agents of VHF are zoonotic pathogens. Thus, the risk of infection is strongly inﬂuenced by the local environment and ecology, and exposure to infected animal vectors (e.g. through occupational exposure, consumption of food, or inhalation of aerosols contaminated by infected animal excretions). Key clinical features • fever • headache • myalgia • abdominal discomfort, nausea, vomiting • erythematous rash (may be difﬁcult to see in dark skin) • haemorrhagic manifestation (typically conjunctival haemorrhage, oozing from puncture sites, ecchymoses, petechiae, purpura, and occasionally gastrointestinal haemorrhage) • oedema • long-term sequelae: deafness (Lassa fever), blindness (Rift Valley fever) Standardized case deﬁnitions: acute haemorrhagic fever39 Acute haemorrhagic fever syndrome Suspected case: acute onset of fever of less than 3 weeks duration in a severely ill patient AND any 2 of the following: haemorrhagic or purpuric rash; epistaxis (nose bleed); haematemesis (blood in vomit); haemoptysis (blood in sputum); blood in stool; other haemorrhagic symptoms and no known predisposing factors for haemorrhagic manifestations. Conﬁrmed case: a suspected case with laboratory conﬁrmation or epidemiologic link to conﬁrmed cases or outbreak. Note: During an outbreak, case deﬁnitions may be changed to correspond to the local event.

39 Technical Guidelines for Integrated Disease Surveillance and Response in the African Region. WHO Brazzaville and Centers for Disease Control and Prevention, 2010. Available at http://www.afro.who.int/en/clusters-aprogrammes/dpc/integrated-disease-surveillance.html

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Laboratory investigations • full blood count (may demonstrate lymphopaenia, thrombocytopaenia, or rise in haematocrit due to haemoconcentration); • proteinuria; • evidence of disseminated intravascular coagulation (elevated ﬁbrin split products and D-dimer). Treatment Intravenous ribavirin may be effective against arenaviridae (the South American haemorrhagic fevers and Lassa fever) and bunyaviridae (Crimean-Congo haemorrhagic fever, hantaviruses), based on small case series. Consult with the national programme and experts on its use. Supportive care • Infection control ° Standard precautions should be implemented, augmented by gowns, boots, masks, and protective eyewear. ° Respiratory precautions (e.g. HEPA mask) should be taken if risk of exposure to aerosols (e.g. during intubation, bronchoscopy). ° Isolate infected patients from others to the extent possible. ° Minimize invasive procedures (including blood draws) to limit the risk of occupational exposure. • Hypotension and shock must be carefully monitored and treated judiciously with intravenous ﬂuid (Lactated Ringer’s Solution or normal saline). If the patient is in shock, see septic shock management in Section 3.1.5. Overhydration may precipitate pulmonary oedema. • Pain control. • A careful search should be made for evidence (clinical or laboratory) of other infections, such as typhoid or malaria, that could mimic the effects of a VHF. In addition, dually-infected patients have been reported during some outbreaks.

11.47 Yellow fever Yellow fever is caused by a ﬂavivirus and is transmitted by mosquito bites. It is found in sub-Saharan Africa and South America. Yellow fever can be prevented by vaccination, but several hundred cases are still reported every year. Yellow fever is a classic viral haemorrhagic fever and is difﬁcult to identify, particularly in the early stages when signs and symptoms are not speciﬁc. Key clinical features Acute phase: fever, malaise, backache, muscle aches, headache, nausea, and vomiting. This phase improves after 3–5 days. Toxic phase: affects about 15% of patients. • Recrudescence of high fever. • Liver damage with jaundice, abdominal pain, and nausea with vomiting. • Bleeding can be severe: gastric bleeding (black vomit), ears, eyes, and nose can be affected.

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• Kidney failure follows, with decreased urine production and confusion due to increased blood urea. Severe disease: 50% of patients in the toxic phase die within 10–14 days. Investigations • Liver function tests: high bilirubin (conjugated) and elevated AST and ALT. • Blood leukocyte counts are decreased early on, but can be high at terminal stages. • Urine protein levels are increased. • Blood urea nitrogen increases in severe cases with renal failure. Treatment Supportive treatment is essential. There is no recognized drug therapy available for yellow fever. Patients should be managed in hospital in severe cases. If the patient is in shock, see septic shock management in Section 3.1.5. Mortality is relatively high, but those who recover do so without any residual organ damage.

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Chronic and long-term care Table of contents 12. General principles of good chronic care . . . . . . . . . . . . . . . . . . . 509 Your role as health-care providers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509 For the patient in chronic or long-term care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510

13. Chronic HIV care, antiretroviral therapy (ART), and prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sequence of care after positive HIV test . . . . . . . . . . . . . . . . . . 13.1 Clinical approach when the district clinician is consulted on a HIV patient in chronic HIV care . . . . . . . . . . . . . . . . . 13.2 Determine HIV clinical stage . . . . . . . . . . . . . . . . . . . . . 13.3 Prophylaxis for PLHIV . . . . . . . . . . . . . . . . . . . . . . . . . . Cotrimoxazole prophylaxis . . . . . . . . . . . . . . . . . . . . . Isoniazid preventive therapy . . . . . . . . . . . . . . . . . . . . 13.4 Initiate and manage patients on ART . . . . . . . . . . . . . . . . . Determine ART eligibility . . . . . . . . . . . . . . . . . . . . . . Determine appropriate ARV regimen . . . . . . . . . . . . . . . Preferred ﬁrst-line ARV regimens for treatment-naive adults and adolescents. . . . . . . . . . . . . . . . . . . . . . . . . . . . Drug interactions with ﬁrst-line ARV regimens . . . . . . . . . 13.5 ART monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitoring for new clinical events. . . . . . . . . . . . . . . . . Monitor and support adherence . . . . . . . . . . . . . . . . . . Monitoring response to ART . . . . . . . . . . . . . . . . . . . . Laboratory monitoring . . . . . . . . . . . . . . . . . . . . . . . . 13.6 ART initiation in complicated patients . . . . . . . . . . . . . . . . 13.7 Second-line ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Deﬁning ART failure . . . . . . . . . . . . . . . . . . . . . . . . . Second-line ARV regimens . . . . . . . . . . . . . . . . . . . . . Monitoring second-line regimens . . . . . . . . . . . . . . . . . 13.8 ART toxicity and management . . . . . . . . . . . . . . . . . . . . . Short- and long-term toxicities on ART . . . . . . . . . . . . . . Clinical and laboratory monitoring for ART toxicity . . . . . . . Side-effects of ﬁrst-line ARVs . . . . . . . . . . . . . . . . . . . Management of ART toxicity . . . . . . . . . . . . . . . . . . . . 13.9 Management of speciﬁc ART toxicities . . . . . . . . . . . . . . . Haematological toxicity . . . . . . . . . . . . . . . . . . . . . . . Hepatotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rash and hypersensitivity . . . . . . . . . . . . . . . . . . . . . . Dyslipidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hyperlactataemia and lactic acidosis . . . . . . . . . . . . . . . Peripheral neuropathy . . . . . . . . . . . . . . . . . . . . . . . . Lipodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abdominal pain and symptoms . . . . . . . . . . . . . . . . . . .

511 512 514 517 523 523 526 529 529 529 531 532 532 532 533 533 533 535 542 542 543 543 544 544 545 545 546 546 546 548 549 552 552 554 554 554

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13.10

13.11 13.12

13.13

13.14

Clinical toxicities grading and management . . . . . . . . . . . ARVs and other HIV-related medications associated with selected toxicities . . . . . . . . . . . . . . . . . . . . . . . . . . IRIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HIV/TB co-management . . . . . . . . . . . . . . . . . . . . . . . . . Cotrimoxazole prophylaxis . . . . . . . . . . . . . . . . . . . . . When to start ART in patients with TB . . . . . . . . . . . . . . Recommended ART for patients with TB . . . . . . . . . . . . . Women of childbearing potential (ore pregnant women) with TB and eligible for ART . . . . . . . . . . . . . . . . . . . . Summary of ﬁrst-line ART for TB patients . . . . . . . . . . . . TB immune reconstitution inﬂammatory syndrome (TB-IRIS) . New TB in patients already receiving ART . . . . . . . . . . . . ART recommendations for patients who develop TB within 6 months of starting a ﬁrst-line or second-line ART regimen . Second-line ART regimens for patients with TB . . . . . . . . . Adherence preparation, monitoring, and support. . . . . . . . . . Barriers to adherence and suggestions for addressing them . Positive health, dignity, and prevention for PLHIV . . . . . . . . . Preventing sexual transmission of HIV . . . . . . . . . . . . . . Preventing non-sexual transmission of HIV . . . . . . . . . . . Reproductive choice and family planning . . . . . . . . . . . . Positive living for PLHIV . . . . . . . . . . . . . . . . . . . . . . . . . Counsel PLHIV on how to prevent other infections . . . . . . . Encourage physical activity as appropriate . . . . . . . . . . . Support adequate and balanced nutrition . . . . . . . . . . . . Assess alcohol use . . . . . . . . . . . . . . . . . . . . . . . . . . Brief interventions for patients with hazardous or harmful alcohol use. . . . . . . . . . . . . . . . . . . . . . . . . . Special considerations for adolescents in chronic HIV care . . Psychosocial support . . . . . . . . . . . . . . . . . . . . . . . . Differences among adolescents . . . . . . . . . . . . . . . . . . What to do and what to avoid when communicating with adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . ART in adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . Tanner stage for female and male adolescents . . . . . . . . .

555 556 559 560 560 560 560 560 561 561 562 562 563 563 564 566 566 567 567 568 568 569 569 569 570 570 570 570 572 573 573

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12. General principles of good chronic care1,2 These general principles of good chronic care were derived from the WHO NMH Innovative Care for Chronic Conditions framework for assisting countries to reorganize their health care for more effective and efﬁcient prevention and management of chronic conditions. The Framework is centred on the idea that optimal outcomes occur when a health-care triad is formed. This triad is a partnership among patients and families, health-care teams, and community supporters that functions at its best when each member is informed, motivated, and prepared to manage their health, and communicates and collaborates with the other members of the triad. The triad is inﬂuenced and supported by the larger healthcare organization, the broader community, and the policy environment. When the integration of the components is optimal, the patient and family become active participants in their care, supported by the community and the health-care team. These principles are also relevant to long-term care of, for example, TB, pregnancy, family planning, and mental health problems (where care extends over months or years).

Your role as health-care providers 1. 2. Develop a treatment partnership with your patient. Focus on your patient’s concerns and priorities. Patient-centred care is health care that establishes a partnership among practitioners, patients, and their families (when appropriate) to ensure that decisions respect the patients’ wants, needs, and preferences, and that patients have the education and support they need to make decisions and participate in their own care. Studies show that orienting health care around the preferences and needs of patients improves a range of clinical outcomes. Use the 5 A’s: Assess, Advise, Agree, Assist, and Arrange. The 5 A’s approach is a proven behavioural strategy to guide clinical interactions. Support patient self-management. Organize proactive follow-up. Involve “expert patients”, peer educators and support staff in your health facility. • Choose patients who: ° understand their disease well; ° are good communicators; ° are respected by other patients; and ° have time to be involved on a regular basis. • Ensure they understand and will respect shared conﬁdentiality. • Ensure they do not exceed their expertise or areas of responsibility.

4. 5. 6.

1 IMAI General Principles of Good Chronic Care, WHO, 2004. http://www.who.int/hiv/pub/imai/primary_general/en/ index.html 2 Innovative Care for Chronic Conditions: Building Blocks for Action, WHO, 2002. http://www.who.int/chp/ knowledge/publications/icccreport/en/index.html

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7. 8.

Link the patient to community-based resources and support. Use written information – registers, treatment plan, treatment cards and written information for patients – to document, monitor and remind. See Section 21.1 on longitudinal monitoring of patients in chronic or long-term care. Work as a clinical team.

10. Assure continuity of care.

For the patient in chronic or long term care Your proactive role as a patient: • • • • • • Develop a treatment partnership with your care providers. Adhere to treatment. Seek care as needed. Ask your care provider if you have questions. Express your concern to your care provider. Know when to return urgently or on a scheduled visit.

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13. Chronic HIV care, ART, and prevention A team approach to chronic HIV care that highlights the potential contribution of all staff, and links district hospital services with those provided at health centres and at higher levels of care is important. In this Section, the tasks that are best done by the district clinician are highlighted, as well as those that should usually be done by other members of the clinical team. The district clinician is responsible for overseeing the clinical team working in the outpatient department of the district hospital, and clinical teams at the health centre level in the surrounding area. Therefore, this Section summarizes basic, ﬁrst-level HIV care (as appears in the IMAI-IMCI Chronic HIV Care with ART and Prevention guideline module1) that nurse-led clinical teams can deliver, and then relates this ﬁrst level of care to the speciﬁc services provided by the district clinician. The interventions for chronic HIV care in this Section constitute a “continuum of care”, building on services in ﬁrst-level facilities that are supported by clearly deﬁned referral or consultation points with the district. In addition, this Section provides an approach for the HIV-positive patient with conditions requiring secondlevel interventions. This may include patients: • with complicated HIV disease; • suspected of having extrapulmonary or smear negative pulmonary TB where more recent diagnostic technologies are not available at ﬁrst-level facilities; • with additional medical conditions that require referral; • with serious side-effects or toxicities from ARV or other drugs (e.g. cotrimoxazole); • suspected or with ARV regimen failure. This Section assumes an HIV diagnosis has been made and that patients are aware they have HIV infection (see Section 9 HIV diagnosis). The management of acute opportunistic infections (OI) is addressed in Section 11 Multisystem communicable diseases. OI management is found also in the skin (10.2), chest (10.6) and eye (10.12) Sections.

1 IMAI-IMCI Chronic HIV care with ART and prevention. WHO, 2007. Available at: http://www.who.int/hiv/pub/imai/ primary_arv/en/index.html

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13.1 Clinical approach when the district clinician is consulted on a patient in chronic HIV care Step 1: Perform Quick Check Use the Quick Check at the beginning of this manual, and ensure that there are no serious or lifethreatening conditions. Be aware that people with HIV may present with serious illness as a result of advanced HIV disease, opportunistic infections, drug toxicities, or HIV unrelated conditions. Take a history There are many problems related to HIV infection and treatment. Take a good medical history to screen for problems and to identify those patients requiring rapid treatment planning, or isolation for infection control purposes (see HIV sequence of care). Examine the patient Examine the patient to determine the reason for presentation. Perform investigations Perform investigations Work through a differential diagnosis People with HIV infection may present due to: • complicated or advanced HIV disease • tuberculosis • drug side-effects and toxicities • failure of the ART regimen and its consequences • other medical conditions (not related to HIV-infection). Initiate management and monitor the response Management will depend on the presenting problem and scenario. A symptom approach and disease-speciﬁc approach are presented in Sections 10 and 11 respectively. This Section covers chronic HIV care and management of problems related to ART with cross-referencing to other Sections as required.

Step 2:

Step 3: Step 4: Step 5:

Step 6:

Triage • Establish the reason for the visit. Is this the ﬁrst visit, or a scheduled or unscheduled visit? • Take an interval history and use the Quick Check (Section 2). Identify and fast-track the following patients. • Patients with high risk of mortality or serious complications who require urgent interventions. • Patients with risk of transmitting TB or acute respiratory diseases (ARDs). ° Separate coughing patients from the general waiting area. ° Promote cough hygiene and cough etiquette (see Section 6 Infection prevention and control). • HIV-positive pregnant women who generally need rapid preparation and initiation of ART or ARV prophylaxis as early as indicated during their pregnancy.

History Targeted medical history: • main complaint, onset, and duration; • history of opportunistic infections, particularly TB; • other co-morbidities, e.g. diabetes, heart, kidney, or liver disease, depression

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or other psychiatric illness; • pregnancy status; • include information from accompanying persons. Drug or treatment history Current or prior ARV exposure What regimens? Duration of treatment Adherence to regimens Treatment interruptions ARV exposure for PMTCT of HIV Partners with ART exposure TB treatment OI treatment Prophylaxis – cotrimoxazole, ﬂuconazole, INH preventive therapy Other medications for co-morbidities Hormonal contraceptives Traditional medicines Drug interactions (rifampicin, antiepileptics) Poor absorption from prolonged diarrhoea or vomiting Liver or renal disease Previous drug-related reaction

Other medications

Conditions that may interfere with ARV drug levels Drug allergies

Social history: • alcohol or drug use • HIV status of partner, children, and other family members, and disclosure. Ask about the presence and duration of symptoms that may point to an underlying problem. Symptoms can include: • cough, chest pain, dyspnoea • reﬂux, heartburn, dysphagia • tingling, painful or numb feet or legs • fever • skin rash • muscle weakness • night sweats • yellow sclera • visual disturbances • weight loss or gain • fatigue • STI symptoms • loss of appetite • mouth sores • behavioural changes • nausea, vomiting, diarrhoea • headache • cognitive problems.

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Full examination in patients with new signs, symptoms, or problems Basic examinations on returning or new patients due to see the health worker include: • vital signs – temperature, pulse, blood pressure (BP), respiratory rate • weight, height, body mass index (BMI) calculation. The physical examination based on the presenting complaint may include looking for the following signs. General examination: • pallor • cyanosis • jaundice • lymphadenopathy – site and size • hydration status • body shape – wasting, lipo-atrophy/hypertrophy. Skin: • rashes • pruritic papular eruption (PPE) • fungal infections • herpes zoster • manifestations of underlying disease processes ° erythema nodosum (TB), cryptococcosis, syphilis. Eyes: • change or loss of vision • fundoscopy (See Section 10.12) • jaundice Mouth: • Candida – tongue, palate, pharynx, gums, angular cheilitis • oral hairy leukoplakia • dental caries • Kaposi sarcoma lesions on palate or gums • oral ulcers. Respiratory: • respiratory distress or acidotic breathing • signs of pneumonia or pleural effusion. Cardiovascular: • pericardial effusion • cardiac failure. Abdomen: • tenderness – site and type

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• organomegaly • other masses • ascites. Genitourinary: • vaginal or penile exam to look for discharge, ulcers, or warts. Neurology: • mental state exam • meningeal signs • cranial nerve palsies • motor system review • sensory system review ° especially if the patient is complaining of paraesthesias.

13.2 Determine HIV clinical stage Use the Table below to determine HIV clinical stage in adolescents and adults.2 Table: WHO clinical staging for HIV in adolescents and adults Clinical diagnosis – no laboratory tests needed Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual

Clinical event Clinical stage 1 Asymptomatic Persistent generalized lymphadenopathy (PGL) Clinical stage 2 Moderate unexplained weight loss (<10%) Recurrent bacterial upper respiratory tract infections (Current event plus 1 or more in last 6 months)

• No HIV-related symptoms reported • No signs on examination • Painless enlarged lymph nodes >1 cm in 2 or more non-contiguous sites (excluding inguinal) • Absence of known cause • Persisting for ≥3 months

• Not applicable • See Section 10.5 Lymphadenopathy

• Reported unexplained weight loss (<10% of body weight) • In pregnancy, failure to gain weight • Symptom complex: ° Sinusitis – unilateral face pain with nasal discharge ° Otitis media – painful inﬂamed eardrum ° Pharyngotonsillitis without features of viral infection (e.g. coryza, cough)

• Documented weight loss <10% of body weight • See Section 10.3 Weight loss and malnutrition • Laboratory studies where available, e.g. microscopy and culture of suitable body ﬂuid

2 Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach. WHO, 2010. Available at: http://www.who.int/hiv/pub/arv/adult2010/en/index.html

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Clinical event Herpes zoster

Clinical diagnosis – no laboratory tests needed • Painful vesicular rash in dermatomal distribution of a nerve supply • Does not cross midline • Splits or cracks at the angle of the mouth, not due to iron or vitamin deﬁciency • Usually responds to antifungal treatment • Aphthous ulceration: ° usually painful ° halo of inﬂammation ° yellow-grey pseudomembrane • Papular pruritic lesions, often with marked post-inﬂammatory pigmentation • Itchy scaly skin condition • Usually affects hairy areas, e.g. scalp, axillae, upper trunk, groin • Paronychia ° painful, red, swollen nail bed • Onycholysis ° white discolouration especially on proximal part of nail plate ° thickening and separation of nail from nail bed

Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual • Clinical diagnosis only See Section 10.2 Skin • Clinical diagnosis only See Section 10.17 Mouth problems • Clinical diagnosis only See Section 10.17 Mouth problems • Clinical diagnosis only See Section 10.2 Skin • Clinical diagnosis only See Section 10.2 Skin • Clinical diagnosis only

Angular cheilitis

Recurrent oral ulcerations (2 or more episodes in last 6 months) Papular pruritic eruption (PPE) Seborrhoeic dermatitis Fungal nail infections

Clinical stage 3 Severe unexplained weight loss (>10%) • Reported unexplained weight loss (>10% of body weight) • Visible thinning of face, waist, and extremities, with obvious wasting • Body mass index <18.5 • In pregnancy weight loss may be masked • Reported loose or watery stools, 3 or more times a day, for longer than 1 month • No cause found • Documented loss >10% of body weight or BMI<18.5 See Section 10.3 Malnutrition and Weight loss

Unexplained chronic diarrhoea (>1 month)

• Conﬁrmed if stools are observed and 2 or more stool tests show no pathogens See Section 10.7d Diarrhoea for other causes See Section 10.1 Fever

Prolonged fever (>1 month)

• Reports of fever or night sweats for more than 1 month • No other cause • Lack of response to antibiotics or antimalarials. (Malaria must be excluded in malarious areas.) • Persistent or recurring lesions either: ° pseudomembranous type – creamy white, curd-like plaques ° erythematous type – red patches on tongue, palate, or lining of mouth, usually painful or tender

Oral candidiasis

• Clinical diagnosis only See Sections 10.17 Mouth problems and 11.4 Candida

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Clinical event Oral hairy leukoplakia Pulmonary TB (PTB) current

Clinical diagnosis – no laboratory tests needed • Fine, white, small, linear, or corrugated lesions on lateral borders of the tongue • Do not scrape off • Symptom of cough, weight loss, fever, or night sweats with or without haemoptysis, chest pain, shortness of breath PLUS EITHER • Positive nationally or WHO approved molecular testing such as Xpert MTB/RIF if available or positive sputum smear for AFB OR • Negative sputum smear for AFB, in the absence of WHO approved molecular testing such as Xpert MTB/RIF testing AND • Compatible chest X-ray that may include upper lobe inﬁltrates, cavitation, pulmonary ﬁbrosis • No evidence of extrapulmonary disease • Fever • Speciﬁc symptoms or signs that localize infection • Response to appropriate antibiotic

Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual • Clinical diagnosis only See Section 10.17 Mouth problems See Section 15 Tuberculosis

Severe bacterial infection (e.g. pneumonia, meningitis, empyaema, pyomyositis, bone or joint infection, bacteraemia, pelvic inﬂammatory disease) Acute necrotizing ulcerative gingivitis or necrotizing ulcerative periodontitis Anaemia (<8 grams/dl) Neutropenia (<0.5 ×109/litre) or >1 month Thrombocytopenia (<50 ×109/litre)

• Gram stain and culture if available (isolate bacteria from appropriate sites, e.g. sputum, blood, urine, CSF, joint aspirate, vaginal swab)

• • • • • •

Severe pain Ulcerated gingival papillae Loosening of teeth Spontaneous bleeding Bad odour Loss of bone or soft tissue

• Clinical diagnosis only See Section 10.17 Mouth problems

• No presumptive clinical diagnosis • Clinical suspicion if: ° petechiae ° bleeding gums ° pallor

• Full blood count and differential needed • Not explained by other nonHIV conditions • Not responding to standard therapy with haematinics, antimalarials or antihelminthics See Sections 10.18 Anaemia and 10.19 Abnormal bleeding and low platelets

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Clinical event Clinical stage 4 HIV wasting syndrome

Clinical diagnosis – no laboratory tests needed

Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual

• Reported unexplained weight loss (>10% body weight) • Obvious wasting or BMI <18.5 PLUS EITHER • Unexplained chronic diarrhoea (>1 month) OR • Unexplained prolonged fever (>1 month)

• Documented weight loss >10% of body weight PLUS • 2 or more stools negative for pathogens (unformed) OR • Documented temperature of >37.5oC, no other cause found, negative blood culture, malaria smear, and normal or unchanged chest X-ray See Sections 10.1 Fever and 10.3 Malnutrition and weight loss • Induced sputum, bronchoalveolar lavage, lung biopsy. Specimens sent for cytology or immunoﬂuorescent microscopy. See Section 10.6 Chest

Pneumocystis jirovecii pneumonia

• Fever, dyspnoea on exertion, non-productive cough of recent onset (<3 months), tachypnoea, bilateral crepitations AND • Chest X-ray evidence of diffuse bilateral interstitial inﬁltrates AND • No evidence of a bacterial pneumonia • Current episode plus 1 or more previous episodes in last 6 months • Acute onset (<2 weeks) of symptoms (e.g. fever, cough, dyspnoea, chest pain) PLUS • New consolidation on clinical examination or chest X-ray • Response to antibiotics • Painful, progressive anogenital or orolabial ulceration caused by recurrent HSV infection • Present for more than 1 month • History of previous episodes

Recurrent severe bacterial pneumonia (This episode, plus 1 or more episodes in last 6 months)

• Bacterial microbiology (microscopy with Gram stain) of sputa or blood and culture if required See Section 10.6 Chest

Chronic herpes simplex virus (HSV) infection (orolabial/anogenital for >1 month or visceral of any duration) Oesophageal candidiasis

• Visceral HSV requires deﬁnitive diagnosis See Sections 10.2 Skin, 10.17 Mouth, and 11.15 Herpes infection

• • • •

Recent onset of retrosternal pain Difﬁculty swallowing (food and ﬂuids) Oral candidiasis usually present Responds to empirical therapy

• If not responding, then endoscopy or bronchoscopy to biopsy lesions for microscopy or histology See Sections 10.7 Abdominal complaints and 11.4 Candida

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Clinical event Extrapulmonary TB (EPTB)

Clinical diagnosis – no laboratory tests needed • Systemic illness (e.g. fever, night sweats, weakness, and weight loss) • Other evidence for extrapulmonary or disseminated TB varies by site: ° pleural, pericardial, peritoneal involvement ° meningitis, mediastinal, or abdominal lymphadenopathy ° osteitis • Chest X-ray in miliary TB shows diffuse uniformly distributed small miliary shadows or micronodules • Discrete cervical lymph node with M. tuberculosis infection is considered to be a less severe EPTB • Mostly clinical diagnosis • Typical appearance in skin or oropharynx: ° persistent, initially ﬂat, patches ° pink or blood-bruise colour ° develop into violaceous plaques or nodules • Retinitis lesions, seen on fundoscopy: ° discrete patches of retinal whitening with distinct borders ° spreading centrifugally along blood vessels ° associated retinal vasculitis, haemorrhage, necrosis • Recent onset focal neurological abnormality OR • Reduced level of consciousness AND • Response within 10 days to speciﬁc therapy

Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual • M. tuberculosis isolation or compatible histology from appropriate site, together with compatible symptoms or signs • If culture or histology is from respiratory specimen, then must have other evidence of extrapulmonary disease See Section 15 Tuberculosis

Kaposi sarcoma

• Abnormal chest X-ray • Macroscopic appearance at endoscopy or bronchoscopy • Deﬁnitive diagnosis: biopsy of cutaneous lesions for histology See Section 11.19 Kaposi sarcoma • Compatible histology • CMV demonstrated in CSF by culture See Section 11.8 Cytomegalovirus

Cytomegalovirus (CMV) disease (Retinitis or infection of other organs)

CNS toxoplasmosis

• Consider sending serum toxoplasma antibody • Neuro-imaging to look for intracranial mass lesions, usually ring-enhancing See Sections 10.10 Neurology and 11.40 Toxoplasmosis • CT to rule out other causes • Diagnosis of exclusion (see Sections 3.4, 10.10a.3)

HIV encephalopathy

• Disabling cognitive or motor dysfunction • Interference with activities of daily living • Progression over weeks or months in the absence of a cause other than HIV • LP excludes other causes • Meningitis ° usually subacute onset ° fever, increasing severe headache ° meningism ° confusion, behavioural changes ° response to cryptococcal therapy • Typical skin rash

Extrapulmonary cryptococcosis (including meningitis)

• LP for CSF microscopy including India ink stain, Gram stain, AFB smear • Cryptococcal antigen (CrAg) in CSF or serum • Culture of blood, CSF, other sites See Sections 10.10b Headache, 10.2 Skin and 11.5 Cryptococcosis

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Clinical event Disseminated non-tuberculous mycobacteria infection (MAC, MAI)

Clinical diagnosis – no laboratory tests needed • No presumptive clinical diagnosis • Suspect if diarrhoea, fever, hepatosplenomegaly, pallor, lymphadenopathy, CD4 <50

Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual • Specimens from various sites (stool, blood, urine, CSF, other body ﬂuid or tissue except lung) for culture of atypical mycobacterium See Section 11.27 Mycobacterium avium complex • Hypodense white matter lesions on neuro-imaging See Section 10.10a Neurological deﬁcits • Cysts identiﬁed on modiﬁed ZN-stained microscopic examination of unformed stool See Sections 10.7d Diarrhoea and 11.6 Cryptosporidiosis • Identiﬁcation of Isospora on stool microscopy See Sections 10.7d Diarrhoea and 11.18 Isosporiasis • Histology, antigen detection or culture from clinical specimen or blood culture See Section 11.16 Histoplasmosis • Blood culture if available

Progressive multi-focal leukoencephalopathy (PML) Chronic cryptosporidiosis (diarrhoea lasting >1 month) Chronic isosporiasis

• Progressive neurological disorder (cognitive problems, gait or speech disturbances, visual loss, peripheral and cranial nerve palsies) • No presumptive clinical diagnosis • No presumptive clinical diagnosis • Consider if ° watery diarrhoea >1 month ° no response to cotrimoxazole ° CD4 <200 • No presumptive clinical diagnosis • Consider if response to empirical cotrimoxazole • No presumptive clinical diagnosis

Disseminated mycosis (coccidiomycosis, histoplasmosis) Recurrent septicaemia (including non-typhoid salmonella) Lymphoma (cerebral or B-cell non-Hodgkins) or other HIV-associated solid tumours Invasive cervical carcinoma

• No presumptive clinical diagnosis

• No presumptive clinical diagnosis • Consider if rapidly enlarging lymph nodes, or poor response to TB treatment

• Send relevant specimen for histology. May require referral of patient. • Neuro-imaging for CNS tumours • Send relevant specimen for histology. May require referral of patient See Section 10.15 Female genitourinary problems • Send relevant specimen for histology (amastigotes visualized) or culture See Sections 10.1 Fever and 11.20 Leishmaniasis

• No presumptive clinical diagnosis • Suspect if offensive persistent vaginal discharge, visible cervical lesion, abnormal post-menopausal vaginal bleeding • No presumptive clinical diagnosis

Visceral leishmaniasis

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Clinical event HIV-associated nephropathy (HIVAN)

Clinical diagnosis – no laboratory tests needed • No presumptive clinical diagnosis • Consider if ° decreased renal function AND ° nephrotic range proteinuria AND ° absence of other risk factors for kidney disease • Cardiomegaly and evidence of poor left ventricular function • No other cause found

Diagnosis by district clinician with laboratory facilities and where to ﬁnd in this manual • Consistent ultrasound ﬁndings • Renal biopsy for deﬁnitive diagnosis See Section 11.31.6 in Renal problems

HIV-associated cardiomyopathy

• Conﬁrmed by echocardiography

Italics assume that laboratory tests or investigations usually are not available at the district hospital, and require referral to higher level facilities.

13.3 Prophylaxis for PLHIV Cotrimoxazole prophylaxis3 Cotrimoxazole is a broad-spectrum antimicrobial agent that acts against Pneumocystis jirovecii, Toxoplasma gondii, Plasmodium falciparum malaria, and many other pathogens. Cotrimoxazole prophylaxis is also referred to as cotrimoxazole preventive therapy (CPT). Use the table below to determine when to start and stop cotrimoxazole prophylaxis in PLHIV. Follow national guideline recommendations. Table: Indications for cotrimoxazole prophylaxis and when to stop CD4 not available When to start primary cotrimoxazole prophylaxis WHO clinical stages 2, 3, 4 CD4 available CD4 <350 cells/mm3, irrespective of clinical stage OR WHO clinical stage 3 or 4, irrespective of CD4 count

Secondary cotrimoxazole prophylaxis Timing to start cotrimoxazole prophylaxis in relation to initiating ART Cotrimoxazole prophylaxis dose

Secondary prophylaxis is recommended for all patients who have completed treatment for PCP. Start cotrimoxazole prophylaxis ﬁrst. Generally, start ART within 2 weeks if patient is tolerating cotrimoxazole and has no symptoms of allergy (e.g. rash, hepatotoxicity). A 2-week separation will assist clinical management if some of the side-effects of cotrimoxazole occur (especially if starting a nevirapine-based regimen). 1 double-strength tablet or 2 single-strength tablets once daily. Total daily dose is 960 mg (800 mg SMZ + 160 mg TMP).

3 Guidelines on co-trimoxazole prophylaxis for HIV-related infections in children, adolescents and adults: Recommendations for a public health approach. WHO, 2006. Available at: http://www.who.int/hiv/pub/plhiv/ctx/ en/index.html

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CD4 not available Cotrimoxazole in pregnant and breastfeeding women

CD4 available

If a pregnant woman requires cotrimoxazole prophylaxis, it should be started regardless of the stage of pregnancy. Breastfeeding women should continue to receive cotrimoxazole prophylaxis. Pregnant women in malarial areas who are taking cotrimoxazole should not be given sulfadoxine-pyrimethamine (SP) for intermittent preventive therapy for malaria. See Section 14 PMTCT, HIV care and treatment. Give dapsone 100 mg per day, if available. Cotrimoxazole desensitization may be attempted, but not in patients with a previous severe reaction to cotrimoxazole or other sulfa-containing drugs. (See Table on management of cotrimoxazole side-effects below.) Monitor and support adherence. No speciﬁc laboratory testing is required in monitoring cotrimoxazole. Option 1 Continue prophylaxis indeﬁnitely Option 2 Consider discontinuation in patients after 1 year on ART without WHO stages 2, 3, or 4 events, with good adherence and secure access to ART CD4 count >350 cells/mm3, and on ART for at least 6 months.

Patients allergic to sulfa-based medications Monitoring patients on cotrimoxazole prophylaxis When to stop cotrimoxazole prophylaxis in patients on ART

Monitoring patients on cotrimoxazole prophylaxis On each facility visit, assess and support adherence, and check for and manage side-effects. Table: Management of cotrimoxazole side-effects according level of care Side-effect Nausea First-level • Continue drug and take with food • Use antiemetic drugs. • Refer if severe or persistent vomiting • Stop drug and refer urgently to hospital if: ° generalized rash or ﬁxed drug reaction ° peeling skin ° eye or mouth involvement • Do not give cotrimoxazole again • Stop cotrimoxazole • Call for advice or refer • Stop cotrimoxazole • Call for advice or refer District-level clinician Continue cotrimoxazole See Section 10.7c Nausea and vomiting • Stop cotrimoxazole • Grade the adverse event • If grade 4 – permanently discontinue cotrimoxazole • If grade 3 – attempt desensitization or commence dapsone See Section 10.2 Skin See Section 10.18 Anaemia, and toxicities in this Section • Conﬁrm jaundice due to drug reaction • Manage the underlying problem See 10.8 Jaundice, and toxicities in this Section

Rash

Pallor (Hb <8) Bleeding gums New jaundice

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Use the following Table to grade and manage cotrimoxazole toxicity. Table: Grading skin rash due to cotrimoxazole toxicity Toxicity Grade 1 Grade 2 Grade 3 Clinical description Erythema Diffuse maculopapular rash Dry desquamation Vesiculation Mucosal ulceration Recommendation • Continue cotrimoxazole – monitor closely • Symptomatic treatment with antihistamines • Continue cotrimoxazole – monitor closely • Symptomatic treatment with antihistamines • Discontinue cotrimoxazole until the rash has resolved completely (usually 2 weeks) • Reintroduction or desensitization can be considered (see next table on Steps for cotrimoxazole desensitization) • Cotrimoxazole should be permanently discontinued • Start dapsone for prophylaxis once patient stabilizes

Grade 4

Exfoliative dermatitis, StevensJohnson syndrome, erythema multiforme, moist desquamation

Cotrimoxazole desensitization • Desensitization is usually successful and rarely causes serious reactions. • Desensitization should not be attempted in patients with history of grade 4 toxicity. • It can be attempted 2 weeks after a non-severe (grade 3 or less) cotrimoxazole toxicity. • Initiate an antihistamine drug the day before desensitization, and continue daily until completing the dose escalation. On day 1, give the step 1 dose of cotrimoxazole in the table Steps for cotrimoxazole desensitization below. This is increased by 1 step each day: • If severe reaction occurs, stop the desensitization. • If minor reaction occurs, repeat the same step for another day: ° if the reaction subsides, proceed to the next step ° if the reaction worsens, desensitization should be terminated. Table: Steps for cotrimoxazole desensitization Step Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 onward Dose 80 mg sulfamethoxazole + 16 mg trimethoprim (2 ml of oral suspension*) 160 mg sulfamethoxazole + 32 mg trimethoprim (4 ml of oral suspension*) 240 mg sulfamethoxazole + 48 mg trimethoprim (6 ml of oral suspension*) 320 mg sulfamethoxazole + 64 mg trimethoprim (8 ml of oral suspension*) 1 single-strength tablet (400 mg sulfamethoxazole + 80 mg trimethoprim) 2 single-strength tablets or 1 double-strength tablet (800 mg sulfamethoxazole + 160 mg trimethoprim)

* Cotrimoxazole oral suspension is 40 mg trimethoprim + 200 mg sulfamethoxazole per 5 ml.

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Isoniazid preventive therapy4 Isoniazid preventive therapy (IPT) is the use of INH for individuals with latent infection with M. tuberculosis in order to prevent progression to TB disease. IPT is a package of HIV care to prevent TB-related morbidity and mortality in PLHIV. HIV is the most powerful known risk factor for progression from latent infection with M. tuberculosis to active TB; therefore, preventive therapy against tuberculosis should be considered for all HIV-positive patients. HIV-positive pregnant women also are at increased risk of acquiring TB. Tuberculosis has a negative impact on the health and survival of the mother and her infant.

It is strongly recommended to follow national guidelines on IPT

Initiate and monitor IPT All persons living with HIV, including pregnant women, should be screened routinely for active TB at each facility visit. Patients with current cough, fever, weight loss, or night sweats should be evaluated for TB and other diseases. Patients with active TB should be put on anti-TB treatment right away. Use the algorithm below for rapid clinical screening of HIV-positive adults and adolescents to offer IPT. Patients with no current cough, fever, weight loss, or night sweats are unlikely to have active TB and should be offered IPT as part of a comprehensive package of HIV care. Tuberculin skin test (TST) is not a requirement for initiating IPT in PLHIV. IPT is recommended irrespective of stage of HIV infection or immunosuppression, to those on ART or PreART, those who successfully completed TB treatment in the past, and pregnant women. IPT is not recommended for patients who have successfully completed MDR or XDR TB treatment. PLHIV in congregate settings, such as prisons and centres for refugees or internally displaced persons, are at higher risk for TB. Give special attention to screening for TB and offering IPT in these groups. Defer IPT in the presence of active hepatitis (acute or chronic), regular and heavy alcohol consumption, and symptoms of peripheral neuropathy. Advise the patient on the beneﬁts of IPT. INH 300 mg daily for at least 6 months is recommended, and up to 36 months in HIV-prevalent settings with a high prevalence and transmission of TB. It is desirable that pyridoxine 10 mg daily is given additionally to prevent peripheral neuropathy. Medication can be selfadministered, or administered under the supervision of a treatment supporter. Patients should be seen by a health worker monthly.

4 Guidelines for intensiﬁed tuberculosis case-ﬁnding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. WHO, 2011. Available at: http://www.who.int/hiv/pub/tb/9789241500708/en/index. html

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For patients on IPT, monitor and support adherence, and assess for any new signs and symptoms at each facility visit. New signs and symptoms may be due to drug side-effects, active tuberculosis, other HIV-related conditions, or non-HIV related ailments. Patients suspected of active TB and drug toxicity should be evaluated and managed accordingly. INH is generally well-tolerated in recommended doses. Hepatitis is an important potential side-effect of INH. Patients should be educated about symptoms of hepatitis and, if symptoms occur, they should be instructed to discontinue the drug and seek advice from a health worker. Use the Table below to recognize and manage common side-effects of INH. Table: Common side-effects of INH and their management Side-effects of INH Burning, numbness or tingling sensation in the hands and feet Recommendation Give pyridoxine 50–70 mg daily. Monitor and support adherence to pyridoxine. The risk of peripheral neuropathy can be reduced if patients receive daily supplements of pyridoxine. Reassure patient. Instruct to take INH at bedtime. Give drug with small meals. If symptoms persist, stop INH immediately. Stop INH. Usually during the ﬁrst week of therapy. Stop INH immediately. Patient may need hospital admission.

Drowsiness Anorexia, nausea, abdominal pain Jaundice (other causes excluded), hepatitis Skin rash with or without itching (rare, but can be serious, e.g. Stevens-Johnson syndrome)

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Figure: Algorithm for TB screening in HIV-positive adults and adolescents in HIV-prevalent and resource-constrained settings Adults and adolescents living with HIV a

Screen for TB if any one of the following: ͻ Current cough ͻ Fever ͻ Weight loss ͻ Night sweats No c

Yes d

Assess for contraindications to IPT

Investigate for TB and other diseases

Yes

Other diagnosis

Not TB

Give IPT

Defer IPT

Appropriate treatment and consider IPT

Follow up and consider IPT

Treat for TB

Screen for TB regularly at each encounter with a health worker or visit to health facility

Every HIV-positive patient needs to be evaluated for ART eligibility, and infection control measures should be prioritized to reduce TB transmission in all settings providing care. Chest X-ray can be done if available, but it is not required to classify patients into TB and non-TB groups. In high HIV-prevalent settings, with a high TB prevalence among people living with HIV (e.g. greater than 10%), strong consideration must be given to adding additional sensitive investigations. Contraindications include: active hepatitis (acute or chronic) or regular and heavy alcohol consumption or symptoms of peripheral neuropathy. Past history of TB and current pregnancy should not be contraindications for starting IPT. Investigations for TB should be done in accordance with existing national guidelines.

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13.4 Initiate and manage patients on ART Determine ART eligibility The optimum time to start ART is once patients are eligible for ART. Where available, CD4 count is ideal to guide the decision of when to start ART. However, where CD4 testing is not available, do not withhold ART for patients who are in WHO clinical stage 3 or 4. Table: ART eligibility criteria in adults and adolescents CD4 cells counta ≤350 >350 Treatment recommendationsb Start ART irrespective of clinical stagec Do not initiate ART except for those in WHO clinical stage 3 or 4, in cases of HIV/TB co-infection, or HIV/HBV co-infection (where HBV treatment is indicated). All patients with HIV/TB coinfection, and all those with HIV/HBV coinfection who have chronic active hepatitis B should start ART irrespective of CD4 cell count.d Start ART irrespective of CD4 count

WHO clinical stages 3 and 4 a b c d

CD4 count should be measured after stabilization of any intercurrent conditions. CD4 count complements clinical assessment. Use in conjunction with clinical staging in decision-making. The initiation of ART is recommended for all patients with any WHO clinical stage 3- or 4-deﬁning condition. The deﬁnition of chronic active hepatitis in resource-limited settings is difﬁcult.

Determine the appropriate ARV regimen • The recommended ﬁrst-line ARV regimens include 2 NRTIs as a backbone in combination with an NNRTI. • In speciﬁc circumstances, a triple NRTI regimen may be used.

Refer to national guidelines for the choice of ARV regimen

Table: Classes of antiretroviral (ARV) drugs and their side-effects Drug class Nucleoside RTI (NRTI) Drug name zidovudine (AZT) Side-effects common and mild Headache, nausea, fatigue, muscle pain Side-effects severe and life-threatening Bone marrow suppression – rapid onset of life-threatening anaemia, lactic acidosis, myopathy Comments, indications, contraindications • Determine Hb at baseline and repeat if patient develops signs or symptoms suggestive of anaemia. • Stop or do not start AZT if Hb <7 g/dl. • FBC, if indicated. Active against HBV.

lamivudine (3TC)

Well tolerated – occasional nausea and diarrhoea

Pancreatitis

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Drug class Nucleoside RTI (NRTI)

Drug name emtricitabine (FTC) stavudine (d4T)

Side-effects common and mild Well tolerated – occasional nausea and diarrhoea Lipoatrophy

Side-effects severe and life-threatening

Comments, indications, contraindications Active against HBV.

Lactic acidosis, pancreatitis, peripheral neuropathy, diabetes Lactic acidosis, pancreatitis, peripheral neuropathy, diabetes Hypersensitivity reaction (2–5%)

DO NOT use with AZT or ddI. Avoid if BMI >28 (increased risk of lactic acidosis). Do not use with d4T.

didanosine (ddI)

Lipoatrophy

abacavir (ABC)

Diarrhoea, nausea, vomiting

Safe to use after lactic acidosis. Do not use after ABChypersensitivity reaction. Avoid in renal impairment. Do not use with ddI (levels increased). Active against HBV. Renal monitoring is desirable if available, but its absence does not preclude the use of TDF. Careful clinical assessment at 2 weeks (with or without ALT) before dose escalation. Avoid in pregnant women with CD4 >250 if possible, otherwise monitor for hepatitis. Increases metabolism of estrogen – use alternative contraceptive methods. Avoid during ﬁrst trimester of pregnancy. Avoid in patients with severe psychiatric illness. Avoid taking with fatty food. Preferred for TB/HIV coinfected patients.

Nucleotide RTI (NtRTI)

tenofovir (TDF)

Diarrhoea, nausea, decreased bone mineral density

Renal failure

Non-nucleoside RTI (NNRTI)

nevirapine (NVP)

Nausea Rash 20%

Stevens-Johnson syndrome Severe hepatitis Hypersensitivity reactions

efavirenz (EFV)

Rash – usually mild and self-limiting CNS symptoms (ﬁrst 2–4 wks)

Protease inhibitors (PIs)

lopinavir/ ritonavir (LPV/r) atazanavir/ ritonavir (ATV/r)

Diarrhoea Headache Lipodystrophy Diarrhoea

Dyslipidaemia Hyperglycaemia Hepatitis Unconjugated hyperbilirubinaemia

Monitor lipid proﬁles 6 monthly. Take with meal.

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Preferred ﬁrst-line ARV regimens for treatment-naive adults and adolescents Table: Preferred ﬁrst-line ARV regimens for treatment-naive adults and adolescents Target population Adults and adolescents Pregnant women Preferred optionsa,b AZT or TDF + 3TC + EFV or NVP OR AZT or TDF + FTC+ EFV or NVP AZT+ 3TC + EFV or NVP Comments Use ﬁxed dose combination, if available.

Avoid EFV during ﬁrst trimester. TDF is an acceptable option to AZT. In HIV-positive women with prior exposure to PMTCT regimens, see Section 13. EFV preferred in pregnant women with CD4 >250, in 2nd and 3rd trimester. EFV preferred in patients taking rifampicin. Initiate ART as soon as possible (within the ﬁrst 8 weeks) after starting TB treatment. NVP or triple NRTIs are alternative options if EFV cannot be used. Consider HBsAg screening before starting ART, especially if TDF is not a choice of ﬁrst-line ARV drug.

HIV/TB coinfection

AZT or TDF +3TC or FTC + EFV

HIV/HBV coinfection

TDF + 3TC or FTC + EFV or NVP

d4T has signiﬁcant toxicities and its use should be phased out according to the national timeline depending on feasibility, availability of resources, and replacement drugs. Follow national guideline recommendations. Follow national ART guideline recommendations for choice of ARV regimens.

Box: Special considerations in starting and stopping NNRTIs When starting nevirapinea • Lead-in NVP dose for the ﬁrst 2 weeks – 200 mg daily • Escalate to full NVP dose after 2 weeks – 200 mg twice daily; • If switching to NVP in a patient who is on EFV, no lead-in dose needed. a

When stopping either NVP- or EFV-based regimenb • Stop NVP or EFV ﬁrst; • Continue NRTI backbone (2 drugs only) for 7 days, and then stop all drugs.

The lead-in dose of 200 mg daily produces adequate drug levels in the ﬁrst 2 weeks after initiation; thereafter, the levels decline due to hepatic enzyme induction. Dose escalation to 200 mg twice daily is then required to maintain adequate drug levels. Starting at 200 mg twice daily results in high-serum concentrations of NVP, and an increased risk of rash and hepatotoxicity. This is to cover the long half-life of the NNRTI, and to reduce the risk of NNRTI resistance.

Box: Triple NRTI-based regimens in initial therapy • Triple NRTI regimens are not preferred ﬁrst-line regimens, as they are inferior to NNRTI-based regimens. • AZT + 3TC + ABC may be considered in special situations where NNRTIs are contraindicated or are likely to cause complications, including: ° pregnant women with a CD4 count of 250–350 cells/mm3 ° intolerance or known resistance to NNRTIs • Use of triple NRTI regimens preserves PIs for second-line options.

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Box: PIs in initial therapy • PIs are not preferred for use in ﬁrst-line regimens. • Use of PIs in ﬁrst-line regimens markedly limits options for second-line therapy. • PIs may be considered in ﬁrst-line regimens (with a standard dual NRTI backbone) in the following situations: ° treatment of HIV-2 infection ° women with a CD4 count of 250–350 cells/mm3 who need ART and cannot take EFV ° patients with NNRTI intolerance.

Drug interactions with ﬁrst-line ARV regimens Table: Drug-drug interactions with ﬁrst-line ARV regimens If patient is taking nevirapine (NVP) Do not co-administer (obtain advice on alternative therapy) • rifampicin • ketoconazole • St John’s wort – Hypericum perforatum (also known as Tipton’s weed, Chasedevil, or Klamath weed) • FTC • zidovudine (AZT, ZDV) • stavudine (d4T) • ganciclovir • diazepam (OK for convulsions in emergency) • other benzodiazepines other than lorazepam • phenobarbitol • phenytoin • protease inhibitor ARVs No clinically signiﬁcant interactions Higher risk of d4T neuropathy when also taking INH. Higher risk of anaemia when also taking aciclovir or sulfa drugs. • Do not take with high-fat meal. • If on methadone, increase dose of methadone. • Monitor for withdrawal signs. • Do not give during ﬁrst trimester of pregnancy. Other precautions If patient is on methadone, will need to increase dose. Monitor for withdrawal signs.

lamivudine (3TC) stavudine (d4T) zidovudine (AZT, ZDV) efavirenz (EFV)

tenofovir

13.5 ART monitoring Patients on ART should be monitored carefully for: • new clinical events • adherence • response to ART, including laboratory monitoring.

Monitoring for new clinical events Use the symptom checklist in the next box to assess for new clinical events that could indicate IRIS, drug side-effects or toxicity, new OIs, or adherence related issues.

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Box: Symptom checklist for clinical monitoring of new event Drug toxicity or side-effects Nausea, vomiting Poor appetite Rash Fever Jaundice Fatigue Diarrhoea Numbness, tingling Pain in legs, feet Abdominal pain Shortness of breath Weight gain, lipohypertrophy New illness, IRIS, OIs Cough Fever Night sweats Weight loss Diarrhoea Thrush Weakness Headache Visual problems Abdominal pain Poor appetite Nausea, vomiting Difﬁculty swallowing Depression Consider as challenges to adherence Memory problems Drug or alcohol abuse Social stressors Disclosure-related issues Traditional medicine use Patient relocation or dissatisfaction High pill burden Co-morbidities Drug toxicities or side-effects Depression Poor patient-provider relations

For side-effects of ﬁrst-line ARV drugs, see the table Section 13.8 below.

Monitor and support adherence Adherence monitoring and support should happen at each visit. See Section 13.11 below for an approach to adherence.

Monitoring response to ART Where CD4 and viral load testing is not available, treatment success must be monitored clinically. Where available, CD4 and viral load testing should be used to determine treatment response: • Clinical – monitor weight and conditions that may indicate progression of HIV disease. • Immunological – monitor CD4 count. • Virological – viral suppression to <400 copies/ml within 6 months of initiation of ART indicates treatment response.

Laboratory monitoring Suggested laboratory tests for monitoring patients on ART are shown in the following. Table: Routine laboratory investigations for monitoring patients on ART Laboratory investigation CD4 cell count Haemoglobin ARV regimen All AZT Baseline/ pre-ART Y Y Every 6 months Y Y Interval of testing If clinically indicated At baseline, every 3 months for high risk patients, otherwise symptom directed Comments See priority table. See toxicity table. High risk patients for anaemia: CD4 count <200, BMI <18.5 or body weight <50 kg, or anaemia at baseline.

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Laboratory investigation CD4 cell count Haemoglobin

ARV regimen All AZT

Baseline/ pre-ART Y Y Y Y

Every 6 months

Interval of testing If clinically indicated At baseline, every 3 months for high risk patients, otherwise symptom directed Symptom directed or at week 2, 4, 8 if available

Comments See priority table. See toxicity table. High risk patients for anaemia: CD4 count <200, BMI <18.5 or body weight <50 kg, or anaemia at baseline.

ALT

NVP

Routine monitoring is not indicated if not readily available. Routine monitoring if available, otherwise symptom-directed monitoring is desirable for women CD4 >250, HBV/HCV co-infection, alcohol abuse. Baseline ALT may be used, but its unavailability should not preclude the use of NVP.

TG/ cholesterol/ glucose Creatinine

PIs

TDF

At week 4, 8, 12

While creatinine monitoring is desirable, it is not a prerequisite to initiating TDF. Patients with renal diseases, diabetes, BMI <18 or body weight <50 kg, elderly patients, and patients on protease inhibitors are at high risk and need creatinine monitoring. See table ART regimens, laboratory monitoring, and treatment plan for initiating complicated patients on ART in Section 13.6 for TDF dose adjustment based on creatinine clearance. Avoid in the ﬁrst-trimester of pregnancy. See Section 13.8 on ART toxicity, It is recommended to use VL to conﬁrm suspected treatment failure based on clinical or immunological criteria.

Pregnancy test Serum lactate Viral load

EFV All NRTIs All

Y N N

N N N

If pregnancy suspected If clinically indicated Routine monitoring if feasible, or targeted use to conﬁrm treatment failure

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13.6 ART initiation in complicated patients There are a number of different problems that a patient may have prior to starting ART. The table below outlines an approach to management of patients in terms of when and which ART regimen to start and how to monitor it. Any additional information can be found in the other Sections of the manual as indicated in the last column. • For ART in TB, see Section 15 Tuberculosis and Section 13.8 below. • For ART in pregnancy, see Section 14.

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536 Recommended ﬁrst-line regimen Lab monitoring Monitor Hb monthly for at least 3 months Depends on treatment of the cause of the anaemia Treat underlying causes for anaemia Monitor platelets for response to ART and other therapy Depends on treatment References See Section 10.18 – look for treatable cause. Warn patient about early symptoms of anaemia Warn patient about risk of bleeding Avoid AZT Use TDF or ABC, or if not available or cannot be given, use d4T Drug considerations and comments Caution with NVP Least hepatotoxic: TDF/ EFV/3TC/ FTC Avoid NVP Least hepatotoxic: TDF/ EFV/3TC/ FTC Avoid all ART Only start once mild to moderate Monitor ALT frequently to detect resolution or fulminant failure Monitor ALT and continue clinical monitoring NVP, d4T+ddI are contraindicated in severe hepatic dysfunction Stop all other hepatotoxic drugs in severe liver dysfunction Look for treatable cause that may improve liver function Screen for hepatitis A, B, C Assess traditional medicine and alcohol use See Section 11.23 Liver abscess

Table: ART regimens, laboratory monitoring, and treatment plan for initiating complicated patients on ART

Complication

Initiation

Anaemia

Hb <7 g/dl

Investigate cause and treat anaemia

Do not delay ART as anaemia may respond to treatment

ART initiation in complicated patients

Thrombocytopenia

Platelets <50 000

Look for underlying cause and treat Do not delay ART as the complication may respond to treatment ITP and TTP are indications to start ART

Elevated transaminase

Mild <2.5 x ULN

Repeat after 2 weeks

If stable, start ART

Moderate 2.5-5 x ULN

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Severe >5 x ULN

Delay ART initiation Look for cause and manage patient Consult

Complication None

Initiation

Recommended ﬁrst-line regimen Lab monitoring References

Drug considerations and comments

Elevated total bilirubin Avoid NVP Least hepatotoxic: TDF/ EFV/3TC/ FTC Monitor bilirubin and continue clinical monitoring Stop all hepatotoxic drugs Avoid all ART Only start once mild Stop all drugs Avoid all ART

Mild <2.5 x ULN

Repeat after 4 weeks

If stable, start ART

Look for treatable cause that may improve liver function Screen for viral hepatitis – see Section 11.14 Liver ultrasound if available Assess traditional medicine and alcohol use See Section 11.23 Liver abscess

Moderate 2.5–5 x ULN

Delay ART initiation

Investigate cause

Severe >5 x ULN Only start once mild to moderate Adjust doses accordingly, see Section 11.31, Annex 2 Monitor creatinine monthly

Investigate cause, treat appropriately

Delay initiation

Vol. 2 • 13. Chronic HIV care, antiretroviral therapy (ART) and prevention at second level: July 2011 Adjust TDF dose based on CrCl See Section 11.31, Annex 2 Look for treatable cause See Section 11.31 Renal problems Adjust doses accordingly, see Section 11.31, Annex 2 Monitor creatinine monthly See Section 11.31 Renal problems

Elevated creatinine clearance

Moderate CrCl <60 ml/ min (Cockcroft Gault formula see Section 11.31)

Do not delay ART initiation

ART is indicated in HIVAN and renal function may improve with ART

Severe CrCl <50 ml/ min

ART initiation in complicated patients

CrCl < 10, replace TDF with another NRTI

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538 Recommended ﬁrst-line regimen Lab monitoring Monitor Hb and renal function Monitor closely for response and toxicity PIs increase concentration of quinine – avoid concomitant use NNRTIs and PIs reduce the concentration of coartem (artemetherlumefantrine) – avoid concomitant use No interaction between ART and meﬂoquine/ doxycycline Any standard ﬁrst-line regimen No drug interactions with ﬂuconazole See Section 10.7b Painful or difﬁcult swallowing See Section 11.37 Syphilis NNRTIs reduce concentration of quinine – monitor closely for efﬁcacy References See Sections 10.1 Fever and 11.25 Malaria Any standard ﬁrst-line regimen Caution with AZT if patient is anaemic Drug considerations and comments Any ﬁrst-line regimen Repeat syphilis serology at 3, 6, 9, 24 months

Complication

Initiation

Malaria

Treat malaria ﬁrst per national recommendations

ART initiation in complicated patients

Start ART when patient is stable

Oesophageal candidiasis

Suspected on history or conﬁrmed on endoscopy

Treat with ﬂuconazole Start ART as soon as patient can swallow comfortably

Latent syphilis

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Positive VDRL/ RPR titre >1:2 and no signs of infection

Treat syphilis, notify and treat partner

Do not delay initiation of ART

Complication Regimen should include 3TC/FTC plus TDF as these have anti-HIV and anti-HBV activity Monitor ALT at 1, 3, 6 months after starting ART Using 3TC/FTC without TDF results in HBV resistance in 60–80% of patients within 12 months Avoid NVP and PIs If on TDF, monitor creatinine at 1, 2, 3 months Close monitoring if ART is changed or stopped Interruption of these drugs can lead to lifethreatening hepatitis ﬂares and should therefore be continued when switching to second-line. Avoid other hepatotoxic drugs Any standard ﬁrst-line regimen Additional therapy such as INF-α or chemotherapy may be available Monitor renal function if on amphotericin B Adjust doses of NRTIs if renal dysfunction from amphotericin B See section 11.19, Kaposi’s

Initiation

Recommended ﬁrst-line regimen Lab monitoring References

Drug considerations and comments

Hepatitis B coinfection

Hepatitis B surface antigen +ve

Do not delay initiation of ART

Vol. 2 • 13. Chronic HIV care, antiretroviral therapy (ART) and prevention at second level: July 2011 Flare up of hepatitis may occur within 3 months of starting ART (hepatitis B IRIS) and must be distinguished from drug hepatotoxicity Any standard ﬁrst-line regimen Avoid TDF if renal dysfunction Watch for IRIS May need serial LPs Needs secondary prophylaxis with ﬂuconazole See Section 11.5 Any standard ﬁrst-line regimen Watch for IRIS Watch for IRIS See Sections 11.5 and 10.10a Focal neurological problems

Or history of infection

Kaposi sarcoma

Suspected or conﬁrmed on biopsy

Start ART as soon as possible

Cryptococcal meningitis

Conﬁrmed on CSF examination

Start ART after 2 weeks of cryptococcal therapy to avoid IRIS

ART initiation in complicated patients

Previously treated cryptococcal meningitis or toxoplasmosis of the brain, patient now stable

Do not delay initiation of ART

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540 Recommended ﬁrst-line regimen Lab monitoring Continue secondary prophylaxis after treatment completed See Section 11.27 References See Section 10.6 Chest symptoms Any standard ﬁrst-line regimen Drug considerations and comments Any standard ﬁrst-line regimen Severe IRIS may develop, consider managing with steroids Adherence might be a challenge Any standard ﬁrst-line regimen Watch out for benzodiazepine antiepileptics, other sedatives Treat psychiatric illness See Section 10.11 Mental problems Adherence might be a challenge Avoid EFV See Section 10.11 Mental problems Any standard ﬁrst-line regimen Avoid D4T or ddI It is better to use AZT/ TDF Severe illness See speciﬁc Sections Beware of other drugs that cause peripheral neuropathy, particularly INH Some peripheral neuropathies may respond to ART See Section 10.10a Neurological deﬁcit

Complication

Initiation

Pneumocystis jiroveci pneumonia

Conﬁrmed or suspected

Stabilize patient then start ART

Do not delay initiation

ART initiation in complicated patients

MAC

Suspected or conﬁrmed

Do not delay initiation of ART MAC often responds to immune restoration with ART

HIV dementia/ encephalopathy

Do not delay initiation of ART

Mental illness

History of severe psychiatric illness

Co-manage HIV and psychiatric illness

Acute illness requiring antibiotics

Stabilize active infections prior to ART

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Peripheral neuropathy

Look for treatable causes

Do not delay initiation of ART

Complication Refer to table above, Drug-drug interactions with ﬁrst-line ARV regimens NVP and EFV reduce methadone levels and may lead to methadone withdrawal The dose of methadone may need to be increased by 50-100% Sudden cessation of NNRTIs without corresponding reduction in the methadone dose can also result in a sudden increase in methadone level and opioid overdose Avoid TDF Monitor blood glucose, lipids, TG Metformin and NRTIs can both cause lactic acidosis

Initiation

Recommended ﬁrst-line regimen Lab monitoring References See Section 17.6 ART and substance use

Drug considerations and comments

On methadone

Methadone undergoes metabolism in the liver by pathways that are common to some ARTs and anti-TB drugs

Vol. 2 • 13. Chronic HIV care, antiretroviral therapy (ART) and prevention at second level: July 2011 Refer to table above, Drug-drug interactions with ﬁrst-line ARV regimens Do not use EFV in women of childbearing potential unless they are using consistent and effective contraception Levels of hormonal contraceptives are affected by some ARVs. See Section 14.5 for details. See NVP and EFV above See Section 10.15 Female genitourinary problems See Section 10.2 Skin

It is preferable to use AZT+3TC+ABC OR AZT+3TC+TDF

Diabetes

Do not delay initiation of ART

Epilepsy

Stabilize patient then start ART

Childbearing potential

Ideally, give pregnancy test prior to initiation of EFV

ART initiation in complicated patients

Drug reaction

Do not start ART during drug reaction as it might not be distinguishable from an ARV drug reaction

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ART for patients with prior ARV exposure Patients who have been exposed to ARV drugs before should be managed depending on what drugs were used and the duration of exposure and adherence, e.g. exposure for PMTCT, previous incorrect dual therapy, or previous ART with interrupted therapy due to adherence, toxicity, or intolerance. See Section 14 for PMTCT.

13.7 Second-line ART Second-line ART is the next regimen to be used after the ﬁrst-line regimen has failed (see below for deﬁnition of treatment failure). Second-line ART does not include regimen changes due to toxicity, drug interactions, or drug intolerances. Changing to second-line ART is a major treatment decision. The drugs used in second-line are not as well-tolerated, are more expensive, and the decision to switch should be based on accurate diagnosis of failure of ﬁrst-line regimen, and made in consultation with the patient, the treatment supporter, and the clinical team. Input from an ART expert is recommended. Adherence support for patients starting second-line ART is especially critical (see Section 13.11 on adherence) as in most settings there are no or few options for subsequent regimens (salvage therapy) if second-line therapy fails. If a second-line regimen is not available, patients can continue the failing regimen, but should be referred to the next level for expert advice. This decision should not be made alone. The patient must understand the rationale behind any decision as well as the potential risks associated with each option. The ART expert should act as clinical mentor to the district clinician by providing decision-making support and ongoing education around treatment failure and second-line therapy.

Deﬁning ART failure Treatment failure can be deﬁned on a clinical, immunological, or virological basis in a patient on ART for more than 6 months. Where viral load testing is available, this allows for early detection of treatment failure; otherwise clinical or immunological criteria can be used.

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Table: Deﬁnitions of treatment failure for patients on ﬁrst-line antiretroviral regimen Clinical failurea Immunological failured A new or recurrent WHO stage 4 conditionb,c • Fall of CD4 count to pre-therapy baseline (or below) • 50% fall from the on-treatment peak value (if known) • Persistent CD4 levels below 100 cells/mm3e Plasma viral load above 5000 copies/mlf

Virological failure

a Current event must be differentiated from IRIS. b Certain WHO clinical stage 3 conditions (e.g. pulmonary TB, severe bacterial infections) may be an indication of treatment failure, and thus require consideration of second-line therapy. c Some WHO clinical stage 4 conditions (lymph node TB, uncomplicated TB pleural disease, oesophageal candidiasis, recurrent bacterial pneumonia) may not indicate treatment failure and thus do not require consideration of second-line therapy. d Without concomitant infection to cause transient CD4 cell decrease. e Some experts consider that patients with persistent CD4 cell counts below 50/mm3 after 12 months on ART may be more appropriate. f The optimal viral load value at which ART should be switched has not been deﬁned. However, values of more than 5000 copies/ml have been associated with subsequent clinical progression and signiﬁcant CD4 cell count decline.

Second-line ARV regimens Second-line regimens consist of a boosted PI supported by 2 NRTIs, one of which is new and was not used in the ﬁrst-line regimen. Based on efﬁcacy, simplicity, toxicity, population coverage, potential for low cost, and compatibility with paediatric formulations, the WHO-preferred PIs are lopinavir/r or atazanavir/r. If thymidine analogues (AZT, d4T) are used in the ﬁrstline regimen, the preferred second-line NRTI backbone is TDF/3TC. The priority option for patients who fail a TDF ﬁrst-line regimen is AZT/3TC. 3TC is maintained in all second-line regimens, even if used in the ﬁrst-line regimen, as the M184V mutation to 3TC sensitizes the virus to AZT and TDF, and reduces its capacity for viral replication. Table: Choice of second-line ART based on ﬁrst-line NRTIs used2 NRTI used in ﬁrst-line (AZT or d4T) + 3TC TDF + 3TCa a

Preferred second-line NRTIs TDF + 3TC a

Preferred PIs LPV/rb or ATV/r

AZT + 3TCa

a FTC is interchangeable with 3TC b LPV/r is currently the only ﬁxed-dose combination of PI + RTV available. LPV/r is available as a heat-stable tablet.

Monitoring second-line regimens PIs adversely affect lipid and glucose metabolism. If available, routine monitoring of lipids (triglycerides and cholesterol) and glucose is recommended. ATV/r can cause unconjugated hyperbilirubinaemia, and there have been a few cases of kidney stones reported in patients taking this drug.

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13.8 ART toxicity and management At the clinic, you will most likely see patients with one or more ART-related adverse event during the course of their treatment. These adverse events may be drug toxicities, drug intolerances, or IRIS. Drug intolerance is the inability of a patient to continue taking a drug due to unacceptable side-effects, for example dizziness or vivid dreams from EFV, and diarrhoea from PIs. On the other hand, drug toxicity refers to an allergic reaction to a drug. These reactions range from mild disturbances to life-threatening events, for example NVP-associated rash or hepatotoxicity. Patients starting ART should be well-informed about potential side-effects, both before and after starting treatment. Most mild toxicities can be managed symptomatically or by substituting the offending drug in the regimen. Lifethreatening episodes may necessitate stopping the treatment temporarily and stabilizing the patient before re-introduction of a different regimen. ART toxicity must be distinguished from other causes of symptoms in PLHIV, for example: • toxicity from concurrently administered medications other than ART • drug interactions causing increased drug levels with resultant toxicity • OIs that develop after initiation of treatment IRIS • other diseases (e.g. infectious hepatitis, gastroenteritis). ART toxicities can be divided into short- and long-term, depending on when they are likely to occur after treatment initiation. The following table provides guidance on short- and long-term toxicities of ART. Table: Short- and long-term toxicities on ART Short-term toxicities Time from initiation of new ARV Duration or course • Days to weeks • Typically improve spontaneously within a few weeks • Some may persist longer • • • • GI disturbance (AZT, PIs) Rash (NNRTIs, ABC) Hepatotoxicity (NNRTIs, PIs) Drowsiness, dizziness, vivid dreams (EFV) Long-term toxicities • Months to years • Less likely to resolve quickly upon discontinuation of the offending agent • • • • Lipodystrophy (d4T, ddI, AZT, PIs) Dyslipidaemia (d4T, PIs) Peripheral neuropathy (d4T, ddI) Lactic acidosis (d4T, ddI, AZT)

Examples

Treatment

• Often managed symptomatically without interrupting or changing the drug • Some require interruption of treatment and intensive management until the toxicity resolves, e.g. Stevens-Johnson syndrome, hepatotoxicity • Removal of offending drug typically leads to prompt resolution

• Substitution of the offending drug

Resolution

• Best to prevent by using drugs with lowest risk for toxicity, if possible

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Clinical and laboratory monitoring for ART toxicity Signs and symptoms that suggest toxicity warrant prompt investigation and management. Monitoring of certain blood parameters (haematology, chemistry, liver function) is indicated for patients on ART in order to screen for toxicities. However, the absence of laboratory resources should not be a barrier to providing ART to patients who otherwise qualify for treatment. General recommendations for baseline and follow-up monitoring are discussed in Section 13.5 above. Most drug-related toxicities appear within the ﬁrst few months of starting treatment; therefore, it is reasonable to decrease the frequency of monitoring in patients who initially display no evidence of toxicity. Table: Side-effects of ﬁrst-line ARVs Drugs probably responsible AZT or d4T d4T b

Common associated toxicity Lactic acidosis Lipoatrophya Neuropsychiatric toxicity

Suggested substitute TDF TDF NVP or TDF (or any PId) AZT or d4T TDF (or any PId) TDF or d4T AZT or TDF AZT or TDF or d4T TDF (or any PId) TDF or d4T NVP or TDF (or any PId) EFV or TDF (or any PId)

EFV TDF c

Renal toxicity (renal tubular dysfunction) Severe or life-threatening rash (Stevens-Johnson syndrome) Severe anaemia or neutropaenia Peripheral neuropathy Hypersensitivity reaction Severe gastrointestinal intolerance Potential teratogenicity (during ﬁrst trimester or in women not on adequate contraception) Hepatitis

NVP AZT d4T ABC NVP AZT EFV NVP

a Substitution of d4T may not reverse lipoatrophy. b For example, persistent hallucinations or psychosis. c Severe rash is deﬁned as extensive rash with desquamation, angioedema, or a reaction resembling serum sickness; or a rash with constitutional ﬁndings such as fever, oral lesions, blistering, facial oedema, or conjunctivitis. Stevens-Johnson syndrome can be life-threatening. For a life-threatening rash, substitution with EFV is not recommended. d PI class should ideally be reserved for second-line therapy. Consider stopping all drugs in severe reactions. Consult with an expert HIV clinician when a regimen change is needed.

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Management of ART toxicity Table: ART toxicity classiﬁcation and general management principles5 Toxicity grade Grade 1: Mild Description Transient or mild discomfort No limitation in activity No medical intervention required Limitation of activity – some assistance may be needed Minimal medical intervention required Marked limitation of activity – some assistance usually required Medical intervention required Hospitalization possible Extreme limitation in activity Signiﬁcant assistance required Signiﬁcant medical intervention required Hospitalization or hospice care General management principles Continue current ART regimen Counsel patient regarding importance of adherence despite toxicity Consider continuation of ART If the patient does not improve on symptomatic therapy, consider single-drug substitutions Substitute the offending drug without stopping ART

Grade 2: Moderate

Grade 3: Severe

Grade 4: Severe or lifethreatening

Discontinue all ARVs immediately Give symptomatic and supportive therapy Reintroduce ARVs once patient is stabilized, using modiﬁed regimen (substitute the offending drug)

See Section 13.9 following for further details of speciﬁc ARV toxicity management.

13.9 Management of speciﬁc ART toxicities Recommendations for the management of several common toxicities, including management tables and ﬂowcharts, are presented below. Annex C lists ARVs and other HIV-related medications that can cause or contribute to several common toxicities.

Haematological toxicity • Drugs that cause haematological toxicity include AZT, d4T, and cotrimoxazole. • AZT causes anaemia and neutropenia (platelet count often increases with AZT). • Screen for anaemia with Hb at baseline, and at 3 and 6 months for high-risk patients (see Table: Routine laboratory investigations for monitoring patients on ART). Otherwise, check Hb if patient has symptoms of anaemia. • The onset is usually within 6 weeks of starting AZT. • It is unlikely to cause toxicity after 6 months on AZT (late-onset toxicity can occur). • Bone marrow toxicity from cotrimoxazole is usually associated with high doses used to treat opportunistic infections. However, it has been seen in patients on low-dose prophylaxis. 5 Adapted from Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach (2006 revision). WHO, 2006. Available at: http://www.who.int/hiv/pub/guidelines/adult/en/

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Table: Guidelines for managing haematological toxicity (Management is written in italics) Haematology Haemoglobin Grade 1 8.0–9.4 g/dl or 80–94 g/litre Grade 2 7.0–7.9 g/dl or 70–79 g/litre Grade 3 6.5–6.9 g/dl or 65–69 g/litre Grade 4 <6.5 g/dl or <65 g/litre

Monitor clinically

Repeat in 4 weeks, or Change to another drug

Repeat in 2 weeks Change to another drug

Stop AZT Change to another drug with minimal or no bone marrow toxicity (e.g. TDF or d4T), once stable Consider transfusion if indicated

Absolute neutrophil count

1000–1500/mm3 or 1.0–1.5/g/litre

750–999/mm3 or 0.75–0.99/g/litre

500–749/mm3 or 0.5–0.749/g/litre

<500/mm3 or <0.5/g/litre

Repeat in 4 weeks

Repeat in 2 weeks

Repeat in 2 weeks Consider stopping drug

Stop drug

Figure: Algorithm for management of AZT-related anaemia Suspected AZT-induced anaemia

Seek and correct other causes: iron deficiency, malaria, other drugs that may suppress the bone marrow

Recheck Hb level

Grade 1 and 2

Grade 3 and 4

Close monitoring of Hb (recheck in 1 week)

x x x

Substitute TDF for AZT; recheck Hb in 4 weeks d4T can be used as back-up drug if TDF is not available Consider transfusion if indicated

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Hepatotoxicity • All ARVs may cause hepatotoxicity, but NVP is the most common. • Long-term use of NRTIs can cause fatty inﬁltration of the liver. Other hepatotoxic drugs are TB drugs and azoles. • Transient, mild elevation of ALT occurs commonly with many drugs and does not require speciﬁc management. • With severe abnormalities, stop all hepatotoxic drugs immediately and do not attempt to restart the drugs. • Any associated systemic illness should be regarded as a severe reaction, and treatment should be stopped immediately. • Isolated, mild, unconjugated hyperbilirubinaemia is associated with some PIs (atazanavir). Hepatic ﬂares • Typically present as an unexpected increase in ALT/AST with symptoms of clinical hepatitis (fatigue, nausea, abdominal pain, jaundice) within 6–12 weeks of commencing ART. • Hepatic ﬂares may occur following: ° initiation of ART, as part of IRIS ° stopping of 3TC or tenofovir, due to their activity against HBV. • Flares may be difﬁcult to distinguish from ART-induced hepatic toxicity. • Drugs active against HBV/HCV should be continued during a suspected ﬂare. • If it is not possible to distinguish a hepatitis B or C ﬂare from grade 4 drug toxicity, all ART should be temporarily stopped until the patient stabilizes. An EFV-based regimen is preferred when ART is restarted. Table: Guidelines for managing hepatotoxicity (Management is written in italics) LFT ALT/AST Grade 1 1.25 – 2.5 X ULN Grade 2 >2.5 – 5.0 X ULN Grade 3 >5.0 – 10.0 X ULN Grade 4 >10.0 X ULN

Monitor

Repeat in 1 week

Discontinue relevant drugs

Discontinue all drugs

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Rash and hypersensitivity Rash is a common side-effect of NNRTIs (NVP and EFV). NNRTI-associated rash usually presents in the few weeks after initiation of therapy. Management depends on clinical grading of the severity: Grade 1 Cutaneous reaction – rash Localized macular rash Grade 2 Diffuse maculopapular OR morbilliform rash OR target lesions Grade 3 Diffuse maculopapular OR morbilliform rash with vesicles or limited number of bulla OR superﬁcial ulcerations of mucous membranes limited to 1 site Grade 4 Extensive or generalized bullous lesions OR Stevens-Johnson syndrome OR ulceration or mucous membranes involving 2 or more distinct mucosal sites OR toxic epidermal necrolysis

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NVP rash occurs in 15–30% of patients ART interruption is required in 6–8% of patients

Figure: NVP hypersensitivity management NVP 200 mg once daily

Rash develops

Rash on dose increase

Grade 1

Grade 2

Grade 3

Grade 4

Continue NVP 200 under medical supervision for not more than 2 weeks Antihistamines for symptom relief

Stop NVP (tail regimen for 7 days)

Check rash after 2 weeks

Grade 3

Stop ARV until rash is Grade 1 or gone

Grade 1 or 2

Grade 4

Increase to NVP 200 mg twice daily if on lead-in dose Continue NVP 200 mg twice daily if on full dose

EFV 600 mg under careful supervision If giving PI, no tail regimen needed PI

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EFV rash occurs in 10% of patients but rarely severe (<1%)

Figure: EFV hypersensitivity management EFZ 600 mg

Follow up visit: ask and look for rash, enquire about other drugs that cause skin toxicity

No toxicity or Grade 1 skin rash

Grade 2 skin rash

Grade 3 or 4 Skin rash

Continue EFV 600 mg once daily, review patient in 2 weeks or before if worsening Stop ARVs until Grade 1 No change or improvement

Continue EFV 600 mg once daily

Continue EFV 600 mg once daily and monitor

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ABC hypersensitivity This is a systemic reaction that usually occurs within the ﬁrst 8 weeks of therapy in about 3% of patients. Deaths have been reported after reintroducing ABC; therefore, ABC should never be reintroduced after discontinuation due to hypersensitivity. Signs of ABC hypersensitivity include: • rash • fever • fatigue • abdominal or respiratory symptoms. See Table: ARVs and other HIV-related medications associated with selected toxicities below for grading clinical toxicities.

Dyslipidaemia • PIs can cause elevated triglycerides and elevated LDL cholesterol. • d4T can cause elevated triglycerides, and EFV can cause elevated total cholesterol. • Markedly elevated triglycerides can cause pancreatitis. • Solve by substituting for the offending drugs, e.g. substitute d4t with AZT, LPV/r with atazanavir. • Fibrates are the treatment of choice for treating hypertriglyceridaemia. • Simvastatin interacts with PIs and should not be used. It creates toxic concentrations of statins in the blood. • Suggest lifestyle changes to the patient, such as a reduced fat diet, exercise, weight reduction, smoking cessation, and control of hypertension and diabetes.

Hyperlactataemia and lactic acidosis • All NRTIs, particularly d4T and ddI, can cause mitochondrial toxicity, which results in elevated levels of serum lactate and potentially fatal lactic acidosis. • 3TC, ABC, and TDF are the least likely to cause this side-effect. • Symptoms are non-speciﬁc and include abdominal pain, malaise, lethargy, weight loss, and respiratory distress, and may be associated with other symptoms, such as peripheral neuropathy. • The mortality rate with lactic acidosis is 30–60%; maintain a high level of suspicion. • If available, lactate levels will conﬁrm the diagnosis.

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Figure: Management of suspected hyperlactataemia or lactic acidosis

Approach to hyperlactataemia or lactic acidosis

x x x x x x

Risk factors On d4T or ddI or AZT Good adherence to treatment Good response to treatment Overweight (BMI >28) or rapid weight gain after starting ART On ART >2 months (usually >6 months) Associated leg cramps or weakness

Suspect lactic acidosis

Lactate measurement available?

x x x x x x x x

Suggestive symptoms Fatigue Anorexia Nausea and vomiting Unexplained weight loss Abdominal pain Tachypnoea (not respiratory) Tachycardia Peripheral oedema

YES

Lactate <2.5

Lactate 2.5–5

Lactate 5–10

Lactate >10

x Stop all ARVs for 1 month (no tail regimen). x Supportive treatment: hospitalization, IV fluid, respiratory support if needed

Lactic acidosis excluded, consider other causes of symptoms

x STOP all ARVs x Supportive therapy: Hospitalization, oral fluids, thiamine x STOP all ART, admit to hospital for high-level care x Supportive therapy: thiamine 100 mg IV every 12 hours, IV fluids x If very acidiotic: Broad spectrum antibiotics and IV bicarbonate x Note: It may take many weeks for serum lactate to normalize.

x Change to new NRTI regimen: 3TC+AZT/ABC/TDF x Repeat lactate weekly until normal x Stop ART if: symptoms or lactate worsening

Consider other causes of weight loss/abdominal pain x OI or IRIS (check for TB) x Chronic diarrhoea or malabsorption x Pancreatitis or hepatitis x Diabetes x GI intolerance of drugs

Once symptoms improved, plan to start new regimen

x x x x x x

Consider other causes of raised lactate Sepsis Severe dehydration Severe anaemia Kidney or liver disease Pancreatitis Heart failure, DKA

Start new regimen once lactate <2.5 and symptoms improved

NEW REGIMEN OPTIONS 3TC + TDF + NNRTI or TDF +NNRTI + PI/b or NNRTI + PI/b

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Peripheral neuropathy Distal symmetric peripheral neuropathy (DSPN), also known as “peripheral neuropathy,» is a common adverse effect associated with long-term use of NRTIs, especially d4T and ddI, and occasionally AZT. DSPN can also result from other medications, such as isoniazid, and from medical conditions such as diabetes mellitus, vitamin B6 deﬁciency, CMV, and HIV infection itself. See Sections 10.10a and 10.10a.6. DSPN typically presents as tingling, burning, numbness or paraesthesia that begins in the soles of the feet (usually the toes), and advances up the foot and leg in a stocking distribution. Involvement of the arms in a glove distribution starting at the ﬁngers is seen in more advanced cases. Decreased ankle jerk reﬂexes and decreased vibratory sensation are important signs to look for during physical examination. ART-associated DSPN may reverse on discontinuation of the offending drug, although recovery is often slow, and the condition may continue to worsen even after discontinuation. For this reason, it is important to respond quickly to worsening symptoms to prevent or minimize its progression. See Table: Clinical toxicities grading and management below. As part of plans to phase out d4T, it is recommended to target those with any established d4T-related toxicity for priority replacement of d4T with either AZT or TDF.

Lipodystrophy Long-term use of NRTIs (especially d4T, ddI, AZT), as well as PIs, is associated with changes in body fat distribution known as lipodystrophy. These changes include fat accumulation (central obesity, buffalo-hump, breast enlargement, lipomas) and lipoatrophy (fat loss from face, buttocks, and limbs). Lipodystrophy may be unacceptable to some patients, and may therefore have an impact on adherence if it is not properly addressed. There is currently no speciﬁc therapy, but a low-fat diet and aerobic exercise may be partly effective. Substituting d4T/ddI/AZT for another NRTI such as TDF/ABC may be of help. The recovery is usually slow and incomplete, so consider changing early to avoid ongoing lipodystrophy. Central obesity is associated with an increased risk of insulin resistance and dyslipidaemias.

Abdominal pain and symptoms Abdominal pain is a common side-effect of ART. Many ARVs can cause abdominal pain through a variety of mechanisms such as pancreatitis, hepatitis, steatohepatitis, lactic acidosis, IRIS with abdominal TB, and GI intolerance. Establishing a probable etiology is critically important because some of these underlying conditions (e.g. pancreatitis, lactic acidosis) may be fatal if not diagnosed and managed in a timely fashion. See Section 10.7a.2.

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Table: Clinical toxicities grading and management Grade 1 Diarrhoea Mild or transient 3 to 4 loose stools per day OR Diarrhoea for <1 week Grade 2 Moderate or persistent 5–7 loose stools per day OR Diarrhoea for ≥1 week Grade 3 Bloody diarrhoea OR Orthostatic hypotension OR IV Rx required OR >7 loose stools per day Generalized urticaria angioedema Vesiculation OR Ulceration OR Moist desquamation Grade 4 Hypotensive shock OR Hospitalization required

Allergic reaction Rash or hypersensitivity

Pruritus without rash

Localized urticaria

Anaphylaxis

Erythema Pruritus

Diffuse maculopapular rash OR Dry desquamation

Mucous membrane involvement OR Stevens-Johnson syndrome or toxic epidermal necrolysis OR Erythema multiforme OR Exfoliative dermatitis Unable to care for self Hypotensive shock OR Hospitalization for IV ﬂuids required

Fatigue

Normal activity reduced <25% Mild or transient (lasting <1 week) Reasonable intake maintained

Normal activity reduced 25–50% Moderate or persistent Intake decreased for <3 days Vomiting for ≥1 week

Normal activity reduced >50%, cannot work Severe discomfort minimal intake for ≥3 days OR Severe vomiting of all food and ﬂuids in 24 hours OR IV ﬂuids required OR Orthostatic hypotension Severe discomfort Narcotic analgesia required Severe impairment –loss of sensation to the knee OR Moderate in multiple body sites

Nausea and Vomiting

Paraesthesia

Mild discomfort

Moderate discomfort Non-narcotic analgesia required Moderate impairment of sensation OR Mild, asymmetrical

Incapacitating Not responding to narcotic analgesia Sensation loss involving limbs or trunk

Neurosensory

Mild impairment of sensation Focal, symmetrical

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556 Associated ARVs d4T, ddI Alcohol abuse, gallstone pancreatitis, other medications (rare) Other possible aetiologies General management recommendations Discontinue ART. Give supportive treatment and do laboratory monitoring. Resume ART with an NRTI with low pancreatic toxicity risk. AZT, ABC, TDF, and 3TC are less likely to cause this type of toxicity. See Section 10.7a Abdominal pain for symptomatic management. Usually self-limited, without need to discontinue ART. Symptomatic treatment should be offered, e.g. anti-diarrhoeal agent or dietary modiﬁcation. See10.7d.2 and 10.7d.3 for suggested management of diarrhoea. In mild cases there may be regression without the need to change ARV drug. Give antihistamines or NSAIDS and monitor closely, including AST if available. If moderate rash, nonprogressing and without mucosal involvement or systemic signs, consider a single NNRTI substitution (i.e. from NVP to EFV). See Figures for NVP and EFV above for suggested management algorithms. Discontinue all ARVs and give supportive treatment; these patients are managed intensively, similar to burn victims. Monitor AST and ALT, as co-morbid hepatitis is common. After resolution, resume ART with 3 NRTIs or 2 NRTIs + PI; however, use of EFV following NVP-induced severe rash is controversial.6 See Figures for NVP and EFV above for suggested management algorithms. ddI, LPV/r,SQV/r Infectious gastroenteritis (parasitic; bacterial; viral), HIV enteropathy, other medications Other medications, e.g. cotrimoxazole, sulfadoxinepyrimethamine (SP, Fansidar); viral exanthem NVP, EFV NVP, EFV (especially NVP) Other medications, e.g. cotrimoxazole (TMPSMX), sulfadoxinepyrimethamine (SP);

Table: ARVs and other HIV-related medications associated with selected toxicities

ARV toxicity

Key features

Acute pancreatitis

Abdominal pain, either elevated lipase or amylase, or both

Management of speciﬁc ART toxicities

Diarrhoea

Frequent loose or watery bowel movements (without blood or mucous) Systemic symptoms are rare

Drug rashes: mild to moderate (excluding Stevens-Johnson syndrome or toxic epidermal necrolysis)

Red or hyperpigmented maculopapular rash, predominantly on torso, thighs With or without Pruritus No mucosal involvement No systemic signs or symptoms

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Drug rashes severe (including Stevens-Johnson syndrome or toxic epidermal necrolysis)

Diffuse, blistering rash involving mucous membranes (conjunctival, urethral, nares, or anorectal); with or without fever

6 Severe rash is deﬁned as extensive rash with desquamation, angioedema, or a reaction resembling serum sickness; or a rash with constitutional ﬁndings, such as fever, oral lesions, blistering, facial oedema, or conjunctivitis; Stevens-Johnson syndrome can be life-threatening. For life-threatening rash, substitution with EFV is not recommended, although this approach has been reported in a small number of patients in Thailand without recurrence of rash.

ARV toxicity PIs, EFV, d4T (especially PIs, except ATV) Dyslipidaemia independent of ART, other medications

Key features

Associated ARVs

Other possible aetiologies General management recommendations

Dyslipidemia

Elevated triglycerides or LDL; low HDL

Dietary changes and physical exercise. Lipid-lowering agents (e.g. pravastatin, ﬁbrates – avoid simvastatin). Consider replacing offending ARV with a different agent with lower risk of this toxicity (NVP, ATV, and most NRTIs have low risk of inducing dyslipidaemia). Do not give simvastatin and PIs together. Replacement of offending ARV with a different agent. Dietary changes and increased physical exercise. Hypoglycaemic agents for established diabetes. Usually self-limited, without need to discontinue ART. Symptomatic treatment should be offered, e.g. antidiarrhoeal agents, dietary changes, antiemetics. Consider single ARV substitution if condition is persistent and severe enough to disrupt nutrition or adherence. See Section 10.7a.1 for suggested management of abdominal pain and Section 10.7d.2 and 10.7d.3 for suggested management of diarrhoea. If not severe, monitor closely and consider replacing AZT with a different NRTI with minimal or no bone marrow toxicity (e.g. d4T or TDF). If severe (Hg <6.5 g% or absolute neutrophil count <500 cells/mm3), replace with a different NRTI and consider blood transfusion. See Figure: Algorithm for management of AZT-related anaemia above for suggested management. Signiﬁcant elevations of ALT associated with clinical features are most often described with NVP. However, changes (of varying degree) may be observed with all ARVs. If ALT >5-fold the basal level, discontinue ART and monitor. After resolution, replace the drug most likely associated.

Insulin resistance, diabetes PIs (except ATV, APV, fos-APV); EFV, d4T Obesity or genetic predisposition, other medications Infectious gastroenteritis (parasitic; bacterial; viral), HIV enteropathy, other medications All ARVs (less frequent with d4T, 3TC, FTC, and ABC)

Elevated blood glucose

Vol. 2 • 13. Chronic HIV care, antiretroviral therapy (ART) and prevention at second level: July 2011 AZT Other medications (e.g. CTX); infectious diseases (malaria, hookworm, other parasites); HIV or OI-induced marrow suppression; iron or other nutritional deﬁciencies Infectious hepatitis; other medications (e.g. anti-microbials), drugdrug interactions All ARVs (especially NVP and ritonavirboosted PIs)

General gastro-intestinal intolerance

Taste changes, nausea, vomiting, abdominal pain or diarrhoea

Haematological toxicities (particularly anaemia and leukopenia)

Low Hb, low WBC, low neutrophil count

Management of speciﬁc ART toxicities

Hepatitis

Elevations of liver function tests, especially AST/ALT; with or without right upper quadrant abdominal pain, nausea or vomiting, fever, malaise, jaundice

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558 Associated ARVs ATV Cholestatic disease; hepatitis (if other liver enzyme abnormalities present); genetic predisposition (e.g. Gilbert’s syndrome) Other ARV or medication toxicities; acute viral, bacterial, or parasitic infectious process; IRIS Other possible aetiologies General management recommendations Generally asymptomatic, without indication for change in therapy. However, for persistent jaundice you may replace ATV with a different PI or an NNRTI. ABC Discontinue ABC and never re-challenge. Re-exposure to ABC may lead to a severe and potentially lifethreatening allergic (anaphylactic) reaction. All NRTIs (especially d4T and ddI) Other causes of anion gap acidosis: salicylate overdose, ethanol, isoniazid toxicity, uraemia, diabetic ketoacidosis Generalized wasting Discontinue ART and give supportive treatment. After clinical resolution, resume ART, replacing the offending NRTIs. ABC, TDF, and 3TC are less likely to cause this type of toxicity. See Figure: Management of suspected hyperlactataemia or lactic acidosis above for suggested management. Early replacement of the suspected ARV drug (e.g. d4T) with an agent less likely to cause this effect (e.g. TDF or ABC). Very gradual improvement often follows. Cosmetic treatments are effective, but expensive and not widely available. All NRTIs (especially d4T)

ARV toxicity

Key features

Hyperbilirubinaemia (indirect)

Elevated unconjugated (indirect) bilirubin; with or without jaundice, icterus

Management of speciﬁc ART toxicities

ABC hypersensitivity reaction

Multi-organ system syndrome that may include rash, fever, dyspnoea, abdominal discomfort, AST/ALT elevation, or malaise

Hyperlactataemia or lactic acidosis

Anion gap acidosis with low serum pH, malaise, fatigue, abdominal pain, with or without respiratory distress

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Lipoatrophy

Subcutaneous fat wasting, most visible in face, buttocks, extremities

IRIS Figure: Management of suspected hyperlactataemia or lactic acidosis

Unexpected deterioration in clinical condition with signs and symptoms of inflammation or infection soon after commencing ART (typically 2–12 weeks)

Suspect IRIS

CNS symptoms

Reported IRIS events Cryptococcal meningitis TB meningitis or abscess Toxoplasmosis PML CMV Lymphoma Reported IRIS events Flare of hepatitis B or C Visceral leishmaniasis TB abscess Reported IRIS events Disseminated TB Invasive fungal disease MAC CMV Reported IRIS events Extra pulmonary TB MAC Kaposi sarcoma Histoplasmosis 4. Reported IRIS events Pulmonary TB Invasive fungal pneumonia PCP 5. Reported IRIS events Herpes zoster and simplex HPV infection (warts) Molluscum contagiosum Kaposi sarcoma Psoriasis Eczema, folliculitis, PPE Leprosy Leishmaniasis Cutaneous fungal infections Reported IRIS events Sarcoidosis Graves disease Guillain-Barré syndrome Reiter’s syndrome

Hepatobiliary symptoms

Management principles 1. 2. Continue ART. Treat the specific pathogen in order to decrease the antigen load. Consider corticosteroids in moderate to severe cases of IRIS (prednisolone (or prednisone) at 0.5–1.0 mg/kg/day orally or IV for 5–10 days or longer depending on the severity of the inflammation. Aspirate and drain infected lymph nodes and abscesses (may need to be repeated several times). Perform emergency surgical decompression in cases of tracheal or intestinal obstruction.

Fever without localizing signs

Focal adenopathy

Respiratory symptoms with worsening changes on chest X-ray

Mucocutaneous conditions

Autoimmune diseases

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13.10 HIV/TB co-management TB is a common cause of morbidity and death among people living with HIV. HIVpositive TB patients require ART in addition to TB treatment. TB also is a signiﬁcant cause of IRIS in patients who are started on ART. Early diagnosis and treatment of TB in HIV-positive patients, and the provision of ART, signiﬁcantly reduce the mortality of HIV-positive patients from TB. See Section 15 for diagnosis and treatment of TB.

Cotrimoxazole prophylaxis Provide cotrimoxazole prophylaxis for all HIV-positive TB patients throughout the course of anti-TB treatment. Support and monitor adherence to cotrimoxazole and to all the treatments. Refer to Section 13.3 for cotrimoxazole prophylaxis dosage, side-effects and their management, and monitoring.

When to start ART in patients with TB All HIV-positive TB patients are eligible for ART, irrespective of their CD4 count. Assess or review the WHO clinical stage, whether they are already on ART, and their CD4 count. ART in patients who are taking TB treatment deserves special consideration. This is because HIV and TB co-management can be complicated by pill burden, drugto-drug interaction, IRIS, overlapping drug toxicities, and adherence issues. Guide to determine when to initiate ﬁrst-line ART in TB patients • Start ART in all HIV-positive individuals with active TB irrespective of their CD4 cell count. • Start TB treatment ﬁrst, followed by ART as soon as possible afterwards – usually within 8 weeks of starting TB treatment. • Use an EFV-based regimen in patients starting ART while on TB treatment.

Recommended ART for patients with TB Patients who are on TB/HIV co-treatment are more likely to experience pill burden, drug side-effects and drug-to-drug interactions. Therefore, patients should be adequately prepared for adherence. See Table: Summary of recommended ﬁrstline ART for TB patients below.

Women of childbearing potential (or pregnant women) with TB and eligible for ART An EFV-containing regimen should not be used during the ﬁrst-trimester of pregnancy. Provide effective contraception for women of childbearing potential. For pregnant women in the second or third trimester, use EFV-containing regimen. An alternate is a 3 NRTI regimen, e.g. AZT + 3TC + ABC.

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Table: Summary of recommended ﬁrst-line ART for TB patients Recommendation Preferred ﬁrst-line regimen ARV regimen TDF or AZT + 3TC + EFV Comments EFV is preferred because the interaction with rifampicin is easier to manage. But EFV is contraindicated in pregnant women in the ﬁrst trimester. Provide adequate contraception to women of childbearing age who are on EFV. AZT may cause anaemia, and Hb monitoring is necessary. AZT is preferred over d4T because of d4T toxicity. Alternative ﬁrst-line regimens TDF or AZT + 3TC + NVP NVP blood level is decreased in the presence of rifampicin. Close clinical and laboratory monitoring of liver enzymes at 4, 8, and 12 weeks is advised for all patients receiving NVP and rifampicin. There is risk of symptomatic or fatal hepatitis in women with CD4 counts between 250 and 350 cells/mm3. An NVPcontaining regimen should only be considered when no alternative is available for women on rifampin-containing regimens whose CD4 count is in the range of 250–350 cells/ mm3. Other options AZT + 3TC + TDF If available, TDF can be used safely with rifampicin, and can be used in patients with higher CD4 counts. Limited data on antiviral potency and hypersensitivity reactions for patients with TB. ABC is registered in many countries, but the cost is high. ABC can be used safely with rifampicin, and can be used in patients with higher CD4 counts. Limited data on antiviral potency and hypersensitivity reactions for patients with TB. FTC can be substituted for 3TC in any ﬁrst-line regimen. FTC/TDF co-formulation is available.

TDF or AZT+ 3TC + ABC

FTC

Note: All HIV-positive patients receiving an anti-TB drug regimen containing isoniazid should also receive pyridoxine 10 mg daily to prevent peripheral neuropathy.

TB immune reconstitution inﬂammatory syndrome (TB-IRIS) IRIS may present as a worsening of a clinical condition after initial improvement. It may occur in up to one third of persons with TB who initiate ART. IRIS typically presents within 3 months of the initiation of ART, but can occur as early as 5 days after initiation. TB-IRIS is a recognized complication of ART. Paradoxical TB-IRIS presents as worsening of the clinical condition of a patient on anti-TB treatment after a period of improvement following initiation of ART. Paradoxical forms of TB-IRIS have been reported in 8%–43% of TB patients starting on ART. It most commonly presents with fever and a worsening of pre-existing lymphadenopathy or respiratory conditions. It is similar to, but more frequent than, the paradoxical reactions seen in immunocompetent patients on anti-TB treatment. In addition, subclinical or undiagnosed TB often presents within the ﬁrst 6 months after the initiation of ART, frequently as part of IRIS.

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Most cases of IRIS are self-limited and resolve without any intervention, and ART can safely be continued. Serious reactions may occur, such as tracheal compression caused by massive adenopathy or respiratory difﬁculty. Therapy may require the use of corticosteroids in such patients. However, mortality due to TB-IRIS remains limited, and the risk of TB-IRIS must be weighed against the beneﬁt of early initiation of ART in patients with advanced immunosuppression.

New TB in patients already receiving ART There are 2 issues to consider in patients who are diagnosed with TB while on ART. The ﬁrst issue is whether ARV drug substitution is required. This may be recommended for patients who develop TB within 6 months of initiating ﬁrst-line or second-line ART, which is most likely TB-IRIS. The ART recommendation in these patients is summarized in the following Table. Table: ART recommendations for patients who develop TB within 6 months of starting a ﬁrstline or second-line ART regimen First-line or second-line ART First-line ART regimen ART regimen at the time active TB occurs 2 NRTIs + EFV 2 NRTIs + NVP Options Continue with the same regimen Substitute to EFVa,b OR Substitute to triple NRTI regimena OR Continue with 2 NRTIs + NVPc Continue triple NRTI regimen Substitute to or continue (if already being taken) LPV/r- or SQV/r-containing regimen and adjust dose of RTVa

Triple NRTI regimen 2 NRTIs + PI Second-line ART

a Substituting back to the original regimens once the rifampicin-containing regimen is completed can be considered. When switching back from EFV to NVP, no lead-in dose is required. b The use of EFV-containing regimens is not recommended during the ﬁrst trimester of pregnancy. Provide adequate contraception in women of childbearing potential. c Careful clinical and laboratory monitoring (ALT) is advised when NVP or boosted PIs are administered concurrently with rifampicin.

The second issue to consider in patients who are diagnosed with TB while on ART is whether the diagnosis of TB constitutes treatment failure. ART signiﬁcantly decreases the risks of TB in treated patients, but rates of TB nevertheless remain persistently higher than among HIV-negative individuals. An episode of TB can occur across a wide range of CD4 cell counts, and does not necessarily indicate ART failure and the need to switch to second-line regimens. Therefore, if an episode of TB occurs during the ﬁrst 6 months following the initiation of ART, this should not be considered a treatment failure, and the ART regimen should be adjusted for TB-ART co-treatment. If an episode of TB develops more than 6 months after initiation of ART, the decision about whether the TB diagnosis represents ART failure is based on the CD4 cell count and, if available, the viral load. If a CD4 cell count is not available, assess the patient for signs and symptoms of progression of HIV-infection. This includes whether the TB is pulmonary or extrapulmonary (extrapulmonary TB is

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WHO stage 4), and whether there are other non-TB WHO stage 3 or 4 conditions. While waiting for CD4 count, the development of an episode of pulmonary TB after 6 months of ART, without other clinical and immunological evidence of disease progression, should not be regarded as ART failure. Extrapulmonary TB should be considered as an indication of ART failure, although simple TB lymphadenitis or uncomplicated pleural disease may be less signiﬁcant than disseminated TB. If there is a good response to anti-TB treatment, the decision to switch to a secondline regimen can be delayed until short-course TB therapy has been completed.

Second-line ART regimen for patients with TB An episode of TB in patients receiving ﬁrst-line ART may indicate that the ﬁrst-line regimen probably has failed. The effectiveness of second-line therapy for patients in whom an NNRTI regimen has failed depends on the introduction of PIs in the new regimen. However, there are signiﬁcant drug interactions with the PIs and rifampicin. Unboosted PIs cannot be used with rifampicin-containing regimens because the PI levels are sub-therapeutic. Option 1 • Rifabutin 150 mg 3 times per week with boosted PI (LPV/r or ATV/r) at normal standard dose. • Rifabutin can cause uveitis. Option 2 • Rifampicin-containing TB therapy plus super-boosted LPV/r (400 mg/400 mg BID or SQV/r 400 mg/400 mg BID) under close clinical and laboratory monitoring to detect hepatotoxicity. The recommendations and precautions for the use of PI-based regimens in combination with rifampicin in women of childbearing potential, and in pregnant women, are the same as for other TB patients.

Good clinical practice: Follow national TB and HIV guidelines and co-treatment recommendations

13.11 Adherence preparation, monitoring and support Adherence support should not just focus on medical issues; there are many other issues that affect adherence. Take steps to educate patients, their families, and community members on adherence principles. If the patient agrees, home visits can be useful. Partially or fully observed therapy for a deﬁned period of time can be helpful, especially for some patients such as IDUs. Poor adherence may signify an

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underlying unstable social situation, heavy alcohol dependence, or serious psychiatric illness. These barriers to adherence need to be addressed. Adherence may improve with the development of a trusting relationship between the patient and the health workers. Health workers need to develop listening skills, and look into issues that may be affecting good adherence. Uncoordinated or chaotic clinical circumstances may hamper adherence. Table: Barriers to adherence and suggestions to address them Reasons for poor adherence Forgot to take pills Possible barriers Patient forgot because of: • travelling • alcohol or active drug use • depression or psychiatric illness • living alone and sick • no family support, e.g. not disclosed, homeless, prisoner, displaced person Problem solving • • • • • • • • • Pills do not help Felt better, so did not continue Inadequate knowledge Incorrect beliefs and attitudes Plan before travel, take extra pills. Use reminder cues. Address alcohol and drugs use. Enlist family support. Treat depression or any other psychiatric illness. Use PLHIV support groups. Develop links with local community-based organizations and support groups. Discuss and encourage disclosure. Consider other, e.g. nutrition support.

• Improve counselling (review ART and adherence). • Take time and use all encounters to educate the patient and explain the goals of therapy and the reasons for adherence. Provide information and examples. • Ask family and friends to support the treatment plan. • Use PLHIV support groups, particularly those taking ART. • Provide family counselling and support, information, and examples on antiretroviral therapy and adherence. • Link with family and community-based support groups. • Use literacy materials and individually tailored information. • Negotiate a treatment plan that the patient understands and to which the patient is committed. • If possible, reduce dose frequency and number of pills, e.g. by using FDCs. • Use demonstration pills and repeat instructions. Ask patient to repeat instructions. • Ask family and friends to support treatment plan. • Consider the impact of co-morbidities on adherence and co-manage: treat depression, address alcohol and drug use.

Family said no to medications

Inadequate knowledge Incorrect beliefs and attitudes

Instructions were not clear Did not understand how to take medications

Co-treatment, pill burden Literacy levels – sequence of dosing might be confusing, or the regimen might be complex Poor instructions and insufﬁcient time to counsel Depression or other psychiatric illness Alcohol or active drug use

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Reasons for poor adherence Unable to care for self

Possible barriers Living alone No employment AIDS dementia or mental illness

Problem solving • Use PLHIV support groups. • Link with community and home-based care programmes and NGOs support groups. • Consider nutrition and other support. • Locate family and support. • Identify friends and peers who could help. • Provide counselling. • Give support to help with disclosure. • Identify a friend or family members who could help. • Inform patient, anticipate and manage side-effects. • Avoid or minimize adverse drug interactions, if possible. • Provide accurate information on what to expect and what to do. • Counsel on the dangers of non-adherence. • Establish trust with all patients and their families. • Use a team approach to care. Share tasks among members of clinical team; involve trained peer educators, lay counsellors, and expert patients in the clinical team. • Avoid being judgemental – in attitude, language, or action; anticipate and educate staff. • Provide accurate information and support at each encounter and for all patients; be resourceful. • Prevent, identify, and manage burnout among staff. • Consider and anticipate the impact of more than one family member needing life-long HIV care and multiple visits on adherence: ° proactively coordinate care ° provide family-focused care ° triage patient ﬂow ° reduce waiting time by organizing service delivery, including lab, pharmacy and clinical services.

Did not want others to see patient taking medications

Stigma at place of work Non-disclosure in the family or at the workplace Insufﬁcient preparation Inadequate knowledge

Fear of toxicity

Poor patient-health worker relationship

Over-burdened clinical team Insufﬁcient time to counsel and provide information Being judgemental Stigma in the health sector related to HIV, MSM, IDU, sex work

Long waiting time at the facility

Uncoordinated clinic visits and care

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13.12 Positive health, dignity, and prevention for PLHIV1 Preventing sexual transmission of HIV Counsel on safer sex and reducing risk of transmission Be sure to include the following topics. Encourage questions throughout. Answer accurately, clearly, and honestly. • For a patient on ART, emphasize that he or she can still transmit HIV even though ART signiﬁcantly reduces the risk of transmission of HIV. • Counsel on ways to reduce risk of transmission: ° mutual faithfulness; ° limiting the number of partners; ° consistent and correct condom use; ° engaging in only sexual activities that do not allow semen, ﬂuid from the vagina or blood to enter the anus, vagina, or mouth of the partner; ° not having sex; ◊ for adult men, emphasize that they should not have sex with teenagers or girls (or boys); • Help the patient assess his or her current risk of transmission and make an individual risk reduction plan. • Emphasize that sexual activity can continue if desired, with the above-stated precautions. Respond to any concerns about sexual function. • Dispel any prevailing myths on the cleansing of HIV infection through sexual intercourse with young people, virgins, or others. Discuss any other locally common myths that may hinder HIV prevention, e.g. the belief that condoms transmit HIV. Counsel on the consistent and correct use of condoms during every sexual encounter (most risk-reduction plans will include condom use) • Educate the patient that it is essential to consistently use condoms, even when they are already infected with HIV. The patient should use condoms for all acts of vaginal, anal, and oral intercourse. • Point out that condoms help prevent pregnancy and infection with other STIs. For better pregnancy prevention, an additional family planning method can be used along with condoms. • Provide male or female condoms, as the patient prefers, and discuss where and how to keep them at home and where to get them. • Demonstrate how to use condoms. ° Use a model to demonstrate correct use. ° Advise the patient to put a condom on or in before penetrative sex, and not to wait until just before ejaculation. ° Request that the patient demonstrate the correct use of condoms using a model. Give advice and gently correct mistakes. (See the reproductive health (RH) counselling ﬂipchart, for basic instructions on condom use.)7 • Discuss facts about male and female condoms (see RH counselling ﬂipchart7).

7 Reproductive choice and family planning for people living with HIV. Counselling tool. WHO, 2007. Available at: http://www.who.int/reproductivehealth/publications/family_planning/9241595132/en/index.html

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• For male (latex) condoms, advise patients to use only water-based lubricants and to avoid oil-based lubricants, which damage the latex. • Discuss and advise that condoms and lubricants should be used together. For anal sex, using lubricants in the absence of condoms may increase both anal mucosal inﬂammation and HIV risk due to the damage to epithelial cells from the hyperosmolar nature of most lubricants. (See Section 19.3) • Discuss potential barriers to consistent and correct use of condoms: ° Explore barriers that the patient foresees and ways to overcome them. ° Discuss techniques and skills for negotiating condom use, and help the patient decide on an appropriate approach. ° Role-play condom negotiation with the patient. Discuss disclosure and encourage partner testing • Explore the beneﬁts of disclosure and discuss barriers to it. • Develop a strategy for disclosure if the client is ready. • Refer to PLHIV support groups or others for additional support, if required. • Encourage and facilitate partner testing. Explain that it is possible for partners of PLHIV to be HIV-negative. (Record the result in the patient’s medical record.) • Discuss and offer HIV testing of children. • Provide ongoing counselling to discordant couples. Important information, particularly for discordant couples • In a discordant couple, the HIV-negative partner faces very high risk of infection through penetrative sexual contact (anal, vaginal, or oral). • Effective risk-reduction options are: ° condoms ° abstinence See Section 19.2 Discordant couples counselling and services.

Preventing non-sexual transmission of HIV Explain how sharing needles, syringes, razor blades, or other sharp instruments can infect others. • Educate patients to cover any open sores or cuts. • Educate health workers to wear appropriate personal protective equipment when indicated, and to use gloves and disinfectants when cleaning up any blood or body ﬂuids. Explain that this is normal procedure. See Section 6. • See Section 14 for preventing mother-to-child transmission of HIV.

Reproductive choice and family planning (See Section 14.5.) Counselling on reproductive choice and family planning can and should be conducted routinely at the ﬁrst level of care. Likewise, most services related to reproductive choice and family planning can and should be provided at the ﬁrst level in MCH/PMTCT/RH service settings (see Section 14.5). Health workers at the ﬁrst level can provide a number of family planning methods, such as condoms, pills, and injectables. Methods requiring procedures – IUDs, implants, female

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sterilization, and vasectomy – usually require referral to a clinician with further training in family planning. Follow country guideline recommendations. Note: The information and guidance in Section 14.5 is consistent with WHO reproductive health guidance. It comes largely from the RH counselling ﬂipchart.7 In counselling, this tool helps guide and inform patients’ reproductive choices and practices. The information on reproductive choice and family planning in this manual can help the district team meet the reproductive health needs of patients referred to them for other reasons, if those needs are not being met at the ﬁrst level. It is not expected that most reproductive health needs or services themselves will require referral to the second level of HIV care.

13.13 Positive living for PLHIV1 PLHIV can live full and healthy lives if they take care of themselves and obtain treatment.

Counsel PLHIV on how to prevent other infections • Use condoms to prevent STIs and re-infection with HIV. • Avoid other people with infections (e.g. ﬂu, boils, impetigo, herpes zoster, chickenpox, pulmonary TB). • Use safe drinking water – chlorinate water or drink boiled water or tea when possible. Store the water in a container that prevents contamination. • Eat well-cooked food. • Practice hand hygiene, especially after going to the toilet. Caregivers and patients should wash their hands often: after using the toilet, before preparing food, or before touching any blood, semen, vaginal ﬂuid, or faeces. (See Section 6.) • Have a local antiseptic (such as gentian violet or chlorhexidine) at home to apply to minor wounds after washing them. • Sleep under an insecticide-treated bednet to prevent malaria. • Get vaccinations to prevent illness:8 ° Hepatitis B: Where serological testing for hepatitis B virus is available, WHO recommends 3 doses of standard- or double-strength hepatitis B vaccine for adults with HIV who are susceptible (i.e. antibody to hepatitis B core antigen-negative) and have not been vaccinated previously. Vaccine response (titre of hepatitis B surface antibody after 3 doses of hepatitis B vaccine) can be measured and, if suboptimal, revaccination may be considered. In settings where serologic testing is not available, and hepatitis B prevalence is substantial, programme managers may choose to offer 3 doses of hepatitis B vaccine to all adults with HIV. Follow national guideline recommendations. ° Hepatitis A: Prior exposure to hepatitis A in childhood and early adulthood is common in many resource-limited settings and insufﬁcient data exist on the effectiveness of hepatitis A vaccinations in adults with HIV. 8 Priority Interventions: HIV/AIDS prevention, treatment and care in the health sector. WHO, 2010. Available at: http://whqlibdoc.who.int/publications/2010/9789241500234_eng.pdf

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° Inﬂuenza: Where available and feasible, annual inﬂuenza vaccination with the inactivated subunit inﬂuenza vaccine should be offered to adults with HIV. If inﬂuenza vaccine is indicated in the context of a large epidemic or pandemic, adults with HIV should receive inactivated inﬂuenza vaccine. ° Yellow fever: In general, yellow fever vaccine is not recommended for PLHIV. ° Pneumococcal and HPV: Pneumococcal conjugate vaccine and human papilloma (HPV) vaccine are not recommended for PLHIV due to insufﬁcient data.

Encourage physical activity as appropriate • Help the patient develop his or her own activity programme. • Exercise can make the person feel better and maintain muscle tone. • Physical activity is important to prevent weight loss because it: ° stimulates appetite ° reduces nausea ° improves functioning of the digestive system ° strengthens muscles. Note: Avoid ineffective or expensive therapies and supplements.

Support adequate and balanced nutrition Advise the patient on adequate nutrition, and encourage a diet with adequate energy, protein, and micronutrients. • Nutrient-dense foods include (adapt to national guidelines): ° Examples include: soya products, meat, ﬁsh, nuts and seeds, beans, lentils, potatoes, rice, barley, wheat, maize. • Eat frequent, small meals each day to increase intake. • Avoid excessive alcohol and drugs. • Arrange nutritional support for patient and family if it is available and needed (requires local adaptation). Address food security. • Give priority to patients with moderate or severe malnutrition. • Manage with appropriate feeding regimens as available (requires local adaptation). • Have a peer demonstrate preparation of nutritious foods. See Section 10.3.

Assess alcohol use • Classify the patient’s risk level for alcohol abuse and provide brief interventions (see Section 16 Alcohol use disorders). • Assess how alcohol use is affecting adoption of safer sex practices. • Ask if alcohol misuse by a partner is undermining safer sex practices. • Provide advice on how to help the partner and encourage treatment. • Assess whether alcohol use is affecting adherence to ARVs or the safety of these and other drugs. ° Alcohol may worsen liver problems in people with hepatitis B or C.

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• Misuse of alcohol is associated with several factors: ° Poor nutrition, social problems, and other health problems that may worsen HIV disease. ° The safety of sexual behaviours is lowered by impaired decision-making, poorer condom negotiation skills, and increased condom accidents during heavy drinking episodes. This places PLHIV at risk for acquiring STIs and others at risk for acquiring HIV.

Brief interventions for patients with hazardous or harmful alcohol use (see Section 16) • Use brief interventions to raise the person’s awareness of the risks associated with alcohol use, and to identify patients who require further intervention. This involves 3 steps: 1. Assess and classify the patient’s alcohol use. 2. Advise the patient on the health risks associated with alcohol use and recommend reducing consumption (using the FLAGS approach. See Section 16.5). 3. Provide more intensive or specialized services for those who require it. • Encourage patients with hazardous or harmful alcohol use to adopt a low-risk approach or to stop alcohol altogether. • Ensure that people with alcohol dependency understand that the goal of treatment is abstinence from alcohol.

13.14 Special consideration for adolescents in chronic HIV care Psychosocial support Adolescents living with HIV are an important group that requires special psychosocial support for adherence, for dealing with discrimination and disclosure, and for preventing high-risk behaviours. The special needs of adolescents differ between those who were perinatally infected and those infected during adolescence, although the majority of this latter group are unlikely to require treatment during adolescence. It is important to understand that adolescents are different from adults in terms of their psychological development; they may not respond to information in the same way as adults. Information needs to be available in a format that adolescents can understand and relate to. They need to have links to peer support (other PLHIV) and they need guidance on taking medicines. Adolescents may be sexually active, or may be intending to become sexually active, and may have MANY questions and concerns. They need information to which that they can relate, they need opportunities to talk, and they need access to properly informed peers. They also need support with disclosure and dealing with stigma or rejection.

Differences among adolescents It is important to realize that all adolescents are not the same; there are various stages of adolescence. This realization has important implications for the health worker, especially in regard to effective communication with this population. Vol. 2 • 13. Chronic HIV care, antiretroviral therapy (ART) and prevention at second level: July 2011

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• Age: if the patient is a minor (e.g. parental or guardian consent may be needed to provide treatment, and there may be issues of conﬁdentiality); if the patient is a younger or older adolescent (sexually active or not – they may need appropriate prevention information). • Stage of development and maturity, physical, and cognitive growth (e.g. sexually active, psychosocial and family support, importance of peer group, ability to understand information, understanding consequences of action, adherence to medication). • Gender differences: different social and cultural inﬂuences on boys and girls that effect how they view themselves and relate to others (e.g. sexuality, contraception, condom use, social acceptance of and tolerance for being sexually active). • Married or unmarried (e.g. couples counselling, fertility, consent of partner, other sexual partner). • Home situation: living alone, living with parents, guardians, or other relatives, living on the street, orphan, in- or out-of-school (e.g. available support and care, referral to peer support). • Education level: (e.g. how to explain health issues, literacy level, future prospects). • Level of information and knowledge on risk factors for STI, HIV, IDU (e.g. able to understand risks of behaviour, well- or poorly-informed peers). • Disposable income (e.g. whether the adolescent patient has money for health care, basic needs, transport costs to health services). • HIV transmission pattern: acquired HIV perinatally or as an adolescent (e.g. how long they have known (or suspected) that they are HIV-positive, implications for mother, clinical status, timing for entering care, new diagnosis, health-risk behaviour). • Who else knows they are HIV-positive and whether they can control who knows: issues of disclosure and conﬁdentiality (e.g. support, prevention, coping with stigma). • Health and stage of HIV disease (may be asymptomatic for many years, symptomatic, needs ART). • Personal and family experience of stigma and discrimination (disclosure, support, fear).

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Box: What to do and what to avoid when communicating with adolescents Do Be truthful about what you know and what you do not know. Be professional and technically competent. Avoid Telling a patient lies (to scare them or to “make them behave”). Threatening to break conﬁdentiality “for their own good”. Giving inaccurate information to “make them behave”. Giving them only the information that you think they will understand. Using medical terms they will not understand.

Use words and concepts that they can understand and to which they can relate. Assess if they understand. Use pictures and the Flipchart for Patient Education referred to above to explain. Treat them with respect and use respectful words. Give all the information and choices and then let them decide what to do. Encourage them to develop life skills (e.g. problem-solving, decision-making). Treat all equally. Be respectful even if you do not approve of their behaviour. Accept that they may choose to show their individuality in dress or language.

Talking down to them, shouting, getting angry, blaming. Telling them what to do because you know best and they “are young”. Being judgemental about their behaviour, showing disapproval, imposing your own values. Being critical of their appearance or behaviour (unless it relates to their health or well-being).

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ART in adolescents Determine the Tanner Stage to decide whether to use a paediatric or adult dose of ART. Box: Tanner stage for female and male adolescents9 Female breast Scale 1: no breast tissue with ﬂat areola

Scale 2: breast budding with widening of the areola

Scale 3: larger and more elevated breast extending beyond the areola

Scale 4: larger and even more elevated breast – areola and nipple projecting from the breast contours

Scale 5: adult size with nipple projecting above areola

9 Tanner JM. Growth at Adolescence. 2nd ed. New York, NY: Appleton-Century-Crofts, 1966.

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Male and female pubic hair Scale 1: none Scale 2: small amount of long hair at base of male scrotum or female labia majora Scale 3: moderate amount of curly and coarser hair extending outwards Scale 4: resembles adult hair but does not extend to inner surface of thigh Scale 5: adult type and quantity extending to the medial thigh surface Male genitalia Scale 1: testes small in size with childlike penis Scale 2: testes reddened, thinner and larger (1.6–6.0 cc) with childlike penis Scale 3: testes larger (6–12 cc), scrotum enlarging, increase in penile length Scale 4: testes larger (12–20 cc) with greater enlargement and darkening of the scrotum; increase in length and circumference of penis Scale 5: testes over 20 cc with adult scrotum and penis

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• Tanner Stage I, II, and III are pre-pubertal adolescents – use paediatric dosing. These patients require careful monitoring because hormonal changes associated with the growth spurt are occurring. • Tanner Stage IV and V are post-pubertal adolescents – use adult ARV dose. Adherence is a challenge during adolescence for patients with any chronic disease. Giving adequate attention to the transition from paediatric to adolescent/adult care is important for the clinical team. Simplicity and anticipated long-term adherence are additional important criteria for selecting an appropriate ﬁrst-line regimen for adolescents. With adolescents, the health worker should be especially attentive to: • readiness for ARV therapy • adherence preparation • mental health • family and other support. If an adolescent patient is non-adherent, it is very important to assess the reasons why. Adolescents may have many reasons why they do not take their medication (as with many chronic conditions) and need relevant support to encourage adherence. In particular, when perinatally infected adolescents make the transition of care from the child to adolescent/adult level, they need to take more responsibility for their own treatment and care (rather than continuing to rely on their parents to handle it). Health workers should provide streamlined regimens with a low pill burden and fewer doses per day to maximize adherence. This may be particularly important for adolescents.

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14. PMTCT, HIV prevention, care, and treatment during pregnancy, and family planning Table of contents 14.1 HIV prevention, care, and treatment during pregnancy . . . . . . . . . . . . . . . 14.1.1 Recommend HIV testing and counselling, and optimize care for HIV-positive pregnant women and their infants . . . . . . . . . . . . Optimization of care for HIV-positive women and their infants . . . . 14.1.2 Identify and treat opportunistic infections (OIs) . . . . . . . . . . . . . . 14.1.3 Offer ART or ARV prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . Eligibility criteria for ART or ARV prophylaxis in HIV-positive pregnant women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Considerations for choice of ART regimen . . . . . . . . . . . . . . . . Considerations for the choice of ﬁrst-line ART for pregnant women in need of treatment for their own health . . . . . . . . . . . . . . . . . Immune reconstitution inﬂammatory syndrome (IRIS) . . . . . . . . . 14.1.4 Women who become pregnant while taking ART . . . . . . . . . . . . . 14.1.5 Monitoring antiretroviral response in pregnant women. . . . . . . . . . 14.1.6 Use of second-line ART in pregnancy . . . . . . . . . . . . . . . . . . . . 14.1.7 ARV prophylaxis for infants of HIV-positive women taking ART . . . . . 14.1.8 ARV prophylaxis to prevent MTCT of HIV . . . . . . . . . . . . . . . . . . Maternal ARV prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . Recommended ARV-prophylaxis for pregnant women not yet eligible for ART and their infants . . . . . . . . . . . . . . . . . Infant ARV prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of infant ARV prophylaxis regimens . . . . . . . . . . . . . . Infant ARV prophylaxis dosing recommendations . . . . . . . . . . . . 14.1.9 Safety of antiretroviral and other medicines in pregnancy . . . . . . . . Safety monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Anaemia in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . NVP rash and hepatitis in pregnancy . . . . . . . . . . . . . . . . . . . Management of NVP-associated rash and liver toxicity . . . . . . . . EFV use in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lactic acidosis in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . Rash and hypersensitivity due to abacavir (ABC) . . . . . . . . . . . . Safety of medicines in pregnancy . . . . . . . . . . . . . . . . . . . . . 14.1.10 Antiretroviral drug resistance . . . . . . . . . . . . . . . . . . . . . . . . . Choice of ART regimen for HIV-positive women with prior exposure to ARV prophylaxis for PMTCT . . . . . . . . . . . . . . . . . 14.1.11 Improved care and support for HIV-positive pregnant women . . . . . Nausea and vomiting in pregnancy . . . . . . . . . . . . . . . . . . . . Antiemetic medication in pregnancy. . . . . . . . . . . . . . . . . . . . 14.2 Intrapartum care for HIV-positive women . . . . . . . . . . . . . . . . . . . . . . . Summary of ARV regimens during pregnancy, intrapartum, postpartum, and breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Safer intrapartum practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Caesarean delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Breast care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

579 579 580 581 582 583 583 585 586 586 586 586 587 587 587 588 589 589 589 589 589 590 590 591 591 591 592 592 592 593 593 593 594 594 594 595 595 595

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14.3 Infant feeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Replacement feeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.4 Postpartum care for HIV-positive women . . . . . . . . . . . . . . . . . . Care for HIV-exposed infants . . . . . . . . . . . . . . . . . . . . . . . . 14.5 Reproductive choice and family planning . . . . . . . . . . . . . . . . . . 14.5.1 Dual protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5.2 Guidance on the use of contraceptive methods . . . . . . . . . Drug-drug interactions . . . . . . . . . . . . . . . . . . . . . . . Medical eligibility criteria for contraceptive use: conditions relevant to HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5.3 Contraceptive method mix . . . . . . . . . . . . . . . . . . . . . . Emergency contraception . . . . . . . . . . . . . . . . . . . . . Indications for pregnancy testing . . . . . . . . . . . . . . . . Special considerations when pregnancy is desired by a discordant couple . . . . . . . . . . . . . . . . . . . . . . .

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596 596 597 599 600 601 601 602 602 603 603 604 605 605

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14. PMTCT, HIV prevention, care, and treatment during pregnancy, and family planning This Section summarizes services for prevention of mother-to-child transmission (PMTCT) of HIV at ﬁrst-level facilities and discusses the HIV care required at the district level for positive pregnant women and postpartum women with complications.

14.1 HIV prevention, care, and treatment during pregnancy Antenatal care (ANC) is an important entry point for pregnant women and their partners to learn about their HIV status, and to receive HIV prevention, care and treatment services. Interventions for prevention of mother-to-child transmission (PMTCT) of HIV need to be integrated into maternal, newborn and child health (MNCH) services. They are an important intervention for HIV prevention (including for HIV-negative pregnant women and partners) and are an entry point for HIV treatment, care and support of HIV-positive women, their children, and partners. Such services also should be able to provide the essential package of antenatal and postnatal services.1 HIV-positive pregnant women need initiation of ART or highly efﬁcacious ARV prophylaxis as early as indicated during their pregnancy. Given the poor acceptance of referral to a second clinic during pregnancy, services close to the client’s home are necessary. This includes primary and outpatient services for initiation and monitoring of ART and ARV prophylaxis, ongoing HIV care, and MNCH care as well as other priority HIV, TB, and malaria services. It has been shown in several resource-limited settings that most services can and must be provided by adequately prepared teams led by nurses or clinical ofﬁcers, with district clinicians who are equipped to mentor and provide support to these teams, including management of complications.

14.1.1 Recommend HIV testing and counselling, and optimize care for HIV-positive pregnant women and their infants2 Early identiﬁcation of HIV infection through testing and counselling plays a central role in providing HIV services during pregnancy, childbirth, and breastfeeding. It will enable women and their partners to gain maximum beneﬁt for their own health and for preventing HIV transmission to their infants. In settings with a generalized epidemic, health workers should recommend HIV testing and counselling to all pregnant women at their ﬁrst ANC visit, unless the woman is already documented to be HIV-positive. The following interventions support early identiﬁcation of HIV-positive pregnant women and initiation of ARVs (ART or ARV prophylaxis): • Rapid HIV test technology (see Section 9). • HIV testing and counselling:

1 IMPAC Pregnancy, childbirth, postpartum and newborn care: A guide for essential care. WHO, 2006. Available at http://www.who.int/making_pregnancy_safer/documents/924159084x/en/index.html 2 IMAI-IMCI Chronic HIV Care with ART and prevention guideline module. WHO, 2007. Available at http://www. who.int/hiv/pub/imai/primary_arv/en/index.html

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° at ﬁrst ANC visit (provider-initiated testing and counselling)3 ° offer male partner testing and counselling ° offer voluntary couples HIV testing and counselling with mutual disclosure.4 In settings with a generalizaed epidemic, recommend re-testing in the third trimester to pregnant women who tested negative in their ﬁrst or second trimesters, preferably between the 28th and 36th weeks of gestation.5 Provide HIV test result on same day as testing. Determine CD4 count on the same day as HIV testing (for those testing positive). Prioritize HIV-positive pregnant women for CD4 count, particularly those in WHO clinical stage 1 or 2. Health workers, including laboratory and pharmacy personnel, prioritize timely PMTCT interventions in pregnant women. Rapid adherence preparation, e.g. arranging facility visits within short intervals and coordinating care across services. Support for HIV-positive pregnant women, throughout their pregnancy, childbirth, breastfeeding and thereafter, as much as possible, e.g. involve their partners in PMTCT services, facilitate peer support from other HIV-positive pregnant women who are already receiving care, as pertinent to each woman.

It is important that pregnant women receive their HIV test result on same day, and those who test positive receive HIV prevention, care, and treatment services. It is also very important that HIV-negative pregnant women receive services, including partner testing, to prevent HIV infection. Seroconversion during pregnancy and the postpartum period is a problem in some settings and recent infection has a high risk of MTCT of HIV.4 (See Section 19 for HIV prevention.)

Optimize care for HIV-positive women and their infants To maximize PMTCT and to improve maternal and infant health and survival, it is critical that care of both HIV-positive mothers and their infants is optimized as follows. During antenatal visits, HIV-positive pregnant women should be offered and counselled on: • routine antenatal care and birth preparedness; • additional counselling and support to encourage partner and couple testing and disclosure, adoption of HIV and STI risk reduction and safer sex practices, including correct and consistent use of condoms during pregnancy; • ART or ARV prophylaxis as indicated; • infant feeding including ARV interventions to prevent MTCT of HIV during breastfeeding; • family planning; • adherence to care and treatment; • adequate nutrition and self-care;

3 Guidance on provider-initiated HIV testing and counselling in health facilities. WHO, 2007. Available at http:// www.who.int/hiv/pub/vct/pitc/en/index.html 4 Interim guidance on couples HIV testing and counselling and antiretroviral therapy for treatment and prevention in serodiscordant couples. Work in progress at WHO, 2011. 5 Delivering HIV test results and messages for re-testing and counselling in adults. WHO, 2010. Available at http:// www.who.int/hiv/pub/vct/hiv_re_testing/en/index.html

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• importance of adequate rest; • stopping smoking; • avoiding alcohol and drugs (other than medicines prescribed by their health care provider); • TB screening and treatment when indicated; • INH preventive therapy (IPT) and cotrimoxazole prophylaxis when indicated (see Section 13 for cotrimoxazole prophylaxis, IPT and TB/HIV comanagement, Section 15 for TB diagnosis and treatment); • other prevention interventions, e.g. safe drinking water, malaria prevention. Syphilis screening and treatment is an essential component of antenatal care.6 All pregnant women should be screened for syphilis at the ﬁrst antenatal care visit, ideally within the ﬁrst trimester and again in late pregnancy. At delivery, women who for some reason do not have test results should be tested or retested. Women testing positive should be treated (at least 2.4 million IU benzathine benzylpenicillin intramuscularly as a single dose). Their partners should also be treated and plans should be made to treat their infants at birth.7 (See Section 11.37 Syphilis.) Anaemia among pregnant women is common, particularly in HIV-positive pregnant women in resource-limited settings. HIV infection, in combination with other factors such as malaria, worm infections and nutritional deﬁciencies, can exacerbate anaemia in pregnant women. Severe anaemia in turn increases the risk of adverse maternal outcomes. Routine prevention, screening, and treatment of anaemia and its contributory factors are important components of essential antenatal care for all pregnant women, including HIV-positive pregnant women. (See Section 10.18.) Give preventive iron and folic acid supplementation for pregnant women (1 tablet, 100 mg iron and 400 mcg folic acid, daily throughout pregnancy)1. Give mebendazole (500 mg every 6 months) once, in the second or third trimester (whenever the woman is ﬁrst seen). Do not give mebendazole in the ﬁrst trimester.8 In malaria areas, offer intermittent preventive treatment (IPTp) for P. falciparum malaria. Give sulfadoxine-pyrimethamine in the second and third trimesters, if the HIV-positive pregnant woman is not on cotrimoxazole prophylaxis.9 Encourage women to sleep under an insecticide-treated bed net. Treat malaria in pregnant women promptly with an effective antimalarial regimen in accordance with national guidelines. Treatment of malaria in HIV-positive patients who are receiving ZDV or EFV, if possible, should avoid amodiaquine-containing artemisinin-based combination therapy (ACT) regimens. (See Section 11.25.)

14.1.2 Identify and treat opportunistic infections (OIs) Most HIV-positive pregnant women in ANC settings are in their early stage of HIV infection and are less likely to have OIs. However, routine assessment should include screening for TB, clinical staging, and identifying and treating OIs. This is

6 Guideline for the management of sexually transmitted infections. WHO, 2003 (updated 2011 version in press). Available at http://www.who.int/reproductivehealth/publications/rtis/9241546263/en/index.html 7 Standards for maternal and newborn care: Standard for prevention of mother-to-child transmission of syphilis. WHO, 2002. Available at http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/ prevention_mtct_syphilis.pdf. 8 WHO model list of essential medicines. WHO, 2011. WHO model formulary. WHO, 2008. Available at http://www. who.int/selection_medicines/list/en/ 9 Guidelines for the treatment of malaria (second edition). WHO, 2010. Available at http://www.who.int/malaria/ publications/atoz/9789241547925/en/index.html

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important to maintain the health of the woman and her baby. During pregnancy, it is important to consider the need to rapidly start ARVs for the health of the woman and for PMTCT of HIV. It may sometimes be necessary to initiate ART or ARV prophylaxis once the woman has been stabilized, even though the OI has not fully resolved. See Section 13. Symptoms and signs in an HIV-positive pregnant woman may be due to: • obstetric causes • HIV-related illness including opportunistic infections • drug side-effects • other intercurrent illnesses. Severe pre-eclampsia or eclampsia should be included in the differential diagnosis of an HIV-positive pregnant woman who has severe headache, changes in mental status or convulsions. HIV-related illness or adverse effects of drugs can cause nausea and vomiting, which may also be due to morning sickness. In any HIV-positive pregnant woman with fever, rule out obstetrical causes such as chorioamnionitis or sepsis, as well as HIV-related opportunistic infections, TB, and other conditions, such as malaria or urinary tract infection (UTI). (See Sections 11.25 Malaria and 11.44 Urinary tract infection.) Assess all HIV-positive pregnant women for tuberculosis during each visit. Offer isoniazid preventive therapy if there is no current cough, fever, weight loss (or poor weight gain during pregnancy), or night sweats. Those with a cough, fever, weight loss (or poor weight gain during pregnancy), or night sweats should be assessed for TB. HIV-positive pregnant women with active tuberculosis should ﬁrst start anti-TB treatment, and initiate ART irrespective of their CD4 cell count, as soon as clinically possible (often within 8 weeks after the start of anti-TB treatment). (See Sections 13.10 TB-HIV co-management and 15 Tuberculosis.)

14.1.3 Offer ART or ARV prophylaxis10 ART is recommended to all eligible pregnant and postpartum women for their own health, and is a highly effective intervention for PMTCT of HIV. Once started, ART is a lifelong treatment. For women who do not yet need ART for their own health, ARV prophylaxis is indicated for PMTCT of HIV. ARV prophylaxis is not a lifelong intervention, and its primary purpose is prevention of the transmission of HIV from the mother to her infant during pregnancy, childbirth, and breastfeeding. Pregnant women who need treatment should start ART irrespective of gestational age, following adequate and rapid preparation. Once ART is started, it should continue throughout pregnancy, childbirth, breastfeeding, and thereafter. The criteria for when to initiate ART in pregnant women are the same as for nonpregnant adults. WHO recommends initiation of ART for: • all with a CD4 count ≤350 cells/mm3, irrespective of WHO clinical stage; • all in WHO clinical stage 3 or 4, irrespective of the CD4 cell count (see Table below to determine ART or ARV prophylaxis eligibility in HIV-positive pregnant women). (See Section 13 for WHO clinical staging.)

10 Antiretroviral drugs for treating pregnant women and preventing HIV infections in infants. WHO, 2010. Available at http://www.who.int/hiv/pub/mtct/antiretroviral2010/en/index.html

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Follow national guideline recommendations on ART eligibility criteria for pregnant women.

The timing of ART initiation for HIV-positive pregnant women is the same as for non-pregnant women, i.e. as soon as eligible. It is important to consider the risk-beneﬁt of any drugs offered in pregnancy with the severity of the mother’s condition, the risk to the fetus, and alternative treatment options. Whenever possible, identify all pregnant women who require ART by using CD4 cell count. Send the specimen and assure prompt receipt of the result and action. If there is limited laboratory capacity to do CD4 counts, prioritize pregnant women in WHO clinical stages 1 and 2. Do not delay ART for pregnant women in WHO clinical stage 3 or 4 by waiting for CD4 count result. Women in stages 3 and 4 are eligible for ART irrespective of CD4 count. All HIV-positive pregnant women who are not yet eligible for ART require efﬁcacious ARV prophylaxis to prevent MTCT of HIV during pregnancy, childbirth, and breastfeeding. Table: Eligibility criteria for ART or ARV prophylaxis in HIV-positive pregnant women CD4 cell count CD4 cell count not available ARV prophylaxis ARV prophylaxis ART ART CD4 cell count available CD4 ≤350 cells/mm3 ART ART ART ART CD4 >350 cells/mm3 ARV prophylaxis ARV prophylaxis ART ART

WHO clinical stage Stage 1 Stage 2 Stage 3 Stage 4

From Antiretroviral drugs for treating pregnant women and preventing HIV infections in infants. WHO, 2010. Available at http://www.who.int/hiv/pub/mtct/antiretroviral2010/en/index.html

Considerations for choice of ART regimen The preferred ﬁrst-line ART regimens for HIV-positive pregnant women are the same as for non-pregnant women, and for adults in general (see Section 13) and depends on: • potential adverse effects to the woman or the fetus • presence of co-morbidities, e.g. TB, hepatitis • ease of formulation and dosing, e.g. ﬁxed-dose combination • packaging and availability of the regimen. The preferred ﬁrst-line ART regimens in pregnancy is: AZT+3TC+NVP OR AZT+3TC+EFV (See Table: Considerations for the choice of ﬁrst-line ART for pregnant women in need of treatment for their own health.)

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Alternative regimens are: TDF+3TC+NVP OR TDF+ FTC+NVP OR TDF+3TC+EFV OR TDF+FTC+EFV • Whenever possible, recommend ﬁxed-dose combinations or co-packaged formulations as these reduce pill burden and support treatment adherence. • EFV is not recommended during the ﬁrst trimester. EFV can be used during the second and third trimesters. • Avoid AZT in women with severe anaemia (Hb <7 g/dl). Treat the anaemia and its contributing factors and consider using a TDF-based regimen rather than AZT. Use a d4T-based regimen only if AZT and TDF are contraindicated or not available. • Women with baseline CD4 cell counts between 250−350 cells/mm are potentially at increased risk for drug-related hepatitis when receiving a NVPbased regimen. For women in their second or third trimester who have CD4 counts between 250–350 cells/mm3, consider using an EFV-based regimen. During the ﬁrst trimester, for women who require ART, the beneﬁts of using a NVP-based regimen outweigh the risks of not initiating ART. In such cases, close clinical monitoring (with laboratory, when available) during the ﬁrst 12 weeks of therapy is recommended (see Section 13). • For HIV-positive pregnant women with active TB: ° Initiate standard anti-TB treatment in accordance with national guideline recommendations. (See Sections 15 TB and 13.10 TB-HIV co-management). ° In HIV-positive TB patients, ART is indicated irrespective of CD4 cell count and should be started as soon as clinically possible – often within 8 weeks after starting anti-TB treatment. ° An EFV-based regimen is preferred (after the ﬁrst trimester) for pregnant women who are on anti-TB treatment. ° A NVP-based regimen or a triple NNRTI regimen (e.g. AZT+3TC+ABC or AZT+3TC+TDF) are alternative options for those who do not tolerate EFV. In the presence of rifampicin, a lead-in dose of NVP is not required.

It is important to follow national ART and PMTCT guideline recommendations on choice of treatment regimens

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Table: Considerations for the choice of ﬁrst-line ART for pregnant women in need of treatment for their own health10 Recommended regimens AZT+3TC+NVP Dosing AZT 300 mg twice daily 3TC 150 mg twice daily NVP 200 mg twice daily Feasibility and operational considerations • Regimen could potentially be provided as a ﬁxed-dose combination • Extensive experience with AZT+3TC in pregnancy • Hb assessment is recommended (but not necessary) before use of AZT • NVP dose escalation from once-daily in the ﬁrst 2 weeks to twice-daily regimen after 2 weeks • Extensive experience with AZT+3TC in pregnancy • Hb assessment is recommended (but not necessary) before use of AZT • Effective contraception after delivery is required to prevent (subsequent) pregnancy when using EFV • EFV is recommended for women with TB • Could be given as once daily regimen in a ﬁxed-dose combination • Effective contraception after delivery is required to prevent (subsequent) pregnancy with use of EFV • EFV use is recommended for women with TB • TDF+3TC (or FTC) use is recommended for women with HBV infection requiring treatment • NVP dose escalation from once-daily in the ﬁrst 2 weeks to twice-daily regimen after 2 weeks • TDF+3TC (or FTC) use is recommended for women with HBV infection requiring treatment Safety considerations • Risk of anaemia with prolonged use of AZT • Risk of hepatotoxicity and hypersensitivity with use of NVP that needs close monitoring for ﬁrst 12 weeks • Not recommended in pregnant women with CD4 >350

AZT+3TC+EFV

AZT 300 mg twice daily 3TC 150 mg twice daily EFV 600 mg once daily

• Risk of anaemia with prolonged use of AZT • Potential risk (likely <1%) of neural tube defect with use of EFV in ﬁrst month of pregnancy. Avoid using EFV during the ﬁrst trimester.

TDF+3TC+EFV

TDF 300 mg once daily 3TC 150 mg twice daily EFV 600 mg once daily OR TDF 300 mg once daily FTC 200 mg once daily EFV 600 mg once daily

OR TDF+FTC+EFV

• Risk of nephrotoxicity with use of TDF • Limited data available on potential maternal and infant bone toxicity with use of TDF • Potential risk (likely <1%) of neural tube defect with use of EFV in ﬁrst month of pregnancy. Avoid using EFV during the ﬁrst trimester.

TDF+3TC+NVP

TDF 300 mg once daily 3TC 150 mg twice daily NVP 200 mg twice daily OR TDF 300 mg once daily FTC 200 mg once daily NVP 200 mg twice daily

OR TDF+FTC+NVP

• Risk of nephrotoxicity with use of TDF • Limited data available on potential maternal and infant bone toxicity with use of TDF • Risk of hepatotoxicity and hypersensitivity with use of NVP resulting in need for close clinical observation for ﬁrst 12 weeks • Not recommended in pregnant women with CD4 >350

As with all adults, give NVP 200 mg once daily for the ﬁrst 2 weeks then 200 mg twice daily (see Section 13).

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Immune reconstitution inﬂammatory syndrome (IRIS) Transient worsening of clinical condition due to IRIS may occur in up to a third of patients who initiate ART. It typically presents within 3 months of ART initiation, but can occur as early as 5 days. (See Section 13.)

14.1.4 Women who become pregnant while taking ART10 Discuss and review any plans for pregnancy with all women enrolled in chronic HIV care during each facility visit. For women planning pregnancy or who become pregnant while receiving ART, the choice of ARV regimen may be based on: • gestational age of the pregnancy; and • the clinical and laboratory ﬁndings. With all women enrolled in HIV care, discuss the beneﬁts and potential risks of ARV use during pregnancy (particularly during the ﬁrst trimester) and during breastfeeding. Do not interrupt ART before or during pregnancy, as this has been associated with rebound rise in the viral load and decline in CD4 cell count increasing the risk of MTCT and HIV disease progression. Women who are planning to become pregnant should not use an EFVbased regimen. For these women, offer a NVP-based regimen for at least the periconception period. If a woman receiving EFV is recognized as pregnant before 28 days gestation, EFV should be stopped and substituted with NVP (immediately start at NVP 200 mg twice a day) or a protease inhibitor (PI). If a woman is on an EFV-based ART regimen and is diagnosed as pregnant after 28 days gestation, EFV should be continued.

14.1.5 Monitoring antiretroviral response in pregnant women Treatment success, as well as effective prevention of MTCT, is dependent on antiretroviral drug adherence. Assess and support adherence at each visit. Monitor the therapeutic response to ART clinically and immunologically, as for all adults (see Section 13). HIV disease stage and potential disease progression can be monitored through assessment of WHO clinical stage. It can be difﬁcult to use weight in monitoring treatment response during pregnancy. When deﬁning the clinical stage of a pregnant woman, take into consideration her expected weight gain in relation to the gestational age of the pregnancy and her potential weight loss from HIV. Monitoring of immunological status through measurement of CD4 cell count is not essential for patients on ART, but can be used to conﬁrm clinically suspected treatment failure. A decrease in absolute CD4 count in a pregnant woman should be interpreted with caution. Due to pregnancy-related haemodilution, absolute CD4 cell count decreases during pregnancy; after delivery, body ﬂuid changes normalize to the non-pregnant state, and CD4 levels may rise by 50–100 cells/mm3.

14.1.6 Use of second-line ART in pregnancy10 When ﬁrst-line ART failure occurs, a second-line regimen is indicated (see Section 13). Consider the following as differential diagnosis to ART failure: • IRIS • untreated intercurrent OIs

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• intercurrent infections causing transient decrease in CD4 count (repeat CD4 to conﬁrm immunological failure) • poor treatment adherence • inadequate drug dosing • drug-to-drug interactions resulting in reduced blood levels of ARV drugs • poor absorption of drugs due to adverse effects such as vomiting. When ﬁrst-line treatment failure occurs, the entire regimen should be changed to a regimen containing a boosted PI plus two NRTIs, one of which is new and not taken in the ﬁrst-line regimen (see Section 13). There are some concerns that levels of PI drugs may be lowered in pregnancy, but standard second-line regimens can be used in pregnant women, as with other adults.

14.1.7 ARV prophylaxis for infants of HIV-positive pregnant women taking ART10 All infants, whether breastfeeding or receiving replacement feeding only, who are born to HIV-positive women receiving ART should be given: NVP daily; OR AZT twice daily from birth or as soon as feasible thereafter until 4−6 weeks of age. See Table: Summary of infant ARV prophylaxis regimen and Table: Infant ARV prophylaxis dosing recommendations.

14.1.8 ARV prophylaxis to prevent MTCT of HIV10 Maternal ARV prophylaxis Pregnant women who do not need ART for their own health should be started on ARV prophylaxis from as early as 14 weeks of gestation (second trimester). Women who present later in pregnancy, labour, postpartum, or during breastfeeding should be started on ARV prophylaxis as soon as possible. A choice of 1 or 2 equally efﬁcacious ARV prophylaxis options is recommended (see table below). Both recommended ARV prophylaxis options provide a signiﬁcant reduction in the risk of MTCT of HIV. There are advantages and disadvantages of both options in terms of feasibility, acceptability and safety for mothers and infants, as well as cost. Follow national PMTCT guideline recommendations.

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Table: Recommended ARV-prophylaxis for pregnant women not yet eligible for ART and their infants Maternal AZT + infant ARV prophylaxis (Option A) Maternal AZT prophylaxis AZT 300 mg twice daily starting from as early as 14 weeks of gestation. At onset of labour, single-dose NVP (sd-NVP) 200 mg + AZT 300 mg twice daily + 3TC 150 mg twice daily for 7 days postpartum. (Note: If maternal AZT was provided for more than 4 weeks during pregnancy, omission of the sd-NVP and AZT+3TC “tail” can be considered. In this case, continue maternal AZT during labour until delivery.) For breastfeeding infants Daily NVP from birth (within 6–12 hours) until 1 week after all exposure to breast milk has ended or, if breastfeeding stops prior to age 6 weeks, for a minimum of 4−6 weeks following birth. Infants receiving replacement feeding only Daily NVP or sd-NVP+ twice daily AZT from birth until 4−6 weeks of age (irrespective of mode of infant feeding). Maternal triple ARV prophylaxis (Option B) Maternal triple ARV prophylaxis AZT+3TC+LPV/r; OR AZT+3TC+ABC; OR AZT+3TC+EFV; OR TDF+3TC (or FTC)+EFV Starting from as early as 14 weeks gestation and continued until delivery, or if breastfeeding, continued until 1 week after all infant exposure to breast milk has ended.

For infants Daily NVP or twice daily AZT from birth until 4−6 weeks of age (irrespective of mode of infant feeding).

For women not in need of ART for their own health with clinically signiﬁcant or severe anaemia (Hb <7 g/dl), a non-AZT-containing regimen should be considered (e.g. TDF+3TC (or FTC)+ EFV – option B). Alternatively, an AZT-based prophylaxis (Option A) could be initiated after the severe anaemia has been corrected. For all women on ARV prophylaxis, monitoring of immunological status through measurement of CD4 cell count should be done every 6 months in order to determine the possible need for treatment. Clinical assessment and CD4 cell count should be done to assist the decision to stop triple ARV prophylaxis.

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Infant ARV prophylaxis10 Table: Summary of infant ARV prophylaxis regimens Infant feeding practice Maternal ARV regimen Maternal AZT prophylaxis (Option A) Breastfeeding infants Daily NVP from birth (within 6–12 hours) until 1 week after all exposure to breast milk has ended or, if breastfeeding stops prior to age 6 weeks, for a minimum of 4−6 weeks following birth. Replacement feeding only Daily NVP or sd-NVP+AZT twice daily from birth until 4−6 weeks of age.

Maternal triple ARV prophylaxis (Option B) OR Maternal ART

Daily NVP or twice daily AZT from birth until 4−6 weeks of age (irrespective of mode of infant feeding).

Table: Infant ARV prophylaxis dosing recommendations ARV drug NVP liquid formulation 10 mg/ml Infant age Birth* to 6 weeks Dose Birth weight 2000–2500 g: 10 mg (1 ml) once daily Birth weight >2500 g: 15 mg (1.5 ml) once daily If infant weight is not available, administer 10 mg (1 ml) liquid and follow national dosing recommendations thereafter. 20 mg (2 ml) once daily 30 mg (3 ml) once daily 40 mg (4 ml) once daily

>6 weeks to 6 months >6 months to 9 months >9 months to 1 week after end of BF

Give the ﬁrst dose of NVP for the infant as early as possible after delivery, preferably within the ﬁrst 6 hours. Shake well before use; store at room temperature. A bottle of liquid should be used within 6 months of opening.11 AZT liquid formulation 10 mg/ml Birth** to 6 weeks Birth weight 2000–2500 g: 10 mg (1 ml) twice daily Birth weight >2500 g: 15 mg (1.5 ml) twice daily

Stable at room temperature, but needs storage in a glass jar and is light sensitive.10

* Low birth weight infants should receive NVP 2 mg/kg once daily as a starting dose. Therapeutic drug monitoring is recommended. ** Low birth weight infants should receive mg/kg dosing.

14.1.9 Safety of antiretroviral and other medicines in pregnancy10 Safety monitoring Clinical and laboratory monitoring of pregnancy in HIV-positive women should be the same as is recommended for non-HIV-infected pregnant women and be part of a package of antenatal care interventions. Assess the woman carefully, looking for signs and symptoms, especially for pallor, jaundice, mucosal sores, and rash.

11 Antiretroviral therapy for HIV infection in infants and children: Towards universal access. WHO, 2010. Available at http://www.who.int/hiv/pub/paediatric/infants2010/en/index.html

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Clinical and laboratory monitoring of HIV-positive women includes monitoring of HIV and related drugs, in addition to routine monitoring of pregnancy. Consider the following in HIV-positive pregnant and postpartum women with new signs and symptoms: • medication adverse effects or toxicity, e.g. ARV drugs • pregnancy or childbirth-related problems or complications • HIV disease, e.g. the natural progression of HIV if a woman is not yet taking ART including opportunistic infections • an infection or condition that is not directly related to HIV, e.g. malaria • IRIS in a patient recently started on ART • failure of an ART regimen. In general, adverse effects and toxicity of ARVs seen in pregnancy are similar to those in non-pregnant adults. The development of a new or recurrent OI soon after starting ART is not necessarily evidence of regimen failure, and could be due to IRIS (see Section 13).

Anaemia in pregnancy Assess for signs of clinically signiﬁcant anaemia in HIV-positive pregnant women. The major toxicity of AZT is haematological, including risk of anaemia and neutropaenia. Thus, in pregnant women with clinically signiﬁcant anaemia or documented severe anaemia (haemoglobin <7 g/dl), the use of alternative drugs instead of AZT (e.g. TDF or d4T) or delayed initiation until after the anaemia is corrected should be considered. However, in pregnancy, there has been extensive experience with the use of AZT and 3TC and these have been shown to be welltolerated. Therefore, the combination of AZT+3TC is preferred in pregnancy for women receiving ART or triple ARV prophylaxis (Option B).

NVP rash and hepatitis in pregnancy Women initiating ART, particularly those with CD4 count >250 cells/mm3, have an increased risk of developing symptomatic, often rash-associated liver toxicity with NVP. Pregnant women may be at increased risk. This complication is most likely to occur during the ﬁrst 12 weeks after an NVP-based regimen has been started. When possible, monitor ALT and AST levels at 2, 4, 8, and 12 weeks after starting an NVP-based regimen if the woman’s CD4 count is >250 cells/mm3.

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Table: Management of NVP-associated rash and liver toxicity (see Section 13) Side-effects Major Nausea, vomiting, jaundice, and right upper quadrant pain (i.e. symptoms suggestive of liver-toxicity) ALT or AST are signiﬁcantly elevated (>5 times the upper limits of normal) Moderate to severe cases of rash with mucosal involvement or systemic signs, Stevens-Johnson syndrome Mild to moderate rash Mild to moderate rash without mucosal involvement, and no systemic signs Consider switching from NVP to EFV if woman is in second or third trimester. If in the ﬁrst trimester: • switch NVP with LPV/r or another PI; OR • temporarily discontinue the entire regimen. Stop NVP. Do not restart NVP in the future, even in the absence of symptoms. Stop all ART and give supportive treatment. Consider referring the patient to a third-level facility. Management

Mild rash Carefully monitor. If it worsens, manage as above.

EFV use in pregnancy EFV is primarily associated with toxicities related to: • the central nervous system (CNS) • rash • teratogenicity (possible if taken during the ﬁrst trimester of pregnancy). Since neural tube closure occurs by approximately 28 days of gestation and very few pregnancies are recognized by this time, the potential risk with the use of EFV is primarily in women who become pregnant while already receiving the drug. Rash associated with EFV use is generally mild, self-resolving, and usually does not require discontinuation of therapy. The CNS-related side-effects of EFV are more common. While they typically resolve shortly, they may persist for months, and may require discontinuation of the drug. EFV should not be used in patients: • with a history of severe psychiatric illness • when there is a potential for pregnancy (unless effective contraception can be assured) • during the ﬁrst trimester of pregnancy.

Lactic acidosis in pregnant women Lactic acidosis is a very rare but severe toxicity of NRTI use caused by mitochondrial dysfunction. Regimens containing d4T have the highest rates of lactic acidosis. It is particularly important to avoid using the combination of d4T+ddI in pregnancy.

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Lactic acidosis often develops slowly and is characterized by several non-speciﬁc symptoms, including shortness of breath or hyperventilation, abdominal pain, nausea, fatigue, and weight loss. The symptoms can be vague, therefore a high degree of suspicion is needed. Many of these symptoms could occur as part of a normal pregnancy, and extra vigilance for lactic acidosis among pregnant women using NRTIs is required. Lactic acidosis can sometimes be confused with obstetrical complications (such as pre-eclampsia or HELLP syndrome) or with an HIV-related illness. (See Section 13.)

Rash and hypersensitivity due to abacavir (ABC) Fever, fatigue, rash, sore throat, or shortness of breath may indicate ABC hypersensitivity syndrome (see Section 13 Toxicity and drug substitutions).

Safety of medicines in pregnancy Refer to Section 8 Medicines and the WHO Model Formulary8 for each medication.

14.1.10 Antiretroviral drug resistance ARV drug resistance, in the context of PMTCT interventions, most commonly occurs with poor adherence and with the use of single-dose NVP in pregnancy. NVP has a prolonged half-life, with signiﬁcant drug levels measurable for up to 3 weeks after a single dose. Further, a single viral point mutation can cause high levels of resistance to NVP. This may lower the effectiveness of later ART containing an NNRTI drug. The following strategies can minimize these effects. • Identify all women who are eligible for ART as early as possible in order to initiate combination ART while ensuring good adherence. • If ART is not yet indicated, offer AZT prophylaxis (Option A) or triple ARV prophylaxis (Option B). In Option A, a single-dose of NVP is given in combination with AZT+3TC intrapartum, and for 7 days postpartum, to reduce the potential for resistance. • For women receiving single-dose NVP who are in false labour, a repeat NVP dose should not be given during established labour. After delivery, the infant should receive the recommended ARV prophylaxis. For women previously exposed to an ARV prophylaxis regimen for PMTCT in an earlier pregnancy and who are not in need of ART for their own health, the recommendations for ARV prophylaxis in a subsequent pregnancy are the same as for women not previously exposed. For women who initiate ART within 12 months after sd-NVP exposure, a non-NNRTI-based regimen is recommended (see the table below).

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Table: Choice of ART regimen for HIV-positive women with prior exposure to ARV prophylaxis for PMTCT10 Characteristics of previous PMTCT ARV exposure sd-NVP (+/- short-course AZT) with no NRTI tail within the last 12 months sd-NVP (+/- short-course AZT) with an NRTI tail within the last 12 months sd-NVP (+/- short-course AZT) with or without an NRTI tail more than 12 months before All triple ARV regimens, irrespective of duration of exposure and time since exposure Recommendation • Initiate a non-NNRTI regimen • 2 NRTIs + PI preferred over 3 NRTIs • Initiate an NNRTI regimen • If available, check viral load at 6 months and if >5000 copies/ml, switch to second-line ART with PI • Initiate an NNRTI regimen • If available, check viral load at 6 months and if >5000 copies/ml, switch to second-line ART with PI • Initiate NNRTI regimen • If earlier triple ARV regimen was NNRTI-based and was stopped without administration of an NRTI tail, check viral load at 6 months, and if >5000 copies/ml, switch to second-line ART with PI

See Section 13 for the different classes of antiretroviral (ARV) drugs.

14.1.11 Improved care and support for HIV-positive pregnant women Nausea and vomiting in pregnancy Nausea and vomiting are common problems in the ﬁrst trimester especially in ﬁrst pregnancies, affecting up to 80% and 50% of all pregnant women, respectively. About 1% of pregnant women will have severe nausea and vomiting, known as hyperemesis gravidarum. A district clinician should assess women who have severe nausea and vomiting, who are unable to tolerate oral ﬂuids, or who are severely dehydrated. The goal of treatment is to manage symptoms and minimize risks to the mother and the fetus, and may vary depending on the severity. Assess the hydration status carefully (see Section 10.7d Classify dehydration). A woman may require hospitalization for rehydration with intravenous ﬂuids if she is unable to tolerate ﬂuids by mouth. • Encourage the woman to eat smaller portions of food more frequently and to drink lots of ﬂuids. Bland and low fat food may be preferable, as fatty foods may delay gastric emptying. Serve cold food, if the smell of hot food is noxious. • Ginger drinks and pyridoxine (vitamin B6) are helpful in reducing nausea and vomiting in pregnancy. Promethazine may also be used, as indicated (see table below, Antiemetic medication in pregnancy for dose). Some antiemetics can be given intramuscularly or as rectal suppositories if the woman is unable to tolerate oral medications. See Section 10.7c and Section 20. If vomiting persists for longer than 2 weeks, give thiamine (vitamin B1) replacement. Nausea and vomiting can severely affect adherence to ART or ARV prophylaxis. Manage nausea and vomiting so that ART or ARV prophylaxis can be continued. Encourage the woman to continue taking her ARV drugs, and to repeat the dose if she vomits whole tablets.

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Table: Antiemetic medication in pregnancy (see speciﬁcs in Section 8.4 Medicines) Antiemetic Pyridoxine (vitamin B6) Dose 25 mg PO, up to 3–4 times daily

Promethazine Metoclopramide Ondansetron

10–25 mg PO, IM, or IV, up to 4 times daily 10 mg PO up to 3–4 times daily; 5–10 mg IM, up to 3–4 times daily 4 to 8 mg PO every 12 hours

14.2 Intrapartum care for HIV-positive women1,2,5 Recommend HIV testing during labour if not already done. In settings with a generalized HIV epidemic, pregnant women who tested negative in their ﬁrst or second trimesters of pregnancy should be recommended to have HIV testing and counselling in the third trimester. If this is not done, HIV testing should be recommended during labour or immediately after delivery. A new diagnosis of HIV infection can be made in labour (i.e. positive rapid test during labour). Give ARV prophylaxis while waiting for a conﬁrmatory test result. For women identiﬁed HIV-positive during labour or immediately postpartum, it may be better to give Option A, which provides daily NVP prophylaxis for the infant. Assess the mother for ART eligibility immediately postpartum. If she is eligible, initiate ART. The infant should continue daily NVP until the mother has received at least 6 weeks of ART before the infant prophylaxis is discontinued. Follow national PMTCT guideline recommendations. If the woman is already on ARV prophylaxis or ART, continue the same regimen throughout labour and delivery. (See table below.) Table: Summary of ARV regimens during pregnancy, intrapartum, postpartum, and breastfeeding ARV regimen during pregnancy Maternal ART Intrapartum ARV regimen ART Postpartum ARV regimen ART ARV regimen if Breastfeeding Mother: ART Infant: AZT or NVP prophylaxis from birth until 4−6 weeks of age Mother: AZT+3TC for 7 days only Infant: NVP prophylaxis from birth until 1 week after all breast milk exposure ends Mother: Triple ARV prophylaxis until 1 week after all breast milk exposure ends Infant: AZT or NVP prophylaxis from birth until 4−6 weeks of age Replacement feeding only Mother: ART Infant: AZT or NVP prophylaxis from birth until 4−6 weeks of age Mother: AZT+3TC for 7 days Infant: AZT or NVP prophylaxis from birth until 4−6 weeks of age Assess the woman regularly; start ART as soon as eligible. Assess the woman regularly; start ART as soon as eligible.

Maternal AZT prophylaxis (Option A)

At onset of labour, AZT+ sdNVP + 3TC

AZT+3TC for 7 days

Maternal triple ARV prophylaxis (Option B)

Maternal triple ARV prophylaxis

Mother: NONE Infant: AZT or NVP prophylaxis from birth until 4−6 weeks of age

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Safer intrapartum practices Use safer intrapartum practices for both the mother and the newborn to minimize the risks of MTCT. • Use standard precautions to prevent infection (see Section 6). • Minimize the number of cervical exams. • Avoid artiﬁcial membrane rupture. • Avoid invasive obstetrical procedures, such as episiotomy, invasive fetal monitoring, or nasal suction of newborns. • Use the partograph and active management of labour to reduce the duration of labour. • Avoid the use of vacuum or forceps, except in selected cases when one of these techniques is required because of fetal distress, or to shorten the duration of labour or membrane rupture (e.g. cases of maternal exhaustion). • Vaginal cleansing with 0.25% chlorhexidine solution does not decrease the overall risk of MTCT, but may decrease MTCT in a subgroup of women with prolonged membrane rupture, and may decrease early maternal and neonatal infectious morbidity. • Dry the infant as soon as possible after delivery and remove any cloths with blood and maternal secretions.

Caesarean delivery Elective caesarean delivery decreases MTCT of HIV in women not receiving ARV prophylaxis. There is no evidence that caesarean delivery reduces risk of MTCT if performed after the onset of labour or membrane rupture, or that it offers any additional beneﬁt to women already taking effective ART with optimal viral load suppression. In limited-resource settings, caesarean delivery should only be performed for obstetrical indications. Concerns about routine caesarean deliveries in such settings include: • increased risk of maternal mortality and morbidity • anaesthesia availability • availability of safe blood supply should transfusion be needed • the need for antibiotic prophylaxis • lack of human and material resources.

Breast care Prior to discharge from the maternity ward, mothers should be educated about appropriate breast care and assisted with proper attachment. They should be informed about signs and symptoms of breast problems and the potential role of breast infections (abscess, mastitis) or nipple trauma in MTCT. They should be encouraged to seek care promptly if these occur.

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14.3 Infant feeding12 Mothers known to be HIV-infected (and whose infants are HIV-uninfected or of unknown HIV status) should follow national policy and recommendations on infant feeding. National ministries of health should decide which infant feeding practice will be promoted and supported in clinics and hospitals of their individual countries. The decision should be guided by which feeding practice will give infants the best chance of HIV-free survival, i.e. remaining HIV-uninfected, as well as protecting infants from other serious illnesses, such as diarrhoea or pneumonia, that are common causes of infant mortality. In making this decision, the national ministry should consider: • the prevalence of HIV and the type of HIV epidemic in the region or country; • the socio-economic conditions of most families attending public health facilities; • the quality of water and sanitation; • the distribution and quality of MCH services including availability of HIV and PMTCT interventions; • the main causes of infant and child mortality; • the prevalence of infant and child under-nutrition. It is expected that ministries of health will recommend one of two infant feeding practices for HIV-positive mothers and their infants: either that HIV-positive mothers breastfeed and be provided with appropriate ARVs or that HIV-positive mothers avoid breastfeeding and give replacement feeds only. This decision and how it should be implemented should be clearly communicated to health workers.

Breastfeeding In settings where breastfeeding is recommended, HIV-positive mothers should exclusively breastfeed their infants for the ﬁrst 6 months of life, introducing appropriate complementary foods thereafter, and then continue breastfeeding for the ﬁrst 12 months of life. Health workers need to assist the mother to initiate breastfeeding within 30 minutes of birth and support exclusive breastfeeding over the ﬁrst 6 months of life. This includes advising and encouraging the mother about correct positioning and attachment of the baby to the breast. Mothers should also be informed about growth spurts in the infant and how she will need to increase breastfeeding to meet the infant’s needs. These practices are the same as for the HIV-negative mothers and their infants. In places where diarrhoea, pneumonia, and malnutrition are common, continuing to breastfeed over the ﬁrst 12 months protects the infant from death (during this time and afterwards) caused by these serious illnesses. At the same time, antiretroviral drugs should be given to reduce the risk of HIV transmission.

12 Guidelines on HIV and infant feeding. WHO, 2010. Available at http://www.who.int/child_adolescent_health/ documents/9789241599535/en/

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HIV-positive pregnant women and mothers who are eligible for lifelong treatment should be started on antiretroviral therapy. ART eligibility criteria for breastfeeding women are the same as for pregnant and non-pregnant adults. (See above Table: Eligibility criteria for ART or ARV prophylaxis in HIV-positive pregnant women, and Table: Considerations for the choice of ﬁrst-line ART for pregnant women in need of treatment for their own health). HIV-positive mothers who are not yet eligible to start ART should be provided with appropriate ARVs, that either the mother gives to the infant (Option A) or takes herself (Option B) to prevent HIV transmission through breastfeeding. (See above Table: Recommended ARV-prophylaxis for pregnant women not yet eligible for ART; see above Table: Summary of infant ARV prophylaxis regimens; and see above Table: Infant ARV prophylaxis dosing recommendations). Option A: Daily NVP to the infant while breastfeeding and until 1 week after all breast milk exposure ends. Option B: Triple ARVs to the mother while breastfeeding and until 1 week after all breast milk exposure ends. Note: These are continuations of ARVs provided during pregnancy and labour. All children need complementary foods from 6 months of age. Details of how much food should be given in addition to milk are provided in other guidance documents.13 In general, HIV-positive mothers should stop breastfeeding after 12 months and provide a nutritionally adequate and safe diet without breast milk. If, however, she is unable to do this, the mother may need to continue to breastfeed while using ARVs to prevent HIV transmission. Health workers should counsel the mother at around 12 months in order to help her make this decision, to consider how she will manage the change to no breastfeeding, how she will comfort the infant when crying, and how she will feed her infant afterwards. When stopping breastfeeding, mothers should do so gradually over about 1 month. Health workers need to provide information to the mother about ARVs and how they reduce HIV transmission during breastfeeding. Mothers need to know: • where they will get the ARVs, how often and from whom; • where to go if her ARV supplies are running low; • what to do when she plans to stop breastfeeding, and when to stop the ARVs; • when to go to the clinic for immunization, cotrimoxazole prophylaxis, and HIV testing of her infant.

Replacement feeding In settings where ministries of health recommend that HIV-positive mothers give replacement feeds, health workers should conﬁrm that HIV-positive mothers (or other carers) have the following. • Assured safe water and sanitation at the household level and in the community.

13 Guiding principles for feeding non-breastfed children 6–24 months of age. WHO, 2005. Available at http://www. who.int/child_adolescent_health/documents/9241593431/en/index.html

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• Reliably provide sufﬁcient infant formula milk to support normal growth and development. • Prepare infant formula milk cleanly so that it is safe and carries a low risk for diarrhoea and frequently enough to avoid malnutrition. • In the ﬁrst 6 months, exclusively give infant formula milk. • The family is supportive of giving infant formula milk. • Access to health care that offers comprehensive child health services. If these conditions are met, health workers should demonstrate to mothers why and how to safely prepare replacement feeds, how to sterilize cups and bottles, and what to do if the infant becomes ill with diarrhoea or develops oral thrush. Health workers should continue regularly to see mothers and infants, to check hygienic feeding practices (especially preparation of feeds), monitor weight gain, and to detect complications. Mothers should be advised about when to attend health facilities with her infant for ﬁnal HIV testing. When infants are not or no longer breastfed (either from birth or after a period of breastfeeding), the mother should provide a nutritional, adequate, and safe diet. When infants are <6 months of age, mothers should give either of the following: • Commercial infant formula milk (as long as the conditions listed above are fulﬁlled); or • Expressed, heat-treated breast milk. This can be considered as an interim feeding strategy in the following circumstances: ° when the infant is born with low birth weight or is otherwise ill in the neonatal period and unable to breastfeed; ° when the mother is unwell and temporarily unable to breastfeed or has a temporary breast health problem, such as mastitis; ° to assist mothers to stop breastfeeding; ° if ARV drugs are temporarily not available. When infants are >6 months of age mothers can give either of the following: • Commercial infant formula milk (as long as the conditions listed above are fulﬁlled). • Animal milk (boiled for infants <12 months), as part of a diet providing adequate micronutrient intake. Meals, including milk-only feeds, other foods, and combinations of milk feeds and other foods, should be provided 4 or 5 times per day. When infants become HIV-infected during pregnancy, labour, or delivery, and test HIV-positive at 6 weeks of age (i.e. virological test) or any other time, mothers are strongly encouraged to exclusively breastfeed for 6 months and to continue to breastfeed for 2 years (the same as infants of mothers who are HIV-negative or who do not know their HIV status). If an infant is already infected with HIV, there is no reason to avoid breastfeeding. Rather, HIV-positive infants will beneﬁt from breastfeeding and the protection that it provides against other infectious diseases. Facility managers and district health teams should monitor feeding practices over time. Health workers can ascertain feeding practices at speciﬁc points in time, such as at 3 months, as a proxy of practices at other times. If breastfeeding with ARVs is the recommended practice, then monitoring of ARV adherence among breastfeeding mothers is important.

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Whatever the recommended feeding practice, health workers in clinics and hospitals need to communicate to the broader community the infant feeding practice that is promoted and supported by local health facilities, and the rationale for the chosen public health approach. Given the history and confusion concerning infant feeding in the context of HIV, health-care workers need to convey the new opportunities for HIV-positive mothers to breastfeed while giving ARVs to prevent transmission and to improve HIV-free survival of HIV-exposed infants. Health services should make particular efforts to reach and gain the support of the fathers of infants to support optimal feeding practices. This provides a major opportunity to better link HIV-speciﬁc interventions with general maternal, newborn, and child health services that also promote breastfeeding to improve child survival.

14.4 Postpartum care for HIV-positive women If the postpartum woman presents to the facility for the ﬁrst time after childbirth, recommend HIV testing and counselling if not already done. For those testing positive, assess WHO clinical stage and CD4 cell count to determine eligibility for ART. Clinical assessment of the HIV-positive woman should be performed each time she presents for postpartum care and for child health visits. Review TB status at each visit. Offer INH preventive therapy if the woman has no cough, fever, weight loss, or night sweats. If the woman is already receiving ART or triple ARV prophylaxis, monitor and support adherence. If the woman is on triple ARV prophylaxis and breastfeeding, she should continue with same regimen until 1 week after all breast milk exposure of the infant ends. If she is on ART, she should continue the treatment for life. See above Table: Summary of ARV regimens during pregnancy, intrapartum, postpartum and breastfeeding for the ARV regimens to follow during postpartum and breastfeeding period.

Postpartum follow up of HIV-infected mothers and their infants is a critical part of PMTCT interventions and clinical management

Ensure that HIV-positive women, their infants and their partners continue to receive HIV prevention, care, and treatment services postpartum. • Support HIV-positive breastfeeding women as much as possible, e.g. involve their partners in PMTCT services, and facilitate peer support from other HIV-infected women who are already receiving care, as appropriate for each woman. • Coordinate facility visits for the woman, her infant, partner, and family. • Integrate and support single point of care as much as possible. Facilitate linkages across services, e.g. MNCH, family planning, HIV care and treatment. • Provide family-focused care. Counsel women on the advantages of birth spacing and planning future pregnancies, and how ARVs can protect women during breastfeeding and prevent transmission of HIV to their infants. Review a woman’s family planning and fertility

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desires. Emphasize the importance of dual protection, including condom use (dual methods or dual protection using only condoms). See Section 14.5 Reproductive choice and family planning.

Care for HIV-exposed infants See IMCI Chart Booklet for High HIV Prevalence Settings14 and Child Pocket Book for Hospital Care.15 • Ensure follow up care of HIV-exposed infants. The following are essential care for HIV-exposed infants. ° Routine newborn and infant care, including immunization, growth monitoring, and nutrition. ° Completion of ARV prophylaxis. Support and monitor adherence, and give adherence counselling to caregivers. ° Continued infant feeding counselling and support, and nutritional support throughout the ﬁrst year of life. ° Early HIV diagnostic testing and diagnosis of HIV-related conditions. Early infant diagnosis is critical to provide ART for those who are infected. Recommend virological testing at 4–6 weeks of age or at ﬁrst presentation after 4–6 weeks of age.16 If HIV-infected, the infant is eligible for ART. If the test is negative the mother or her breastfeeding infant should continue with the ARV regimen. See above Table: Summary of ARV regimens during pregnancy, intrapartum, postpartum, and breastfeeding for reference. ° Cotrimoxazole prophylaxis starting at 4–6 weeks of age and continuing until HIV infection has been excluded and there is no risk of HIV exposure. It is recommended for all HIV-exposed infants until HIV infection is excluded. ° INH preventive therapy when indicated. ° Malaria prevention and treatment when indicated. ° Diagnosis and management of common childhood infections and conditions, TB, and integrated management of childhood illnesses (IMCI). ° Establishing ﬁnal diagnosis of HIV-exposed infants at 15–18 months of age.

Early diagnosis of HIV-infection in infants is critical to reduce HIV-related morbidity and mortality in this age group

14 IMCI chart booklet for high HIV settings. WHO, 2008. Available at http://www.who.int/child_adolescent_health/ documents/9789241597388/en/index.html 15 Manual on paediatric HIV care and treatment for district hospitals. WHO, 2011. Available at http://www.who.int/ child_adolescent_health/documents/9789241501026/en/index.html 16 WHO recommendations on the diagnosis of HIV infection in infants and children. WHO, 2010. Available at http:// www.who.int/hiv/pub/paediatric/diagnosis/en/index.html

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14.5 Reproductive choice and family planning17 Discuss fertility intentions and provide family planning counselling with each woman. The goals of counselling and discussion are to prevent unintended pregnancy, and to help achieve a safe pregnancy, for both mother and child, when pregnancy is desired. The discussion should never be coercive; the woman has the right to make her own decisions about reproduction. She should be provided with the available options. Family planning services and counselling are especially important at the following times: • after HIV diagnosis, and at regular intervals during ongoing care; • when there is a new marriage or relationship; • when a desire is expressed not to become pregnant; • when the woman is not using effective or consistent contraception; • during pregnancy or the postpartum period (to reinforce the value of birth spacing); • following the death of a child; • when a woman is using ART, which may be associated with resumption of sexual activity and fertility, and therefore an increased risk for unintended pregnancy; • when a woman takes ART that includes EFV. She should use an effective method of contraception due to the possible risk of teratogenicity from EFV use during early pregnancy exposure.

14.5.1 Dual protection Provision of family planning counselling and of contraception services should occur within the context of HIV clinical care. It is recommended that family planning services need to integrate into and support HIV clinical services. If this is not possible, the woman should be referred to a nearby family planning service. The condom is the only contraceptive method that protects against STIs, including HIV, as well as against pregnancy. Male latex condoms are the most popular and protect against both female-to-male and male-to-female transmission of HIV, as shown in studies of discordant couples. Female condoms are still an underused method of dual protection against both pregnancy and HIV. When a signiﬁcant risk of STI or HIV transmission exists, dual protection against both pregnancy and STI and HIV transmission should be strongly recommended. Consider these 5 dual protection strategies, each of which might be appropriate in different situations and at different times for an individual. The best strategy is the one that a person is able to practice effectively in the situation she or he is facing. Strategy 1: Use a male or female condom correctly with every act of sex. Strategy 2: Use condoms consistently and correctly, plus another family planning method. This may be a good choice for women who want to conﬁdently avoid pregnancy, but who cannot always count on their partners to use condoms. Strategy 3: If both partners know they are not HIV-infected, use any family planning method to prevent pregnancy and stay in a mutually faithful relationship. This strategy depends on communication and trust between partners. 17 Family planning: a global handbook for providers (updated). WHO, 2011. Available at http://www.who.int/ reproductivehealth/publications/family_planning/9780978856304/en/index.html

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Strategy 4: Engage only in safe sexual intimacy that avoids intercourse, and otherwise prevents semen and vaginal ﬂuids from coming in contact with each other’s genitals. This depends on communication, trust, and self-control. Strategy 5: Delay or avoid sexual activity (either avoiding sex at any time that it might be risky, or abstaining for a longer time). The latter two strategies do not involve contraceptives. Many patients need help and guidance to ensure their speciﬁc dual protection strategy will succeed. Seroconcordant couples may be less likely to use condoms consistently, and require a more effective contraceptive method if pregnancy is not desired.

14.5.2 Guidance on the use of contraceptive methods There are guidance references that policy makers and programme managers can use to support the safe and effective provision and use of family planning methods. These evidence-based guidance documents dispel any lack of information or misinformation about using various methods. The WHO Medical eligibility criteria for contraceptive use (4th edition, 2010) provides guidance on whether people with certain medical conditions can safely and effectively use speciﬁc contraceptive methods.18 There is a section on recommendations for persons living with HIV. Drug interactions and other effects of hormonal methods need to be considered in making recommendations (see below Table: Medical eligibility criteria for contraceptive use: conditions relevant to HIV. Use this table to guide the selection of a contraceptive method.) Category 1: Use this method in any circumstances; use the method with limited clinical judgement. Category 2: With clinical judgment, generally use the method; with limited clinical judgment, use the method. Category 3: With clinical judgment, use of the method not generally recommended unless more appropriate methods are not available or acceptable. With limited clinical judgment, do not use the method. Category 4: Method not to be used.

Drug-drug interactions There are drug-drug interactions between hormonal contraceptives and many PIs and NNRTIs. The interactions may either increase or decrease contraceptive steroid levels, which may potentially either decrease contraceptive effectiveness when co-administered, or increase hormonal side-effects or toxicity when steroid levels are increased. The medical eligibility categories assigned to ART in the table below take into account these potential interactions. • Women taking ritonavir-boosted PIs generally should not use combined hormonal methods (combined pills, monthly injectables, patch, and vaginal ring) or progestogen-only pills. • Progestogen-only injectables and implants generally can be used with any ART.

Selected Practice Recommendations for Contraceptive Use answers speciﬁc questions about how to use various contraceptive methods.19 18 Medical eligibility criteria for contraceptive use. 4th ed. WHO, 2009. Available at http://www.who.int/ reproductivehealth/publications/family_planning/9789241563888/en/index.html 19 Selected Practice Recommendations for Contraceptive Use. 2nd ed. WHO, 2004. (With selected 2008 update). Available at http://www.who.int/reproductivehealth/publications/family_planning/9241562846index/en/index.html

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Table: Medical eligibility criteria for contraceptive use: conditions relevant to HIV Diaphragm (with spermicide) Cervical cap 4 3 3 3 3 3 1

LNG implant*

Condition HIV risk HIV AIDS Drug interactions NRTIs NNRTIs Ritonavirboosted PIs Rifampicin 1 2 3 3 1 1 1

1 1 1

2 2 I=3 C=2

4 3 3

1 2 3 2

1 2 3 3

DMPA=1 NET-EN=1 DMPA=1 NET-EN=2 DMPA=1 NET-EN=2 DMPA=1 NET-EN=2

1 2 2 2

I=2/3 C=2 I=2/3 C=2 I=2/3 C=2 1

3 3 3 1

*Also includes etonogestrel implant. COC=combined oral contraceptives with ≤35 mcg ethinyl estradiol; CIC=combined injectable contraceptives; P=patch; R=ring; POP=progestogen only pills; DMPA=depot medroxyprogesterone acetate, NETEN=norethisterone enantate; LNG-implant=levonorgestrel implant; I=initiation; C=continuation

14.5.2 Contraceptive method mix Hormonal methods (combined pills and injectables, progestogen-only pills, injectables, implants and IUDs: As discussed above and shown in the table, some hormonal methods may have interactions with some antiretroviral drugs. However, the hormonal methods have non-contraceptive beneﬁts that may have particular relevance for HIV-infected women. Proven health beneﬁts of combined oral contraceptives include: decreased iron-deﬁciency anaemia, increased menstrual regularity, decreased dysmenorrhoea (menstrual cramps), decreased risk of pelvic inﬂammatory disease (PID), and decreased incidence of endometrial, ovarian, and possibly colorectal cancer. Proven health beneﬁts of depot medroxyprogesterone acetate (DMPA) include: decreased iron-deﬁciency anaemia, decreased risk of PID, decreased uterine ﬁbroids, reduced symptoms of endometriosis, and decreased incidence of endometrial cancer. Intrauterine devices (Copper-bearing IUD, LNG IUD): A woman with HIV can have an IUD inserted. A woman with AIDS should not have an IUD inserted unless she is clinically well on ART. A woman who develops AIDS while using an IUD can safely continue using the IUD, and initiate ART. A woman using an IUD is not at increased risk of HIV transmission to sexual partners. Condoms: Male and female condoms are the only contraceptive methods that also provide protection against HIV transmission to uninfected partners and against STI acquisition.

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DMPA/ NET-EN

Copper IUD

COC

POP

LNG IUD

CIC

P/R

603

Spermicides: Repeated and high-dose use of the spermicide nonoxynol-9 was associated with increased risk of genital lesions in women, which may increase the risk of acquiring HIV infection. Therefore, for women at high risk of HIV, the use of spermicides, or diaphragms or cervical caps with spermicides are a category 4 (do not use). For women who are HIV-positive, the use of spermicides, or diaphragms or cervical caps with spermicides are a category 3 (generally do not use) due to concerns about increased risk of transmission to uninfected partners. Lactational amenorrhoea (LAM): In circumstances in which a woman with HIV decides to breastfeed, LAM can be used for family planning purposes. For adequate protection from an unplanned pregnancy, she must have the main requirements for LAM: amenorrhoea, exclusive breastfeeding, and <6 months postpartum. See the previous subsection on infant feeding. Female sterilization (tubal ligation): Women, who are infected with HIV, have AIDS, or who are on ART can safely undergo female sterilization. Special care must be taken to ensure that the woman makes a voluntary, informed choice of method. Health workers should ensure that women are not pressured or coerced to undergo the procedure, and that the decision is not made in a moment of crisis. Standard infection prevention practices should be followed. Special arrangements are needed to perform female sterilization on a woman with AIDS. The procedure should be delayed if the woman currently has an AIDS-related illness. Female sterilization does not protect against acquiring and transmitting HIV. Condom use should be emphasized post-procedure. Male sterilization (vasectomy): Men, who are infected with HIV, have AIDS, or who are on ART can safely undergo male sterilization. Special care must be taken to ensure that the man makes a voluntary, informed choice of method. Health workers should ensure that men are not pressured or coerced to undergo the procedure, and that the decision is not made in a moment of crisis. Good infection prevention practices should be followed. Special arrangements are needed to perform male sterilization on a man with AIDS. The procedure should be delayed if the man currently has an AIDS-related illness. Male sterilization does not protect against acquiring and transmitting HIV. Condom use should be emphasized postprocedure.

Emergency contraception18 Women with HIV or on ART can safely use emergency contraception. It can be used when a woman has made a mistake using contraception, when a condom breaks, in the case of rape, or when the woman was not protected by a reliable method of contraception. It is not recommended as a routine method of contraception as it is not as effective as non-emergency methods. It does not provide protection against STIs or HIV. • Oral contraceptive pills for emergency contraception should be used within 120 hours (5 days) after unprotected intercourse: ° Use LNG 0.75 mg at once followed by same dose 12 hours later OR alternatively 1.5 mg at once, or ° LNG 0.25 mg + ethinyl estradiol 50 mcg (less well-tolerated and less effective). • An alternative is a copper IUD inserted within 120 hours (5 days) of unprotected intercourse. This is the most effective form of emergency contraception and appropriate for a woman who wants an IUD as her

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continuing method. However, avoid use if the woman is at high risk for gonorrhoea or Chlamydia or has AIDS and is not clinically well.

Indications for pregnancy testing Women who have been sexually active and are experiencing any of the following should take a pregnancy test. • missed menses, unless on progestogen-only injectable or implant (can cause amenorrhoea) • irregular bleeding, unless on progestogen-only injectable or implant • new onset of irregular bleeding after prolonged amenorrhoea on progestogen-only injectable or implant • new onset of pelvic pain • enlarged uterus or adnexal mass • prior to the initiation of an EFV-based ARV regimen.

Special considerations when pregnancy is desired by a discordant couple When, after preconception counselling, a discordant couple (where one partner is HIV-positive and the other partner is HIV-negative or of unknown status) wishes to become pregnant, they should limit unprotected sexual exposure. This can be done by having unprotected sex only at times of greatest fertility, as determined with fertility awareness methods. During other times they may engage in sex using a condom, to ensure that the uninfected partner remains uninfected. • PLHIV in a serodiscordant couple who have been started on ART for their own health should be informed that ART also is recommended to reduce HIV transmission to their HIV-uninfected partners. • See Sections 13 and 19 for prevention.

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15. Tuberculosis Table of contents 15.1 Suspect TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Extrapulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2 Diagnose TB (with DDx table) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Case deﬁnitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laboratory and radiology in TB diagnosis . . . . . . . . . . . . . . . . . . . . Extrapulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Case deﬁnitions for the diagnosis of TB . . . . . . . . . . . . . . . . . . . . . Algorithm for the diagnosis of AFB smear-negative PTB in HIV-negative patients where Xpert MTB/RIF test is not available . . . . . . . . . . . . . Algorithm for the management of ambulatory HIV-positive patients with presumptive TB where Xpert MTB/RIF test is available . . . . . . . . Algorithm for the diagnosis of TB in ambulatory patients in HIV-prevalent settings where Xpert MTB/RIF test is not available . . . . . . . . . . . . . . Summary of signs and symptoms of EPTB . . . . . . . . . . . . . . . . . . . . Diagnosis of TB in the seriously ill patient with danger signs . . . . . . . . . Algorithm for the diagnosis of TB in seriously ill patients in HIV-prevalent settings where Xpert MTB/RIF test is possible . . . . . . . . . . . . . . . . Algorithm for the diagnosis of TB in seriously ill patients in HIV-prevalent settings at ﬁrst-level facilities where Xpert MTB/RIF test is not available Differential diagnosis of PTB in PLHIV . . . . . . . . . . . . . . . . . . . . . . DDx: PTB in PLHIV by stage of immunosuppression . . . . . . . . . . . . . . TB in pregnant and postpartum women. . . . . . . . . . . . . . . . . . . . . . 15.3 Treatment of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Standardized TB treatment regimens . . . . . . . . . . . . . . . . . . . . . . . Standard code for TB treatment regimens . . . . . . . . . . . . . . . . . . . . First-line anti-tuberculosis drugs. . . . . . . . . . . . . . . . . . . . . . . . . . Standard anti-TB regimen and dosing frequency in new TB cases . . . . . Dose of ﬁrst-line anti-tuberculosis drugs for adults . . . . . . . . . . . . . . Registration group by outcome of most recent TB treatment . . . . . . . . . TB treatment in special situations . . . . . . . . . . . . . . . . . . . . . . . . . Anti-TB treatment regimens in special situations . . . . . . . . . . . . . . . . Empirical treatment in EPTB . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adjuvant corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.4 Monitor TB treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitor response to TB treatment . . . . . . . . . . . . . . . . . . . . . . . . . Manage drug side-effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Symptom-based approach to managing side-effects of anti-TB drugs . . . Determine TB treatment outcomes . . . . . . . . . . . . . . . . . . . . . . . . Standard deﬁnitions of TB treatment outcomes . . . . . . . . . . . . . . . . . 15.5 Drug-resistant TB (with DDx table) . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of recommended TB treatment regimens . . . . . . . . . . . . . . MDR-TB treatment regimen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MDR-TB and HIV infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Manage common problems in patients with MDR-TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

609 609 610 610 610 610 613 613 615

. . . . .

617 618 619 620 621 622 623 623 624 624 624 624 625 625 626 626 627 627 627 628 628 628 629 630 630 630 631 631 632 632

15. Tuberculosis Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tuberculosis), which is transmitted from a patient with pulmonary TB who is often sputum smear positive. Coughing and sneezing produce tiny infectious droplets that can remain suspended in the air for long periods of time. Poorly ventilated settings increase the risk of TB transmission.

It is very important that clinicians follow the recommendations of country speciﬁc national TB and HIV treatment guidelines

Despite infection with M. tuberculosis, only 5–10% of people with normal immune systems develop TB. HIV infection signiﬁcantly increases the risk of contracting TB. HIV-positive patients are more likely to acquire TB compared to HIV-negative patients. Early diagnosis and prompt treatment of TB and HIV is essential to reduce morbidity and death among persons living with HIV. The diagnosis of TB refers to the recognition of an active case, i.e. a patient with current disease due to M. tuberculosis. Deﬁning its anatomical site is important for recording and reporting purposes, and to identify the more infectious patients. In addition, the diagnosis of extrapulmonary TB in a HIV-positive patient signiﬁes an advanced stage of HIV infection (WHO clinical stage 4). In general, the recommended TB treatment regimens are the same irrespective of anatomical site. • Pulmonary tuberculosis (PTB) refers to a case of TB involving the lung parenchyma. Globally, PTB is the most common presentation of TB patients. • Extrapulmonary tuberculosis (EPTB) refers to a case of TB involving organs other than the lungs, e.g. pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, meninges.

15.1 Suspect TB Pulmonary TB Generally, the most common symptom of PTB is a productive cough for more than 2 weeks, which may be accompanied by other respiratory symptoms, such as shortness of breath, chest pain, or haemoptysis, with or without constitutional symptoms, such as fever, night sweats, weight loss, loss of appetite, and fatigue1. In HIV-positive patients or in HIV-prevalent settings, suspect PTB and EPTB in patients who present with any one of these symptoms – cough, fever, weight loss, or night sweats. The presentation of TB may vary in HIV-positive patients, particularly in those with advanced immunosuppression. They are more likely

1 Treatment of tuberculosis: guidelines. 4th edition. WHO, 2010. Available at http://whqlibdoc.who.int/ publications/2010/9789241547833_eng.pdf

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to present with EPTB or sputum smear-negative TB compared to HIV-negative patients, especially as their immunosuppression advances. HIV-positive patients also are more likely to be very ill when they present with possible TB.

Extrapulmonary TB Generally, suspect EPTB in patients with: • cough, unintentional weight loss with night sweats, or temperature more than> 37.5°C or feels feverish; • breathlessness (effusion or pericarditis) • enlarged glands in neck or armpit • chest X-ray (see Section 10.6) with ° miliary or diffuse shadowing ° large heart (especially if symmetrical and rounded) ° suggestive of pleural effusion ° enlarged lymph nodes inside the chest • chronic headache or altered mental state. Good clinical practice • HIV-positive patients should be screened for TB at each clinic visit. • Recommend HIV testing and counselling for patients suspected of having TB and TB patients, if not already done. • Encourage disclosure and partner testing, and provide HIV prevention, care, and treatment services. These are good clinical practices because diagnosis and management of both TB and HIV is critical for good treatment outcome in a HIV-positive TB patient. Note: HIV-positive patients can develop TB at any time, before initiation of ART or while on ﬁrst-line or second-line ART.

15.2 Diagnose TB Case deﬁnitions Case deﬁnitions used for the diagnosis of TB, both in HIV-positive and HIV-negative patients, are summarized in the Table: Case deﬁnitions for the diagnosis of TB below.

Laboratory and radiology in TB diagnosis Sputum microscopy for acid-fast bacilli (AFB) (Ziehl-Neelsen stain) Patients suspected of having PTB (i.e. those with suggestive signs and symptoms or with chest X-ray ﬁndings suggestive of TB) should have at least 2 sputum specimens submitted for microscopic examination to a quality-assured laboratory, if the WHO-approved newer method for the diagnosis of TB is not available.

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At least one early morning specimen should be obtained, as this sputum collection time has the highest yield. A patient with one positive AFB sputum smear is considered a deﬁnite case of smear-positive PTB.2 Good clinical practice Assure rapid diagnosis of TB and initiation of anti-TB treatment. This helps to reduce the risk of further transmission of TB, and minimizes treatment delay, which may be lifesaving particularly for HIV-positive TB patients. Microscopy of other specimens for AFB Microscopy for AFB can also be done on specimens obtained from extrapulmonary sites including: • pleural ﬂuid • cerebrospinal ﬂuid (CSF) • ﬁne needle aspiration of lymph nodes. Newer methods recommended by WHO such as Xpert MTB/RIF test3 Xpert MTB/RIF test, where available, can assure rapid diagnosis of TB. In such settings, one sputum specimen should be tested for diagnosis of TB from the following selected patients: • HIV-positive individuals or patients with unknown HIV status in high HIV prevalence settings who are suspected of having TB. • Seriously ill patients who are suspected of having TB, regardless of their HIV status. • Individuals at risk of multidrug-resistant TB (MDR-TB) who are either diagnosed with TB or suspected of having TB. • If resources permit, HIV-negative individuals or those with unknown HIV status (not seriously ill and in low HIV prevalence settings) not at risk of MDRTB with either: ° abnormal X-ray or ° suspected of having TB with sputum AFB smear-negative result. Where resources are limited, the national programme might prioritize speciﬁc groups of patients for the WHO-approved newer method for the diagnosis of TB. Molecular tests, including Xpert MTB/RIF, are not suitable for patient monitoring as these tests also detect DNA from non-viable bacilli. Instruct and support patients in the collection of a good quality sputum specimen.

Follow national guideline recommendations on the newer WHO-approved diagnostic testing method such as Xpert MTB/RIF

2 External quality assessment for AFB smear microscopy. CDC, WHO, 2007. Available at http://wwwn.cdc.gov/dls/ ila/documents/eqa_afb.pdf 3 Rapid implementation of Xpert MTB/RIF diagnostic test: Technical and operational “How-to” practical considerations. WHO, 2011. Available at http://whqlibdoc.who.int/publications/2011/9789241501569_eng.pdf

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Radiography A chest X-ray is not necessary in most cases of smear-positive PTB. It can support diagnosis of: • smear-negative PTB, in the absence of the WHO-approved newer method for the diagnosis of TB. In such settings, a chest X-ray is necessary to support diagnosis and to prevent unnecessary delay of the diagnosis of smearnegative PTB, while waiting for culture result; • complications of PTB, e.g. pneumothorax; • complications of EPTB, e.g. pericardial effusion; • other causes of frequent or severe haemoptysis (e.g. bronchiectasis, aspergilloma, or TB sequelae). A chest X-ray is suggestive of active TB if there is: • upper lobe inﬁltrate, cavitation, pleural effusion, miliary pattern; or • non-speciﬁc patchy inﬁltrates with or without hilar lymphadenopathy in HIVpositive patients. A normal chest X-ray does not exclude TB. In a HIV-positive patient with TB, the chest X-ray ﬁndings may largely depend upon the degree of immunodeﬁciency. In mild immunodeﬁciency, the appearance of the chest X-ray may not be different compared with a HIV-negative patient. Refer to Section 10.6 for differential diagnosis of chest X-ray ﬁndings. Sputum culture for M. tuberculosis Sputum culture is the “gold standard” for the diagnosis of PTB, but it may not be readily available in most settings and results may take longer. • Sputum culture is recommended for patients suspected of smear-negative PTB in settings with a HIV prevalence of more than 1% in pregnant women, or a HIV prevalence of ≥5% in TB patients to conﬁrm the diagnosis of TB if newer diagnostic methods recommended by WHO such as Xpert MTB/RIF test are not available. • Sputum culture and drug susceptibility testing (DST) are recommended for patients with previous TB treatment, those suspected of having MDR-TB, or patients with Xpert MTB+/RIF+ test result. Other than sputum, cerebrospinal ﬂuid (CSF) and lymph node aspirate may be cultured in patients suspected of having TB meningitis or TB lymphadenitis respectively. Ultrasound (see Section 7) Features of abdominal TB on ultrasound include: • lymphadenopathy; ° multiple, discrete, enlarged (more than 1.5 cm) para-aortic or mesenteric nodes, matted nodes with central necrosis; • hepatosplenomegaly with or without multiple hypoechogenic nodules or abscesses; • ascites (free or loculated). Lymph node biopsy (see Section 7.2) ﬁne needle aspiration with cytology, AFB smear, and culture; open biopsy with pathology, AFB smear, and culture.

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HIV-testing Recommend HIV testing and counselling to all TB patients and patients suspected of having TB.4

Extrapulmonary TB TB lymphadenitis, pleural TB (usually unilateral), and disseminated (miliary) TB are the most common forms of EPTB. Pericardial TB and meningeal TB are less frequent.

Suspect disseminated TB in HIV-positive patients with rapid or marked weight loss, fever and night sweats

EPTB is more common in HIV-positive patients compared with HIV-negative patients. In HIV-positive patients, the presenting signs and symptoms might overlap with other HIV-related conditions, especially in patients with an advanced stage of HIV-infection. The Table: Summary of signs and symptoms of EPTB below summarizes when to suspect EPTB. Table: Case deﬁnitions for the diagnosis of TB1,3 Cases of TB TB case Deﬁnition used for diagnosis • A patient with M. tuberculosis complex identiﬁed from a clinical specimen either by conventional culture or by WHO-approved newer methods such as line probe assay or Xpert MTB/RIF* OR • Where there is lack of laboratory capacity to routinely identify M. tuberculosis complex, a patient with one or more initial sputum smear examinations positive for AFB, provided that there is a functional external quality assurance (EQA) system OR • A case in which a health worker (clinician or other medical practitioner) has diagnosed TB and has decided to treat the patient with a full course TB treatment. Where capacity to routinely identify M. tuberculosis complex is not available, a patient with one or more initial sputum smear examinations positive for acid-fast bacilli (AFB), provided that there is a functional external quality assurance (EQA) system with blind rechecking. In the absence of a functional qualityassured laboratory: • two or more initial sputum smear examinations positive for AFB OR • one sputum smear examination positive for AFB plus radiographic abnormalities consistent with active pulmonary tuberculosis as determined by a clinician OR • one sputum smear positive for AFB plus sputum culture positive for M. tuberculosis.

Smear-positive pulmonary tuberculosis (PTB+) Where newer WHOapproved tests are not available

4 Guidance on provider-initiated HIV testing and counselling in health facilities. WHO, 2007. Available at http:// www.who.int/hiv/pub/vct/pitc/en/index.html

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Cases of TB Where newer WHOapproved tests are not available Smear-negative pulmonary tuberculosis (PTB –)

Deﬁnition used for diagnosis At least 2 sputum specimens at the start of treatment are negative for AFB2 and culturepositive for M. tuberculosis. (If HIV prevalence is more than 1% in pregnant women or ≥5% in TB patients, sputum culture for M. tuberculosis should be performed in patients who are sputum smear-negative to conﬁrm the diagnosis of TB.) OR At least 2 sputum specimens negative for AFB plus radiographic abnormalities consistent with active tuberculosis, and a decision by a clinician to treat with a full course of anti-TB treatment, and a laboratory conﬁrmation or strong clinical evidence of HIV infection or, if HIV-negative (or unknown HIV status in low prevalence settings), no improvement in response to a course of broad spectrum antibiotics (excluding anti-TB drugs and ﬂuoroquinolones and aminoglycosides). One specimen from an extrapulmonary site smear-positive for AFB or a culture positive for M. tuberculosis OR Histological or strong clinical evidence consistent with active EPTB and laboratory conﬁrmation, or strong clinical evidence of HIV infection, and a decision by a clinician to treat with a full course of antituberculosis antibiotics. A patient with M. tuberculosis conﬁrmed to have resistance to both rifampicin and isoniazid identiﬁed from a clinical specimen, either by conventional DST or by a newer method such as line probe assay.

Extrapulmonary tuberculosis (EPTB)

Case of MDR-TB

* All TB cases diagnosed with Xpert MTB/RIF and rifampicin-susceptible, irrespective of smear result, should be registered as Xpert MTB/RIF-positive TB cases. All TB cases diagnosed with Xpert MTB/RIF and rifampicinresistant should be registered as Xpert MTB/RIF-positive rifampicin resistance. If isoniazid resistance is conﬁrmed by conventional or molecular techniques, the case should be registered as MDR-TB.

The algorithm below provides guidance for the diagnosis of smear-negative PTB in HIV-negative patients where Xpert MTB/RIF test or other WHO-approved new tests are not available.

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Figure: Algorithm for the diagnosis of AFB smear-negative PTB in HIVnegative patients where Xpert MTB/RIF test is not available5 All patients suspected of having PTB

Sputum microscopy for AFB Recommend HIV testing and counselling

2 negative sputum smears for AFB HIV-negative

Broad-spectrum antimicrobials (excluding anti-TB drugs and fluoroquinolones)

No improvement

Improved

Repeat sputum microscopy

All smears negative for AFB 1 or more positive smears Chest radiograph and physician’s judgment

No TB

Source: Modified from WHO, 2007

5 Improving the diagnosis and treatment of smear-negative pulmonary tuberculosis among adults and adolescents: Recommendations for HIV-prevalent and resource-constrained settings. WHO, 2007. Available at http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.379_eng.pdf

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Figure: Algorithm for the management of ambulatory HIV-positive patients with presumptive TB where Xpert MTB/RIF test is available3 Ambulatory TB suspect b HIV-positive c No danger signs a

Xpert MTB/RIF

Xpert MTB+/RIF+

Xpert MTB+/RIF-

Xpert MTB-/RIFPTB unlikely

a Among adults and adolescents living with HIV, a TB suspect is deﬁned as a person who reports any one of current cough, fever, weight loss or night sweats. b In all persons with unknown HIV status, HIV testing should be recommended according to national guidelines. In patients who are HIV-negative or remain HIV unknown (e.g. decline testing), a TB suspect is deﬁned according to national case deﬁnitions. A person with unknown HIV status can still be classiﬁed as HIV-positive if there is strong clinical evidence of HIV infection. c The danger signs include any one of: respiratory rate >30/minute, temperature >39°C, pulse >120/minute, and inability to walk unaided. d CPT = cotrimoxazole prophylaxis. See Section 13. e ART = antiretroviral therapy. All TB patients living with HIV are eligible for ART irrespective of CD4 count. See Section 13. f DST FLD+SLD = drug susceptibility test, ﬁrst-line drugs + second-line drugs. In low MDR-TB prevalence settings, a conﬁrmatory test for rifampicin resistance should be performed. g A chest X-ray can assist with the diagnosis of extra-pulmonary TB (e.g. pleural, pericardial) and help assess for other etiologies of respiratory illness. It should only be performed in those settings where the quality of the ﬁlm and its interpretation are assured. h Antibiotics (except ﬂuoroquinolones) to cover both typical and atypical bacteria should be considered. i A HIV treatment assessment includes WHO clinical staging and/or CD4 count to assess eligibility for antiretroviral therapy. See Section 13. j PCP = Pneumocystis jirovecii pneumonia.

1 visit

- Treat for MDR-TB d - CPT e - ART f - DST FLD+SLD

- Treat for TB d - CPT e - ART

Clinical assessment for EPTB or g other diseases with chest X-ray

2 visit

EPTB likely

EPTB unlikely

Treat for TB e ART d CPT

Treat for bacterial h infection i ART assessment d CPT

Treat for PCP i ART assessment d CPT

3 visit

No or partial response

Response

Reassess for TB Repeat Xpert MTB/RIF

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Figure: Algorithm for the diagnosis of TB in ambulatory patients in HIVprevalent settings where Xpert MTB/RIF test is not available Ambulatory patient with cough and no danger signs a

Sputum for AFB Recommend HIV testing and counselling

a The danger signs include any one of respiratory rate more than 30/minute, fever more than 39oC, pulse more than 120/minute or unable to walk unaided. b In the absence of a HIV test, classifying HIV status unknown into HIV-positive depends on clinical assessment, or national or local policy guidance. c AFB-positive is deﬁned as one or more sputum smears test positive. AFB-negative is deﬁned as two or more sputum smears test negative. d These investigations should be done at the same time in order to decrease the number of visits and speed up the diagnosis. Additional investigations for extrapulmonary TB may include lymph node aspirations for AFB microscopy and culture, and abdominal ultrasound. e HIV assessment includes HIV clinical staging, CD4 count if available. See Section 13. f PCP = Pneumocystis jirovecii pneumonia. g Antibiotics (except ﬂuoroquinolones) to cover both typical and atypical bacteria should be considered. h Advise to return for reassessment if symptoms recur.

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1st VISIT AFB-positive c

HIV-positive or status unknown

AFB-negative

2nd VISIT 3rd VISIT 4th VISIT

Treat for TB Cotrimoxazole prophylaxis e HIV assessment ART

TB likely

Chest X-ray , sputum AFB and culture e HIV assessment

TB unlikely

Treat for PCP e HIV assessment

Treat for bacterial infection e HIV assessment Cotrimoxazole prophylaxis

Response

No or partial response

Response

Reassess for TB

Treatment of TB

617

Table: Summary of signs and symptoms of EPTB Suspect Lymph node TB (peripheral) When Enlarged lymph node: • painless swelling • 2 cm or more in size • asymmetrical and localized • ﬁrm, ﬂuctuant, or ﬁstulated • cervical location common Weight loss, night sweats, fever What to do Recommend HIV testing and counselling Use WHO-approved newer testing method such as Xpert MTB/RIF test, otherwise send sputum for AFB if coughing Fine needle aspirate (see Section 7.2.5 for procedure) for AFB Excision biopsy if aspirate nondiagnostic Recommend HIV testing and counselling Use WHO-approved newer testing method such as Xpert MTB/RIF test, otherwise send sputum for AFB if coughing Aspirate and inspect* (Section 7.2.5) Start anti-TB treatment immediately if suggestive of TB, or if the only unusual feature is failure of aspirate to clot, or no other diagnosis by 7 days Recommend HIV testing and counselling Chest X-ray Use WHO-approved newer testing method such as Xpert MTB/RIF test, otherwise send sputum for AFB if coughing Cardiac ultrasound ECG if ultrasound not available Urgent aspiration if breathless (see Section 7.2.5 for procedure) Recommend HIV testing and counselling Abdominal tap Abdominal ultrasound might show lymphadenopathy Recommend HIV testing and counselling CSF analysis Use WHO-approved newer testing method such as Xpert MTB/RIF test, or send sputum for AFB if coughing Recommend HIV testing and counselling CT scan if available Offer empirical TB treatment See Section 10.9 Differential diagnosis See Section 10.5

Pleural effusion

High suspicion of TB if: • unilateral effusion • weight loss, night sweats, fever • evidence of TB elsewhere • aspirated ﬂuid is clear and straw coloured, and clots on standing in a tube without anticoagulants

See Section 10.6

Pericardial effusion

High suspicion of TB if: • lung ﬁelds clear (but may have bilateral pleural effusion) • weight loss, night sweats, fever, evidence of TB elsewhere

Abdominal TB

Abdominal distension, ascites

Tuberculous meningitis

Neck stiffness, fever, confusion, abnormal neurological ﬁndings

See Section 10.10b

Tuberculoma

Abnormal neurologic ﬁndings, fever, confusion, coma

See Section 10.10a

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Bone TB

TB can affect any bones but is most common in vertebrae Signs might vary based on involved bones In vertebral bone TB, back pain or signs of neurological deﬁcit, e.g. weakness, paraesthesia, paralysis, bowel or bladder dysfunction High suspicion of TB if: • weight loss, fever, and cough • abnormal chest X-ray (which can include miliary pattern) • enlarged spleen/liver • night sweats • anaemia

Recommend HIV testing and counselling Bone radiology Vertebral TB: X-ray of spine with vertebral collapse

Disseminated TB

Recommend HIV testing and counselling Chest X-ray Malaria blood ﬁlm Use WHO-approved newer testing method such as Xpert MTB/RIF test, or send sputum for AFB if coughing Suspect disseminated TB in febrile HIV-positive patients with wasting syndrome

See Section 10.6 for differential diagnosis of cough and chest X-ray ﬁndings

* The aspirate should be put into a plain tube (with no anticoagulant) in order to observe its appearance and clotting. A second aliquot should be placed into an anticoagulated tube so that differential WBC count and protein determination can be requested if there are any ﬁndings to suggest a non-TB diagnosis.

Diagnosis of TB in the seriously ill patient with danger signs HIV-positive patients with PTB and EPTB are at high risk of rapid clinical deterioration and death. At the primary facility level, use the following two algorithms for the diagnosis of TB in HIV-positive (or status unknown) patients or patients in HIV-prevalent settings who are suspected of having TB and present with danger signs. The ﬁrst algorithm is suitable where Xpert MTB/RIF testing is available, and use the second algorithm where laboratory capacity lacks Xpert MTB/RIF testing. Danger signs include: • respiratory rate >30 per minute • fever >39°C • pulse rate >120 per minute • inability to walk unaided.

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Figure: Algorithm for the diagnosis of TB in seriously ill patients at primary facilities in HIV-prevalent settings where Xpert MTB/RIF test is possible a

Ambulatory patient with cough and no danger signs

Sputum for AFB Recommend HIV testing and counselling

a Seriously ill refers to the presence of danger signs, including: respiratory rate >30/minute, temperature >39°C, pulse >120/minute, and inability to walk unaided. b Among adolescents and adults living with HIV, a TB suspect is deﬁned as a person who presents with any one of current cough, fever, weight loss, or night sweats. c In all with unknown HIV status, testing and counselling should be recommended according to national guidelines. In high HIV-prevalent settings, seriously ill patients should be tested using Xpert MTB/RIF as the primary diagnostic test regardless of HIV status. d The highest priority should be to provide the patient with life-sustaining supportive care and treatment, such as oxygen and parenteral antibiotics. If life-sustaining therapy is not available at the initial point-of-care, the patient should be transferred immediately to a higher level facility before further diagnostic testing. e Antibiotics (except ﬂuoroquinolones) to cover both typical and atypical bacteria should be considered. f PCP = Pneumocystis jirovecii pneumonia. See section 13. g CPT = cotrimoxazole preventive therapy. See Section 13. h ART = antiretroviral therapy. All TB patients living with HIV are eligible for ART irrespective of CD4 count. See Section 13. i DST FLD+SLD = drug susceptibility test, ﬁrst-line drugs + second-line drugs. In low MDR-TB prevalence settings, a conﬁrmatory test for rifampicin resistance should be performed. j A HIV treatment assessment includes WHO clinical staging or CD4 count to assess eligibility for ART. See Section 13. k Additional investigations for TB may include chest X-ray, liquid culture of sputum, lymph node aspiration for acid-fast bacilli microscopy and culture, abdominal ultrasound. Non-tuberculosis mycobacterial infection should be considered in the differential diagnosis of patients who have a negative Xpert MTB/RIF but a sputum or extrapulmonary specimen with AFB.

1st VISIT AFB-positive c

HIV-positive or status unknown

AFB-negative

2nd VISIT 3rd VISIT 4th VISIT

Treat for TB Cotrimoxazole prophylaxis e HIV assessment ART

TB likely

Chest X-ray , sputum AFB and culture e HIV assessment

TB unlikely

Treat for PCP e HIV assessment

Treat for bacterial infection e HIV assessment Cotrimoxazole prophylaxis

Response

No or partial response

Response

Reassess for TB

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Figure: Algorithm for the diagnosis of TB in seriously ill patients in HIVprevalent settings at ﬁrst-level facilities where Xpert MTB/RIF test is not available HIV-positive (or status unknowna) patient with danger signs and suspected of having TBb

Referral to higher level facility

Immediate referral not possible

Parenteral antibiotic treatment Sputum for AFB and culture Chest X-ray

Parenteral antibiotic treatment Sputum for AFB and culture Recommend HIV testing if not done d Consider treatment for PCP

No TB

Sputum positive, culture positive, suggestive X-ray or TB likely

One or more smear AFB positive

2 smears AFB negative

Reassess for other HIVrelated disease

Start TB treatment and cotrimoxazole prophylaxis Complete antibiotics ART

Improvement after 3–5 days

No improvement after 3–5 days

TB unlikely

Reassess for e TB

Start TB treatment Complete antibiotics Refer for HIV and TB care

a When HIV testing is not possible, classifying a patient as HIV-infected depends on clinical assessment in accordance with national guideline recommendations. b Danger signs include respiratory rate more than 30/minute, fever more than 39°C, pulse more than 120/minute, and inability to walk unaided. c Antibiotics (except ﬂuoroquinolones) to cover both typical and atypical bacteria should be considered. d Pneumocystis jirovecii pneumonia. See Section 13. e Assessment includes HIV clinical staging, CD4 count if available, ART, and HIV care.

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At the district hospital, patients presenting with severe illness will be identiﬁed during Quick Check as having emergency signs of airway, breathing, circulation, and consciousness, and emergency treatments should be given (see Quick Check). After emergency interventions, urgent treatments will be given based on the most likely or most life-threatening diagnosis (see Section 3.0). For patients with severe respiratory distress, shock, or altered consciousness who also have fever, treatment will be empirical antibiotics for pneumonia, septic shock, or meningitis, respectively. • If a PLHIV (or status unknown in high HIV-prevalent settings) has suspected septic shock, TB must be considered, especially if there is malnutrition and weight loss. See Section 3.1.5 for guidance on management of suspected septic shock. Perform all appropriate TB investigations and HIV testing in severely ill patients (see Section 15.2). Consider early empirical TB treatment in critically ill PLHIV if there is a high suspicion for disseminated disease causing shock, based on suggestive chest X-ray or clinical judgment. This may mean simultaneous treatment for TB and bacterial infection. • If a PLHIV (or status unknown in high HIV prevalent settings) has suspected severe pneumonia, then TB must be considered. See Section 3.2.3 for guidance on management of suspected severe pneumonia. Perform all appropriate TB investigations and recommend HIV testing and counselling (see Section 15.2). Consider early empirical treatment for TB in critically ill PLHIV with severe pneumonia, based on suggestive X-ray or clinical judgement. This may mean simultaneous treatment for bacterial pneumonia, PCP, and TB. • Consult senior clinician.

Differential diagnosis of PTB in PLHIV In a HIV-positive patient consider the following possible diagnoses: • Acute bacterial pneumonia: Common in HIV-positive patients and often has a short history of onset. • PCP is very difﬁcult to distinguish from PTB in a severely ill patient with advanced HIV infection.

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DDx: PTB in PLHIV by stage of immunosuppression Stage of HIV-infection HIV clinical stage (1–2) CD4 >200 Pulmonary TB Clinical picture Cough Productive sputum Weight loss, with or without fever, night sweats, breathlessness, chest pain Upper lobe inﬁltrates Cavitation Nodular or patchy shadows Might not have abnormal ﬁndings Dry cough Weight loss and fever TB should be excluded in any patient presenting with cough, fever, weight loss, or night sweats Lower lobe inﬁltrates, no cavitation Often mediastinal lymphadenopathy or pleural effusion Sometimes miliary or interstitial pneumonia Might not have abnormal ﬁndings AFB often negative HIV clinical stage (3–4) CD4 <200

X-ray appearance

Sputum smear for AFB or newer WHOapproved method such as Xpert MTB/RIF test

AFB often positive

Sputum positive for Xpert testing

Pneumocystis pneumonia Clinical picture Unlikely Fever Dry cough Dyspnoea (progressive and exertional) Subacute and insidious onset Bilateral diffuse inﬁltrates (ground glass appearance) May be normal May have ﬁndings of spontaneous pneumothorax Not useful

X-ray appearance

Laboratory Acute bacterial pneumonia Clinical picture Productive cough High fever Patient appears ill Short history of onset Lobar inﬁltrate but may be less apparent Might be negative Gram stain may be positive May also be AFB-positive Xpert MTB/RIF testing negative

Productive cough High fever Patient appears ill Short history of onset Lobar inﬁltrate Might be negative Xpert MTB/RIF testing negative

X-ray appearance Sputum smear or newer WHO-approved method such as Xpert MTB/RIF test

TB in pregnant and postpartum women • Pregnant and postpartum women are at risk of developing TB. • The symptoms of TB are the same in pregnant and postpartum women compared with non-pregnant women. • All HIV-positive pregnant women should be screened for TB at each visit.

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15.3 Treatment of TB Standardized TB treatment regimens Standardized treatment means that all patients in a deﬁned group receive the same treatment regimen. Standard regimens have the advantage of reducing the risk of emergence of drug resistance. These regimens facilitate estimates of drug needs, procurement, distribution and monitoring, support regular drug supply when patients move from one area to another, and make outcome evaluation convenient and comparable across different facilities. It is important that clinicians follow the national standardized TB treatment regimens. Good clinical practice • TB treatment regimen should be based on recommendations of national TB guidelines. • Once started, a full course of TB treatment is indicated for all deﬁnite cases of TB and those started based on a clinician’s decision.

Standard code for TB treatment regimens A standard code for TB treatment regimens includes a number before a phase that is the duration of that phase in months. Letters in parenthesis indicate ﬁxed-dose combinations (FDCs) of those drugs. A subscript number (e.g. 3) after a letter or letters in parentheses indicates the number of doses of that drug per week. If there is no subscript number, treatment is daily (or for 6 days per week, excluding, for instance, Sunday). For example, 2(HRZE)/4(HR): this regimen uses two FDCs, each in separate parenthesis. In the intensive phase of 2 months (i.e. the number before the ﬁrst parenthesis), each day the patient would take an FDC tablet of isoniazid, rifampicin, pyrazinamide, and ethambutol (i.e. the drugs in the ﬁrst parentheses). In the continuation phase, the patient would take FDCs of isoniazid and rifampicin (i.e. the drug in the second parentheses) daily for 4 months (i.e. the number before the second parenthesis).

First-line anti-tuberculosis drugs A TB treatment regimen consists of 2 phases – an intensive phase and a continuation phase. Treatment for PTB should be a regimen containing 6 months of rifampicin. Whenever feasible, patients with PTB should receive treatment daily throughout the course of therapy. The alternative recommendations can be used as long as the patient is receiving directly observed therapy of every dose, and is NOT living with HIV or living in a HIV-prevalent setting. See the Table: Standard anti-TB regimen and dosing frequency in new TB cases on the next page.

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Table: Standard anti-TB regimen and dosing frequency in new TB cases1 Regimen and dosing frequency for new TB patients: 2HRZE/4HR Intensive phase 2 months of HRZE Daily Daily 3 times a week Continuation phase 4 months of HR Daily 3 times a week 3 times a week

Comment Optimal Acceptable alternative for any new TB patient receiving directly observed therapy. Acceptable alternative if the patient is receiving directly observed therapy and is NOT living with HIV or from a HIV-prevalent setting.

H= isoniazid R = rifampicin Z = pyrazinamide E = ethambutol S = streptomycin WHO no longer recommends omission of ethambutol during the intensive phase of treatment for patients with non-cavitary, smear-negative PTB or EPTB who are HIV-negative.

Table: Dose of ﬁrst-line anti-tuberculosis drugs for adults1 Recommended dose Daily Drug isoniazid rifampicin pyrazinamide ethambutol streptomycin* Dose and range (mg/kg body weight) 5 (4–6) 10 (8–12) 25 (20–30) 15 (15–20) 15 (12–18) Maximum (mg) 300 600 — — — 3 times per week Dose and range (mg/kg body weight) 10 (8–12) 10 (8–12) 35 (30–40) 30 (25–35) 15 (12–18) Daily maximum (mg) 900 600 — — 1000

* Patients over 60 years of age may not be able to tolerate more than 500–750 mg daily, so some guidelines recommend reduction of the dose to 10 mg/kg/day in patients in this age group. Patients weighing less than 50 kg may not tolerate doses above 500–750 mg daily.6

6 Essential Medicines List and WHO Model Formulary. WHO, 2008. Available at http://www.who.int/selection_ medicines/list/en/

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Table: Registration group by outcome of most recent TB treatment1 Registration group (any anatomical site) New Previously treated Relapse Failure Default Transfer in: A patient who has been transferred from another district to continue treatment. Other + Treatment completed + + + or Treatment failed Defaulted Still on treatment Bacteriology + or Cured Outcome of most recent prior treatment

+ or -

All cases that do not ﬁt the above deﬁnitions: • not known whether or not previously treated • previously treated but outcome is unknown • returned to treatment with AFB smearnegative PTB or bacteriologically negative EPTB

+ bacteriology indicates positive AFB smear, culture, or other newer means of identifying M. tuberculosis. - bacteriology indicates that any specimens tested were negative.

Category of patient for registration In order to identify patients at increased risk of acquired drug resistance, and to recommend appropriate treatment, deﬁne a case based on whether or not the patient has previously received TB treatment.

TB treatment in special situations The next table summarizes special situations that might require consideration during TB treatment. Rifampicin is a strong inducer of the cytochrome P450 (a liver enzyme), and lowers the plasma concentrations of boosted protease inhibitors (bPIs). All bPIs, at standard doses, are contraindicated with rifampicin. See Section 13.10 for TB/ HIV co-management.

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Table: Anti-TB treatment regimens in special situations Conditions Pregnancy Special considerations Avoid streptomycin during pregnancy. Streptomycin is ototoxic to the fetus. Assess women of childbearing age for current or planned pregnancy before starting TB treatment. Advise pregnant women with TB that successful treatment is important for their own health and the health of their baby. Support and monitor adherence to treatment. For the infant, offer INH prophylaxis for at least 3 months beyond the time the mother is considered non-infectious. BCG vaccination should be given at completion of course of isoniazid preventive therapy. Advise her to use another contraceptive while taking rifampicin.. Monitor for any hepatotoxic reactions.

Breastfeeding

Give a full course of TB treatment to the mother. Timely and proper TB treatment of the mother is important to reduce risks of TB transmission to the infant. Rifampicin can decrease efﬁcacy of oral contraceptives. Give the usual regimen for patients with chronic viral hepatitis, past acute hepatitis, and excessive alcohol consumption. Advanced liver disease.

Women on oral contraceptives Liver disorder

Obtain liver function test (LFT) at the start of treatment, if possible. If ALT level is more than 3 times the normal level, consider alternative TB treatment regimens per your national guideline recommendations. Give pyridoxine for patients with severe renal insufﬁciency.

Renal failure and severe renal insufﬁciency

Avoid streptomycin. Adjust dosage of ethambutol and pyrazinamide.

Empirical treatment in EPTB Culture, biopsy or other investigations (such as ultrasound, CT scan) may not readily be available in most resource-limited settings. With the exception of lymph node TB, which usually can be conﬁrmed through ﬁne needle aspiration, most patients with EPTB are managed without bacteriological or histological conﬁrmation, based on the decision by a clinician to treat with a full course of TB treatment. TB treatment should be started as soon as other common conditions have been excluded. Do not delay treatment until culture or other investigations are available, especially in patients suspected of TB pericarditis, TB meningitis, or disseminated TB, and in HIV-positive patients.

Adjuvant corticosteroids Corticosteroids are recommended for HIV-negative patients with TB meningitis. Dose: 1 mg/kg/day, to be slowly tapered down over 4–6 weeks.

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15.4 Monitor TB treatment Monitor response to TB treatment Monitor all patients on TB treatment to assess their response to treatment. Link with existing community DOTS mechanisms – conﬁrm that the medication is being taken as instructed, by direct observation of each dose. • Monitor the patient’s weight. • Clinical improvement should be seen within 1 month of initiation of TB treatment. If this is not attained, review the case, check adherence and reconsider the diagnosis. • For smear-positive pulmonary TB patients, monitor sputum smear microscopy based on national guideline recommendations. Molecular tests, including Xpert MTB/RIF, are not suitable for patient monitoring as these tests also detect DNA from non-viable bacilli. • There is a higher recurrence rate of TB in HIV-positive than in HIV-negative TB patients. Monitor treatment response in all patients on TB treatment. • In patients with EPTB, response to treatment can only be monitored clinically. As in cases of smear-negative PTB, the weight of the patient is important to monitor response to treatment. • Monitor and support treatment adherence.

Manage drug side-effects Few patients on TB treatment experience adverse drug effects. Monitor patients clinically so that adverse effects can be detected early and managed promptly. Routine laboratory monitoring is not necessary. Inform patients about possible side-effects, and what to do if they experience them. Isoniazid-induced peripheral neuropathy usually presents as numbness, tingling or burning sensation of the feet. It more commonly occurs in pregnant women and in persons with one of the following: • HIV infection • alcohol abuse • malnutrition • diabetes • chronic liver disease • renal failure. Give pyridoxine 10 mg daily, with anti-TB drugs, or as per national TB guideline recommendations for these groups of patients.

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Table: Symptom-based approach to managing side-effects of anti-TB drugs Side-effects Major Skin rash with or without itching Drug(s) probably responsible Management

Stop responsible drug(s), manage the condition S, H, R, Z Stop anti-TB drugs. If itching without rash, try antihistamine, avoid drying of skin, observe the patient closely and continue anti-TB treatment. If patient has itching with rash, stop all anti-TB drugs and consider to re-introduce one by one per your country TB guideline recommendations. Stop streptomycin Stop streptomycin Stop anti-TB drugs Stop anti-TB drugs

Deafness (no wax on otoscopy) Dizziness (vertigo and nystagmus) Jaundice (other causes excluded), hepatitis Confusion (suspect druginduced acute liver failure if jaundice present) Visual impairment (other causes excluded) Shock, purpura, acute renal failure Decreased urine output Minor Anorexia, nausea, abdominal pain

streptomycin streptomycin H, Z, R Most anti-TB drugs

ethambutol rifampicin streptomycin

Stop ethambutol Stop rifampicin Stop streptomycin

Continue anti-TB drugs; check drug doses pyrazinamide, rifampicin, isoniazid Give drugs with small meals or just before bedtime. Advise patient to swallow pills slowly with small sips of water. If symptoms persist or worsen, or there is protracted vomiting or signs of bleeding, consider the side-effect to be major and refer to a clinician urgently. Aspirin or nonsteroidal anti-inﬂammatory drug, or paracetamol Pyridoxine 50–75 mg daily Reassurance. Give drugs before bedtime. Reassurance. Inform the patient this may happen when starting treatment and is normal. Change from intermittent to daily rifampicin.

Joint pains Burning, numbness or tingling sensation in the hands or feet Drowsiness Orange/red urine Flu syndrome (fever, chills, malaise, headache, bone pain)

pyrazinamide isoniazid isoniazid rifampicin Intermittent dosing of rifampicin

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Determine TB treatment outcomes At the end of the treatment course for each patient with sputum smear-positive PTB, the treatment outcome should be recorded in the district TB register. The following table illustrates the standard deﬁnitions of TB treatment outcomes. Refer to your national TB guidelines. Table: Standard deﬁnitions of TB treatment outcomes Outcomea Cure Treatment completed Treatment failure Deﬁnitiona Sputum smear or culture positive at the beginning of TB treatment, but which was smear or culture negative in the last month of treatment and on at least 1 previous occasion. Completed treatment but does not have a negative sputum smear or culture result in the last month of treatment and on at least 1 previous occasion.b Sputum smear or culture is positive at 5 months or later during treatment. Also included are MDR patients at any point of time during the treatment, whether they are smear negative or positive. Dies for any reason during the course of treatment. Treatment was interrupted for 2 consecutive months or more. Transferred to another unit and for whom the treatment outcome is not known. A sum of cured and completed treatment.c

Died Default Transfer out Treatment successc

a Applies to pulmonary smear-positive and smear-negative patients, and to patients with EPTB. b The sputum examination may not have been done, or the results may not be available. c For smear or culture positive patients only.

Good clinical practice Follow national TB guideline recommendations.

15.5 Drug-resistant TB (DR-TB)7 DR-TB is diagnosed if sputum culture shows in vitro growth of M. tuberculosis in the presence of one or more anti-TB drugs. Prompt diagnosis and effective treatment of DR-TB is important to reduce the risks of further spread and for a good treatment outcome. Multiple factors related both to the health-care delivery system and to the patient play a role in the emergence of a DR-TB strain, of which previous TB treatment is a strong determinant. MDR-TB is diagnosed in a patient with M. tuberculosis who is conﬁrmed to have resistance to both rifampicin and isoniazid identiﬁed from a clinical specimen, either by conventional DST or by a newer diagnostic method recommended by WHO, such as line probe assay. Rifampicin resistance is a reliable proxy for MDRTB in high burden settings and its detection by Xpert MTB/RIF is usually enough to start a patient on a second-line TB regimen. These patients should provide an additional sputum specimen for conventional culture and DST against other ﬁrstand second-line anti-TB drugs, and their treatment should be adjusted based on

7 Guidelines for the programmatic management of drug-resistant tuberculosis. WHO, 2011. Available at http:// whqlibdoc.who.int/publications/2011/9789241501583_eng.pdf

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the results of further DST results. However, in low MDR-TB-prevalence settings, testing new TB cases not at risk for MDR-TB will result in a low positive predictive value for rifampicin resistance, and will require that rifampicin resistance detected by Xpert MTB/RIF be conﬁrmed ﬁrst by conventional DST or line probe assay. • Rapid DST of isoniazid and rifampicin or of rifampicin alone is recommended at the time of diagnosis where resources permit. • Where resources are limited, the following patients can be prioritized for rapid DST for isoniazid and rifampicin or rifampicin alone at the time of diagnosis: ° those who fail re-treatment; ° those exposed to a known DR-TB case; ° those who fail antituberculosis treatment in the private sector; ° those who remain sputum smear-positive at month 2 or 3; ° those exposed in institutions that have DR-TB outbreaks or a high DR-TB prevalence; ° those resident in areas with high DR-TB prevalence; ° those with a history of using anti-TB drugs of poor or unknown quality; ° those on treatment in programmes that operate poorly (especially programmes with recent or frequent drug stock-outs); ° those with certain co-morbidities, e.g. malabsorption, substance dependency disorders. If MDR-TB is highly prevalent in PLHIV, they should be screened for MDR-TB with a DST if diagnosed with active TB. Patients at high risk of MDR-TB are those: • with probable treatment failure or whose ﬁrst-line treatment has failed; • who developed TB after contact with a documented MDR-TB case; • who are relapsing or returning from their second or subsequent course of treatment. Patients returning after defaulting or relapsing from their ﬁrst course of treatment have medium risk of MDR-TB. Table: Summary of recommended TB treatment regimens Standard treatment New patients Retreatment with ﬁrst-line drugs MDR- drug-susceptibility testingTB 2HRZE/4HR 2HRZES/1HRZE/5HRE Follow national recommendation for treatment of MDR-TB

MDR-TB treatment regimen Before or at the start of treatment, all previously treated TB patients and patients suspected of having MDR-TB should have sputum, as well as appropriate specimens for EPTB, obtained for culture and DST. Referral of the patients or transportation of specimens might be needed if culture and DST are not available in the hospital. Rapid, molecular-based DST results are obtainable in 1 to 2 days, and will guide choice of treatment. This minimizes delay before effective treatment. Where rapid

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molecular-based DST is not available, the choice of regimen should be guided by conventional specimen culture. This necessitates initiation of empirical treatment while waiting for the result. Refer to national guideline recommendations for second-line anti-TB regimens. Once the diagnosis of MDR-TB is conﬁrmed (through culture and DST), patients can be treated with a standardized or individualized regimen, depending on the TB and MDR-TB treatment guideline recommendations of the country.

MDR-TB and HIV infection There is a high rate of mortality in patients coinfected with MDR-TB and HIV. Early diagnosis of MDR-TB and HIV, prompt treatment with adequate regimens, good patient support, and strong infection control measures are all essential components in the management of MDR-TB in HIV-positive patients. Good clinical practice • MDR-TB contact investigation should be given high priority • Close contacts of MDR-TB patients should receive careful clinical follow-up

Manage common problems in patients with MDR-TB8 Common problems Cough or difﬁcult breathing Cough due to TB may not improve for several months after starting MDR-TB therapy. Patient may wheeze as lungs scar during healing. Exclude superimposed bronchitis or pneumonia, consider PCP if patient is HIV-positive. • If patient has recently started ART, consider IRIS. Dangerous if large (patients may die of asphyxiation, not blood loss) or if TB has not been treated. • No special treatment for haemoptysis except for TB treatment. Cough suppressant (e.g. codeine) may decrease the frequency of episodes. • May continue for months after starting MDRTB therapy. Chronic haemoptysis with small amounts of blood is not dangerous, and will resolve slowly as the lungs heal. Fever due to TB may not improve for several months after starting MDR-TB therapy. Consider common causes of fever if patient has recently started ART. New fevers may be a sign of IRIS. Prevent dehydration: increase ﬂuid intake. Paracetamol, but avoid excessive doses. Tepid sponging if patient likes it. See Section 10.6 for differential diagnosis.

Haemoptysis

Persistent fever

8 Management of MDR-TB: A ﬁeld guide. WHO and Partners in Health, 2009. Available at http://whqlibdoc.who.int/ publications/2009/9789241547765_eng.pdf

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Persistent nausea or vomiting

Usually caused by ethionamide or paraaminosalicylic acid (PAS). Nausea due to AZT is usually self-limiting. Ethionamide has a direct toxic effect on the stomach lining and nausea is usually immediate. PAS toxicity is usually more delayed in onset: both have a “dose-dependent” effect. May be caused by PAS. If HIV-positive, consider chronic infectious diarrhoea and treat empirically.

See Section 10.7 for differential diagnosis and management of nausea and vomiting.

Persistent diarrhoea

Increase ﬂuid intake to prevent dehydration. Give ORS if large volume diarrhoea. Give constipating drug unless blood in stool or fever or elderly. Advise on special care of the rectal area. Advise on a supportive diet for patients with diarrhoea. See Section 10.10a for differential diagnosis. See Section 10.11 for differential diagnosis.

Peripheral neuropathy Severe depression, anxiety or psychosis

Many TB and HIV drugs can cause burning or tingling sensations. Usually due to terizidone or cycloserine. If due to EFV, consider switching to NVP. Symptoms usually improve when the dose of cycloserine is decreased. Stop cycloserine immediately if patient is suicidal or psychotic. Decreasing the dose of cycloserine may increase the risk of treatment failure. The injectable drugs, particularly capreomycin, can cause hypokalaemia. This is due to their direct effect on the kidneys. The kidneys start to excrete large amounts of electrolytes, the most important of which is potassium.

Hypokalaemia (low potassium)

See Section 5.2 for differential diagnosis.

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16. Assessment and therapy for alcohol use disorders Table of contents 16.1 Deﬁnitions of hazardous and harmful alcohol use and alcohol dependence . . . . 16.2 Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alcohol Use Disorders Identiﬁcation Test (AUDIT) . . . . . . . . . . . . . . . . . . Brief assessment using AUDIT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laboratory ﬁndings suggestive of harmful alcohol use or alcohol dependence . 16.3 Classify, then advise and treat the patient . . . . . . . . . . . . . . . . . . . . . . . . If the AUDIT score is 8–19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . If the AUDIT score is ≥20 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Special advice for pregnant patients . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of interventions by classiﬁcation of alcohol use disorder . . . . . . . . 16.4 Brief interventions for those with hazardous or harmful drinking . . . . . . . . . . . FLAGS approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.5 Treatment and care for those with alcohol dependence . . . . . . . . . . . . . . . . Withdrawal management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Relapse prevention after withdrawal from alcohol . . . . . . . . . . . . . . . . . . Psychosocial support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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16. Assessment and therapy for alcohol use disorders1 This Section outlines how district-level clinicians (and their teams) can provide services to reduce the harm caused by alcohol. Most of these services can be provided at the primary-care level and by health workers who are supervised by the district clinician. For most patients management consists of a brief assessment and intervention. A 5-minute intervention session, described below, can lead to a substantial reduction in a person’s alcohol use. More intensive services may be required for alcohol-dependent patients. Alcohol use varies widely from country to country and from person to person. In some countries alcohol is prohibited or is rarely consumed; in others a high proportion of the adult population drinks alcohol to some extent. There is no level of alcohol consumption that is without any health risk. Some patterns and levels of alcohol consumption are associated with higher health risks than others. Alcohol use disorders are a major cause of poor health and social problems. They cause or contribute to a wide range of acute and chronic physical and mental disorders. In many countries a high proportion of people attending primary and district hospitals and clinics use alcohol hazardously or harmfully; and yet alcohol use disorders often are not identiﬁed or treated. Patients may even be unaware of the role of alcohol in their problems. Screening for alcohol use disorders and offering advice and help accordingly can assist patients to reduce or cease alcohol consumption and reduce alcohol related harm. Management of acute alcohol withdrawal and alcohol intoxication are described in Section 3.7.

16.1 Deﬁnitions of hazardous and harmful alcohol use and alcohol dependence Hazardous alcohol consumption is a pattern of alcohol use that puts a person at risk of harmful consequences, such as injuries, mental disorders, liver and cardiovascular diseases, problems in relationships and at work, and other problems. Hazardous alcohol use includes but is not limited to: • having on a daily basis more than 4 drinks (men) or 2 drinks (women); • having more than 5 drinks on a single occasion; • drinking on more than 4 days per week • using alcohol when ° driving or operating machinery ° pregnant or breastfeeding ° taking medications that react with alcohol ° there are medical conditions present that are made worse by alcohol. 1 mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-specialized Health Settings. WHO and mhGAP Evidence Resource Centre, 2010. Available at http://www.who.int/mental_health/ evidence/mhGAP_intervention_guide/en/index.html. The mhGAP Guidelines and the mhGAP-IG will be reviewed and updated in 5 years. Any revision and update before that will be made to the online version of the document.

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Harmful alcohol use is a pattern of alcohol consumption that is causing damage to health. The degree of hazard and the degree of harm vary not only according to the amount of alcohol consumed but also according to the pattern of consumption and individual factors such as the age, gender, body weight, and medical status of the individual. Alcohol intoxication is associated with impaired thinking and reactions, which put that person at risk of injuries and other harms. Alcohol has disinhibiting effects that can affect decisions about having sex as well as affecting skills for negotiating condom use and their correct use. Together, these impairments can result in unsafe sex and condom use accidents, with resulting transmission of HIV and other sexually-transmitted illnesses (STIs). Acute problems, such as trauma or unsafe sex, may occur after a session of alcohol consumption. Chronic medical and social problems may be induced or exacerbated by repeated alcohol use over a period of time. Even in amounts that do not cause acute intoxication, alcohol use can still cause long-term harm to health. In the long term, harmful and hazardous alcohol use can result in a range of cancers, injuries, and infections and cause serious diseases in nearly every organ system in the body (e.g. liver cirrhosis, pancreatitis and neurological diseases) as well as social problems such as domestic violence, unemployment ,and occupational difﬁculties. Harmful use of alcohol is a pattern of alcohol consumption that is causing actual physical or mental problems but has not reached the point of being considered alcohol dependence. When harmful use of alcohol results in alcohol dependence, the latter diagnosis is made in preference. Alcohol dependence is a disorder with a psychological and physiological drive to consume alcohol, even in the face of serious alcohol-related harm. The diagnosis of alcohol dependence is based on several key symptoms, which include a strong (often overpowering) desire to drink, difﬁculties in controlling drinking behaviour, progressive neglect of alternative pleasures or interests, evidence of tolerance to alcohol, and withdrawal features when stopping or trying to reduce drinking. People with alcohol dependence have a repetitive pattern of drinking large amounts of alcohol and ﬁnd it difﬁcult to limit their consumption. Alcohol withdrawal can be a medical emergency (see Section 3.7 Acute alcohol withdrawal).

16.2 Assessment The earlier that hazardous or harmful drinking is identiﬁed or a diagnosis of alcohol dependence is made, the better the response to intervention. A systematic assessment enables detection of hazardous alcohol use, harmful alcohol use, and alcohol dependence syndrome. In an assessment of substance use, it is important to address the patient in an empathic and non-judgemental way and to be sensitive to the patient’s cultural background and situation. This encourages the patient to be open and to report their substance use accurately. The ability to elicit this information will be diminished if the health worker’s personal views about substance use are communicated in the interaction with a patient, Review of the patient’s records for previous evidence of hazardous drinking or alcohol use disorders can provide valuable information.

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Alcohol Use Disorders Identiﬁcation Test (AUDIT)2 The AUDIT was developed as a simple method of screening for excessive drinking and to assist brief assessment. It can help identify excessive drinking as the cause of the presenting illness. It provides a framework for intervention to help risky drinkers reduce or cease alcohol consumption and thereby avoid the harmful consequences of drinking. The AUDIT also helps to identify alcohol dependence and some speciﬁc consequences of harmful drinking. Of utmost importance for screening is the fact that people who are not dependent on alcohol may stop or reduce their alcohol consumption with appropriate assistance and effort. The AUDIT is particularly designed for health workers to use in a range of health settings.

Brief assessment using AUDIT (see Figure AUDIT below) 1. Be alert to possible alcohol misuse. Alcohol problems often are missed and untreated. Many common symptoms prompt suspicion of alcohol misuse. These include: • appearing to be under the inﬂuence of alcohol (e.g. smells of alcohol or looks intoxicated), tiredness, dyspepsia, anorexia, vomiting, diarrhoea, and headaches; • accidents at work or home and difﬁculties carrying out usual work, school, domestic, or social activities; • psychological symptoms, such as anxiety and depression and repeated requests for medical certiﬁcates of absence from work; these may have alcohol as the underlying cause. Think about alcohol use in every patient. 2. Ask each patient about alcohol use: “How often do you have a drink containing alcohol?” (see AUDIT question 1). If the patient indicates that they do not drink alcohol, then just ask questions 9 and 10 to see if they have had a problem in the past (see AUDIT question 9). 3. If patients drink alcohol, determine the amount and pattern of alcohol use. Ask, “How many drinks containing alcohol do you have on a typical day when you are drinking?” (AUDIT question 2) and “How often do you have 6 or more drinks on one occasion?”(AUDIT question 3). Ask about both commercial (i.e. purchased) alcohol and domestic or illicit alcohol (i.e. home-produced alcohol). 4. If the score for the ﬁrst 3 AUDIT questions is 3 or more (or if there is any suspicion of alcohol misuse (symptoms or signs possibly due to alcohol), complete the full AUDIT questionnaire. Add up the AUDIT scores. An AUDIT score of 8–12 indicates hazardous or harmful drinking. A score of ≥13 suggests alcohol dependence. This information is sufficient to decide whether to offer the patient a brief intervention for hazardous or harmful alcohol use.

2 The Alcohol Use Disorders Identiﬁcation Test: Guidelines for Use in Primary Care, 2nd ed. WHO, 2001. Available at http://whqlibdoc.who.int/hq/2001/WHO_MSD_MSB_01.6a.pdf

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Figure: AUDIT − Alcohol Use Disorders Identiﬁcation Test questionnaire Please select an answer for each of the 10 questions below and total the scores. 1. How often do you have a drink containing alcohol? [0] Never [1] Monthly or less [2] 2–4 times a month [3] 2–3 times a week [4] 4 or more times a week

2. How many drinks containing alcohol do you have on a typical day when you are drinking? [0] 0, 1 or 2 [1] 3 or 4 [2] 5 or 6 [3] 7 to 9 [4] 10 or more

3. How often do you have 6 or more drinks on one occasion? [0] Never [1] Less than monthly [2] Monthly [3] Weekly [4] Daily or almost daily

4. How often during the last year have you found it difﬁcult to get the thought of alcohol out of your mind? [0] Never [1] Less than monthly [2] Monthly [3] Weekly [4] Daily or almost daily

5. How often during the last year have you found that you were not able to stop drinking once you had started? [0] Never [1] Less than monthly [2] Monthly [3] Weekly [4] Daily or almost daily

6. How often during the last year have you been unable to remember what happened the night before because you were drinking? [0] Never [1] Less than monthly [2] Monthly [3] Weekly [4] Daily or almost daily

7. How often during the last year have you needed a drink ﬁrst thing in the morning to get yourself over a heavy drinking session? [0] Never [1] Less than monthly [2] Monthly [3] Weekly [4] Daily or almost daily

8. How often during the last year have you had a feeling of guilt or remorse after drinking? [0] Never [1] Less than monthly [2] Monthly [3] Weekly [4] Daily or almost daily

9. Have you or someone else been injured as a result of your drinking? [0] No [2] Yes, but not in the last year [4] Yes, during the last year

10. Has a friend, or relative, or doctor, or other health worker been concerned about your drinking or suggested that you cut down? [0] No [2] Yes, but not in the last year [4] Yes, during the last year

Total score: [ ] Scores from 8–10 suggest hazardous or harmful drinking. Scores of 13 or more suggest the likelihood of alcohol dependence.

Use this AUDIT version in face-to-face interviews. The questionnaire can be selfadministered, in which case the score for each response should be omitted.

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Further assessment A more comprehensive assessment of alcohol use and its complications may be necessary in some patients, especially those with suspected alcohol dependence. Ask the patient about the following: 1. Alcohol use • the amount of alcohol (in grams, standard drinks or bottles, cans, or other containers) that the person consumes in a session of drinking, or during a day; • the frequency of drinking, e.g. the number of days per week or month when alcohol is consumed; • the pattern of drinking; • the duration of drinking overall – in months or years; • the time of their last drink; • the typical drinking context, e.g. at home, in a local gathering, in a club or licensed premises, in a public place. 2. Alcohol dependence • difﬁculty in controlling the amount of alcohol consumed in an episode of drinking; • giving up activities or responsibilities in favour of drinking; • increased tolerance to alcohol; • withdrawal symptoms when not drinking; • previous attempts to stop. 3. Alcohol problems • physical health problems, such as liver disease, neuropathy; • anxiety, depression, or suicide attempts; • social and legal problems from alcohol.

What is a standard drink? 1 unit (10 gm alcohol) of alcohol. Show pictures of common local drinks (for local adaptation) Other aspects of the assessment 4. Co-existing mental disorder (see Section 10.11 Mental problems) 5. Use of other substances such as tobacco, opiates, or benzodiazepines. Enquire about the use of prescribed medication and adherence to these. 6. Use of alcohol by their partner or family members. 7. Signs of alcohol use disorders and organ damage.

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Signs are more common in people with alcohol dependence; there may be no obvious signs in early stages of alcohol misuse. Signs may include: • tremor of the hands (which typically indicates either alcohol withdrawal or cerebellum injury); • a reddish blush of the face, abnormal appearance of blood vessels in the face and neck, and changes in the mucous membranes (e.g. conjunctivitis) or oral cavity (e.g. glossitis); • both the size (number of ﬁnger breadths below the costal margin) and consistency (normal, ﬁrm, hard, or very hard) of the liver (assess the liver); • mental state − examination and mini mental state tests may reveal confusion or short-term memory loss. Laboratory tests, such as red blood cell macrocytosis and liver function tests (e.g. GGT), may be helpful, especially in the assessment of patients with harmful alcohol consumption or dependence (see below, Table: Laboratory ﬁndings suggestive of harmful alcohol use or alcohol dependence). Table: Laboratory ﬁndings suggestive of harmful alcohol use or alcohol dependence Investigations Full blood count Results Anaemia Leucocytosis Leucopoenia Macrocytosis Thrombocytopenia Elevated GGT AST/ALT >2 Isolated rise in ALT Hypokalaemia Hyponatraemia Raised Lowered Raised Raised >0.05 g% Interpretation of results GI or other bleeding Infections Reduced immunity Harmful alcohol use − folate deﬁciency or B12 deﬁciency Hypersplenism or bone marrow toxicity Harmful alcohol use Likely alcoholic liver disease Other forms of liver disease including hepatitis C Vomiting, diarrhoea, excessive sweating Harmful alcohol use Possible gout Harmful alcohol use Alcoholic pancreatitis Harmful alcohol use Recent alcohol consumption Person is at increased risk of a motor vehicle accident

Liver function tests

Electrolyte tests Serum uric acid Serum magnesium Serum amylase/lipase Cholesterol, triglyceride Blood alcohol concentration or breathalyser

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16.3 Classify, then advise and treat the patient Based on the assessment, decide if the patient has hazardous or harmful alcohol consumption or has alcohol dependence. List any harmful experiences or incidents the person has experienced so far.

If the AUDIT score is 8–19 • The diagnosis is likely to be hazardous or harmful alcohol consumption. • The treatment is an early intervention using the FLAGS (see below) approach. • The goal of treatment is reduced or controlled drinking to reduce risk of alcohol-related problems.

If the AUDIT score is ≥20 • The diagnosis is likely to be alcohol dependence; the higher the score, the greater the likelihood. • The next step is to conﬁrm the diagnosis. Look for evidence of impaired control of alcohol consumption, alcohol being a central part of the person’s life, withdrawal symptoms, and continued drinking despite harm. • The treatment is withdrawal from alcohol, treatment with an alcohol pharmacotherapy, and counselling to prevent relapse or else referral to a specialist facility where available. • The goal of treatment is abstinence from alcohol.

Special advice for pregnant patients Pregnant women and women who are at risk of pregnancy should be strongly advised not to use alcohol. Encourage patients who drink alcohol to limit themselves to low-risk alcohol use or to stop alcohol altogether. If time constraints do not allow deﬁnitive treatment during a consultation, still provide some advice, even if limited, and arrange a follow-up visit.

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Table: Summary of interventions by classiﬁcation of alcohol use disorder Diagnosis Low-risk alcohol consumption Main effects of problem In general, none Intervention required In general, none Women who are (or may become) pregnant are best advised to abstain from alcohol. Brief intervention to reduce alcohol consumption Advise women who are (or may become) pregnant to abstain from alcohol. Brief intervention Reduce the effects of harm Detoxiﬁcation Pharmacotherapy Psychological therapies and support groups Management of withdrawal Reduced or controlled drinking Goal of therapy

Hazardous alcohol consumption

Risk of harm in the future

Harmful alcohol consumption Alcohol dependence syndrome

Physical, mental, and social harms are present. Disabilities and complications: • physical • psychological • social Hyperactivity after cessation or reduction of drinking; may have seizures

Reduced drinking or abstinence from alcohol Abstinence from alcohol

Alcohol withdrawal syndrome

Stabilize the patient, relieve symptoms then treat the alcohol dependence.

16.4 Brief interventions for hazardous or harmful drinking Much can be done at primary care and district level to help people adopt low-risk drinking practices or stop alcohol altogether. A 5-minute session of brief therapy is outlined here. This is particularly useful for people with hazardous or harmful drinking, but the intervention can be adapted for providing initial treatment for people with alcohol dependence. Brief interventions Brief interventions are used for people with hazardous or harmful alcohol consumption. This ranges from those who have high-risk drinking patterns to drinkers already experiencing harmful effects of excessive alcohol and to those who would develop dependence without early intervention. Women who engage in low-risk drinking but are pregnant or taking drugs that interact with alcohol also require brief interventions. In the brief intervention give simple structured advice. Use the FLAGS approach, which is based on an intervention developed by WHO and evaluated in many countries. It has 5 components: F eedback, L istening, A dvice, G oals, and Strategies (see below, Figure FLAGS approach). The goal is reduced or controlled drinking. The intervention can be provided in 3−4 minutes, although it may be extended to 10 or even 30 minutes if time allows. This simple, brief therapy can be very effective, and on average results in a 30% reduction in drinking. Always offer the patient the opportunity to receive the therapy on a later occasion or in repeated sessions.

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Many different members of the district health team can assist in providing these services, with supervision from the district clinician. Good communication skills are necessary for successful implementation of brief interventions. Therefore, make use of health workers who have developed these speciﬁc skills.

Figure: FLAGS approach eedback Provide the AUDIT score and levels of alcohol consumption. Give feedback on problems or harm experienced or likely to be experienced.

isten Listen to patient’s response and what they like or dislike about their drinking. Gauge their readiness to change.

If not willing to change,

If willing to change, dvise to reduce drinking. Be unequivocal. Highlight the benefits of reducing hazardous or harmful drinking. Use a visual aid. Assist patient to appreciate benefits.

Advise with motivational interviewing techniques.

oals Help to set goals for reduced drinking. Be specific; i.e. advise no more than 2 standard drinks a day with at least 2 alcohol-free days per week, or advise to stop drinking completely.

trategies Suggest strategies and practical approaches to achieve the goal of reduced drinking; offer self help pamphlets and drink diaries.

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Arrange follow-up visits to assess whether the patient has been able to reduce or stop drinking, to review progress, to renegotiate goals and strategies, and to reinforce, support, and advise. Arrange support through peer and self-help groups. Alcohol interacts with many medications, and many medications can increase the toxic effects of other medications or of alcohol. Alcohol can change the metabolism of some medications and make them ineffective. Review the medications that a patient is receiving and whether they interact with alcohol. Alcohol misuse lowers adherence to medications. Family members and health workers have an important role in supporting adherence in people with hazardous or harmful drinking. For those with more established alcohol-related harm (or alcohol dependence), the FLAGS intervention offers an important initial approach that often is successful. People with patterns of harmful alcohol use who are unable to reduce or stop their drinking are showing signs that they may be alcohol dependent and require more intensive treatments. These are described next.

16.5 Treatment and care for those with alcohol dependence In patients with alcohol dependence, recovery usually will require total abstinence from alcohol. Often, this will alleviate the symptoms and signs of the disease. For this reason, patients with alcohol dependence are best advised to abstain completely from alcohol. Every effort must be made to support and encourage the patient to abstain. Primary health care workers play an important role in this, together with family members. In some cases it may be necessary to refer a patient for residential treatment or for brief periods of hospitalization. These options provide a much greater guarantee of abstinence than the patient’s usual setting. Patients with more severe alcohol dependence and related harm should be encouraged to seek specialist treatment services. The aim of treatment is to stop drinking completely, join support groups, and obtain the support of family members or other persons in helping them work on their long-term recovery. For many alcohol-related disorders, especially the various forms of brain damage, correction of vitamin and nutritional deﬁciencies is vital. Give thiamine and multivitamins to all patients with alcohol dependence or with any physical damage due to alcohol. Maintain patient records and document carefully the physical, mental, and social consequences of the patient’s condition, as well as any coexisting medical or mental problems. Alcohol dependence is a serious disorder, which often takes a progressive or chronic relapsing course. Many patients with alcohol dependence will get withdrawal symptoms when they stop drinking alcohol, such as anxiety, nausea, headache, hand tremors, sweating, and confusion. Severe alcohol withdrawal can be life-threatening, so patients with alcohol withdrawal need careful management of alcohol cessation (see below, Withdrawal management). The initial aim of treatment is to encourage the person to stop drinking alcohol. If the person is not ready or willing to take this step, it might be possible to engage services that are available locally, including counselling, family counselling, and psychosocial support matched to speciﬁc needs. Involvement of self-help and peer groups can help patients considerably. Support from family and friends, a sense that underlying issues can be addressed, and the understanding of other people with substance dependence can help prepare people to stop drinking.

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Specialist services for alcohol dependence treatment are not readily available in many settings. Therefore, most people with alcohol dependence seen at district level will have to be treated with available resources. Find out what services are available and how to refer to them. Some services still can be offered even where specialist services are unavailable.

Withdrawal management Withdrawal management is a planned process that allows patients to cease drinking safely and as comfortably as possible. It can be undertaken at home, in specialized centres, or in district hospitals. It is the ﬁrst step towards a goal of abstinence and recovery. The emphasis is on preventing a withdrawal syndrome from occurring, or, if one does occur, to minimize its effects. Detoxiﬁcation may require medication, depending on the severity of alcohol withdrawal (see Section 3.7 Alcohol withdrawal). People with severe alcohol dependence (a previous history of alcohol withdrawal, seizures, or delirium) or who have concurrent medical disorders are best managed in a specialist unit or hospital. Withdrawal from alcohol can be undertaken in a planned (elective) way in the person’s home. In this situation diazepam is typically administered at a dose of 10 mg 4 times daily, (i.e. up to 40 mg/day) for up to 5 days. It is best for the patient to be reviewed daily by medical staff and to be supported by a family member or friend. If patients become sleepy after the medication, then the dose should be reduced and the next dose withheld until withdrawal symptoms re-emerge. If higher doses are required, it may be necessary to admit the patient to hospital, where higher doses (i.e. up to 100 mg diazepam daily), or sometimes more can be administered in safety. For severe alcohol withdrawal, monitor the patient with the alcohol withdrawal scale (see Section 3.7) and give 10-20 mg diazepam every 1-2 hours until the patient’s withdrawal severity score is low or the patient is lightly sedated. If a patient is requiring 120 mg diazepam or more in a 24 hour period it might be wise to consult with a specialist, if one is available. If patients are known to experience severe alcohol withdrawal, commence diazepam before the patient experiences signiﬁcant alcohol withdrawal symptoms, aiming for light sedation in the ﬁrst 24 hours.

Relapse prevention after withdrawal from alcohol There are several medications useful in the treatment of alcohol dependence that increase the likelihood of the patient maintaining abstinence from alcohol. The principal medications are naltrexone, acamprosate, or disulﬁram.3 Naltrexone suppresses the urge to drink alcohol by blocking opioid receptors. It can be started after withdrawal from alcohol or when the patient is still drinking some alcohol. It is given at a dose of 50 mg/day and then maintained at 50−100 mg/day, usually for 3−12 months. Patients must not have taken any opioid drugs for the previous 5 days. They must be warned that naltrexone will block opioid drugs, in case the patient is likely to need opioid analgesia. Naltrexone should be avoided in pregnant or breastfeeding women and in patients with severe liver disease. In patients with liver disease, and when using the higher dose, monitor liver function tests. 3 To add or substitute disulﬁram for acamprosate or naltrexone, see mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-specialized Health Settings1.

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Acamprosate suppresses the urge to drink alcohol in the alcohol-dependent patient. It is best started immediately after withdrawal from alcohol has been achieved, as a relapse preventive approach. It is given at a dose of 2 tablets (each containing 333 mg acamprosate) 3 times daily (total of 1.998 g), except in people with a body weight of less than 55 kg, when the dose is reduced to 2 tablets twice daily. It has no signiﬁcant interactions with other drugs. Occasionally, it causes diarrhoea, in which case treatment should be stopped for a few days. It should not be used in patients who have renal impairment. Treatment is usually for 12–18 months. Naltrexone and acamprosate are not difﬁcult to use in primary care. Alcohol dependence is a relapsing condition, and on average these medicines double the time between each relapse. Any relapse should not necessarily be seen as a sign that the treatment has not worked, and the medication should still be considered for use again, although it might be worth trying alternative medications (switching from acamprosate or naltrexone or vice versa) to see if they are more effective. Where a specialist centre is available, the patient can be referred there for use of relapse-prevention medications and other treatments.

Psychosocial support Supportive outpatient alcohol treatment involves one-to-one counselling. Involvement of family members in recovery can markedly enhance treatment outcomes. The goal of abstinence requires signiﬁcant changes in many daily activities and way of life. The longer-term recovery of someone from alcohol dependence is based on good initial treatment, support, and self-help. Following that, recovery is based on a gradual process of restoring and establishing supportive relationships and securing a social and work environment that is conducive to maintenance of abstinence from alcohol. Together with continued involvement with a self-help group, these enhance the sense of reward attained through abstinence and the achievement of personal goals.

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17. Substance use Table of contents 17.1 General approach to substance use . . . . . . . . . . . . . . . . . . . . . . . . Patterns of substance use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Deﬁnitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmacological classes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Routes of administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effects of drug use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.2 Assessing drug use and dependence . . . . . . . . . . . . . . . . . . . . . . . . General principles of engaging and assessing the patient . . . . . . . . . Identify the drugs used. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Screening for substance use disorders using the ASSIST questionnaire. 17.3 General approach to managing drug use disorders . . . . . . . . . . . . . . . A pragmatic, client-centred approach . . . . . . . . . . . . . . . . . . . . . Other sources of medical care and psychosocial support. . . . . . . . . . Link with health and social welfare agencies . . . . . . . . . . . . . . . . . 17.4 Management of opioid dependence with opioid substitution treatment . . . What is opioid substitution treatment? . . . . . . . . . . . . . . . . . . . . . Overview of OST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to initiate OST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OST side-effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Psychosocial support during OST . . . . . . . . . . . . . . . . . . . . . . . . Cessation of OST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OST dose reduction and cessation . . . . . . . . . . . . . . . . . . . . . . . 17.5 Harm reduction approaches for injecting drug users . . . . . . . . . . . . . . 17.6 Antiretroviral therapy and substance use . . . . . . . . . . . . . . . . . . . . . Initiation of antiretroviral therapy (ART) . . . . . . . . . . . . . . . . . . . . ARV-methadone interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . Interactions of OST and rifampicin . . . . . . . . . . . . . . . . . . . . . . . 17.7 Pain control in people with drug use disorders. . . . . . . . . . . . . . . . . . Management of acute pain in patients with a drug use disorder . . . . . Management of acute pain in patients receiving opioid OST . . . . . . . . Management of chronic pain in patients with drug use disorders . . . . . 17.8 Management of complications from injecting drug use . . . . . . . . . . . . . Complications of injection-related infections . . . . . . . . . . . . . . . . . 17.9 Involving the family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Social support for the family . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.10 Integrating alcohol and drug use management with HIV care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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17. Substance use1 17.1 General approach to substance use Patterns of substance use Patterns of psychoactive substance use differ from country to country, between areas within a country (rural versus urban, province to province), and even within the same local area. Individuals may take different substances over time and by different routes, and they may also often switch among routes of administration (e.g. between smoking and injecting a drug). The reasons that people use psychoactive substances vary as well – to alter or enhance their mood, to feel better, to alleviate real or imagined pain, to satisfy their desire for pleasure, for entertainment, or to increase sexual enjoyment.

Deﬁnitions Deﬁnitions of psychoactive substance use can be found in the Lexicon of alcohol and drug terms2 published by WHO. In this manual the term psychoactive substance is taken to include (i) alcohol, (ii) prescribed and proprietary medications that have psychoactive effects, and (iii) a range of drugs (often illicit) that are taken primarily for their psychic effects. The unqualiﬁed term “drug” denotes these substances, with the exceptions of alcohol (the subject of Section 16) and tobacco or nicotine.

Pharmacological classes Psychoactive substances are classified according to their pharmacological properties into 3 main groups: 1. Sedatives • alcohol (wine, beer, spirits, home-brew); • sedative-hypnotics (benzodiazepines, z-drugs, methaqualone, barbiturates, chloral hydrate); • opioids (heroin, morphine, opium, codeine, hydroxymorphone, buprenorphine, methadone, pethidine, and compound preparations containing codeine or other opioids); • cannabis3 (marijuana/ganja/bhang/pot/grass, hashish); • volatile solvents (petrol/gasoline, glue, paint thinners, aerosol sprays, butane gas, nitrites, solvents, felt-tip marker ﬂuid); • gamma-hydroxybutyric acid (GHB); • kava.

1 mhGAP Intervention Guide for mental, neurological and substance use disorders in non-specialized health settings. WHO and mhGAP Evidence Resource Centre, 2010. Available at www.who.int/mental_health/evidence/ mhGAP_intervention_guide/en/index.html The mhGAP Guidelines and the mhGAP-IG will be reviewed and updated in ﬁve years. Any revision and update before that will be made to the online version of the document. 2 Lexicon of Alcohol and Drug Terms. WHO, 1994. 3 Cannabis also has hallucinogenic properties.

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2. Stimulants • nicotine (cigarettes, cigars, pipes, chewing tobacco, snuff); • cocaine (crack, crystal, coca products); • amphetamines (methamphetamine [“crystal”, or “ice”], methylene-dioxymethamphetamine [MDMA or “ecstasy”], and other amphetamine-type stimulants (ATS); • caffeine (coffee, tea, certain soft drinks); • betel nut; • khat. 3. Hallucinogens • lysergic acid diethylamide (LSD); • mescaline; • psilocybin; • peyote.

Routes of administration Psychoactive substances can be administered in many ways. They can be injected, chewed, dissolved slowly in the mouth, or swallowed; smoked or inhaled; injected; rubbed into the skin, placed under the eyelid, or inserted in the anus or vagina. Some of the health risks of substance use (e.g. local or general infection, HIV transmission, hepatitis B and C transmission, nasal sepsis, cancer of the airways, etc.) are related directly to the route of administration. Not all drugs can be taken by all routes. Table: Example of routes of substance administration Substances that are commonly... smoked or inhaled ingested or swallowed (as in drinking) injected inhaled into the nostrils (“snorted”) Tobacco, marijuana, opium, heroin, amphetamine-type stimulants, volatile solvents Alcohol, opium, sedatives (e.g. diazepam), compound analgesics, amphetamine-type stimulants, MDMA Heroin, sedatives, ATS, cocaine, buprenorphine Cocaine, tobacco (as snuff)

Effects of drug use When people initially take drugs, it may be for a variety of reasons – curiosity, to experience temporary euphoria (a “high”), to attempt to relieve pain, tension, anxiety, or other unpleasant emotions, or due to social pressure. In many people drug use becomes a repeated activity, and they move into a pattern of regular use. The brain adapts to repeated exposure and can become tolerant to the effects of the drug, thus requiring increasing quantities for the same effect. Drug use tends to become the central focus of that person’s life. Maintaining access to drugs can lead to antisocial behaviours such as stealing and other criminal activities. Drugs become the emotional and social focus at the expense of other interests and activities.

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Drug use often can result in a decline in initiative and drive and a lack of interest in other activities in life, which gradually may cause social, emotional, and physical problems. Loss of control and the breakdown of close relationships may bring about feelings of self-doubt, poor self-esteem, guilt, anxiety, and sadness, which may lead to further drug use as a temporary escape.

The spectrum of drug use There is a wide spectrum of drug use. It ranges from once-only use or occasional use to repeated use, which may have harmful consequences, to drug dependence, when the person’s life revolves around the drug use. The correct diagnosis will capture the various stages of drug use and is the basis of management. Hazardous drug use is a pattern of drug use that puts a person at risk of harmful consequences, such as injuries, medical disorders (including bloodborne virus and bacterial infections), mental disorders, problems in relationships, and difﬁculties at work. Certain drugs have disinhibiting effects, with unsafe sex (being unable to negotiate condom use and to use a condom correctly) being a common consequence. Injecting drug use and unsafe sex can result in the transmission of HIV and other sexually transmitted illnesses (STIs). Hazardous drug use is not a diagnostic term in International Classiﬁcation of Diseases (ICD)-10.4 A drug use disorder is a term used to include both harmful drug use and drug dependence. Harmful drug use is a pattern of drug consumption that is causing damage to health. The damage may be physical (as in cases of infections related to drug use) or mental (e.g. episodes of depressive disorder) and is often associated with damage to social functioning (e.g. family problems, legal problems, or work-related problems). Drug dependence (sometimes also known as addiction) is a cluster of physiological, behavioural, and cognitive phenomena in which drug use takes on a much higher priority for an individual than other behaviours that once had greater value. The central features of drug dependence, as deﬁned in ICD-10 are: • a strong desire or sense of compulsion to take the drug • difﬁculties in controlling drug use (e.g. its onset, termination, or levels of use) • experience of withdrawal symptoms or avoidance of them by taking the drug • tolerance – increased doses are required to achieve the desired effect • persisting with substance use despite harm • neglect of alternative pleasures or interests because of substance use. Drug withdrawal syndrome. A drug dependent person who ceases use or tries to reduce the level of use will likely suffer from a withdrawal syndrome, as a consequence of neuroadaptive changes. The withdrawal syndrome may range from mild discomfort to a severe syndrome (including delirium and convulsions), depending on the type of drug used, the amount of drug being taken, the duration of use, and the presence of any physical disorders. Symptoms of drug withdrawal are usually the opposite of the effects produced by the presence of the drug in the body. For example, opioid intake causes constipation, while one of its withdrawal symptoms is diarrhoea. In addition, the fear of withdrawal can dominate the thoughts of the drug-dependent person. Although initially drugs are often taken to experience particular sensations, later they are typically used to stave off the unpleasant effects of withdrawal. The features of the drug withdrawal syndrome are relatively speciﬁc to the pharmacological class of the drug. Thus, the withdrawal syndrome from a psychostimulant is very different from that of a sedative-hypnotic or of an opioid.

4 International Classiﬁcation of Diseases, 10th rev. WHO, 2007. Available at http://apps.who.int/classiﬁcations/ apps/icd/icd10online/

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17.2 Assessing drug use and dependence Drug use is commonly under-reported and can be missed if the patient is not speciﬁcally asked about it. Gathering the information needed for a complete drug use history requires overcoming a patient’s reluctance to talk about drug use.

General principles of engaging and assessing the patient It is important to establish a good rapport with the patient. Some patients are reluctant to discuss their substance use problems for fear of prejudice or legal consequences. An understanding and non-judgemental approach, demonstrating sensitivity to the patient’s current situation and cultural background, will increase the accuracy of the history. Assessment should: • effectively engage the patient • establish trust and conﬁdentiality • acknowledge to the patient that drug use can be difﬁcult to talk about • obtain the patient’s permission to obtain a drug use history • deal with the presenting issue appropriately and professionally in a ﬂexible and non-judgemental manner • use an appropriate questioning style and content • be non-confrontational • explain that questions on drug use are standard • explain that asking about drug use is important to get the full background to the patient’s current health concerns.

Identify the drugs used People who use drugs commonly use, or have used, more than one drug. It is important to identify all drugs, both legal and illicit, that a patient has used. This includes drugs that he/she uses currently and any used in the past. Ask speciﬁcally about the drugs commonly used in your local area. See lists above. If a patient has used any other substance not listed above, ask him/her to specify what it is. Having identiﬁed the main drugs used, enquire about the following: 1. The pattern of use Because people use drugs differently over time, it is important to gain an understanding of a patient’s pattern of drug use for each drug. Ask questions such as: • How often have you used [name of drug] in the last 30 days – and in the last week? • How much did you use on a typical occasion? • When did you last use [name of drug]? • How long have you used [name of drug] like this? • How old were you when you ﬁrst used [name of drug]? 2. The route of administration Injecting drug use carries the risk of bloodborne virus transmission, and dependence is more likely than with other routes of administration. A patient may have taken a

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particular drug by a number of different routes. Ask, “What are the different ways you have taken [name of drug]?” (e.g. oral, nasal, smoking, injecting (IV and nonIV), rectal). If the patient is not reporting injection, ask speciﬁcally, “Have you ever injected [name of drug]?” 3. Dependence Drug dependence is a disorder characterized by a psychological and physiological drive to use a drug (or a group of drugs, or a range of drugs), even in the face of serious consequences. The diagnosis of drug dependence is based on 6 criteria (see box above), which include a strong (often overpowering) desire to use the drug, difﬁculties in controlling use, progressive neglect of alternative pleasures or interests, evidence of drug tolerance, and withdrawal symptoms when they stop or try to reduce use. Drug dependence is diagnosed on the basis of at least 3 of the 6 criteria being met at some time during the previous year. 4. Problems The problems associated with drug use can be physiological, psychological, and social. They include: physical health problems, due to the drug’s toxic effects or to the mode of administration (e.g. injecting), such as liver disease, septicaemia, endocarditis; anxiety, depression, aggression, violence, suicidal ideation; social and legal problems.

Screening for substance use disorders using the ASSIST questionnaire5 In settings with a high prevalence of drug use, one approach that can be efﬁcient is to screen patients for alcohol, tobacco, and drug use disorders with the WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). ASSIST was developed for WHO by an international group of substance abuse researchers to detect and manage substance use and related problems in different health care settings.

17.3 General approach to managing drug use disorders Patients with drug use disorders may need medical and psychosocial interventions. This involves linkages with other services outside the district hospital (see below, Figure: Link with health and social welfare agencies).

A pragmatic, client-centred approach It is important to develop a pragmatic, client-centred approach to drug use disorders. Drug use disorders vary in severity and complexity. In more severe cases the patient may use drugs seemingly compulsively, showing marked craving and drug-seeking behaviour. Drug use can persist in the face of extreme consequences. Drug use, particularly at the stage of dependence, can take over a person’s life, creating a wide-range of abnormal behaviours that interfere with normal functioning in the family, the workplace, and the broader community. No single treatment is appropriate for all individuals. Persons who use drugs need a pragmatic approach. This begins by addressing the patient’s immediate needs and then establishing the person’s view of their drug use. It is important to respond 5 The ASSIST Project – Alcohol, Smoking and Substance Involvement Screening Test. WHO, 2011. Available at http://www.who.int/substance_abuse/activities/assist/en/index.html

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to tangible needs, such as shelter, clothing, food, transportation, or childcare. This improves the relationship between the patient and the health worker and is more likely to improve understanding of, and compliance with, treatment. Entering treatment may not be an immediate priority for the patient. However, treatment needs should be addressed as soon as possible, even if the patient is uncertain about entering treatment. Effective treatment needs to: • address the patient’s immediate needs; • balance the importance of changing the patient’s drug use (such as cessation, maintenance, less risky use) with the patient’s physical and health needs (such as food, housing, treatment of bloodborne viral infection); • establish an empathic relationship with the patient; • create rapport as the basis of future working together; patients who are experiencing difﬁculties need to feel conﬁdent and comfortable in expressing their concerns to staff; • address the patient’s immediate needs; • inform patients about the available services and community resources; • evaluate the patient’s strengths and needs and help the patient identify those behaviours that may create barriers to obtaining goals; • work toward achievable goals that are observable and time-limited; • be realistic – do not overwhelm the patient with too many things at once; • help the patient to develop a sense of responsibility for the drug use and for treatment.

Other sources of medical care and psychosocial support A wide variety of services can contribute to recovery from drug use disorders. People with these disorders need different kinds of services at different times; thus, a wide range of services may need to be accessed. No single centre will be able to offer all the most appropriate facilities and provide for all the rehabilitation needs of all patients. Whenever necessary and possible, patients should be referred also to other helping units or services. Links need to be established with both health and social welfare agencies, as described below. Link with health and social welfare agencies In addition to knowing the health services provided by hospitals, health centres, and health posts, contact key individuals in government and non-governmental organizations (NGOs, FBOs, CBOs) to learn where the services are, what their eligibility criteria are, whom to contact, and their current telephone numbers. Services may include: • opioid agonist maintenance treatment (methadone and buprenorphine) • detoxiﬁcation centres • self-help groups • social welfare centres • religious and spiritual organizations • legal assistance services • probation service or similar • trade schools or vocational training institutions • job-ﬁnding institutions or placement agencies • mutual help groups such as Narcotics Anonymous (NA).

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17.4 Management of opioid dependence with opioid substitution treatment The single most effective and valuable treatment for people with opioid dependence is opioid substitution treatment (OST), also known as opioid agonist maintenance treatment (OAMT) or opioid agonist pharmacotherapy.

What is opioid substitution treatment? OST involves the prescription of long-acting opioids, such as methadone and buprenorphine, generally on a daily, supervised basis, in combination with psychosocial support. The opioid effect produced by these medications maintains the tolerance to opioids in the patient. In stable doses, however, the substituted opioid produces neither signiﬁcant opioid intoxication nor withdrawal, enabling the patient to function normally and to cease illicit opioid use without withdrawal symptoms. The increased tolerance to opioids that is induced (in the case of methadone) or occupancy of opioid receptors (in the case of buprenorphine) diminishes the opioid effects of any additional opioid use. This reduces the incentive to use additional opioids and lowers the risk of death from opioid overdose. In addition to keeping the patient alive, the goals of treatment are to eliminate, reduce, or modify the use of a particular substance, especially if it is illegal, and in so doing reduce the harms associated with its use (e.g. from needle sharing). The ultimate goal of treatment for most people is to stop using drugs completely. Opioid agonist treatment should be accompanied by the offer of psychological and social support. OST allows people with opioid dependence to: • Reduce or stop their harmful use of illicit or non-prescribed drugs in order to: ° reduce the duration of episodes of harmful drug use ° reduce the risk of overdose or intoxication ° reduce the chance of future relapse to harmful drug use. • Reduce their high-risk behaviours and their consequences in order to: ° reduce the dangers associated with harmful drug use, particularly the risk of HIV, hepatitis B and C, and other bloodborne infections that may be transmitted by injecting and sharing injecting equipment ° reduce mortality associated with drug use ° improve and stabilize their health ° reduce the need for criminal activity to ﬁnance drug use ° reduce the social consequences of harmful drug use ° improve overall personal, social, and family functioning ° focus on normal life activities without the need to obtain and use drugs ° break connections with criminal activity and facilitate changes in lifestyle. There is strong evidence that methadone and buprenorphine maintenance treatment effectively reduce illicit drug use, mortality, the spread of HIV, and criminality and also improve physical and mental health and social functioning. Higher doses of methadone and buprenorphine generally are associated with greater reductions in the use of heroin and other opioids.

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Overview of OST OST is a long-term treatment approach (usually lasting a number of years), which, by controlling drug craving and opioid use, provides the opportunity for patients to distance themselves from a drug-using lifestyle and to re-enter society. The combination of medication with psychosocial services can help to heal the psychological damage and problems with socialization caused by years of illicit drug use and exclusion from mainstream culture. Methadone • the most commonly prescribed and effective substitute medication • synthetic opioid drug with a long duration of action • taken orally once daily • daily dosing under supervision is easy and minimizes diversion and inappropriate use • some take-home doses usually can be given to suitable patients as determined on an individual basis • in adequate doses methadone reduces the desire to use heroin and other opiates, eliminates opioid withdrawal, and blocks the euphoric effects of the other opioid drugs • daily dosing with methadone prevents withdrawal symptoms for approximately 24 hours. Buprenorphine • partial agonist that also blocks other opioids • opioid-like effects (but less risk of depressed respiration than with methadone) but can lead to death if combined with other sedatives • long duration of action • given sublingually (allowed to dissolve under the tongue) • daily dosing under supervision minimizes diversion and inappropriate use • some take-home doses usually can be given to suitable patients as determined on an individual basis • alternate-day dosing may be possible when the patient is stabilized. The choice between methadone and buprenorphine depends upon: • national guidelines and availability • logistics of participating in treatment • response to treatment • individual variation in absorption, metabolism, and clearance of medication • side-effects • ease of withdrawal from medication • lack of or inadequate response to one of the drugs • patient (and health worker) expectations • interactions with concomitant medications (e.g. ARVs) • ﬁnancial issues (e.g. cost).

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Recommended eligibility for OST The minimum requirements to enter OST are that the patient should be opioiddependent, give informed consent, and satisfy any local legal requirements. Usually, there are local requirements for training before health workers can dispense methadone or buprenorphine. In addition, there are often additional criteria for patients, such as a minimum age limit or minimum period of opioid use or dependency or parental consent for adolescents. Persons for whom treatment has the greatest public health impact include: • HIV-positive heroin users requiring ART • pregnant heroin users • patients with active TB requiring DOTS. Giving preference to patients with these conditions can create problems, however. Ideally, treatment would be available to all patients in need. There are no absolute exclusion criteria, apart from not wanting OST. Some comorbid conditions require extra care when commencing substitution treatment (particularly with methadone). These patients include: • high-risk polydrug users • heroin users with a low level of neuroadaptation or a short duration of use • those below the legal age of consent for treatment • people with severe psychiatric conditions • those who have acute or severe medical conditions (e.g. severe hepatic disease, respiratory illness, or head injury) • patients with chronic pain disorders. Most of these conditions respond well to methadone treatment in particular, but they require additional expertise at assessment, on initiation, and during maintenance. Assessment Accurate assessment of the patient is essential to planning treatment. No prescription should be given until a full assessment has been completed. However, acute withdrawal symptoms can be treated without unnecessary delay. Issues to assess include: • treating the emergency or acute problem, including withdrawal symptoms • conﬁrming that the patient is dependent on opioids (history, examination, and urine analysis); • severity of opioid dependence • history of previous treatment • identifying complications of drug use and assessing risk behaviour • identifying other medical, social, and mental health problems • the patient’s motivations and goals • access to sterile needles and syringes • HIV status and, if seropositive, CD4 count and need for ART (see Section 17.6) • testing for hepatitis B and C and HIV and immunization against hepatitis A and B (see Section 11.14) • need for referral to a dentist or provision of STI, TB, or obstetrical services.

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It is important that a proper physical examination takes place with a focus on medical issues and injection sites. Ideally, a sample of urine should be collected to conﬁrm the history of opioid use, if the results can be available in 2−3 days. If available, an on-the-spot test can be conducted. If the urine sample indicates no recent opioid use, then the use of methadone and buprenorphine should be reconsidered, as there is a risk of oversedation when starting these treatments (particularly with methadone).

How to initiate OST Safe initiation of OST requires achieving a balance between relieving opioid withdrawal symptoms and avoiding opioid toxicity. The latter is particularly important because methadone and buprenorphine accumulate with time. Methadone is started at a low dose, with the purpose of avoiding excessive blood levels that could result in overdose and death. It is important to identify the contributing risk factors at starting (e.g. other drug use, chaotic heroin use, medical or psychiatric conditions) and to assess the level of neuroadaptation (decide whether there is high, medium, or low dependence). Buprenorphine also is started at a low dose to avoid a precipitated withdrawal as a consequence of its displacing any full-potency agonist remaining in the brain. It is vital to explain to the patient the OST programme features, including: • the rationale for the low starting doses and for slow increase of the methadone dose • the risk factors when starting and the importance of minimising them • the factors contributing to risk at starting • the cumulative effect of methadone over a number of days. There should be the opportunity to discuss the side-effects of methadone and buprenorphine, and other questions. Also, if available, written information about OST should be provided. Initiating methadone In the case of methadone, the initial dose is generally 20 mg. In cases where tolerance is low or uncertain, an initial dose of 10 mg is more appropriate. Monitor whether the dose is enough to prevent withdrawal symptoms. An additional 10 mg can be given if necessary after 4 hours. In the ﬁrst week patients should be seen daily in order to monitor withdrawal symptoms and craving and to establish a stabilization dose. The maximum daily increase in dose is 5 mg to 10 mg, and the maximum daily dose at the end of the ﬁrst week should be 40 mg. In general, the optimal dose for patients on methadone maintenance is between 60 mg and 120 mg. The time needed to properly stabilize someone on methadone treatment can be 6 weeks or more. Initiating buprenorphine Ensure that the patient either has objective signs of opioid withdrawal or has not used an opioid in the last several hours. The minimum period before commencement of buprenorphine from the last use of a short-acting drug such as heroin or morphine is 6 hours. The minimum period when the person has used a long-acting opioid is 24 hours. The usual starting dose of buprenorphine is 4 mg.

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On the following day the dose usually can be increased to 8 mg. On subsequent days, depending on the degree of use and the severity of dependence, it can be further increased to 8–16 mg daily. In general, the optimal dose is 12–24 mg daily, with a recommended maximum of 32 mg daily.

OST side-effects It should be noted that tolerance develops to many initial side-effects. • More persistent side-effects include headache, constipation, increased sweating, sleep disturbance, reduced libido, amenorrhoea, reduced concentration, potential for weight gain, and dental problems. • Successful management of these side-effects during maintenance OST can make a dramatic impact on adherence to the programme.

Psychosocial support during OST Psychosocial support while patients are receiving OST is primarily directed to the practical issues that patients are facing. Useful interventions include: • education and in particular the attainment of basic levels of literacy and numeracy • vocational training • occupational assistance • legal advice • parenting interventions • encouragement to attend an appropriate mutual help group.

Cessation of OST Sudden cessation of OST is associated with a high risk of relapse, with its associated morbidity and mortality. In general, the longer patients remain in treatment, the better their outcomes. This is probably because there is a high relapse rate to dependent heroin use for patients who prematurely stop methadone or who have not stopped heroin use for a substantial time when they try to stop methadone. Factors predicting successful completion of OST include: • employment • abstinence from opioids and other drugs use during treatment • changes in the person’s social environment supportive of recovery • stable employment, stable accommodation, and a stable, supportive intimate relationship • stability of dose and good adherence • good relationships with health care workers and the clinic. It is important that these factors be seen as markers of recovery rather than a list of things to do. The answer to one of the most commonly asked questions in OST. “When can I stop the treatment?” is to be answered by, “When you are well on the way to recovery.” Patients and their families should receive good counselling and information about the cessation of OST. It is not possible to keep patients involuntarily on methadone or buprenorphine treatment. Most patients will experience frustration with the OST programme at some stage and attempt at least one premature dose reduction.

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OST dose reduction and cessation To avoid losing the gains from recovery, it is necessary to decrease OST very gradually. Methadone reduction should generally be no faster than 5 mg/month. Many patients reach a dose level (often between 10 mg and 30 mg) at which dysphoria or discomfort increases; if heroin use resumes, re-stabilization on a higher dose will be required. Buprenorphine reduction also should be undertaken gradually. Patients may experience some withdrawal symptoms after cessation of even very low doses (for example, <2 mg per day). Contraindications to OST dose reduction and cessation There are a number of physical, social, and behavioural contraindications to OST reduction and a variety of likely adverse outcomes if withdrawal is not postponed or avoided in these instances. • ongoing heroin use, with a predictable increase in heroin consumption and deterioration in lifestyle control in the presence of decreasing OST support; • pregnancy − severe adverse outcomes for the fetus, including spontaneous abortion, intrauterine fetal death, premature labour, and stillbirth if opioid withdrawal is forced; • chronic pain or depression – expect worsening of symptoms with OST reduction; • critical social events, such as school or university examinations, new employment, or a new relationship, are likely to be disrupted by the dysphoria of opioid withdrawal; • other unstable drug use. If possible, in the presence of these factors, opioid agonist reduction should be postponed until recovery has reached a more stable and resilient stage. Interventions prior to and after withdrawal of OST Psychosocial interventions prior to and after cessation of OST should focus on: • relapse prevention • problem-solving approaches • continuation of educational and occupational assistance • attendance at mutual help groups. Family support groups can be helpful to the patient and can help propagate accurate information about OST in the community.

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17.5 Harm reduction approaches for injecting drug users Harm reduction approaches are widely employed in the management of injecting drug use. The aim of these approaches is to prevent avoidable death and major complications, such as overdose and the acquisition of bloodborne viral infections (e.g. HIV). Often, patients with drug-use disorders take time to recognize that cessation of drug use is necessary. Harm reduction can prevent the worst adverse effects of injecting drugs pending engagement in treatment. Harm reduction initiatives can engage patients so that they eventually take up the offer of treatment.

Advise • On the risks of injecting drugs: ° HIV, hepatitis B and C can be transmitted via all injecting equipment – needles, syringes, spoons. ° overdose of heroin or other opioids when injected ° other co-morbidities related to IDU or other drug use, including infections, mental health problems, and liver and kidney problems ° the risk of dependence developing or progressing ° interference with the ability to function in society. • On ways to minimize risks: ° the use of sterile equipment (needles, syringes, and diluting solution) ° using own equipment (not others’) if sterile equipment is not available (especially syringes) ° using bleach to clean equipment if sterile equipment is not available ° avoiding sharing of injecting equipment, blades, and tattoo equipment ° ceasing or reducing the use of injection drugs. • On how to inject safely and how to protect veins: ° disinfecting skin prior to injecting, which reduces the risk of developing deep skin infections that can affect the veins ° regularly changing veins used for injection ° the use of new needles and syringes (used needles can be more damaging to veins) ° reducing the number of injections per day or per week. • On encouraging OST: ° establishing relationships of trust and offering OST when appropriate ° informing patients that there are programmes that can help them to stop drugs ° educating patients that this is the best option, if OST is available ° considering detoxiﬁcation as an entry point to drug rehabilitation and treatment ° counselling and promoting consistent condom use to prevent the sexual transmission of HIV, viral hepatitis and STIs ° educating the patient on special nutrition needs. Assist • Refer the patient to needle and syringe programmes offering sterile equipment (needles, syringes, and diluting solution) and safe injection information, or to outlets to purchase sterile equipment • Provide clean new needles and syringes. Arrange • Follow-up visits: you need to establish a long-term relationship of trust before offering most interventions to IDU patients. This might take several visits. Do not lose hope and do not have unreal expectations. High rates of drug use relapse and low rates of patient retention in programmes are common. • Establish links and know-how to track the IDU client in the community. • Schedule appointments with needle and syringe programmes. • Detoxiﬁcation and opioid substitution treatment • Hepatitis B vaccinations • If patient not yet tested, recommend HIV testing and counselling for clients and partners.

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17.6 Antiretroviral therapy and substance use Initiation of antiretroviral therapy (ART) Initiation of ART in HIV-infected IDUs should follow the current recommendations for initiation of ART in HIV-infected patients generally. Initiation of ART is rarely an emergency, and IDU patients should be well-informed, motivated, and have had potential barriers to adherence addressed prior to starting ART. It is extremely important to take time to assess and prepare the patient for ART. Laying the groundwork for adherence to treatment begins before ART is started. ART is best initiated when the patient: • has emotional and practical support • ﬁts the treatment regimen into a daily routine • understands that non-adherence leads to resistance to ARV drugs • recognizes that all doses must be taken • feels comfortable taking treatment drugs in front of others • keeps clinic appointments • knows alarm signs and when to see a doctor about them. Usually, the opioid-dependent patient should be stabilized through OST prior to starting ART. However, in some cases, OST may not be available or accessible, or the patient may not want it. In these cases – if ART is indicated and if the patient has proved (like any non-IDU candidate to ART) likely to adhere to treatment – there is no reason to postpone ART. A service that is able to provide and monitor both ART and OST can be very effective in the monitoring of adherence and other outcomes and in management of side-effects and interactions. Once-daily directly administered ART, in conjunction with methadone or buprenorphine maintenance, is recommended because it: • results in signiﬁcant numbers of patients achieving maximum viral suppression; • achieves higher levels of viral suppression than among those injecting drug users receiving either standard care or treatment adherence support; • minimizes the impact of ART on the daily routine of the injecting drug user. Consideration should be given to the treatment of hepatitis C infection prior to ART if the former is available. Note: Patients with liver disease (especially when severe or when liver failure is present) will likely require consultation and referral to an appropriate specialist service.

ARV-methadone interactions Methadone undergoes metabolism in the liver by pathways that are common to some ARTs and anti-TB drugs but is highly variable due to genetic factors. Management of these interactions requires close collaboration and clear communication between the drug dependence and the HIV treatment clinicians/ services, if the treatments are not being provided by the same clinicians/services.

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If available and affordable it may be preferable to use ARV combinations (AZT-3TCABC or AZT-3TC-TDF) that have minimal interactions with methadone. NNRTIs and boosted PIs in particular should be used with appropriate caution. Methadone and NRTIs Methadone can inhibit the elimination of AZT from the body and increases AZT concentrations. The clinical signiﬁcance of this is variable and unclear, and no AZT dose reduction currently is recommended. Patients should nevertheless be monitored closely for signs of AZT toxicity, such as anaemia. Methadone levels are not affected by ddI but methadone can decrease ddI concentrations and consequent incomplete viral suppression. An increase in ddI dosage (speciﬁcally for buffered tablet formulation) may be indicated for patients on methadone. Methadone and NNRTIs NNRTIs (EFV and NVP) can decrease steady state methadone concentrations through the induction of drug metabolism in the liver. They can produce clinically signiﬁcant opioid withdrawal. In patients receiving an NNRTI, the patient requires titration and monitoring of the dose of methadone which may need to be increased by 50-100%. Sudden cessation of NNRTIs without a corresponding reduction in the methadone dose can result in a sudden increase in methadone levels and methadone toxicity. If NNRTIs are to be used, EFV appears to have less impact on methadone levels than NVP. The appropriate management is to monitor closely for the ﬁrst week when starting NNRTIs in stable methadone patients and to adjust the methadone dose upwards, signiﬁcantly and frequently as needed. Caution, close monitoring and signiﬁcant and frequent reductions in the methadone dose should be used if NNRTIs are ceased for any reason, recognising that there may be a delay in the impact of the medication cessation ( Methadone and PIs As with NNRTIs, boosted protease inhibitors also increase the clearance of methadone by enzyme induction, and clinical symptoms of opioid withdrawal are unusual but well documented. If PIs and methadone are co-administered, use the same considerations on titration and monitoring of the methadone dose as for with NNRTIs.

Interactions of OST and rifampicin Rifampicin is a potent inducer of liver drug metabolism and increases the elimination of methadone, lowering its blood levels. When effective clinical alternatives exist (eg rifabutin), rifampicin should not be administered to patients receiving methadone. If rifampicin and methadone are co-administered, use the same considerations on titration and monitoring of methadone dose as for NNRTIs.

17.7 Pain control in people with drug use disorders Pain control is a common and often challenging issue when a patient has a history of harmful drug use, in particular harmful opioid use. However, there are certain principles that help the development of a rational plan for pain relief and reduce its potential complications. People engaged in harmful drug use are at a higher risk than the general population for trauma and hospitalization and therefore more often in need of pain management. In particular, several painful medical disorders, such as

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abscesses, cellulitis, septic arthritis, osteomyelitis, and HIV-related disorders, such as neuropathy, are more common. Drug users, especially those with opioid dependence, often have signiﬁcant tolerance to most analgesics and sedatives. A key difﬁculty in pain management is the emergence of drug-seeking behaviour in which the patient’s demand for drugs is out of proportion to the demonstrable disease or symptoms. Consultation with an expert in pain management and drug dependence can be very helpful in the management of the more complex situations.

Management of acute pain in patients with a drug use disorder Management requires: • assessment of pain, ensuring that the drug use and related symptoms are not masking severe illness, such as a perforated peptic ulcer or bowel obstruction; • correct classiﬁcation of pain, such as nociceptive versus neuropathic pain (see Section 20 Palliative care); • simultaneous management of underlying medical conditions, of the drug dependence, and of acute pain related to the medical condition; • ensuring adequate analgesia for the acute pain; • managing the risks associated with prescribing opioids; • avoiding withdrawal symptoms.

Use the WHO pain ladder in Section 20 Palliative care.

As with all patients: • Give oral analgesics in preference to IV or IM drugs. • Give preference to non-opioids if these provide adequate analgesia. For moderate to severe acute pain, the starting dose and frequency may need to be increased due to opioid tolerance (for example, oral morphine 30 mg every 3–4 hours; codeine 60 mg every 3−4 hours).6 Consider adding other local approaches to analgesia such as regional anaesthesia or nerve block (in the case of a limb fracture), intercostal blocks for fractured rib(s), anti-inﬂammatory gel or gargling with anaesthetic solution for dental pain. Decisions on the duration of opioid analgesia should be guided by the duration of analgesia usually required for the particular disorder. It may be necessary to switch to a longer-acting opioid prior to terminating analgesia. Consideration should be given to starting the patient on OST or referral to a treatment service with this in mind.

6 Jacox A et al. Management of Cancer Pain. AHCPR, U.S. DHHS, Public Health Service, 1994.

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Management of acute pain in patients receiving opioid OST • Continue methadone dose and add other opioids for analgesia; • If on buprenorphine, stop it and prescribe other opioids; then switch back to buprenorphine when the pain has resolved; or • Continue the buprenorphine dose and use non-opioids such as ketamine, clonidine, and benzodiazepines; or • Continue buprenorphine and use an opioid with a higher potency and/or afﬁnity for opioid receptors, such as fentanyl. On discharge from hospital, the need for ongoing analgesia should be balanced against the risks of unsupervised opioid administration. For patients on methadone, the methadone dose can be increased temporarily to provide additional analgesia.

Management of chronic pain in patients with drug use disorders In the treatment of non-malignant chronic pain in patients dependent on opioids: • Non-opioids should be used in preference to opioids. • If opioids are thought necessary for adequate pain control, supervised doses of long-acting opioids (i.e. once daily, if possible) should be used in preference to unsupervised short acting opioids. • Objectively monitor the problem. • Continue to consider the possibility of a new medical problem or the deterioration of an existing problem as the cause of pain. • Continue to implement other treatments to manage chronic pain, such as physiotherapy. (Review past experience with such treatments, to avoid rejecting modalities due to a single bad experience.)

17.8 Management of complications from injecting drug use “Dirty hit” is slang for an injection that makes the person sick or results in an infection (e.g. an abscess). It can be caused by: • contaminants in the water used to dissolve drugs • bacteria, fungi, or other microbes • chemicals in a cigarette ﬁlter that was used to ﬁlter a shot • adulterants or contaminants in the drugs themselves • not properly cleaning the skin prior to injection. A dirty hit can result in a rapid, intense reaction, or it might take days or weeks to produce an effect. Symptoms often include sweating, headache, fever, and trembling. The effects of a dirty hit may pass by themselves, but medical attention is recommended if they are particularly strong or persistent. Venous injury and bruising are common complications of injecting drug use. Repeated injecting at the same site can cause occlusion, local infections, and scarring of the vein. Bruising occurs when blood leaks out from the vein under the skin during the process of injecting. Bruising at the injection site can reﬂect poor injection techniques. To prevent bruising, advise patients who inject drugs to: • use a soft, ﬂexible, easy to open tourniquet and remove it before injecting

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• • • • •

apply adequate pressure for sufﬁcient time after injecting use a new needle for each injection alternate and rotate injecting sites use the thinnest needle possible, to make the smallest puncture wound always inject in the direction of the body’s blood ﬂow (toward the heart).

Scarring (track marks) is caused by repeated injecting into the same injection site. To prevent track marks, advise patients who inject drugs to: • alternate and rotate the injecting sites • inject at least 2−3 cm from previous injection sites (veins need to recover between injections) • use a sharp, sterile needle for each injection (using blunt needles causes trauma to veins and surrounding tissue). There is no speciﬁc treatment for scarring. If there is severe scarring or keloid formation, the patient may be referred to a skin specialist. Venous thrombosis (clot formation in veins) can result from injecting drug use. Chronic venous damage or infection of skin tissues or veins is a risk factor for deep vein thrombosis (DVT). The repeated trauma of venipuncture, local infections and the irritating qualities of injected substances are the main causes of superﬁcial and deep venous thrombosis. Septic thrombosis is responsible for bacteraemia and can lead to other complications, such as infective endocarditis. High risk locations for complicating embolization include iliofemoral and upper limb deep venous thrombosis. Arterial injury results from inadvertent injection into the artery. This is more common when a vein is located close to an artery such as in the groin, or on the medial side of the cubital fossa. Aneurysms are weaknesses in the wall of the blood vessel resulting in a bulging of the wall. Aneurysms of an artery are a common complication of intra-arterial injections. These can become infected and result in haemorrhage. The inadvertent injection of drugs into the arterial circulation can also result in vascular spasm, with the death of tissues due to ischaemia. This may be complicated by infections (gas gangrene or tetanus) or muscle swelling (compartment syndrome), which may lead to renal failure. To prevent arterial injury, people who inject drugs should be advised: • not to inject into any pulsating blood vessel • to apply adequate pressure for at least 15 minutes if intra-arterial injection occurs. Any problems following injection into an artery should be assessed and treated immediately. Aneurysms may require surgical repair. Pallor of the limb due to arterial spasm or occlusion needs immediate treatment. Consult with a surgical team immediately.

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Figure: Complications of injection-related infections Injection-related skin infections

Bacteraemia Septicaemia

Bacteria lodge in small vessels in any organ Embolization BRAIN Brain abscess/ meningitis HEART VALV ES

J OINTS Septic arthritis BONE Osteomyelitis

Endocarditis

Septicaemia (“blood poisoning”) is a bacterial infection of the blood that can be caused by injecting bacteria inadvertently – by using non-sterile equipment, contaminated water, or failing to clean the skin prior to injection.

Septicaemia is an established blood infection resulting from bacteraemia. Bacteraemia is the presence of bacteria in the bloodstream. It is due to the insertion of skin ﬂora into the vascular system. The risk of septicaemia is heightened by poverty, malnutrition, dental caries, leg ulcers, and abscesses. See Section 3.1.5 for the management of septic shock. Endocarditis is an infection of the heart valves that is caused by bacteria, fungi, and other microorganisms. It is a severe illness, which if untreated has an 85% mortality rate. Risk factors for it (as well as injecting drug use) include a previous history of infective endocarditis, rheumatic heart disease, and HIV infection. See Section 11.10 Endocarditis. Tetanus is a bacterial infection that occurs when tetanus spores enter a wound. If the needle, syringe, or other injection equipment is contaminated with tetanus spores due to dirt or rust, infection can occur. People who inject drugs into the skin (“skin-popping”) or muscle are particularly susceptible to tetanus infection; fresh, sterile equipment always should be used. See Section 11.39 Tetanus for clinical features and management. Tetanus vaccination, or boosters for those vaccinated in the past, are very effective in preventing tetanus. Necrotizing fasciitis is a bacterial infection commonly known as “ﬂesh-eating disease”. Symptoms of necrotizing fasciitis include increasing redness and

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swelling and extreme pain at the wound or injection site accompanied by a fever. The ﬂesh around the site of infection begins to decay and looks as if it has been eaten away. Since this infection often is fatal, early treatment with antibiotics is crucial to survival, although even appropriate therapy does not prevent death in all cases. Wounds must be kept impeccably clean. See Section 10.2.2 Skin and soft tissue infections. Hepatitis is an inﬂammation of the liver that can be caused by alcohol, certain medications, and some illicit drugs (iatrogenic or chemically-induced hepatitis) or is the result of infection with a hepatitis virus (i.e. viral hepatitis; see Section 11.14 Hepatitis). While there are numerous types of hepatitis viruses, hepatitis B and C are the two that most frequently affect IDUs. Hepatitis B is spread through blood-to-blood contact – as when drug-injecting equipment is shared. It is also transmitted through contact with infected body ﬂuids such as semen, blood, urine, saliva, and mucous, and from mother to infant at birth. Hepatitis B infection can be a short-term or a long-term illness. Chronic hepatitis B can cause serious liver damage, including cirrhosis, liver cancer, and death from liver failure. It results in premature death in about 15−25% of individuals affected. Hepatitis B is much more infectious than HIV. It is one of the most important reasons that people who inject drugs should never share injecting equipment and also why they should be immunized against hepatitis B. Hepatitis C is spread mainly through blood-to-blood contact. It is highly infectious. It is readily diagnosed, but there is a window of approximately 3 months after the infection is contracted before antibodies can be detected. There is as yet no vaccine for hepatitis C, and antibodies are not protective. For IDUs prevention consists of using sterile injecting equipment and not sharing injecting equipment. Safer sex also can reduce the risk of acquiring hepatitis C. Hepatitis C can be either chronic but asymptomatic or chronic-active, which means the disease will develop over a long period of time, several years, or perhaps even decades. People with active hepatitis C may have elevated liver function tests (LFTs), fatigue, and jaundice. The active disease can result in cirrhosis, liver cancer, and ultimately liver failure. Embolism can occur when air, fat, or particles are injected that occlude a blood vessel. It also occurs when part of a thrombus detaches. Emboli can be extremely serious, particularly if they lodge in the major vessels supplying the lungs or occlude arterioles supplying the brain or eyes. To prevent embolism: • Avoid injecting material from tablet preparations, no matter how crushed or pulverized it appears to be. • Make sure the injected drug is adequately dissolved. • use a ﬁlter to catch larger particles during injection preparation. • Ensure any venous clots are treated promptly. Cellulitis and abscesses can result from dirty or missed hits (injecting into the tissue surrounding the vein), injecting a particulate solution, failing to clean the injection site prior to injecting, or using non-sterile injecting equipment. (See Section 10.2.2 Skin and soft tissue infections.) Risk factors include poor injection technique, injecting tablets, injecting “cocktails” (for example, mixtures of diazepam, heroin, or antihistamines), repeatedly ﬂushing and pulling back during injection, being HIV−positive, and poor nutrition.

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Complications include the spread of infection into the adjacent tissue, gangrene, and the spread of infection through the bloodstream, causing: • endocarditis • osteomyelitis • multiple new abscesses (“seeding” of infection) • abscess formation on the joints, pleura, or other locations. Thrombophlebitis is infection of the vein wall. It can be an extension of cellulitis or result from the infection of a clot within the vein. For IUDs prevention consists of adopting sterile injecting techniques.

17.9 Involving the family The family can be very important in a drug-dependent person’s life, even though many drug users are estranged from them. Family members are often at a disadvantage, however, because they do not understand the origins and effects of harmful drug use and, therefore, lack the skills necessary to cope with the behaviour of the drug-dependent person. Also, they may lack understanding of how their own behaviour can contribute to someone’s harmful drug use or how they can facilitate or retard the drug user’s engagement in and response to treatment. Family counselling aims to help the family understand and cope with the situation and to enlist family members’ support in achieving the recovery goals of the drug-dependent person. A major challenge to family counselling is to convince family members (who may or may not be using drugs or alcohol themselves) to attend counselling sessions. Even if all the members of a family do not turn up for counselling sessions, it is possible to make headway with those who do. Common family reactions when confronted with their relative’s drug misuse Denial – an unconscious process of blocking out reality, which is usually manifested as failing to recognize the extent or severity of the problem, the connection between alcohol or drug use, and the problems it has caused, and failing to understanding that the drug user needs help to deal with the problem. The family also can deny their own part in the dependence. The longer denial goes on, the longer it takes before drug-using individuals change their behaviour. Co-dependence – Family members may unwittingly develop a pattern of co-dependence with their drug dependent relative. Family members may deny that the relative has a drug problem even when faced with clear evidence. They may cover up for the dependent person, do work that the dependent person does not complete, pay the bills not paid, rescue the person from various kinds of problems, and generally take up the responsibilities that the drug-dependent person has abandoned. Shame – Whether the substance is socially acceptable or is illicitly obtained, people in the family often feel ashamed. Self-blame – Some families often feel they are to blame for the situation and reproach themselves; parents may feel they have failed. Anger – Apportioning blame is another common family response. People may also blame other family members. Confusion – Family members often feel at the mercy of conﬂicting emotions. While they strive to protect the user from harm or censure, they feel furious that he or she has been “so stupid”.

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Social support for the family Many families need support when a drug-using relative is being treated. They often discuss the individual’s problem with other relatives, and this can be a source of resentment for the person with the drug problem. The patient with a drug use disorder should be encouraged to invite family members to discuss how they might help. Family members can help to ensure that the patient’s support system is strengthened. Other signiﬁcant people in the support system (e.g. friends, coworkers) must also encourage the person’s attempts to be drug-free and, if they are willing, can be involved in the process. Family participation during active treatment can be very important. However, family members are frequently extremely distressed and have often exhausted all their resources. They may need a great deal of assistance and encouragement to be able to support the person in treatment. A variety of strategies exist for the health worker to help family members of drug users: • listening in a non-judgemental way to the family’s concerns • providing basic information about the drug use disorder • providing individual support and counselling to family members as appropriate • explaining what is helpful and what is unhelpful in interacting with the recovering dependent person. In particular, it is important to discuss with the family what they should stop doing, or not do, if they want to help the drug user. It is unhelpful to: • become isolated from the person with a drug use disorder • be judgemental • give money to the drug dependent person or pay off their debts • habitually compare the dependent person with others who are healthy or successful. Family members should be encouraged to: • maintain contact and care for the person with a drug use disorder • be understanding toward that person • recognize the drug use disorder as an illness • remain conﬁdent and hopeful.

17.10 Integrating alcohol and drug use management with HIV care In the sequence of care of HIV-infected patients, there is considerable opportunity to integrate alcohol and drug use management (see Section 13 Chronic HIV care and Chronic HIV Care with ART and Prevention7 guideline module – IDU modiﬁcation). This is not just an opportunity but a necessity. In fact, denying the problem of

7 Chronic HIV Care with ART and Prevention. WHO, 2007. Available at http://www.who.int/3by5/capacity/chronic_ care_3_may_06.pdf

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alcohol or drug use or not properly addressing it may put at risk the HIV/AIDS management of an HIV-infected alcohol or drug user. The integration process can occur at different steps of the sequence of care, for example: • Prevention of HIV transmission: Harm reduction education can be part of a broader education programme (see Section 17.5 above) that includes promotion of safe sexual practices, such as condom use. • Education and support: Special adherence support can be offered, not only for ART, but also for any other HIV-related intervention. • OST: The same health facility can provide HIV/AIDS care, including ART, and dispense methadone or buprenorphine. • Other substance abuse treatment: Detoxiﬁcation and psychosocial care can be offered. • Routine clinical assessment of patients can include regular functioning, signs and symptoms of drug intoxication and withdrawal; in addition, the presence of morbidities associated with drug or alcohol use can be assessed and managed (including injection-related complications). • Immunization: Hepatitis B vaccination can be offered. • Referral and linkages: Patients can be enrolled in the network of institutions and organizations taking care of drug and alcohol use and HIV/AIDS, and referred in case of need. This includes linking with existing community and social services to solve socioeconomic problems and with peer support groups to solve problems related to HIV (such as HIV status disclosure, stigma, or discrimination) and ART challenges. Co-location of clinics providing HIV care and ART and those providing OST can be very advantageous in ensuring coordinated and effective treatment.

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18. General principles of geriatric care Table of contents 18.1 Helpful considerations while caring for older adults Frailty . . . . . . . . . . . . . . . . . . . . . . . . . . . Symptoms and signs of frailty. . . . . . . . . . . . . 18.2 Assessment of the older adult . . . . . . . . . . . . . . 18.3 Nutrition and hydration in older adults . . . . . . . . . 18.4 Medicines in older adults . . . . . . . . . . . . . . . . . 18.5 Older adults need ongoing vaccination . . . . . . . . 18.6 Family caregivers for older adults . . . . . . . . . . . . 18.7 Decision-making capacity and legal issues of care . 18.8 End-of-life care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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18. General principles of geriatric care Good management of older adults requires a holistic approach, with attention to overall health, daily physical functioning, and the mental and social well-being of the individual. Ageing is not a disease but instead reﬂects altered physiology, sometimes with multiple, coexisting pathologies. These can be challenging to a clinician, both to diagnose and to manage appropriately. Whatever the age, the older adult should be helped to keep his or her autonomy, e.g. the ability to take decisions concerning his or her own life and wishes.

18.1 Helpful considerations while caring for older adults • Ageing is a normal process, which does not require evaluation and treatment except when speciﬁc problems arise. • Diseases often present atypically. Metabolic diseases and depression are often misdiagnosed because their clinical presentations can be unusual. • Many disorders observed in older adults are multi-factorial in origin (and may result from adverse effects of medicines). • In cases of confusion, temporo-spatial disorientation, wandering, memory loss, impaired reasoning, or recent onset of shaking, consider cognitive disturbances in relation to dementia, Alzheimer disease, cerebro-vascular disturbances, or Parkinson disease (see Sections 3.4 and 10.11). If these symptoms are acute, also consider dehydration, infections, or drug reaction. • Daily functioning, control of pain and symptoms, and wellness all contribute to quality of life, which may be appreciated differently by older adults, their siblings, and caregivers. Quality of life is a multidimensional perception, depending also on spirituality, culture, life history, and project.

Frailty Frailty is a state of age-related physiological vulnerability resulting from impaired homeostatic reserve and reduced capacity of the organism to withstand stress. Frailty should be considered a pre-disability stage. Frailty can result in: • repeated falls, multiple fractures, and various traumas • disability • loss of independence • functional decline • hospitalizations • nosocomial infections • dependence • personal suffering • caregiver burden • institutionalization • death.

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Table: Symptoms and signs of frailty Symptoms • • • • • weight loss weakness fatigue or exhaustion anorexia inactivity Signs or conditions • undernutrition • sarcopaenia (progressive and generalised loss of skeletal muscle mass and strength or function) • osteoporosis (bone mass decrease and altered bone micro-architecture, leading to increased risk of fractures) • slow gait or walking speed • balance abnormalities • deconditioning

18.2 Assessment of the older adult Assessment of the older adult should include: • all systems as indicated • pain (assess physical causes of acute and chronic pain; see Section 20) • physical function, including activities of daily living • psychological function, including cognition, memory, mood • oral health • weight (if weight loss, is it voluntary?) • nutritional status and dietary needs • bowel habits and urinary and faecal continence • skin integrity • foot care • renal function if drugs need to be prescribed • history of any loss of function (transient or lasting), especially hearing and vision • sleep patterns • incidence of falls • smoking, alcohol, and other substance use • medications, including chronic therapy and over-the-counter (OTC) selfmedication.

18.3 Nutrition and hydration in older adults • Regular weighing is necessary. • Investigate involuntary weight loss because often it is linked to diseases with bad prognoses. • Check oral hygiene and mouth health. Difﬁculty chewing and swallowing due to oral health problems often are an unrecognized cause of malnutrition (see Sections 10.17 and 20). • Water and food security are essential. Poor access to food can be due to the cost of food or to social difﬁculties.

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18.4 Medicines in older adults Complex medication regimens and polypharmacy need to be regularly checked because of possible interactions, side-effects, inappropriate dependence, and treatment adherence problems. Inappropriate medication prescribing as well as drug abuse (e.g. with benzodiazepines) should be avoided. At the same time, medicine omissions also can be a problem (e.g. not recognizing and treating depression in older persons). Consider carefully these principles of geriatric pharmacology. • For some medications, start low and go slow. (However, give full doses of antimicrobial and antiretroviral drugs.) The central nervous system (CNS) is a particularly vulnerable drug target in the elderly. For example, there is increased susceptibility to benzodiazepines with long half-lives (diazepam) even at low dose levels. They tend to have serious hangover effects, including drowsiness, unsteady gait, slurred speech, and confusion. • Expect the unexpected, such as unusual side-effects and drug interactions. Confusion is often the presenting symptom (caused by almost any of the commonly used drugs). Other common manifestations are constipation (with antimuscarinics and many tranquillizers) and postural hypotension and falls (with diuretics and many psychotropics). The elderly are more prone to tendon damage with the use of quinolones and GI bleeding with NSAIDs. • There is a need for dynamic monitoring. Medications or dosages may need to be adjusted with changes in weight, renal function, or concurrent illness. Renal function is known to deteriorate with age, but there is large variability among individuals. Examples of medicines that should be used with caution are digoxin and lithium. • Avoid polypharmacy where possible, as it may lead to side-effects. • Some common medications should be used only if there is no alternative. These include analgesics containing codeine. • Consider the possibility of a drug-drug and drug-disease interaction prior to adding any new medicine. For example, NSAIDs can precipitate acute renal failure when used in a patient with concomitant chronic renal disease or can exacerbate high blood pressure in a hypertensive patient.

18.5 Older adults need ongoing vaccination Follow national guidelines for the vaccination requirements of older adults. Tetanus, influenza, and pneumococcal pneumonia are vaccine-preventable diseases that continue to kill more older persons than children.

18.6 Family caregivers for older adults • Respect the importance and needs of family caregivers in the life of the older patient. • Recognize their role, train them to give adequate care to their family member, and support them. Prevent their burn-out, which can lead to mistreatment or hospital admission of the old patient.

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• Pay attention to continuity of care from the home (with informal care by family and non-professionals) to the emergency ward, acute hospitalization, rehabilitation, and then return home. • Ageist attitudes of caregivers or health-care workers can be harmful. • Recognize and prevent mistreatment of the elder by family, caregivers, or guardians.

18.7 Decision-making capacity and legal issues of care Mental capacity and comprehension often ﬂuctuate during ageing and with some diseases. • Clarity of communication and of understanding needs special attention. ° Ask the older adult to reformulate messages to be sure of their understanding. • Regularly check autonomy (see above). ° A legal guardian should be considered if there is loss of autonomy. • Check that there is a last will and testament and advanced care directives; the latter may need regular updating to remain valid.

18.8 End-of-life care Preserve the health and autonomy of older persons while recognizing that decline, disability, and death are inevitable developmental stages of ageing. For control of pain, other symptom management, and end-of-life care, see Section 20. It is important to assure comfort and to respect human dignity.

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19. Prevention services for adolescents, adults and health workers Table of contents 19.1 Prevention services for adolescents and adults . . . . . . . . . . . . . . . . . . . . All acute and chronic patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Special prevention for adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . 19.2 Discordant couples counselling and services . . . . . . . . . . . . . . . . . . . . . 19.3 Special considerations for MSM and transgender persons . . . . . . . . . . . . . MSM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Transgender persons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Societal responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.4 Provide prevention, care and treatment services to health workers and other staff in health facilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.4.1 Manage workplace exposure to HIV . . . . . . . . . . . . . . . . . . . . . . 19.4.2 Facilitate and promote HIV testing, counselling, care and ART for staff . 19.4.3 Address workplace stigma about HIV through education and advocacy 19.4.4 Provide TB prevention and care services for health service workers . . 19.4.5 Prevention of hepatitis B in health workers . . . . . . . . . . . . . . . . . . 19.5 Urgent response to workplace HIV exposure . . . . . . . . . . . . . . . . . . . . . . First aid in the event of possible workplace HIV exposure . . . . . . . . . . . . How to determine if the exposure warrants PEP . . . . . . . . . . . . . . . . . . 19.6 Prevent, recognize and manage stress and burnout in staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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19. Prevention services for adolescents, adults, and health workers 19.1 Prevention services for adolescents and adults Check status of routine screening, prophylaxis, and treatment in all acute and chronic patients. Table: All acute and chronic patients Assess • Ask whether the patient and family are sleeping under a bednet. • If yes, has it been dipped in insecticide? • Is patient sexually active? (For adolescent: have you started having sex yet? See next page.) • Determine if the patient is at risk of HIV infection. • Is patient’s HIV status known? Treat and advise • Encourage use of insecticide-treated bednets.1

• Counsel on safer sex. See next page for adolescents. • Screen and treat for STIs (see Sections 10.14-16). • Offer family planning. • If unknown HIV status, ° recommend HIV testing and explain its advantages, and ° counsel after HIV testing (see Section 9 HIV diagnosis). • If yes, counsel to stop smoking.2 • If adolescent is smoking, educate on hazards, help to say no. If not, provide positive reinforcement. • If more than 21 drinks per week for men, 14 for women, or 5 drinks at once, assess further and counsel to reduce or quit. See Section 16. • If adolescent is drinking, educate on hazards, help to say no. If not, provide positive reinforcement. • Measure blood pressure. • Assess cardiovascular risk. • Follow national guidelines for treatment of hypertension, aspirin, antiplatelet medication, physical activity, diet, weight control.3 • Describe exercises to stretch and strengthen abdomen and back. • Advise on correct lifting.

• Does patient smoke? • If adolescent, “Do you feel pressure to smoke?” • Does patient drink alcohol? If yes, calculate drinks per week over last 3 months. • “Have you had 5 or more drinks on 1 occasion in the last year?” • Has patient been screened for hypertension and for cardiovascular risk (heart attack and stroke)?

• Occupation with back strain or history of back pain?

1 Insecticide-treated mosquito nets: a position statement. WHO, 2007. Available at http://www.who.int/malaria/ publications/atoz/itnspospaperﬁnal/en/index.html 2 mpower: A policy package to reverse the tobacco epidemic. WHO, 2008. Available at http://www.who.int/ tobacco/mpower/mpower_english.pdf 3 Prevention of cardiovascular disease: Guideline for assessment and management of cardiovascular risk. WHO, 2007. Use the appropriate version for subregion and adapt in country. Available at http://www.who.int/ cardiovascular_diseases/resources/publications/en/index.html

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Assess In adolescent girls and women of childbearing age Check when last dose of mebendazole Check tetanus toxoid (TT) immunization status: • When was TT last given? • Which dose of TT was this?

Treat and advise Give mebendazole if due.5 If TT is due: • give 0.5 ml IM, upper arm • advise her when next dose is due • record on her card.

5 TETANUS TOXOID (TT or Td)6 schedule (if no primary series) At ﬁrst contact with woman of childbearing age or at ﬁrst antenatal care visit, as early as possible during pregnancy. • At least 4 weeks after TT1 Ö TT2 • At least 6 months after TT2 Ö TT3 • At least 1 year after TT3 Ö TT4 • At least 1 year after TT4 Ö TT5 Offer HPV vaccine. Priority should be the vaccination of girls before their ﬁrst sexual intercourse (between 9 and 10 through to 13 years). Follow manufacturer’s schedule: 3 doses over 6 months. • If pregnant, discuss her plans, follow antenatal care guidelines, and advise against alcohol use and smoking. • If not pregnant, offer family planning. • Give sexual and reproductive health counselling. • If not circumcised, explain what circumcision is, the beneﬁts of circumcision in protecting against HIV infection, and where circumcision services are available.7 • Explain that male circumcision does not protect completely against HIV infection; it only reduces the risk of becoming infected. It is very important to continue using other ways of reducing the risk of infection – using condoms correctly and consistently, reducing the number of sexual partners, delaying the start of sexual relations, avoiding penetrative sexual intercourse, and avoiding unsafe injections. • Tetanus toxoid ° If received primary series (3 DTP, then booster TT at 4–7 years), give TT booster at 12–15 years. ° Give TT booster to adults. ° If no primary series, give 5 TT as above.

Check HPV vaccination status4 In women of childbearing age • Is she pregnant? In adolescent boys and men

See Section 13 for immunization for PLHIV.

4 Child and adolescent health and development: Which health problems affect adolescents and what can be done to prevent and respond to them? WHO, 2011. Available at http://www.who.int/child_adolescent_health/topics/ prevention_care/adolescent/dev/en/index.html 5 Working to overcome the global impact of neglected tropical diseases. WHO, 2010. Available at http://whqlibdoc. who.int/publications/2010/9789241564090_eng.pdf 6 Maternal immunization against tetanus. WHO, 2006. Available at http://www.who.int/reproductivehealth/ publications/maternal_perinatal_health/immunization_tetanus.pdf 7 For country adaptation.

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Table: Special prevention for adolescents (see Adolescent Job Aid8) Assess • Is patient sexually active? Treat and advise If no, encourage the patient to delay initiation of penetrative vaginal, anal, or oral sexual intercourse and to avoid anything that brings her or him into contact with a partner’s semen or vaginal secretions. • Advise to explore sexual pleasure in other forms of intimacy. • Find non-sexual activities that you and your partner enjoy. If yes – sexually active, provide information and counselling about the prevention of HIV, STIs, and pregnancy, emphasizing that condoms are dual protection against pregnancy and against STIs and HIV. • Advise the patient to reduce the number of partners or, better yet, be faithful to one. • Advise the patient to use condoms correctly and consistently every time he or she has sexual intercourse. Demonstrate how to use a condom. • Discuss appropriate ways of saying no to unwanted sex and negotiating condom use. Reinforce skills to say no (refer to an appropriate organization or group if the patient does not have the skills). Make sure girls understand that they cannot tell by looking at someone if the person is infected with HIV and that HIV risk increases with the age of the man. • Recommend HIV testing and counselling (see Section 9). If there was unprotected sexual intercourse, advise on emergency contraception within 120 hours (5 days) and on the prevention and treatment of STIs. If patient has been forced to have sex or was raped, see Section 4.4.

• If yes – sexually active, also ask: ° Do you use condoms? ° Were you forced to have sex? ° Do you consider yourself to be at risk of HIV, other STIs, or pregnancy? ° Do you know your HIV status?

Young people may know very little about HIV and how it is transmitted. Check their understanding, especially about how to protect themselves.

8 Adolescent job aid. A handy desk reference tool for primary level health workers. WHO, 2010. Available at http:// www.who.int/child_adolescent_health/documents/9789241599962/en/index.html

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19.2 Discordant couples counselling and services9 It is estimated that as many as 50% of PLHIV who have a partner are in a discordant couple (where one partner is HIV-negative and the other is HIV-positive). Therefore, a large proportion of HIV transmission occurs within HIV-discordant couples. Many people, however, have the misconception that discordance is not possible or is not common. In fact, HIV-negative partners in discordant couples are at high risk of HIV infection and are a very important group for HIV prevention efforts. Counselling and the provision of condoms for discordant couples is effective in preventing HIV transmission. The district clinician has a key role to play in ensuring that health care providers and patients are aware how frequent discordance is, especially in populations with high HIV prevalence. Couples counselling, where two people in a relationship come for HIV testing and counselling as a couple, can identify serodiscordant couples and empower them to prevent HIV transmission. A major beneﬁt of couples counselling is that couples can be supported to share their HIV test results with each other with the guidance of a counsellor. This can be important whether or not the couple’s status is discordant, but it can be particularly helpful when a couple has serodiscordant results. Concordant positive partners can be assisted to support each other and to make decisions together about HIV care, ART, and PMTCT. The district clinician and team may need to provide detailed oversight and speciﬁc inputs to encourage and facilitate couples counselling where possible and appropriate. The couples counselling strategy complements other testing models well and plays its part in increasing the overall coverage of testing. Be ﬂexible in choosing the sites for testing and counselling of couples, e.g. by offering these services in community settings as well as in the clinic. More broadly, all people diagnosed as HIV-positive must be encouraged to disclose their HIV status to those who need to know and to propose that these people obtain HIV testing and counselling—not only sexual partners but also, as the case may be, drug-injecting partners, children, and other immediate family members. Support and other services for couples After HIV testing and counselling as a couple, people require ongoing services, especially couples who are concordant positive or discordant. This includes ongoing behavioural counselling and psychosocial support through couples counselling and support groups. The counselling covers topics such as reducing HIV transmission risk, reproductive health and family planning counselling, planning for pregnancy (see Sections 13 and 14), couples communication, and condom provision. See Section 12.4 Positive prevention for further details. Speciﬁc measures may be needed to support and counsel individuals with multiple concurrent partnerships. The counsellor has a crucial opportunity to help discordant couples deal with their test results, and to take steps to reduce the risk of transmission. Key functions of counselling for discordant couples are to: • facilitate understanding and acceptance of results • dispel myths about HIV transmission

9 Interim guidance on couples HIV testing and counselling and antiretroviral therapy for treatment and prevention in serodiscordant couples. Work in progress at WHO, 2011.Guidance on cRelease of the

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• provide clear and accurate prevention messages • empower the couple to commit to risk reduction.

19.3 Special considerations for MSM and transgender persons10 MSM The term “men who have sex with men” (MSM) is a broad term describing a diverse group of sexual identities, including men who self-identify as gay, bisexual, or transgender, as well as those who identify as heterosexuals but who have sex with other men for pleasure or economic exchange. Despite some claims to the contrary, sex between men occurs in every culture and society throughout the world, although its acknowledgement and social and legal acceptance varies greatly. Especially in countries where stigma is widespread or the behaviours are criminalized, MSM often are married to women, and individuals are not open about their behaviour and practice, placing additional HIV risk on them and their otherfemale partners who are often not aware of their risk. Other special contexts include MSM who sell sex, sexual experimentation in youth, sexual violence, including rape, and male-only environments, such as prisons, the military, and some communities of migrant workers. As unprotected sex between men, especially anal sex, carries signiﬁcant risk of HIV transmission, MSM remain a key group in the global HIV epidemic; UNAIDS estimates that globally 5%–10% of infections are in MSM. As MSM are the predominant risk group in many countries, and high transmission rates among MSM also occur in countries with generalized epidemics, these men require targeted prevention, care, support, and treatment. Stigma, discrimination, and punitive laws, and homophobic attitudes of health workers, increase vulnerability to HIV by discouraging access to prevention and treatment services, and HIV testing, and health care in general. In particular, lack of screening and treatment for STIs promotes HIV transmission. Further, stigmatization of MSM can fuel depression and substance use, which further raises vulnerability to HIV. Providing health care to MSM Essential to good patient care is the health worker’s cultural competence, deﬁned as the ability to interact effectively with individuals of different cultures. For most clinicians in several settings, MSM represent, in effect, a “foreign culture”, with different practices and world views. Health workers need to develop skills to better understand and communicate with patients from different social cultures such as MSM. Because of stigma and discrimination, many MSM need reassurance that it is safe to speak openly to health workers and that public services are available to them as to anyone else. Safety can be communicated through attitudes, language, and conﬁdentiality. Creating inclusive health services requires strategies to sensitize and educate health workers. 10 Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender people. WHO, 2011. Available at http://whqlibdoc.who.int/publications/2011/9789241501750_eng. pdf

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• Although attitudes can be deeply rooted, health workers should adopt a nonjudgmental, empathic approach to all patients, including MSM. Being aware of one’s reactions to people who are different is the ﬁrst step. • Health workers’ language should be free of assumptions about patients’ sexual identity and behaviour. Non-assumptive questions around sexual preference include “Are your sexual partners female, male, or both?” or “Some men, although they are married or have a girl friend, also have sex with men. Do you ever have sex with men?” It may be helpful for the health worker to know the words that the patient uses to describe himself and his behaviour, and to use those words. • The assurance of privacy and conﬁdentiality is a fundamental aspect of health care. Before enquiring about a sexual history, the health worker can explain why it is required. This can be reassuring for the patient, e.g. “Sometimes it can be uncomfortable to talk about sex, but in order for me to help you, I need some information that may be very personal to you. Would you mind if I ask you a few questions?” For some patients it may take a while to build trust; others, out of fear, may never disclose. Although not ideal, it may be possible to provide appropriate care to MSM without patients formally acknowledging their sexual practices. Especially in environments where there is criminalization of the behaviour of MSM, the health worker must ensure the conﬁdentiality of shared information and health records. Safer sex and MSM Safer sex is any choice made or behaviours adopted that reduce the risk of transmitting HIV and other STIs. HIV testing and counselling is one component of making sex safer, and health workers should recommend testing to MSM (see Section 9 HIV diagnosis). For MSM unprotected anal sex holds the highest risk for transmitting HIV, whether the person is the insertive partner or receptive partner, but especially for the receptive partner. The best way to lower this risk is through consistent condom use. Insertion without a condom and then withdrawing before ejaculation is not an effective strategy. In anal sex a water- or silicone-based lubricant should be used to avoid breakage of the condom and micro-tears and bleeding in the rectum. Oil-based lubricants should be avoided because they can damage the latex of the condom. Hand lotions and cooking oils are examples of oil-based lubricant substitutes that should be avoided. Oral sex without a condom holds a much lower risk of HIV transmission than anal sex, but it still may transmit the virus, especially if there are lesions, cuts, or infections in the mouth. PLHIV need to practice safer sex consistently to avoid passing HIV to others and to prevent getting infected with other STIs. Health prevention messaging for MSM must stress that condoms and lubricants should be used together. Using lubricants in the absence of condoms for anal sex may increase HIV risk. Lubricants can cause anal mucosal inﬂammation and thus increase HIV risk due to the hyperosmolar nature of most lubricants, which damages epithelial cells. It is not currently known if using lubricant alone is better or worse than dry anal sex, which also physically damages anal epithelium; further studies are required. Safer sex counselling for MSM should aim to normalize, and not moralize about, consensual sex between men. Informing MSM about the potential infectivity of

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various body ﬂuids and how they might be transferred from one sex partner to another will provide information that allows MSM to determine their speciﬁc risk according to their own sexual behaviours and to use this information to develop a risk-reduction strategy. This counselling strategy is likely to be effective in reducing HIV risk and should also inform to protect against STIs that do not require transfer of semen or blood to cause a new infection, e.g. gonorrhoea and chlamydia. Prevention and treatment of sexually transmitted infections STIs increase HIV transmission through open sores and inﬂammation of the urethra, glans, rectum, and oral pharynx. The site where STIs occur in MSM, and thus the screening and diagnosis of STIs, depends on sexual practices. More details on treatment of STIs are in Sections 10.14 Anogenitourinary problems (female and male), 10.16 Male genitourinary problems, 11.13 Gonorrhoea, and 11.37 Syphilis. • Gonorrhoea and Chlamydia infections can be present in the pharynx, rectum, and urethra and are often asymptomatic. Standard treatment usually is sufﬁcient in HIV-positive men, even if immunocompromised. • Syphilis chancres may also develop in the pharynx, rectum, and urethra. Any sexually active MSM should have regular syphilis screening and receive adequate treatment as needed (see Section 11.37). Clinicians should be alert for ocular, auditory, or neurological symptoms in a sexually active HIVpositive MSM as this may indicate neurosyphilis. • Herpes simplex virus (HSV) may be present in the mouth, anus, or penis and may cause a very painful proctitis. Treatment is the same regardless of HIV serostatus, although those with low CD4 cell counts may have frequent recurrences and beneﬁt from aciclovir prophylaxis. See Section 11.15. • Condyloma accuminata (HPV) is less common in the mouth but very common in the penile and perianal regions. Anally, HPV can be present externally or internally up until the dentate line (anal papillae). Treatment of internal anal warts requires anoscopy for visualization and cryotherapy, surgery, or topical acid therapy. Podophylin should not be used internally due to the risk of systemic absorption. There is growing concern that individuals with a history of internal anal HPV may be at increased risk for anal cancers. HIV-positive patients with low CD4 cell counts can be slow to respond to HPV treatment. Improvements in CD4 cell counts with ART will often improve the response. • Hepatitis viruses are very prevalent in some populations of MSM. Hepatitis A is acquired through oral-faecal contact including during sexual practice; hepatitis B, mainly through sexual contact; and hepatitis C is transmitted through sexual contact or intravenous drug use. Immunization for hepatitis A and B is recommended in sexually active MSM (see Section 11.14). MSM should be included as targets of catch-up HBV immunization strategies in settings where infant immunization has not reached full coverage. • In addition to the infectious proctitis and perianal lesions described above, MSM can present with protocolitis or enteritis usually associated with oralfaecal contact. Pathogens include Entamoeba histolytica, Giardia lamblia, Shigella, Yersinia, and Camplylobacter. See Section 10.7. HIV-positive MSM Although recommendations for ART in MSM are consistent with those for other adults, MSM may require different approaches for care and support. Some individuals may view HIV as a punishment for their sexual behaviour and will need counselling to help reframe their self-perceptions. In providing care, the health worker should take into account the relationship and home life of the patient, which may include a male partner. This is especially important in end-of-life care

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(see Section 20 Palliative care). It is the health worker’s responsibility to ensure that the patient does not experience discrimination from other staff or patients. Where possible, it is often useful to work with MSM community organizations to help provide support and care for HIV-positive MSM. Health care workers should be wary of disclosing the HIV status of individual MSM to MSM communitybased organizations, as it opens up the possibility of HIV stigma (even from MSM “friendly” organizations). This should be discussed with the HIV-positive MSM before any referrals are made. Other MSM health issues MSM may have higher rates of depression, suicidal ideation, anxiety, and substance disorders than the general public, especially in adolescence. This is likely due to internalization of stigma and marginalization, potentially compounded by family rejection and lack of social support. These problems increase vulnerability of MSM by interfering with their ability to practice safer sex and to access health services. For more details on treatment, see Section 10.11 Mental health and Section 17 Substance use.

Transgender persons Transgender individuals often are included in discussions of HIV and MSM even if they do not identify themselves as men or are passing as men although biologically female. As with MSM, there is a wide spectrum of gender identity and expression. A number of cultures have special identities for individuals who adopt gender roles different from their natal, anatomical gender, but even in these cultures they can be highly stigmatized. In addition to the health care issues described above for MSM, health problems may stem from treatments to change gender, such as hormone injections, implants, or gender reassignment surgery.

Societal responses Adequate care and HIV prevention among MSM and transgender individuals will require widespread legal and human rights reform in all countries. Development of community organizations run by and for MSM and transgender persons, in combination with legal aid services, will complement the formal health care system and help advocacy for legal and human rights reform. Finally, anti-homophobia campaigns in the general population should be a part of HIV awareness campaigns. Ultimately, it will require widespread acknowledgement that there is a diversity of human sexual experience in all cultures and societies and that everyone deserves non-judgmental prevention, care, and treatment by the health and social services systems and by society at large.

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19.4 Provide prevention, care, and treatment services to health workers and other staff in health facilities 19.4.1 Manage workplace exposure to HIV11 Provide free and timely post-exposure prophylaxis (PEP) to all health workers and other staff, for both occupational and non-occupational exposures. During employee training, workplace procedures that deal with exposure to HIV should be included with other workplace safety guidelines. Pre-speciﬁed monitoring plans should assure that these procedures are implemented. Although prevention measures can reduce workplace exposure to HIV, health workers should be prepared for accidental exposures. Here are some steps to manage HIV exposure in the workplace. A. Identify a contact person to deal with workplace HIV exposure. This person could also be responsible for infection control in general for the facility. Choose someone who is: • responsible • trained • respects conﬁdentiality • trusted and agreed upon by staff • willing and motivated to be available during all working hours (or else the hospital needs to assign more than 1 contact person). Responsibilities: • explain procedures and PEP • coordinate blood test results • arrange and facilitate conﬁdential HIV testing and counselling for the staff • remind the staff when follow-up blood tests are due • complete the necessary forms and reports, and ensure conﬁdential storage of all documentation • complete the incident report (for occupational health and safety review and for possible compensation) and include in the health centre log book.

B. Set up a system to urgently respond to workplace HIV exposure and make HIV PEP available 24 hours a day, 7 days a week (including during holidays and weekends). C. Post the PEP procedures on the clinic wall, on staff notice boards, and in staff rooms, and make PEP clinical guidelines easy for all staff members to obtain at all timesof . D. Keep starter packs – or initial doses of PEP – in the hospital emergency cupboard and ensure that they are accessible 24 hours a day, including during holidays and weekends. Staff should have the option to obtain services away from the worksite for greater privacy and conﬁdentiality. E. Strongly encourage staff to report incidents of exposure to HIV in the workplace. Use the HIV PEP procedures for ALL staff exposed to HIV in the workplace. (This means all categories of health personnel, including public and private employees and auxiliary staff.) F. Routinely educate and inform staff about HIV PEP. This includes how and 11 The joint WHO ILO UNAIDS policy guidelines for improving health workers’ access to HIV and TB prevention., treatment, care and support services. WHO, 2010. Available at http://www.who.int/occupational_health/ publications/hiv_tb_guidelines/en/

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where to obtain information and services, and reporting procedures during working hours. G. Support staff access to conﬁdential HIV testing and counselling services. Ongoing counselling is extremely important in the context of PEP, as the exposed staff member usually is very anxious. If not managed, this high level of stress and anxiety may increase perceived ART side-effects and lead to premature discontinuation of PEP.

19.4.2 Facilitate and promote HIV testing, counselling, care, and ART for staff12 • Encourage every member of staff, including auxiliary staff, to be tested for HIV. • Place information in staff rooms about convenient locations of HIV testing, counselling, care, and treatment services. • Health workers should understand the importance of early HIV diagnosis and receiving HIV care and treatment, including early ART. • Make sure health workers understand that unprotected sex remains the most common route of HIV transmission; emphasize that safer sex practices are very important. • Support the formation of HIV-positive staff support groups. • Respect the choice of staff members to access HIV services in health facilities other than where they are working.

19.4.3 Address workplace stigma about HIV through education and advocacy • Members of staff often are afraid to be tested or to receive treatment for fear of breach of conﬁdentiality and being rejected or stigmatized by others at work. • Understand that stigma can manifest itself in the form of derogatory words, attitudes, and practices. • Develop an HIV/AIDS workplace policy (the district health ofﬁce can assist). • Hang posters with messages that combat stigma. • Communicate with fellow health workers about having positive attitudes towards people living with HIV. • Invite a PLHIV community group to visit the health centre during a regular staff meeting to discuss their experiences with HIV-related stigma and how being HIV-positive affects a person’s life.

19.4.4 Provide TB prevention and care services for health workers All health workers should know the symptoms of TB and undergo TB screening if they have signs and symptoms (see Section 15). PLHIV should be offered a package of prevention, treatment, and care that includes regular screening for active TB, isoniazid preventive therapy (IPT),and antiretroviral therapy (ART).

12 Chronic HIV care with ARV therapy and prevention. WHO, 2007. Available at http://www.who.int/hiv/pub/imai/ primary_arv/en/index.html

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If a staff member is diagnosed with active TB, provide the full regimen of anti-TB treatment. HIV-positive health workers should not be working with patients with known or suspected TB, MDR-TB, or XDR-TB, and they should be relocated from positions where exposure to untreated TB is high to a lower risk area. Particulate respirators provide additional protection against TB. • Make them available and train staff in their proper use. • Prioritize their use (if supply is limited) for: ° care for infectious TB patients, particularly MDR-TB and XDR-TB, ° when caring for patients with ARD caused by a novel pathogen (mode of transmission not known) or with diseases such as measles and Varicella zoster (chicken pox) in their infectious phase.

19.4.5 Prevention of hepatitis B in health workers13 Routine immunization of health workers against infection with HBV is recommended. All health workers who are exposed to the risk of bloodborne pathogens, including waste disposal workers and emergency and safety workers, should be immunized either before training or as soon as possible after commencing work, unless they are already immunized. • Pre-vaccination serological testing is unnecessary. • A common schedule is 3 doses at 0, 1, and 6 months. Many different schedules are available. • The usual adult dose is 1.0 ml IM (twice the monovalent paediatric dose of 0.5 ml). • Perform serological testing 2–6 months after the third dose of HBV vaccine to demonstrate whether an antibody response has developed against hepatitis B surface antigen.

13 WHO best practices for injections and related procedures toolkit. WHO, 2010. Available at http://whqlibdoc.who. int/publications/2010/9789241599252_eng.pdf

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19.5 Urgent response to workplace HIV exposure When a health worker is exposed to HIV through a needle-stick or splash of blood or body ﬂuid, the following steps should be taken to ensure their safety. Step 1: Give ﬁrst aid Table: First aid in the event of possible workplace HIV exposure Needle-stick exposure or other laceration Attend to the injury immediately. Do not squeeze the injury site. After a splash contacts unbroken skin Wash the area immediately. After a splash contacts the eye After a splash contacts the mouth Spit the ﬂuid out immediately. Rinse the mouth thoroughly, using water or saline, and spit again. Repeat this process several times.

Wash the exposed eye immediately with water or NS. Sit in a chair, tilt the head back, and have a colleague gently pour water or NS over the eye, pulling eyelids up and down to make sure the eye is cleaned thoroughly. If contact lenses are worn, leave them in place while irrigating the eye, as they form a barrier over the eye and will help protect it. Once the eye has been cleaned, remove the contact lenses and clean them in the normal manner. This will make them safe to wear again.

Wash site immediately using soap and water or a mild disinfectant Solution (such as chlorhexidine) If running water is not available, clean site with a gel or hand-rub solution.

Do not use any strong solutions, such as bleach or iodine, as these may irritate the wound or skin and make the injury worse.

Do not use soap or disinfectant on the eye or in the mouth.

Step 2: Contact your health centre contact person designated for workplace HIV exposure. See example contact form below: Name Mobile phone Hours available

Step 3: Determine whether PEP is needed14 PEP is needed urgently if all 3 conditions below are present: 1. Workplace exposure occurred within 72 hours. 2. The exposed person is HIV-negative. If their status is unknown, advise them to take an HIV test.

14 Post-exposure prophylaxis to prevent HIV infection. WHO/ILO, 2007. Available at http://www.who.int/hiv/pub/ prophylaxis/guidelines/en/

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3. You have determined that there is a high- or medium-risk exposure to blood, body tissues, blood-stained ﬂuid, or other bodily ﬂuids (see chart below). PEP should be available in the facility 24 hours a day, 7 days a week.

Table: How to determine if the exposure warrants PEP Signs Puncture or cut with: • Large-bore hollow needle • Needle used in source patient’s artery or vein • Deep puncture wound • Visible blood on instrument Classiﬁed as HIGH-RISK EXPOSURE Management • Offer PEP regimen: ° preferred regimen: 28 days AZT+3TC ° alternative regimen: 28 days d4T+3TC or TDF+3TC* • Before starting PEP, strongly recommend HIV testing and counselling. • If the exposed person is HIV-positive, stop PEP and refer for chronic HIV care. • Offer PEP regimen: ° preferred regimen: 28 days AZT+3TC ° alternative regimen: 28 days d4T+3TC or TDF+3TC* • Before starting PEP, strongly recommend HIV testing and counselling. • If the exposed person is HIV-positive, stop PEP and refer for chronic HIV care. • PEP not recommended

Puncture or cut with: • Small-bore or solid needle • Superﬁcial scratch • Splash onto broken skin or mucus membranes

MEDIUM-RISK EXPOSURE

Splash onto intact skin

VERY LOW RISK

*See IMAI Chronic HIV Care with ART and Prevention guideline module and your national PEP guidelines for details.

A regimen comprising two nucleoside-analogue reverse-transcriptase inhibitors plus a boosted protease inhibitor can be considered if: • the source person is HIV positive, taking antiretroviral therapy and is known to have signs of, personal history of or proven antiretroviral therapy resistance; or • the source person’s HIV status is unknown; and • the background prevalence of resistance to antiretroviral therapy in the community exceeds 15% (where this is known). If drug resistance is suspected and a third drug is considered necessary, it should be a boostedprotease inhibitor, not a non-nucleoside reverse-transcriptase inhibitor. Follow your national guideline on the speciﬁc preferred regimen in such situations. If the resistance proﬁle of the source person is known, the selection of PEP medicines should take account of that proﬁle. Nevirapine is not recommended for PEP due to the risk of toxicity and efavirenz should not be given to women who are pregnant and in their ﬁrst trimester or are of childbearing age because it is teratogenic.

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Step 4: HIV testing and counselling – conﬁdential and with informed consent • Recommend testing to the source of the exposure if HIV status is unknown. • Recommend testing to the exposed person as soon as possible and before starting PEP. ° The exposed person should not receive PEP if already HIV-positive as it can cause ARV resistance, which can limit future treatment options. HIV-positive exposed persons should instead be referred for HIV care and ART if eligible. Step 5: Administer PEP as soon as possible Give a ﬁrst dose at the health centre, dispense remaining pills, and arrange followup according to national PEP guidelines. Step 6: Record the workplace exposure incident in the health centre log book Contact your district health ofﬁce for this log book if you do not have one.

19.6 Prevent, recognize, and manage stress and burn-out in staff • Be conﬁdent that you have the skills and resources to care for the patients and their families. • Deﬁne for yourself what is meaningful and valued in care giving. • Be aware of what causes stress, and proactively manage it, or avoid it if possible. • Use strategies that focus on problems rather than emotions. • Change your approach to -caregiving: divide tasks into manageable parts (small acts of care); learn how to adjust the pace of -caregiving; ask others to help; encourage self-care by the patient. • Share or delegate tasks to your colleagues as appropriate. • Be aware that you cannot do everything and that you also need help. • Take care of your life outside of your workplace (ensure you have other interests, family, friends). Take care of your own health. • Use relaxation techniques regularly. • Develop your own psychosocial support network (such as -caregiver support groups, counsellors’ group, etc). • Discuss problems with someone else. • Share problems with your colleagues; consider forming a staff support group. • Take time off on a regular basis. • Include in your week a time to discuss patients with other staff (at staff meetings, case reviews, with your mentor, etc.). • Organize or participate in social events (staff birthdays, marriages, or graduations). Recognize burn-out! Symptoms include irritability, anger, poor sleep patterns, inadequate concentration, avoidance of patients and problems, withdrawal from others, fatigue, and emotional numbing, including lack of pleasure; resorting to alcohol or drugs; and (in survivors of multiple loss) fear of grieving.

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20. Palliative care: symptom management and endof-life care Table of contents 20.1 Assess pain (acute or chronic pain) . . . . . . . . . . . . . . . . . . . . . . . . . . . . Assess the patient for pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Assessment tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.2 Manage chronic pain in lifethreatening diseases including cancer and HIV/AIDS Manage chronic pain with analgesics, other medications for special pain, and non-medical treatments . . . . . . . . . . . . . . . . . . . . . . Speciﬁc considerations regarding the use of oral morphine in chronic pain. . . Teaching the health worker and the patient about the use of pain medications . Reduction or cessation of opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . Non-pharmacological interventions for chronic pain . . . . . . . . . . . . . . . . 20.3 Medications to control special pain problems . . . . . . . . . . . . . . . . . . . . . . The use of adjuvant analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Examples of the use of adjuvant analgesics . . . . . . . . . . . . . . . . . . . . . . Nerve blocks for speciﬁc severe pains . . . . . . . . . . . . . . . . . . . . . . . . . 20.4 Manage acute pain in emergency or acute conditions . . . . . . . . . . . . . . . . . Manage acute severe pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Morphine IV infusion for refractory severe acute pain . . . . . . . . . . . . . . . . 20.5 Symptom management: cough or difﬁculty breathing . . . . . . . . . . . . . . . . . . 20.6 Symptom management: hiccups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.7 Symptom management: trouble sleeping. . . . . . . . . . . . . . . . . . . . . . . . . . 20.8 Manage other symptoms using other Sections of this manual . . . . . . . . . . . . . 20.9 Preventive interventions for all patients . . . . . . . . . . . . . . . . . . . . . . . . . . Oral care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preventing bedsores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preventing pain, stiffness, and contractures in muscles, and moving the bedridden patient . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.10 Special considerations in palliative care for PLHIV . . . . . . . . . . . . . . . . . . . 20.11 Special consideration in palliative care for TB patients . . . . . . . . . . . . . . . . 20.12 Special considerations in palliative care for cancer . . . . . . . . . . . . . . . . . . 20.13 End-of-life care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bereavement care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

700 700 700 701 701 705 706 706 707 708 708 709 710 711 711 711 712 713 714 714 715 715 715 715 716 716 717 718 718

20. Palliative care: symptom management and endof-life care Palliative care includes symptom management during both acute and chronic illness and end-of-life (terminal) care. This includes management of pain but also other symptoms such as nausea, vomiting, itching, etc. This ﬁts with Figure B, rather than the original dichotomous version shown in Figure A, where patients receive curative-restorative care until this fails and then receive palliative care.

Figure A1

Figure B1

When providing palliative care, both speciﬁc treatment for the illness and treatment to relieve symptoms are needed in hospital and as part of home-based care. There are certain interventions for symptom control that may be possible only in a hospital setting. In addition to using these guidelines for symptom management of patients in hospital, ﬁrst-level facility health workers may need to consult with the district clinician for morphine prescriptions, a decision that the patient is terminal, the use of steroids in end-of-life care, and other medical issues.

1 Reprinted with permission of the American Thoracic Society. An ofﬁcial American Thoracic Society clinical policy statement: palliative care for patients with respiratory diseases and critical illnesses. American Journal of Respiratory and Critical Care Medicine, 2008, 177:912–927. (© 2011 American Thoracic Society)

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20.1 Assess pain (acute or chronic pain) Pain is deﬁned as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. There are two types of pain. • Nocioceptive pain (common pain), which is due to the stimulation of pain receptors in the tissues (there is no damage to the nerve). This pain is often described as sharp, dull, aching, throbbing, or spasmodic. • Neuropathic pain (special pain), which is caused by damage to the central or peripheral nervous system. Such pain is often described as burning, tingling, stinging, or “pins and needles”. Chronic pain is associated with a chronic pathological process: • It may have a gradual or ill-deﬁned onset. • Can continue relentlessly for months or years. • Often, chronic pain is not accompanied by clinical signs, so the patients may not appear to be in pain. • May be accompanied by depression or withdrawal.

Assess the patient for pain Assessment is vital for successful pain management. • Remember that “pain is what the patient says it is”. Pain is always subjective; it is important to believe the patient. (For special considerations in people who use drugs, see Section 17 Substance use.) • Determine the cause of the pain by history and examination (for new pain and any change in pain). Ask the following or similar questions: ° Where is the pain? ° What makes it better or worse? ° Describe it, e.g. sharp, dull, shooting, tingling, stinging, etc. (to ascertain the type of pain). ° What are you taking now for the pain? • Use other Sections in this manual to determine if there is an infection or other problem needing speciﬁc treatment. Prompt diagnosis and treatment of infection are important for pain control. • Is there a psychological or spiritual component?

Assessment tools Assessment is an ongoing process and should be carried out regularly to ascertain the pattern of the individual’s pain and the effectiveness of any treatment. There are a variety of assessment tools that can be used. The simplest and easiest to use are body diagrams, pain intensity scales, and the pain faces scale. • Body diagrams ° The body diagrams are used to document the site of pain. ° Patients mark the site of their pain or pains on the body diagrams. • Pain intensity scales ° Pain rating scales are simple scales that help to follow the course of the patient’s pain and the effect of any treatment given. ° Among the most commonly used scales are the numeric pain intensity scale and the Wong-Baker FACES pain rating scale.

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0–10 Numeric Pain Intensity Scale

0 No pain

5 Moderate pain

10 Worst possible pain

The patient is asked to rate the pain along the pain intensity scale (shown above) or to grade the pain with the FACES scale (especially for children) or with your hand (with no ﬁngers being no pain, 1 ﬁnger very mild pain, and 5 ﬁngers the worst possible pain) (shown below). It is important to record the ratings given by the patient, noting the intensity of the pain, the time, and the date.

20.2 Manage chronic pain in lifethreatening diseases including cancer and HIV/AIDS Manage chronic pain with analgesics, other medications for special pain, and non-medical treatments • The aim is to relieve pain as quickly as possible and to prevent it from coming back. • Pain can be managed in several ways: ° with analgesics, according to the analgesic ladder ° with medications to control special pain problems, as appropriate ° with non-pharmacological treatments. • It is important to regularly reassess the need for pain medication and other interventions. Regular grading of the pain, using the above assessment tools, will help to see whether the pain is being managed or not. • Any new problems should be investigated as appropriate. • Use the ABCDE steps for pain assessment and management: ° A – ask about pain regularly. ° B – believe the patient and family in their reports of pain and what relieves it. ° C – choose pain control options appropriate for the patient, family, and setting. ° D – deliver interventions in a timely, logical, and coordinated fashion.

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° E – educate and empower patients and their families; enable them to control their course to the greatest possible extent. • Use the WHO guidelines for pain guidelines for Cancer Pain Relief2, i.e. by mouth, by the clock, by the individual, and by the ladder. 1. By mouth • If possible, give by mouth, as it is the easiest route. • Rectally is an alternative. • Consider continuous IV infusion or intermittent or continuous subcutaneous infusion in a hospital or home setting, under supervision. • Avoid IM, as is shows no added beneﬁt. 2. By the clock • Give pain killers at ﬁxed time intervals (by clock, radio, or sun). • Give pain killers regularly to prevent the pain from returning; do not give analgesics for chronic pain on a PRN (as required) basis. • The next dose should be given before the effect of the previous dose wears off. • For breakthrough pain, give an extra “rescue” dose (same dosing as the four-hourly dose) in addition to the regular schedule. • Start with a small dose, and then titrate the dose against the patient’s pain until the patient is comfortable. 3. By the individual • Link the ﬁrst and the last dose of the day with waking and sleeping times. • Write out the drug regimen in full or present it in a drawing. • Teach patients and their families how and when to take the prescribed medication. • Check to be sure that the patient and family or assistant at home understands the regimen. • Ensure that pain does not return and that the patient is as alert as possible. 4. By the analgesic ladder – for adults • The choice of which analgesic to take should be guided by the WHO 3-step analgesic ladder for cancer pain. • The 3 steps of the ladder represent mild, moderate, and severe pain. • It is usual to start an individual on an analgesic from the ﬁrst step and then progress up the steps as needed. However, sometimes patients present with severe pain that requires going straight to a step 3 analgesic. • It is important to note that, if pain is not controlled by a step 2 analgesic, do not change to another stage 2 analgesic but instead move up to a step 3 analgesic. • Step 2 and step 3 opioids should not be used at the same time. • Patients should be given only 1 drug from the opioid group and 1 drug from the non-opioid group at a time. (Exception: If no codeine is available, aspirin every 4 hours can be combined with paracetamol

2 Cancer Pain Treatment, Including a guide to opioid availability (second edition). WHO, 1996. Geneva, Switzerland. Available at: http://whqlibdoc.who.int/publications/9241544821.pdf

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every 4 hours. They should be overlapped so that one is given every 2 hours.) • Other medications that are helpful for pain can be combined with these drugs (see next sub-section).

* Avoid aspirin in the presence of bleeding or if patient is less than 16 years old.

General issues to consider: • The correct dose of analgesics is the dose that gives the best sustainable balance between symptom relief, function and adverse effects. • Although there is a maximum dose for most analgesics, this is not the case for morphine. It has no maximum dose or ceiling. From a low initial dose, it can be increased slowly until pain relief is obtained. • The choice of analgesic is determined by the severity, site, and type of pain. • The aim is to improve quality of life, balancing pain with physical and mental functioning. • Consider the concept of “total pain”, i.e. that pain can be physical, psychological, social, spiritual, or cultural. These are all overlapping components that result in the “total” pain experienced by the individual. • Treat the underlying disease where possible. • If treatment of the underlying condition reduces pain or improves prognosis, consider reducing or ceasing opioids.

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The following is a guide to the use of various analgesics. Analgesics Non-opioid Paracetamol (also lowers fever) 1 gram every 4–6 hours, but no more than 4 grams in 24 hours Only 1 tablet may be required in elderly or the very ill, or when combined with an opioid. Mild pain might be controlled with doses every 6 hours. 300–900 mg (1–3 tablets of 300 mg) every 4–6 hours Maximum 4 grams daily Do not exceed 4 grams in 24 hours (more can cause serious liver toxicity). Starting dose in adults Range Side-effects and cautions

Aspirin (acetylsalicylic acid) (also anti-inﬂammatory and lowers fever)

600 mg (2 tablets of 300 mg) every 4 hours

Avoid use if gastric problems. Stop if epigastric pain, indigestion, black stools, petechiae, or bleeding. Avoid if any bleeding or renal impairment. Do not give to children under 16 years. With or after food

STEP 1

Ibuprofen (also anti-inﬂammatory, lowers fever)

200–400 mg 3–4 times daily

Maximum daily dose of 2.4 grams

Opioid for mild to moderate pain (give in addition to aspirin or paracetamol) Codeine (if not available, consider alternating aspirin and paracetamol) STEP 2 Codeine phosphate 30 mg every 4 hours Codeine phosphate 30–60 mg every 4 hours. Maximum daily dose for pain 240 mg. Consider switch to morphine when a dose of 180 mg is reached. Unless diarrhoea, give laxative to avoid constipation.

Opioid for moderate to severe pain Oral morphine: 5 mg/5 ml or 50 mg/5 ml or tablets. Give by mouth. If necessary, can be given IV or IM or subcutaneously. Initially, morphine sulphate 2.5–10 mg every 4 hours, increased by 30–50% if pain persists. According to pain There is NO ceiling dose. Unless diarrhoea, give laxative to avoid constipation. Excessive dosage can reduce respiratory rate. STEP 3

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Speciﬁc considerations regarding the use of oral morphine in chronic pain • Either immediate-release oral morphine solution or tablets can be used, as available. • Start with a low dose, e.g. 5–10 mg every 4 hours. • Increase the dose of oral morphine solution if pain persists, e.g. 5 mgÆ10 mg Æ15 mgÆ20 mg as doses every 4 hours. Increase in 30–50% dose increments; anything less is not effective. • Ensure that a breakthrough dose is prescribed initially, in case of pain before the next dose is available. The breakthrough dose can be 50–100% of the full dose in addition to the regular dose. • Explain to the individual that there are side-effects to morphine, which include constipation, nausea, and drowsiness. • Respond to the side-effects of morphine as appropriate (see below). • Always prescribe a laxative at the same time as the oral morphine, unless the individual has persistent diarrhoea.

If patient has a morphine side-effect: Constipation

Then manage as follows: • Increase ﬂuids. • Give stool softener at time of prescribing plus stimulant (senna). • Prevent by prophylaxis (unless diarrhoea, TB on PAS, or HIV). • Give an antiemetic: ° metoclopramide 10 mg IV/orally three times daily; OR ° chlorpromazine 25–50 mg IM/orally four times daily; OR ° ondansetron 4–8 mg twice daily orally or IV (see also Section 10.7c). • Usually resolves in several days. • May need around-the-clock dosing. • If severe, consider withholding next opioid dose; then halve the dose. • Usually occurs at start of treatment or when dose is increased. Usually resolves within a few days. • Can occur at end-of-life with renal failure. • Halve dose or increase time between doses. • Provide time with less analgesia when patient wants to be more fully alert to make decisions. • If on high dose, consider reducing dose or changing opioids (consult or refer). • Reassess the pain and its treatment. • Extended sleep can be from exhaustion due to pain. If it persists more than 2 days after starting treatment, reduce the dose by half. • May occur with normal dose. If present for more than a few days and hard to tolerate, give chlorphenamine. • Pass urinary catheter, if trained to do so – in and out since it usually does not recur.

Nausea or vomiting

Respiratory depression (rare when oral morphine is increased step-by-step for pain) Confusion or drowsiness (if due to opioid) Decreased alertness Trouble making decisions

Myoclonus (twitching), if severe or bothers patient during waking hours Somnolence (excessively sleepy)

Itching Urinary retention

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Misconceptions surrounding morphine have often limited its use in palliative care and led to unnecessary suffering. If necessary, reassure the individual that when used appropriately, morphine is a safe and effective analgesic and is the drug of choice. Although morphine has addictive potential, this is hardly ever a problem when a patient is terminally ill. A high level of tolerance develops, but this is easily overcome by steadily increasing the dose, and this does not usually lead to drowsiness or respiratory depression; neither does it hasten death. There is no ceiling dose. Reduce analgesic, e.g. morphine, when cause of pain is controlled (common in HIV complications) • If used only for a short time, stop or rapidly reduce. • If used for weeks, reduce gradually to avoid withdrawal symptoms.

Teaching the patient and family about the use of pain medications • The health worker must teach patients how to take their medications properly. • This should include discussion of the dosing frequency, with emphasis on adherence. Make clear that pain control must be balanced with side-effects. • If prescribing an oral morphine solution, make clear to the patient and the family how to take the correct amount. • Explain breakthrough analgesia and the importance of recording how much the patient is taking. Explain how this information is used to titrate the dose of the patient’s pain medicine. • Discuss potential side-effects and how these would be managed. See the IMAI-IMCI Palliative care: symptom management and end-of-life guideline module3 on instructing the patient and family to give pain medications, including oral morphine, and on how to use additional methods of pain control.

Reduction or cessation of opioids The above guidelines assume to a certain extent that treatment of pain goes in one direction, i.e. towards stronger medication, in higher doses, and that due to the life-threatening nature of the underlying condition, continued opioid treatment for the rest of the patient’s life does not pose any problem. There are a number of situations in which it might be necessary or desirable to reduce or even cease opioids, moving back down the pain ladder: • There is a reduction in pain severity due to treatment of the underlying condition. • Treatment of the underlying condition leads to cure or an improvement in prognosis. • Adverse effects of opioids are affecting quality of life. • There is evidence of abuse or diversion of opioids. • There is evidence of opioid-induced hyper-algesia.

3 IMAI-IMCI Palliative care: symptom management and end-of-life care. WHO, 2004. Available at: www.who.int/ hiv/pub/imai/genericpalliativecare082004.pdf

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Reduction or cessation of chronic opioid treatment should be conducted gradually. Sudden cessation of opioids will result in a worsening of pain and an opioid withdrawal syndrome, consisting of nausea, vomiting, diarrhoea, anxiety, insomnia, sweating, as well as muscle and joint aches and pains (see section on opioid withdrawal). A general rule of thumb is to start the reduction at not more than 10% per week and adjust as tolerated. If there is evidence of abuse or diversion of opioids then consider if the person has developed opioid dependence (see Section 17). In this case, is may be necessary to provide supervised doses of opioids, preferably with once daily opioids such as methadone. If this is not feasible, then opioid reduction or cessation may be required.

Non-pharmacological interventions for chronic pain • In light of the concept of total pain, it is important to remember that it is not only pharmacological interventions that can help relieve pain; there is also a role for non pharmacological interventions as an alternative to pharmacological interventions or in addition to them. • Psychological, social, spiritual. and cultural factors can play an important part in the perception and relief of pain. • Psychological factors: ° Psychological aspects are often seen in terms of anxiety or depression but may include anger, frustration, withdrawal, etc. ° Individuals struggle with chronic pain, as it is hard to accept and understand. ° Support can help the patient to adapt to and cope with the situation. ° Psychosocial support can help relieve pain. ° Examples of interventions include: ◊ psychosocial support and counselling ◊ support groups ◊ relaxation therapy ◊ meditation ◊ distraction, e.g. listening to the radio. • Spiritual factors ° Spiritual distress is an important part of suffering and may manifest itself in physical symptoms. ° An important part of pain control ° Examples of interventions include: ◊ spiritual support or counselling ◊ support groups ◊ prayer (respect the patient’s practise). • Social factors ° Social problems can contribute to pain; ° Examples of interventions include: ◊ information ◊ supportive counselling ◊ practical assistance ◊ accessing community resources ◊ food support ◊ transport issues ◊ care of the children ◊ provision for a will ◊ care of the corpse.

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• Cultural factors ° Individuals from different cultural backgrounds respond to their pain differently. ° Health workers need to be non-judgmental in their response to an individual’s pain and ◊ Overcome language barriers if possible. ◊ Be sensitive to culture, ethnicity, gender, sexuality, etc. • Other non-pharmacological interventions that help reduce pain ° regular limb exercises (can reduce contractures and therefore pain) ° massage ° acupuncture ° trans-cutaneous electrical nerve stimulation (TENS) ° heat and cold packs ° deep breathing ° music ° yoga ° traditional practises that are helpful and not harmful; it is important to get to know what can help in the local setting.

20.3 Medications to control special pain problems There are nerve injury pains and pains from special conditions that can be relieved by speciﬁc medication (see table below). Provide speciﬁc treatment in combination with drugs from the analgesic ladder.

The use of adjuvant analgesics • Adjuvant analgesics are medications whose primary purpose is not as an analgesic but that may contribute signiﬁcantly to pain relief. • They can be used on their own or in combination with steps 1, 2, and 3 analgesics. • They are particularly useful in neuropathic pain, bone pain, pain related to smooth or skeletal muscle spasm, and pain related to anxiety.

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Examples of adjuvant analgesics are as follows: • antidepressants, e.g. amitriptyline for nerve pain • anticonvulsants, e.g. carbamazepine for nerve pain – used if amitriptyline does not work or is not available • muscle relaxants, benzodiazepines, e.g. diazepam – used for muscle spasm • corticosteroids, dexamethasone – used for bone pain, neuropathic pain, raised intracranial pressure, and pain associated with oedema and inﬂammation. Table: Examples of the use of adjuvant analgesics Adjuvant analgesic Antidepressants Example amitriptyline Dose 25–150 mg at night. Start with a low dose and slowly increase if needed. Start at 100 mg twice a day; can be increased to 800 mg twice a day. 5 mg orally 2–3 times daily 2–4 mg per day for all situations apart from raised intracranial pressure. For raised intracranial pressure, start at 24 mg daily and reduce by 2 mg daily to lowest effective maintenance dose. Use • Neuropathic pain

Anticonvulsants

carbamazepine

• Neuropathic pain

Muscle relaxants or anxiolytics Corticosteroids

diazepam dexamethasone

• Skeletal muscle spasm • Anxiety-related pain • Bone pain • Neuropathic pain • Headache due to raised intracranial pressure • Pain associated with oedema and inﬂammation • Caution in TB and HIV

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• Non-steroidal anti-inﬂammatory drugs (NSAIDs) such as ibuprofen can be helpful for bone pain. • Neuropathic pain is due to damage to the peripheral or central nervous system. It can often be complex and hard to treat, requiring a range of medications, e.g. ° steps 1, 2 or 3 analgesia ° antidepressant or anticonvulsant ° NSAIDs. Special pain problem: For burning pains; abnormal sensation pains; severe, shooting pains with relatively little pain in between; pins and needles Medication – adolescent/adult: Low-dose amitriptyline (25 mg at night or 12.5 mg twice daily; it is possible to start at 12.5 mg daily) allowing 5 days for response, and increase gradually to 50 mg at night or 25 mg twice daily. Carbamazepine can be added or substituted if pain persists. Substitute another antiretroviral for d4T (or ddI) (see Section 13 Chronic HIV Care). Diazepam 5 mg orally or rectally 2–3 times daily. • See Section 11.45. • Low-dose amitriptyline (see above) • Early eruption: Give aciclovir; apply antiseptic if ruptured vesicles. • Consider locally available remedies that have been shown to be safe and effective. Codeine 30 mg every 4 hours

For muscle spasms and anxiety as in endof-life care or paralysed patient Herpes zoster (or the shooting pain following it)

Abdominal pain from colic, only after exclusion of intestinal obstruction (vomiting, no stool, and gas passing, visible bowel movements) Bone pain or renal colic or dysmenorrhoea If pain from: • Swelling around tumour • Nerve or spinal cord compression • Persistent severe headache is likely from increased intracranial pressure

Ibuprofen 400 mg every 6–8 hours (or other NSAID). In end-of-life care consider giving steroids under clinical supervision

Nerve blocks for speciﬁc severe pains Nerve blocks involve the injection of anaesthetic around a nerve to alleviate pain in the distribution of that nerve. Nerve blocks can be technically difﬁcult procedures that should be done by experienced clinicians. • The most common sites for nerve block are: ° brachial plexus – interscalene block for shoulder surgeries and procedures ° sciatic nerve – sciatic nerve block for procedures below the knee ° femoral nerve – femoral nerve block for femoral shaft fractures, knee procedures ° most somatic nerves may be targeted depending on the location of the pain. • Refractory neuropathic pain resulting from herpes zoster may be treated with a block of the relevant thoracic (or other affected) nerve.

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20.4 Manage acute pain in emergency or acute conditions Acute pain is usually due to an acute injury or illness or a complicating infection or problem during a chronic illness. Acute pain often is associated with other symptoms, such as sweating, tachycardia, tachypnoea, pupil dilation, and anxiety. • When administering strong analgesics, use a stepwise approach. • Direct appropriate treatment at the acute injury or illness while managing associated symptoms such as pain. • Regular analgesics need to be provided in both acute and chronic pain and may need to be supplemented with PRN pain medications. For acute pain, patients should be assessed at regular intervals, to evaluate their response and whether repeat doses are required. If pain is treated early, it will be managed more effectively and often with lower doses of medication. • Morphine remains the medicine of choice in the management of moderate-tosevere acute pain. • IM or IV administration of analgesics is more often required in acute pain.

Manage acute severe pain • First use Quick Check and stabilize the circulation. • Treat the reasons for the pain: for example, immobilize a broken leg. • Morphine will lower a patient’s blood pressure and so should be given cautiously in patients in shock. These patients should get small, titrated doses of pain medication and be regularly reassessed. • Morphine dosing is weight-based. The usual dose of morphine is 0.1 mg/kg IV, or carefully titrated doses. Maximum single dose should be 8–10 mg IV. • Patients will develop tolerance to opiates and may require higher dosing. • Naloxone reverses the effects of morphine. Morphine can depress the respiratory rate. When administering morphine, it is important to have naloxone available in case the patient is over-sedated. • Monitor responsiveness, airway, respiratory rate, BP, and pulse every 15 minutes when administering morphine IV in an acute situation. Record in notes: ° If systolic BP <100 or falls more than 20 mm Hg from previous reading, SpO2 <90, or respiratory rate <10/minute, do Quick Check, determine if patient needs more ﬂuids, and give naloxone. ° If continuous monitoring is not possible, give bolus dose, with frequent regular monitoring. IM and subcutaneous dosing are reasonable alternatives for administration, but the patient must be observed for delayed absorption. • Assess and regularly monitor acute pain, using the pain scale (see above). With treatment of the underlying cause, the level of pain and the need for analgesia can rapidly diminish.

Morphine IV infusion for refractory severe acute pain • For patients continuing to experience severe pain in the hospital, morphine can be given by carefully monitored IV drip. A strictly controlled rate, with

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a metal gate-clamp in the IV rather than a roller device (which can become loose), must be guaranteed and closely monitored. • A bolus dose of 2 mg is given initially, followed by a continuous infusion at 1 mg/hour. ° The infusion may be titrated hourly as needed for pain control, usually between 5–35 mg/hour. ° The infusion should be slowed if the patient begins to show signs of somnolence and stopped if there is respiratory depression (RR <16) or hypotension (SBP <90). • Patients with respiratory depression unresponsive to cessation of the morphine infusion may require naloxone for reversal of opioid overdose. ° If systolic BP <90 or falls more than 20 mm Hg, SpO2 <90, or respiratory rate <10/minute, do Quick Check, determine if the patient needs more ﬂuids, and give naloxone. ° Naloxone should be given with great caution, as it will reverse analgesia. ° See Section 3.6.1 Opioid intoxication or overdose for more on the management of opioid overdose. Clinical examples of acute pain and initial analgesia Severe “undifferentiated pain” may require morphine for initial management, e.g: • renal colic from kidney stone • acute nerve compression • acute gangrene • trauma • perforated peptic ulcer • sickle cell crisis • burns • biliary colic • pancreatitis. Pain from the following is usually moderate. Give paracetamol with codeine or a NSAID – the latter for both pain control and its anti-inﬂammatory effects. • sprained ankle • broken rib. Pain from the following is usually mild. Give paracetamol. A NSAID is an option for treatment of mild pain. Do not include aspirin for treatment of mild pain due to viral syndrome or inﬂuenza- like illness. • inﬂuenza • simple headache.

20.5 Symptom management: cough or difﬁculty breathing Use Section 10.6 ﬁrst to decide if the patient has pneumonia or tuberculosis. In addition to speciﬁc antimicrobial management (antibiotics for pneumonia; sputum examination if suspect TB and TB treatment as indicated; see Section 15), do the following: • Control bronchospasm

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° Give bronchodilators by a metered-dose inhaler with spacer or mask, or by nebulizer. In terminal care, stop the use of bronchodilators when the patient is not able to use them anymore or has very shallow or laboured breathing. ° Give steroids (see Section 3). • Relieve excessive sputum ° If there is a cough with thick sputum, give steam inhalations. ° If more than 30 ml/day, try forced expiratory technique (“hufﬁng”) with postural drainage. • For a bothersome dry cough, give codeine tablets 5–10 mg 4 times daily. • If there is hypoxaemia (SpO2 <90), O2 can be given continuously in hospital and, depending on availability and affordability of concentrators or O2 cylinders, at home with training of the patient and family members. If a patient is terminal and is dying from COPD, lung cancer, drug-resistant tuberculosis, or any other terminal pulmonary problem (but NOT acute pneumonia that can be treated with antibiotics), there are additional measures to relieve dyspnoea. • For a bothersome cough not responding to codeine, give oral morphine 2.5–5 mg. • In end-of-life care a small dose of morphine can reduce dyspnoea. Monitor closely but do not let fears of respiratory depression prevent trying this drug. Titrate the dose of the opioid to its effect in relieving dyspnoea using a dyspnoea scale or physical signs of dyspnoea. ° For a patient not on morphine for pain, start with 2.5 mg 4–6 hourly. ° For a patient already on morphine, increase the dose by 25%. If this does not work, increase by another 25%. • If there is heart failure or excess ﬂuid with pitting oedema, give furosemide 40–80 mg orally. Refer if no improvement. • For anxiety or terminal agitation, consider giving small doses of diazepam 2.5–5 mg. • Patients on treatment for tuberculosis should continue treatment even if terminal. The decision to continue or stop treatment must be a team decision, with the patient having full information on toxicity, resources to continue treatment, and the quality-of-life issues. The concept of treatment failure should not be a consideration for stopping treatment, as patients still do convert after years of treatment. See Section 20.9. • Infection control precautions to protect the family, health workers, and other patients are important (see Section 6). For home-care instructions see the IMAI-IMCI Palliative care: symptom management and end-of-life care guideline module.3

20.6 Symptom management: hiccups Investigation: Assess patient for possible cause of hiccups, such as extensive oroesophageal candidiasis, ascites, organomegaly, or metabolic disorders. Treatment • metoclopromide 10 mg every 8 hours in combination with an antacid and antiﬂatulant, e.g. aluminium hydroxide • haloperidol 2.5–5 mg for non-responding hiccups • If ascites, carry out abdominal paracentesis (see Section 7.4.5).

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20.7 Symptom management: trouble sleeping Consider the following reasons: • pain, anxiety, depression, drug withdrawal, nocturia. Treatment • Address the cause of insomnia. • If patient is getting up to urinate at night, consider the cause of the nocturia and treat it. • Reduce noise where possible. • Avoid caffeine-containing beverages at night. • Diazepam 5 mg can be used but only in the short-term (less than 4 weeks).

20.8 Manage other symptoms using other Sections of this manual Fever Peripheral oedema, swelling of limbs Depression Anxiety and agitation Pain on swallowing Mouth ulcers Dementia or delirium Diarrhoea Incontinence of stool and urine Constipation Nausea and vomiting Vaginal discharge from cervical cancer Itching Bedsores Section 10.1 Fever Section 10.4 Swelling of the limbs Section 10.11.6 Sad or low mood (depression) Section 10.11.7 Anxiety and Section 10.11.3 Abnormal behaviour Section 10.7b Painful or difﬁculty swallowing Section 10.17 Mouth problems Section 3.4 Altered consciousness and Section 10.11.3 Abnormal behaviour Section 10.7d Diarrhoea and constipation Section 10.15 and IMAI-IMCI Palliative care guideline module Section 10.7d Diarrhoea and constipation Section 10.7c Nausea and vomiting Section 10.15 Female genitourinary problems Section 10.2 Skin Section 10.2 Skin

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20.9 Preventive interventions for all patients See the IMAI-IMCI Palliative care: symptom management and end-of-life guideline module3 for more information on the following.

Oral care Instruct all patients in oral care. • Use a soft toothbrush to gently brush teeth, tongue, palate, and gums to remove debris. • Use diluted sodium bicarbonate (baking soda) or toothpaste. • Rinse mouth with diluted salt water after eating and at bedtime (usually 3–4 times daily). • Petroleum jelly can be used to moisten the lips when dry.

Preventing bedsores (see also Section 10.2 Skin problems). Remember that prevention of bedsores is better than cure. • Help the bedridden patient to sit in a chair from time to time. • Lift the patient up in the bed (do not drag, as this can break the skin). • Encourage patients to move their bodies in bed if able. • Change the patient’s position on the bed often, if possible every 1 or 2 hours. Use pillows or cushions to keep the position. • Keep the bedding clean and dry. • Look for damaged skin (change of colour) on the back, shoulders, and hips every day. • Put extra soft material, such as a soft cotton towel, under the sick person.

Preventing pain, stiffness, and contractures in muscles, and moving the bedridden patient3 • Check range of motion (ROM); move limbs gently. • Give diazepam if spasms or very spastic. • Check ROM in the key seven joints on both sides (wrist, knee, elbow, ankle, shoulder, hip, and neck). • Encourage mobilization. • If patient is immobile, do simple range-of-motion exercises. ° Exercise limbs and joints on both sides at least twice daily. ° Protect the joint by holding the limb above and below it and supporting as much as possible. ° Bend, straighten, and move joints as far as they normally go; be gentle and move slowly, without causing pain. ° Stretch joints by holding as described but applying ﬁrm, steady pressure. ° Let the patient do it as far as they can and help the rest of the way. ° Massage.

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20.10 Special considerations in palliative care for PLHIV PLHIV have physical, spiritual, social, and emotional care needs. These needs change at different stages of the disease process and are substantially altered on effective ART. The need for good palliative care, both symptom management and end-of-life care, remain. Pain continues to be a problem in people with HIV infection, compromising overall quality of life, both physically and psychologically. PLHIV experience pain for many different reasons: OIs, malignancies, direct effects of the virus such as distal sensory polyneuropathy and HIV-related myopathy; medication side-effects, IRIS, nonspeciﬁc manifestations of late-stage illness, and other, non-HIV-related causes. Identify and treat the underlying cause where possible while at the same time controlling the pain. Illness in PLHIV and symptoms can be unpredictable. The course of the illness can change. Treatment of infection often can improve the patient’s condition and result in reduction of pain and other symptoms. Effective symptom management of ARV therapy side-effects is important to support adherence and respond to serious adverse reactions. See also Section 13 Chronic HIV care.

20.11 Special consideration in palliative care for TB patients Drug-resistant TB (DR-TB) treatment requires adequate support measures to achieve a high level of adherence. These measures include disease education, DOT, socioeconomic support, emotional support, and effective management of adverse effects. The long duration of complicated treatment and the often difﬁcult adverse effects of second-line anti-TB drugs, particularly when combined with ART treatment, require close attention to management and place demands on the health worker’s skill. It is rarely necessary to suspend antituberculosis drugs completely. Ancillary drugs for the management of adverse effects should be available to the patient, without charge for patients without resources. See speciﬁc guidance on managing these adverse effects (Section 15 TB). The clinical team must communicate closely with the DR-TB treatment supporter about adverse effects. Cough, fever, difﬁculty breathing, and chronic haemoptysis caused by TB may not improve for several months after starting MDR-TB therapy. Symptomatic management is summarized in Section 15 and other Sections of this manual, including the use of salbutamol (see Quick Check page 17 and Section 10.6). In some patients, after exhausting all options, treatment of DR-TB fails, and a decision is made to suspend therapy and provide only supportive care. Usually, the process to stop therapy involves a number of visits and is made over several weeks, with discussions with the patient. It is not recommended to suspend therapy before the patient understands and accepts the reasons to do so and agrees with the supportive care offered. Stopping DR-TB treatment is often done because the drugs used in DR-TB treatment have significant adverse effects, and continuing them while the treatment is failing may cause additional suffering. When treatment is stopped,

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the palliative measures described in this Section, with special attention to Section 20.5 on cough and difﬁculty breathing, are needed. A second reason to stop therapy that is not working is the public health concern: Continuing a treatment that is failing can amplify resistance in the patient’s strain, resulting in highly resistant strains, such as XDR-TB, that may subsequently infect others. The patient who is taken off treatment because of failure often remains infectious for long periods of time. Infection control measures should be continued, including both environmental controls and personal protection. Health workers and family members at high risk who are providing close patient care should use N95 particulate respirators (N95 masks) over nose and mouth and other infection control interventions when caring for infectious TB patients, particularly in the presence of MDR-TB and XDR-TB (see Section 6). Make sure the mask ﬁts: • The nose clip is properly bent over the bridge of the nose. • Both elastic bands are in place. • There are no obvious gaps around the nose or cheeks. Check the ﬁt of the N95 mask before entering a high-risk area. Cover the ﬁltration material with a hand and inhale. If there is a good face seal, the front of the mask will suck up against the face.

20.12 Special considerations in palliative care for cancer While the overall 5-year rate of survival from cancer is over 50% in high income countries, cancer patients need symptom management during treatment and, sooner or later, end-of-life care, regardless of the cause of death. In limitedresource countries the proportion of cancer patients receiving only palliative care is much higher because of late presentation and poor access to cancer treatment services. Because of demographic changes and changes in life style, the incidence and mortality from cancer will increase in the next 20 years. HIV infection, since it predisposes to several cancers, is contributing to this increase in cancer incidence. This manual addresses only the management of Kaposi sarcoma (see Section 11.19) and cervical cancer (Section 10.15). Subsequent editions will address additional cancers where diagnosis and management are feasible at the district hospital or at regional or central referral hospitals. For millions of people with cancer who lack access to cancer treatment services, access to palliative care will be their core essential need. Patients with cancer suffer with problems similar to those commonly encountered in other chronic illnesses including AIDS. Pain, dyspnoea, wasting, confusional states, psychosocial distress, and other devastating symptoms commonly afﬂict both AIDS patients and those with cancer. As symptom etiology (AIDS wasting is a possible exception) and the roots of suffering are often common across diseases, the principles of palliative care and speciﬁc interventions can serve patients with a wide range of chronic, potentially fatal disorders.

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20.13 End-of-life care End-of-life care refers to care when death is imminent. Its duration usually varies from a few hours to several weeks and perhaps to one month or more in exceptional cases. In some cases, it is obvious to the health workers that the patient is in this phase, but in other cases even experienced clinicians may be uncertain whether the end of life is truly close at hand. Often, the patient wants to die at home. This is not always possible, however. So end-of-life care may be provided in the hospital as well as in the home. Where possible, respect for the wishes of the patient and family is crucial in providing high-quality end-of-life care. Having a patient die at home can be difﬁcult for the family. Through caregivers and continued support from the clinical team, hospicelike care should be offered to families who want to keep the patient at home. See IMAI-IMCI Palliative care: symptom management and end-of-life guideline module.3 Follow the recommendations in this Section. • Manage pain and other symptoms. • Manage cough or difﬁcult breathing based on Section 20.4. Morphine also provides signiﬁcant relief from respiratory insufﬁciency and should be offered if available. • Provide nutritional support. Small and frequent meals are often best for a person at the end of life. Assisting patients to eat often is necessary. It should be accepted that the intake will reduce as the patient’s condition deteriorates and during end-of-life care, but end-of-life patients should not die of malnutrition. Nausea and vomiting, and any other conditions that interfere with nutritional support, should be treated. It may be decided together with the patient or patient’s family that feeding tubes would not add to the overall quality of the patient’s life. However, in some cases, feeding tubes may be needed, especially in patients not determined to be terminal. • Continue regular medical visits. • Continue ancillary medicines, such as those for depression and anxiety. • Treat fever if the patient is uncomfortable. Fever treatment is not always necessary at the end of life. • Continue preventive measures; oral care, prevention of bedsores, bathing, and prevention of muscle contractures are indicated in all patients. Regular, scheduled movement of the bedridden patient is very important. • Continue infection control measures. The patient who is taken off antituberculosis treatment because of failure often remains infectious for long periods of time. Infection control measures are very important and should be continued.

Bereavement care The support of people who are bereaved is an important aspect of palliative care. This support may be provided at the district level, but it is more likely that the support will be provided at the community level. • It is important that the health worker recognizes the need for bereavement support and can refer people for support where necessary. • After a person’s death, try to support the family with regards to their wishes for disposition of the body and funeral rites.

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• Bereavement support is not only needed for the family but also for the patient prior to their death. The caregiver needs to give them the opportunity to talk about what is happening to them if they want to; do not force this, however. The patient may need some practical help and support, e.g. helping them to make a will, planning for the care of their children, etc. Where possible, respect the patient’s wishes. • It is important to recognize that the health worker may come into contact with many people who are dying and are bereaved. It is important for the health worker to care for themselves and grieve as appropriate, while not letting their grief get in the way of patient or family care. For psychosocial and spiritual support and more detail on bereavement counselling, see also the IMAI-IMCI Palliative care: symptom management and end-of-life guideline module.3

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21. Patient monitoring and reporting including reporting outbreaks and pharmacovigilance Table of contents 21.1 Longitudinal monitoring of patients in chronic or long-term care . 21.2 Monitoring inpatient care . . . . . . . . . . . . . . . . . . . . . . . . . Problem list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Regular monitoring and the monitoring chart . . . . . . . . . . . 21.3 Identifying and reporting notiﬁable diseases . . . . . . . . . . . . . Priority diseases, conditions and events for integrated disease surveillance and response . . . . . . . . . . . . . . . . . . . . . . 21.4 Pharmacovigilance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spontaneous reporting. . . . . . . . . . . . . . . . . . . . . . . . . Cohort event monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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21. Patient monitoring and reporting, including reporting outbreaks and pharmacovigilance Patient monitoring is an important part of high-quality patient care. Monitoring involves documenting all patient encounters by keeping regular, standardized, and accurate records of key aspects of the care and treatment offered. Many district hospitals rely on disease-speciﬁc treatment and reporting protocols, but these present problems since neglected tropical diseases, coinfections, and co-morbidities are less likely to be considered when vertical programmes (HIV, malaria, and TB) predominate. Clinicians are trained to look for one problem rather than to consider the whole patient and the order of importance of their various problems.

21.1 Longitudinal monitoring of patients in chronic or longterm care For chronic care of HIV and other conditions and for long-term care of TB and pregnancy, longitudinal patient monitoring makes it possible to capture the history of a patient or of a group of patients over time and across different clinical sites as well as to collect data for reporting on and evaluating patient care at regular intervals. Information collected through patient or pregnancy registers is critical to better evaluate antiretroviral and patient safety – data that are often missing in low- and middle-income countries. In addition to longitudinal monitoring, cohort event monitoring may be used in some countries to investigate speciﬁc adverse events linked to ARVs. (See the description of cohort event monitoring below in Section 21.4 Pharmacovigilance.) In the context of facility-based HIV, TB, and MCH care, monitoring offers major beneﬁts at 3 levels. 1. It provides essential information for individual case management, particularly to assure continuity of care. 2. It provides key information for managing the health facility (e.g. for ordering drugs and supplies and for making quality improvements). 3. It provides information for operating and improving the HIV/AIDS, TB, and MCH programmes at district, national, and international levels. All health facilities, both health centres and the outpatient and inpatient facilities of the district hospital, should use a nationally adapted, simple, paper-based patient monitoring system that collects a standard minimum data set. Facilities with high patient volume and resources may use an electronic register system and other electronic systems to facilitate care, reporting, and data transfer; these should mirror the paper forms. The three interlinked longitudinal patient monitoring systems for HIV care/ART, MCH/PMTCT, and TB/HIV include the following:1

1 Three interlinked patient monitoring systems for HIV care/ART, MCH/PMTCT (including malaria prevention during pregnancy), and TB/HIV. WHO, 2010. Available at http://www.who.int/hiv/pub/imai/three_patient_monitor/ en/index.html

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1. For HIV prevention, care, and treatment services • patient-held card, if applicable • facility-held HIV care/ART patient card • pre-ART (HIV care) register • ART register • cross-sectional (e.g. quarterly) reporting form (HIV care/ART, MCH/PMTCT, TB/HIV) • cohort reporting form (ART only) • appointment book • transfer or referral form. 2. For MCH/PMTCT services • patient-held maternal health card (with HIV ﬁelds added) • patient-held child health card (with HIV ﬁelds added) • ANC register (with HIV ﬁelds added) • labour and delivery register (with HIV ﬁelds added) • labour record/partograph, postpartum record (with HIV ﬁelds added) • summary forms • HIV-exposed infant register. 3. TB services (with HIV ﬁelds added) • facility-held TB treatment card • TB suspects register • TB laboratory register • TB basic management unit (BMU) register • quarterly report on TB case registration • quarterly report on TB treatment outcome and TB/HIV activities.

The roles of the district clinician within the longitudinal patient monitoring systems • completing clinical sections of the patient card during individual patient management; • using the patient card and registers to provide assistance and guidance to the clinical team to facilitate individual patient management, both in the outpatient clinic and when mentoring clinical teams at the health centre level; • reviewing uncommon or unexplained side-effects and OIs; • consulting concerning unusual or serious patient outcomes and corresponding codes on patient cards; • internally reviewing and analysing patient monitoring data; • ensuring quality through regular review of pre-ART and ART registers, selected patient cards, and aggregated quarterly cross-sectional and cohort analysis reports.

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21.2 Monitoring inpatient care To ensure effective monitoring of a patient admitted to a hospital, the health worker needs to know: • the correct administration of the treatment • the expected progress of the patient • the possible adverse effects of the treatment and the management of adverse effects • the complications that may arise and how these can be identiﬁed • the possible alternative diagnoses in a patient not responding to treatment.

Problem list For a patient hospitalized with an acute illness, it is important to consider the whole patient and to develop a problem list that orders the priority of the various problems. The status and nature of the list might change as test results become available or as the patient’s status changes, as shown in the example that follows. It is important to update the status of each problem regularly. Day 1 problem list 1. Breathlessness 2. Fever with negative malaria ﬁlm 3. Chronic cough awaiting sputum results Day 2 problem list (for same patient) 1. Microcytic anaemia 2. Sputum positive TB 3. Conﬁrmed HIV-positive

Regular monitoring and the monitoring chart All patients treated in hospital require regular monitoring so that any deterioration in their condition, as well as complications, adverse effects of treatment, or errors in the administration of treatment, can be identiﬁed promptly. The frequency of monitoring depends on the severity and nature of the illness. A monitoring chart should include the following items: • the patient’s details • level of consciousness (AVPU or Glasgow Coma Scale (GCS)) • vital signs (temperature, respiratory rate, pulse rate, and weight) • ﬂuid balance • presence of clinical signs, complications, and positive investigation ﬁndings; record any new signs or complications and signs of improvement • treatments ordered, whether medications are taken as ordered, and medication side-effects • feeding and nutrition. Note: A monitoring form for severely ill patients can be found in Section 3.11.

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21.3 Identifying and reporting notiﬁable diseases2 Immediate notiﬁcation of suspicion or diagnosis of epidemic-prone disease, followed by weekly reporting during the epidemic period, is very important. The district clinician should diagnose and manage the patient, use available data to initiate action at the local level, and immediately notify regional and national authorities. Nurse-led clinical teams at the health centre level, following the guidance in IMAI Acute Care, may call the district clinician to report suspicious cases that require further investigation and reporting. The differential diagnosis tables throughout this manual present case deﬁnitions that can help to identify reportable diseases, as well as a reference to this Section. Notiﬁable diseases are marked with a trumpet: The following list is from the comprehensive public health surveillance and response systems in African countries, Integrated disease surveillance and response (second edition 2010, updated with the 2005 International Health Regulations).2 Added to the list for each disease is the Section where it can be found in this manual. Priority diseases, conditions and events for integrated disease surveillance and response – 2010 Diseases, conditions, or events requiring immediate reporting are in italics. Numbers of relevant Sections in this manual appear in [brackets]. Other major diseases, events, or conditions of public health importance included in this manual • acute viral hepatitis [11.14] • HIV/AIDS (new cases) [9, 13] • injuries (road trafﬁc accidents) [2] • malaria [3.1, 11.25] • maternal deaths • mental health (epilepsy) [10.11] • rabies (conﬁrmed cases) [11.30] • STIs [10.14, 10.15, 10.16] • trachoma [10.12] • trypanosomiasis [11.41, 11.42] • tuberculosis [15]

Epidemic-prone diseases • acute haemorrhagic fever syndrome* [11.46] • anthrax [10.2, 10.6, 10.10] • chikungunya [10.1, 10.13] • cholera [10.7] • dengue [11.9] • diarrhoea with blood (Shigella) [10.7d] • measles [10.1] • meningococcal meningitis [10.10b] • plague [10.5, 10.6] • SARI** (cluster of SARI) [3.2] • typhoid fever [10.7, 11.43] • yellow fever [11.47] *Ebola, Marburg, Rift Valley, Lassa, Crimean Congo, West Nile fever. **National programmes may wish to add Inﬂuenza-like illnesses to their priority disease list.

Diseases targeted for eradication or elimination • • • • • • • • Buruli ulcer [10.2.10] dracunculiasis [10.2.10] Leprosy [10.2.10] lymphatic ﬁlariasis [10.4, 11.12] Neonatal tetanus noma [10.17.7] onchocerciasis [11.28] poliomyelitis† (report acute ﬂaccid paralysis) [10.10]

Diseases or events of international concern • • • •

human inﬂuenza due to a new subtype† [11.17], SARS† [3.2]. smallpox† Any public health event of international or national concern (infectious, zoonotic, food-borne, chemical, radio nuclear, or due to an unknown condition).

† Diseases speciﬁed by International Health Regulations (2005) for immediate notiﬁcation (http://www.who.int/ihr/en/)

2 Technical guidelines for integrated disease surveillance and response in the African Region. WHO and Centers for Disease Control and Prevention, 2010. Available at http://www.afro.who.int/en/clusters-a-programmes/dpc/ integrated-disease-surveillance/ids-publications.html

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The above list is meant for country adaptation of notiﬁable diseases and their case deﬁnitions. (Countries have their own lists according to national priorities and the epidemiological situation.) diseases where a single suspected case should be reported urgently (and to whom); diseases where a cluster of cases should be reported (and to whom); how reports are sent, e.g. telephone, radio, automated mobile phone system, messenger, paper, web site.

21.4 Pharmacovigilance Pharmacovigilance (PV) is deﬁned as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem.3 Pharmacovigilance should be standard of care for all patient management. Due to the emergency response to get as many people as possible onto ART and the rapid scale-up of ARVs, PV of ARVs has lagged behind. As HIV-related treatment programmes head into a phase of more sustained response, PV methodologies appropriate to lifelong chronic care within public health programmes need to be developed.

Spontaneous reporting Spontaneous reporting is voluntary, unsolicited reporting of an adverse event (AE) by a clinician providing routine care. It is often part of a national PV programme that may also include active sentinel surveillance and research studies. Reports may also be made by consumers of a drug. Advantages of spontaneous reporting • to help detect adverse drug reactions (ADR) not previously observed in preclinical or clinical studies; • to improve understanding of the potential risks, including reactions resulting from drug interactions or drug effects in particular populations; • to help provide a basis for effective drug regulation, education, and consequent changes in practices by prescribers and consumers. Spontaneous reporting is responsible for more than 90% of all ADR reports globally and is the minimum standard for HIV public health programmes wishing to include PV as standard of care. HIV programmes need to strengthen links to the national PV centre in their country and to encourage treatment providers to complete their national ADR form when an adverse event occurs. These are generic forms capable of capturing ADR information for any disease, including HIV. A separate system does not need to be set up for PV of ART. According to WHO criteria, the following basic information is required before a report is acceptable:

3 A practical handbook on the pharmacovigilance of antiretroviral medicines. WHO, 2009. Available at http://www. who.int/medicines/areas/quality_safety/safety_efﬁcacy/HIVhandbook.pdf

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• • • • •

an identiﬁable source of the information or reporter an identiﬁable patient names of the suspected products a description of the suspected reactions the patient details.

For spontaneous reporting, national programmes may use the Council of International Organizations of Medical Sciences (CIOMS) pharmacovigilance form (http://www.cioms.ch/form/frame_form.htm) and special forms for antiretroviral drugs. These forms should be sent to the national pharmacovigilance centre.

Cohort event monitoring The HIV care/ART clinics in some district hospitals may be recruited to carry out cohort event monitoring. This involves the prospective collection of all events occurring both before and after a patient commences ART, with the objective of detecting known ARV-related side-effects and early warning signals of new or as yet unrecognized adverse events. Cohort event monitoring is more resource-intensive than spontaneous reporting, the more common form of PV. Cohort event monitoring is less prone to missing data and to bias, but spontaneous reporting is more feasible in settings with limited resources. Both spontaneous reporting and cohort event monitoring provide the opportunity to systematically collect drug safety data in populations where little is known, e.g. on the use of TDF in resource-limited settings.

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Index to syndromes, diseases, conditions (in both Volumes 1 and 2) To ﬁnd the indications and Section locations of speciﬁc medicines, as well as dosing, adverse effects, use in pregnancy/breastfeeding, contraindications, cautions, administration details, and patient counselling, see Section 8.4. The Quick Check and Emergency Treatments (Section 2) is referenced as QC followed by the page number. With this exception, the subsections are provided below.

Abbreviations/acronyms . . . . . End of Vol. 1 & 2 ABC emergency signs . . . . . . . . . QC2-3-4-5 Abdominal complaints . . . . . . . . . . . . 10.7 Cholangitis . . . . . . . . . . . . . . . . 10.7a.2 Cholecystitis . . . . . . . . . . . . . . . 10.7a.2 Constipation . . . . . . . . . . . . . . . 10.7d.4 Diarrhoea . . . . . . . . . . . . . . . 10.7d.1-3 Pain . . . . . . . . . . . . . QC8, 10.7a, 10.15.2 Pancreatitis . . . . . . . . . . . . . . . 10.7a.2 Peptic ulcer disease . . . . . . . 10.7a.2, 10.7c.2 Trauma with abdominal pain . . . . . . QC9, 4.2 Abdominal tap (paracentesis) . . . . . . . . 7.4.3 Abnormal behaviour . . . . . . . . . . . . 10.11.3 Abnormal vaginal bleeding . . . . QC24-25, 10.15.2 Abnormal bleeding or bruising . . . . . . . . 10.19 Abortion Septic . . . . . . . . . . . 3.1.5, 10.15.2, 10.15.6 Spontaneous . . . . . . . . . . . . . . . 10.15.2 Abscess Amoebic liver . . . . . . . . . . . . . . 11.1.2 Dental . . . . . . . . . . . . . . . . . . 10.17.5 Liver . . . . . . . . . . . . . . . . . . . . 11.23 Lung . . . . . . . . . . . . . . . . . . . . 10.6 Perianal . . . . . . . . . . . . . . . . . 10.14.2 Peritonsillar . . . . . . . . . . . . . . . 10.17.9 Skin . . . . . . . . . . . . . . . . . . . 10.2.2 Splenic . . . . . . . . . . . . . . . 10.7a.2, 10.20 Tubo-ovarian . . . . . . . . . . . . . . . 10.15.3 Abuse . . . . . . . . . . . . . . . . . . . . . 4.4 Acidosis Lactic acidosis . . . . . . . . . . . 10.7a.2, 13.9 Diabetic ketoacidosis . . . . . . . . . . . 3.4.3 In poisoning . . . . . . . . . . . . . . . . . 3.8 Achalasia . . . . . . . . . . . . . . . . . 10.7b.2 Acne . . . . . . . . . . . . . . . . . . . . 10.2.3 Acute inﬂammatory demyelinating polyneuropathy (AIDP) . . . . . . . . . 10.10a.3 Acute lung injury . . . . . . . . . . . . . . . 3.2.3 Acute poliomyelitis . . . . . . . . . . . . 10.10a.3 Addison’s disease . . . . . . . . . . . . . . 3.4.3 Adjustment disorder . . . . . . . . . . . . 10.11.6

Adherence . . . . . . . . . . . . . . . . . . 13.11 Adolescents and HIV . . . . . . . . . . . . . 13.14 Adrenal insufﬁciency . . . . . . . . . . . . . 3.4.3 Aerosol precautions . . . . . . . . . . . . . . 6.3 AFB . . . . . . . . . . . . . . . . . . . 7.2.20, 15 African human trypanosomiasis . . . . . . . 11.41 Agitated patient management . . . . . . QC29, 3.4 AIDS, see HIV . . . . . . . . . . . . . . . . . 13 Airway Advanced airway management . . . QC31 to 36 Assessment . . . . . . . . . . . . . . . . QC2 Management . . . . . . . . . . . . . . QC12-13 Obstruction . . . . . . . . . . . . . QC12, 3.2.1 Alcohol Assessment . . . . . . . . . . . . . . . . 16.3 Dependence . . . . . . . . . . . . . . . . 16.2 Disorders . . . . . . . . . . . . . . . . . . 16 Harmful use . . . . . . . . . . . . . . . . 16.2 Hazardous use . . . . . . . . . . . . . . . 16.2 Intoxication . . . . . . . . . . . . . . . 3.7,16 Withdrawal . . . . . . . . . . 3.7, 16.6, 10.10c Altered level consciousness/ convulsions . . . . . . . . . . . QC6-7, 3.4, 3.5 American trypanosomiasis (Chagas) . . . . . 11.42 Amoebiasis. . . . . . . . . . . . . . . . . . 11.1 Amphetamine-type stimulants . . . . . . . . 3.6.3 Anaemia . . 3.2.1, 10.18, 13.2, 13.3, 13.4,13.9, 10.6.2 Anaesthetic . . . . . . . . . . . . . . . . . 7.1.2 Anal ﬁssures . . . . . . . . . . . . . . . . 10.14.2 Anal ulcer . . . . . . . . . . . . . . . . . 10.14.2 Analgesia Approach to pain control . . . . . . . . 20.2, 20.4 Medicines . . . . . . . . . . . . . . . . . . . 8.1 Ladder (approach to pain) . . . . . . . . . . 8.2 Anaphylaxis . . . . . . . . . . . . QC 2,4,11, 3.1.1 Anaphylactic shock . . . . . . . . . . . . 3.1.1 Epinephrine (adrenaline) . . . . . . . . . . QC11 Angular cheilitis . . . . . . . . . . . . . . 10.17.3 Anogenital problems–male and female . . . . 10.14 Anthrax Cutaneous . . . . . . . . . . . . . . . . 10.2.10

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Gastrointestinal . . . . . . . . . . . . . 10.7c.2 Pulmonary . . . . . . . . . . . . . . . . 10.6.2 Antibiotics (see individual medicines in 8 and recommendations in Sections by likely disease) Empirical therapy IV/IM . . . . . . QC19 Antiepileptics (see individual medicines in 8) . . . . . . . . . . . . 3.5, 10.10c Antimalarials (see individual medicines in 8) . . . . . . . . . . . QC20, 11.25 Antiretroviral therapy (ART) . . . . . . . . . 13.4 Adherence preparation, monitoring and support . . . . . . . . . . . . . . . 13.11 And substance abuse . . . . . . . . . . . 17.6 ARV drugs (see individual medicines in 8.4 and 13) Eligibility . . . . . . . . . . . . . . . 13.4,14.1.3 Initiation in complicated patients . . . . . . 13.6 Monitoring . . . . . . . . . . . . . . . . . 13.5 Monitoring in pregnancy . . . . . . . . . 14.1.5 Patients with prior ART exposure . . . . . 13.6 Pregnancy eligibility . . . . . . . . . 14.1, 14.1.4 Prevention of mother-to-child transmission . . . . . . . . . . . 14.1.3, 14.1.4 Second-line therapy . . . . . . . . . . . . 13.7 Second-line therapy in pregnancy . . . . 14.1.2 Side-effects, toxicity and management . . . . . . . . . . . . . 13.8, 13.9 Tuberculosis co-management with HIV. . . 13.10 Women who become pregnant on ART . . 14.1.4 Antituberculosis therapy . . . . . . . . . . . . 15 Anxiety . . . . . . . . . . . . . . . . . . . 10.11.7 Aphthous ulcers Genital . . . . . . . . . . . . . . . . . . 10.14.3 Mouth . . . . . . . . . . . . . . . . . . 10.17.5 Aplastic anaemia . . . . . . . . . . . 10.18.3, 10.19 Appendicitis . . . . . . . . . . . . 10.7a.2, 10.15.2 Arthritis Septic . . . . . . . . . . . . . . . . . . 10.13.1 Gonococcal . . . . . . . . . . . . . . . 10.13.1 Rheumatoid . . . . . . . . . . . . . . . 10.13.1 Tuberculous . . . . . . . . . . . . . . . 10.13.1 HIV-associated. . . . . . . . . . . . . . 10.13.1 Arthrocentesis (joint aspiration) . . . . . . . 7.4.4 Ascaris . . . . . . . . . . . . . . . . . . . 10.7a.2 Ascites . . . . . . . . . . . . . . . . . . . 10.9 Aspiration Fine-needle . . . . . . . . . . . . . . . . 7.2.5 Joint (arthrocentesis) . . . . . . . . . . . 7.4.4 Asthma . . . . . . . . . . . . . QC17, 3.2.4,10.6.8 Atrophic urethritis, vaginitis . . . . . . . . 10.15.7 Atrophic glossitis . . . . . . . . . . . . . . 10.17.3 Bacillary angiomatosis . . . . . . . . 10.2.6, 11.2.4 Bacterial vaginosis . . . . . . . . . . . . . 10.15.4 Bag valve mask . . . . . . . . . . . QC13, QC 35 Balanitis . . . . . . . . . . . . . . . . . . 10.16.4 Bartonellosis . . . . . . . . . . . . . . . . . 11.2

Bacillary . . . . . . . . . . . . . . . . . 11.2.4 Cat scratch disease . . . . . . . . . . . 11.2.2 Oroya fever . . . . . . . . . . . . . . . 11.2.1 Trench fever . . . . . . . . . . . . . . . 11.2.3 Behcet’s syndrome . . . . . . . . . . . . . 10.14.3 Benign prostatic hyperplasia . . . . . . . . 10.16.5 Bereavement Uncomplicated . . . . . . . . . . . 10.11.6, 20.13 Biliary parasitosis . . . . . . . . . . . . . . 10.8 Bimanual exam . . . . . . . . . . . . . . . . 7.2.8 Biopsy Bone marrow . . . . . . . . . . . . . . . 7.2.7 Cervical . . . . . . . . . . . . . . . . . 7.2.11 Endometrial . . . . . . . . . . . . . . . 7.2.13 Fine-needle . . . . . . . . . . . . . . . . 7.2.5 Lymph node . . . . . . . . . . . . . . . . 7.2.6 Skin . . . . . . . . . . . 7.2.1, 7.2.2, 7.2.3, 7.2.4 Bipolar disorder . . . . . . . . . . . . . . 10.11.5 Bleeding Abnormal bleeding, bruising . . . . . . . . 10.19 Haemoptysis . . . . . . . . . . . . . . . . QC23 Haemothorax . . . . . . . . . . . . . . . QC22 How to stop (compression) . . . . . . . . . QC22 Nosebleed (epistaxis) . . . . . . . . . . . QC23 Pelvic binder . . . . . . . . . . . . . . . . QC22 Vaginal . . . . . . . . . . QC24-25-26, 10.15.2 Upper gastrointestinal . . . . . . . . . . . QC23 Blood transfusion . . . . . . . . . . . 4.2, 10.19.3 Body mass index . . . . . . . . . . . . . . 10.3.1 Bone marrow aspiration and biopsy . . . . . 7.2.7 Blood smear- malaria Indications . . . . . . . . . . . . . QC2, 11.25.2 Thick and thin smears . . . . . . . . . . 7.2.19 Borreliosis . . . . . . . . . . . . . . . . . . 10.1 Botulism . . . . . . . . . . . . . . . . . 10.10a.3 Bowel obstruction . . . . . . . . . . . . . 10.7a.2 Brain abscess Bacterial . . . . . . . . . . . . . . . . 10.10a.2 Differential diagnosis . . . . . . . . . 10.10a.2 Toxoplasmosis . . . . . . . . . . . . . . . 11.40 Breast examination. . . . . . . . . . . . . 7.2.12 Breathing difﬁculty . . . . . . . QC2, 3.2, 10.6, 20.5 Bronchiectasis . . . . . . . . . . . . . . . 10.6.2 Bronchitis . . . . . . . . . . . . . . . . . 10.6.2 Bronchodilators (see individual medicines in 8) Sequential therapy . . . . . . QC17, 3.2.4, 10.6.4 Bronchospasm . . . . . . . . . QC17, 3.2.4, 10.6.4 Brucellosis . . . . . . . . . . . . . . . . . . 11.3 Bruising, abnormal . . . . . . . . . . . . . . 10.19 Bullous or vesicular lesion . . . . . . . . . 10.2.4 Budd-Chiari syndrome . . . . . . . . . . . . 10.8 Burn Classiﬁcation severity . . . . . . . . . . 3.10.2 Chemical . . . . . . . . . . . . . . . 3.8.3, 3.10 Inhalation . . . . . . . . . . . . . . 3.2.1, 3.10

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Treatment . . . . . . . . . . . . . . . . 3.10.3 Bursitis . . . . . . . . . . . . . . . . . . . 10.13.1 Buruli ulcer. . . . . . . . . . . . . . . . . 10.2.9 Cancer Cervical . . . . . . . . . . . . . . . . . 10.15.8 Kaposi sarcoma . . . . . . . . . . . . . . 11.19 Oesophageal . . . . . . . . . . . . . . . 10.7b.2 Oral . . . . . . . . . . . . . . . 10.17.3, 10.17.4 Uterine . . . . . . . . . . . . . . . . . . 10.15.2 Candida . . . . . . . . . . . . . . . . . . . 11.4 Candidemia . . . . . . . . . . . . . . . . 11.4 Oesophageal . . . . . . . . 11.4, 10.7b.2, 10.7b.3 Oral . . . . . . . . . . . . . . . . . . . 10.17.3 Vaginal . . . . . . . . . . . . . . . 11.4, 10.15.4 Carbon monoxide poisoning . . . . . . . . . 3.8.2 Cardiogenic shock . . . . . . . . . . . . . . 3.1.4 Cardiac tamponade . . . . . . . . . . . 3.1, 3.2.1 Cataract . . . . . . . . . . . . . . . . . . 10.12.4 Cat scratch disease . . . . . . . . . . . . 11.2.2 Catheter, nasogastric- insertion . . . . . . . 7.3.8 Catheter, urinary (see urinary catheter insertion) CD4 testing . . . . . . . . . . . . . . . . . . . 9.3 Cellulitis . . . . . . . . . . . . . 10.2.2, 10.4, 17.8 Central retinal artery occlusion . . . . . . . 10.12.3 Central retinal vein occlusion. . . . . . . . 10.12.3 Cerebral spinal ﬂuid . . . . . . . . . . . . 10.10b Cervical cancer . . . . . . . . . . 10.15.2, 10.15.8 Colposcopy . . . . . . . . . . . . . . . 7.2.11 Pap smear . . . . . . . . . . . . . . . . . 7.2.9 Screen and treat, visual inspection . . . . . . . . . . . 7.2.10, 10.15.8 Chagas disease (American Trypanosomiasis) . . . . . . . . . . . . . 11.42 Chancroid . . . . . . . . . . . . . . . . . 10.14.4 Chest pain . . . . . . . . . . . . . QC8, 3.3, 10.6.2 Chest tap (thoracentesis) . . . . . . . . . . . 7.4.1 Chest tube (intercostal chest drain) . . QC22, 7.3.1 Chest X-ray. . . . . . . . . . . . . . . . . 10.6.2 Chicken pox . . . . . . . . . . . . . 10.2.4, 11.45 Chiggers . . . . . . . . . . . . . . . . . . 10.2.3 Chikungunya Fever . . . . . . . . . . . . . . . . . . . . 10.1 Painful joints . . . . . . . . . . . . . . . 10.13.2 Children, HIV-exposed . . . . . . . . . . . . 14.4 Child-Turcotte-Pugh classiﬁcation . . . . . . 10.9 Chlamydia . . . . . . . . . . . . . . . . . 10.15.4 Choking . . . . . . . . . . . . . . . . . . . QC11 Cholangitis . . . . . . . . . . . . . . . . . 10.7a.2 Cholangiopathy. . . . . . . . . . . . . . . . 10.8 Cholecystitis . . . . . . . . . . . . . . . . 10.7a.2 Choledocholithiasis . . . . . . . . . . . . 10.7a.2 Cholestasis . . . . . . . . . . . . . . . . . . 10.8 Cholera. . . . . . . . . . . . . . . . . . . 10.7d.2 Chorioretinitis . . . . . . . . . . . . . . . 10.12.6 Chronic care- principles . . . . . . . . . . . . 12

Chronic HIV care . . . . . . . . . . . . . . . . 13 Chronic inﬂammatory demyelinating polyneuropathy (CIDP) . . . . . . . . . 10.10a.3 Chronic liver disease . . . . . . . . 10.4,10.9,11.14 Chronic obstructive pulmonary disease . . . . . . . . . . . . . . . 3.2.4,10.6.5 Circulation, assessment Shock/heavy bleeding . . . . . . . . . . . QC4 Circumcision, male . . . . . . . . . . . . . 10.16.5 Cirrhosis . . . . . . . . . . . . . . . . . . . 10.9 Clinical reasoning . . . . . . . . . . . . . 1.6, 5.1 Clostridium difﬁcile colitis . . . . . . . . . 10.7d.2 Cobra spit . . . . . . . . . . . . . . . . . . . 3.9 Cocaine . . . . . . . . . . . . . . . . . . 3.6, 17 Coccidiomycosis . . . . . . . . . . . . . . . 10.1 Cockroft-Gault formula . . . . . . . . . . . . 11.31 Colposcopy. . . . . . . . . . . . . 7.2.11, 10.15.8 Coma . . . . . . . . . . . . . . . . . . QC6, 3.4.1 Communicable diseases – multisystem . . . . . 11 Confusion . . . . . . . . . . . . QC7, 3.4, 10.11.3 Conjunctivitis Allergic . . . . . . . . . . . . . . . . . 10.12.2 Infectious . . . . . . . . . . . . . . . . 10.12.2 Bacterial . . . . . . . . . . . . . . . . . 10.12.2 Viral . . . . . . . . . . . . . . . . . . . 10.12.2 Contact stomatitis . . . . . . . . . . . . . 10.17.3 Contraception, emergency . . . . . . . . . 14.5.3 Consciousness altered . . . . . . . . . . QC6, 3.4 Constipation . . . . . . . . . . . . . . . . 10.7d.4 Convulsions . . . . . . . . . QC6, 3.4, 3.5, 10.10c In pregnancy – eclampsia . . . . . . . . . QC28 COPD (chronic obstructive lung disease) . . . . . . . . . . . . . . 3.2.4, 10.6.5 Corneal problems Dystrophies . . . . . . . . . . . . . . . 10.12.4 Erosion . . . . . . . . . . . . . . . . . . 10.12.4 Foreign body . . . . . . . . . . . . . . . 10.12.2 Fungal . . . . . . . . . . . . . . . . . . 10.12.4 Herpetic . . . . . . . . . . . . . . . . . 10.12.4 Keratitis, keratoconjunctivitis . . . . . . 10.12.2 Ulceration . . . . . . . . . . . . . . . . 10.12.2 Costochondritis . . . . . . . . . . . . . . 10.6.2 Cough . . . . . . . . . . . . . . . . . . . . 10.6 Counselling, HIV . . . . . . . . . . . . . . . . 9.1 Cranial nerve palsies . . . . . . . . . . . 10.10a.7 Creatinine clearance . . . . . . . . . . . . . 11.31 Cricothyroidotomy . . . . . . . . . . . . . . QC36 Crohn’s disease . . . . . . . . . . 10.7a.2,10.14.3 Crude clotting time . . . . . . . . 3.9, 7.2.18, 10.19 Cryptococcosis Meningitis . . . . . . . . . . . . . . . 11.5, 10.1 Cutaneous . . . . . . . . . . . . . . . . 10.2.3 Cryptococcoma . . . . . . . . . . . . . 10.10a Cryptosporidiosis . . . . . . . . 11.6, 10.7d.3, 10.3.2 Cutaneous leishmaniasis . . . . . . . . . . . 11.20

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Cyanide poisoning . . . . . . . . . . . . . . 3.8.2 Cyanosis . . . . . . . . . . . . . . . . . . . QC2 Cysticercosis . . . . . . . . . . . . . . . . . 11.7 Cytomegalovirus (CMV) Retinitis . . . . . . . . . . . . . . 11.8, 10.12.3 Gastrointestinal . . . . . . . . . . . . . . 11.8 Neurological . . . . . . . . . . . . . . . . 11.8 Deep vein thrombosis . . . . . . . . . . . . 10.4 Dehydration . . . . . . . . . . . . . . . . . 10.7d Assessment . . . . . . . . . . . . . . 10.7d.1-2 Severe with shock . . . . . . . . . 3.1.2, 10.7d.2 Treatment . . . . . . . . . . . . . . . . 10.7d.2 Delirium . . . . . . . . . . . . . . . 3.4.1, 10.11.3 Dementia . . . . . . . . . . . . . . . . . . 10.11.3 Dengue Fever . . . . . . . . . . . . . . . . . . 10.1,11.9 Hemorrhagic complications . . . . . . . . 11.9 Shock syndrome . . . . . . . . . . . 3.1.5, 11.9 Dental infections Dental caries . . . . . . . . . . . . . . . 10.17.5 Dental abscess . . . . . . . . . . . . . 10.17.5 Denture-induced hyperplasia. . . . . . . . 10.17.3 Depression . . . . . . . . . . . . . . . . . 10.11.6 Dermatophytosis See ring worm . . . . . . . . . . . . . . 10.2.7 Diabetes Chronic kidney disease . . . . . . . . . 11.31.3 Ketoacidosis . . . . . . . . . . . . . . . . 3.4.1 Low blood glucose (hypoglycaemia) . QC19, 3.4.2 Retinopathy . . . . . . . . . . . . . . . 10.12.4 Skin ulcers . . . . . . . . . . . . . . . . 10.2.10 Diarrhoea . . . . . . . . . . . . . QC5, 3.1, 10.7d Acute . . . . . . . . . . . . . . . . . . 10.7d.2 Clostridium difﬁcile colitis . . . . . . . . 10.7d.2 Cholera . . . . . . . . . . . . . . . . . 10.7d.2 Cryptosporidiosis . . . . . . . . . . . . . 11.6 Isosporiasis . . . . . . . . . . . . . . . . 11.18 Persistent diarrhoea in PLHIV . . . . . . 10.7d.3 Difﬁcult breathing . . . . . . . . . . QC2, 3.2, 10.6 Discordant couples services . . . . . . . . . 19.2 Dissecting abdominal aortic aneurysm . . . 10.7a.2 Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . 10.19.3 Distal symmetrical sensory polyneuropathy . . . . . . . . . . . . 10.10a.3 Diuretics – see individual medicines in 8 . . . . . . . . . . . . . . . 3.2.5, 10.9, 11.31 Diverticulitis . . . . . . . . . . . . . . . . 10.7a.2 Donovanosis . . . . . . . . . . . . . . . . 10.14.3 Dracunculiasis- see Guinea worm . . . . . 10.2.10 Droplet precautions . . . . . . . . . . . . . . 6.3 DR-TB (drug-resistant TB) . . . . . . . . . . 15.5 Drug dosages . . . . . . . . . . . . . . . . . 8.4 Drug eruption . . . . . . . . . . . . . . . 10.2.3 Drug interactions – antiretrovirals . . . . . . 13.4

Drug overdose . . . . . . . . . . . . . . . 3.6, 3.8 Drug side-effects – see individual medicines in 8 . . . . . . . . . . . . . . . . 8.4 Drug-resistant TB (DR-TB) . . . . . . . . . . 15.5 Drugs (medicines)- adolescents/adults, summary . . . . . . . . . . . . . . . . . . . 8.4 Drugs/therapies- see medicines/therapies . . . 8.4 Dry mouth . . . . . . . . . . . . . . . . . 10.17.8 Dysentery . . . . . . . . . . . . . . . . . 10.7d.2 Dyspareunia . . . . . . . . . . . . . . . . 10.15.2 Dysthymia (persistent sad mood) . . . . . . 10.11.6 Dysphagia . . . . . . . . . . . . . . . . . . 10.7b Dysuria . . . . . . . . 10.15.1, 10.15.4, 10.16.3, 11.44 Eclampsia . . . . . . . . . . . . . . QC28, 10.10c Ectopic pregnancy . . . . . . . . . 10.15.2, 10.15.3 Ecthyma . . . . . . . . . . . . . . . . . . 10.2.2 Eczema Contact . . . . . . . . . . . . . . . . . 10.2.7 Nummular . . . . . . . . . . . . . . . . 10.2.7 Seborrhoeic dermatitis . . . . . . . . . . 10.2.7 Electrolytes Disorder management . . . . . . . . . . . . 5.2 Imbalances . . . . . . . . . . . . . . . . . 5.2 In diabetic ketoacidosis . . . . . . . . . . 3.4.1 In poisoning . . . . . . . . . . . . . . . . 3.8.1 Emergency Triage, assessment and treatment . . . . . . QC Trolley . . . . . . . . . . . . . . . . . . . QC38 Emergency contraception . . . . . . . . . 14.5.3 Encephalopathy HIV . . . . . . . . . . . . . . . . . . 3.4.1, 13.2 HSV . . . . . . . . . . . . . . . . . . . . 11.15 Hypertensive . . . . . . . . . . . . . . . 10.10c Encephalitis . . . . . . . . . . . . . 3.4.1,10.10a Endocarditis . . . . . . . . . . . . . . 11.10, 17.8 Endometrial biopsy . . . . . . . . . . . . . 7.2.13 Endometrioma . . . . . . . . . . . . . . . 10.15.3 Endometriosis . . . . . . . . . . . . . . . 10.15.2 Endophthalmitis . . . . . . . . . . . . . . 10.12.5 Endotracheal tube placement . . . . . . QC31-34 Epididymitis or epididymo-orchitis . . . . . 10.16.4 Epilepsy . . . . . . . . . . . . . . . . . . 10.10c Epistaxis . . . . . . . . . . . . . . . . . . . QC23 Epulis . . . . . . . . . . . . . . . . . . . 10.17.3 Erythroplakia . . . . . . . . . . . . . . . . 10.17.3 Erysipelas . . . . . . . . . . . . . . . . . 10.2.2 Erythema nodosum . . . . . . . . . . . . . 10.2.5 Exanthaema, viral . . . . . . . . . . . . . 10.2.6 Eye problems . . . . . . . . . . . . . . . . . 10.12 Cataract . . . . . . . . . . . . . . . . . 10.12.4 Conjunctivitis . . . . . . . . . . . . . . 10.12.2 Corneal ulcers . . . . . . . . . . . . . . 10.12.2 Exam . . . . . . . . . . . . . . . . . . . 10.12.1 Glaucoma . . . . . . . . . . . . 10.12.2,10.12.4 Red eye . . . . . . . . . . . . . . . . . 10.12.2

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Visual loss . . . . . . . . . . . . 10.12.3, 10.2.4 Family planning and HIV infection . . . . . . 14.5 Fasciitis, necrotising . . . . . . . . . . . . 10.2.2 Fascioliasis. . . . . . . . . . . . . . . . . . 11.11 Fever . . . . . . . . . . . . . . . . . 10.1, 11.25.1 Filariasis lymphatic . . . . . . . . . . . . . . 11.12 Fine-needle aspiration . . . . . . . . . . . . 7.2.5 Fistula . . . . . . . . . . . . . . . . . . . 10.15.7 Fluid management . . . . . . . . . . QC18, 3.1, 4.1 Fluid overload . . . . . . . . . . . . . . . . 3.2.5 Folliculitis . . . . . . . . . . . . . . . . . 10.2.3 Eosinophilic pustular . . . . . . . . . . . 10.2.3 Pityrosporum . . . . . . . . . . . . . . . 10.2.3 Foreign body inhalation. . . . . . . . . . . . QC11 Fractures . . . . . . . . . . . . . . . . . . . 4.5.2 Frailty . . . . . . . . . . . . . . . . . . . . 18.1 Frictional keratosis . . . . . . . . . . . . . 10.17.3 Fungal infections, disseminated . 10.1.2, 11.4, 11.16 Furuncle . . . . . . . . . . . . . . . . . . 10.2.2 Gastric lavage . . . . . . . . . . . . . . 3.8, 7.3.9 Gastric reﬂux . . . . . . . . . . . . . . . . 10.7b.2 Gastritis . . . . . . 10.3.2,10.7a.2, 10.7c.2, 10.7d.3 Gastroenteritis, viral . . . . 10.7a.2, 10.7c.2, 10.7d.4 Gastroparesis . . . . . . . . . . . . . . . 10.7c.2 Genital examination, external female (speculum) . . . . . . . . . . . . . . . . . 7.2.8 Genitourinary problems . . . . . . . 10.14, 11.44 Female . . . . . . . . . . . . . . . . . . . 10.15 Male . . . . . . . . . . . . . . . . . . . . 10.16 Genital ulcer . . . . . . . . . . . . . . . . 10.14.3 Geographic tongue . . . . . . . . . . . . . 10.17.3 Geriatric care . . . . . . . . . . . . . . . . . 18 GFR (glomerular ﬁltration rate) . . . . . . . . 11.31 Gingivitis . . . . . . . . . . . . . . . . . . 10.17.6 Glasgow coma scale . . . . . . . . . . . . . . 4.2 Glaucoma Acute angle closure . . . . . . . . . . . 10.12.2 Chronic open angle . . . . . . . . . . . 10.12.4 Glomerular ﬁltration rate (GFR) . . . . . . . . 11.31 Glomerulonephritis . . . . . . . . . . . . . 11.31.2 Glucose Hyperglycaemia, DKA . . . . . . . . . . . 3.4.1 Hypoglycaemia . . . . . . . . . . . QC19, 3.4.2 Gonorrhoea . . . . . 11.13, 10.14.2, 10.15.4, 10.16.3 Gout . . . . . . . . . . . . . . . . . . . . 10.13.1 Gram stain . . . . . . . . . . . . . . . . . 7.2.14 Guinea worm- see dracunculiasis . . . . . 10.2.10 Haematuria. . . . . . . . . . . . . . . . . 11.31.5 Haemolysis . . . . . . . . . . . . . . . . . 10.19.2 Haemolytic-uraemic syndrome . . . . . . . 10.19.2 Haemophilia . . . . . . . . . . . . . . . . 10.19.5 Haemophilus inﬂuenza type b . . . . . . . . 11.17 Haemoptysis . . . . . . . . . . . . . . . . . QC23 Haemorrhage Abnormal bleeding, bruising . . . . . . . . 10.19

Haemoptysis . . . . . . . . . . . . . . . . QC23 Haemothorax . . . . . . . . . . . . . . . QC22 How to stop (compression) . . . . . . . . . QC22 Nosebleed (epistaxis) . . . . . . . . . . . QC23 Pelvic binder . . . . . . . . . . . . . . . . QC22 Vaginal . . . . . . . . . . . QC24-25-26, 10.15.2 Upper gastrointestinal . . . . . . . . . . . QC23 Haemorrhagic fever . . . . . . . . . 11.46,10.19.9 Haemorrhoids . . . . . . . . . . . . . . . 10.14.2 Haemothorax . . . . . . . . . . . . . . . . . QC22 Hand washing . . . . . . . . . . . . . . . . . 6.2 Harm reduction for injecting-drug users . 17.5, 4.2 Head injury . . . . . . . . . . . . . . . . . . QC21 Headache . . . . . . . . . . . . . . . . . 10.10b Cluster . . . . . . . . . . . . . . . . . . 10.10b Meningitis . . . . . . . . . . . . . 10.10b, 11.5 Migraine . . . . . . . . . . . . . . . . . 10.10b Tension . . . . . . . . . . . . . . . . . 10.10b Heart failure . . . . . . . . . . . . . . . . . 3.2.5 Heat stroke . . . . . . . . . . . . . 10.1.4, 10.7c.2 Heimlich manoeuvre . . . . . . . . . . . . . QC11 Helicobacter pylori . . . . . . . . . . . . . 10.7a.2 HELLP syndrome . . . . . . . . . . . . . . . 10.8 Helminthic infection Abdominal pain . . . . . . . . . . . . . 10.7a.2 Prevention . . . . . . . . . . . . . . . . . 19.1 Hepatic encephalopathy . . . . . . . . . 3.4.1,10.9 Hepatitis A, B, C, D . . . . . . . . . . . . . . . . . . 11.14 Prevention hepatitis B in health workers . 19.4.5 Viral . . . . . . . . . . . . . . 11.14, 10.7.3, 10.8 Ischaemic . . . . . . . . . . . . . . . . . 10.8 Hepatosplenomegaly . . . . . . . . . . 10.8, 10.20 Hepatocellular carcinoma . . . . . . . . . . 10.8 Hernia . . . . . . . . . . . . . . . . . . . 10.16.3 Herpes Encephalitis . . . . . . . . . 3.4.1,10.11.3, 11.15 Genital . . . . . . . . . . . . . . . 10.14, 11.15 Keratitis . . . . . . . . . . . . . . . . . 10.12.2 Labialis . . . . . . . . . . . . . . . . . 10.17.3 Simplex . . . . . . . . . . 10.2.5, 11.15, 10.7b.3 Stomatitis . . . . . . . . . . . . . . . . 10.17.3 Zoster/varicella . . . . . . 10.2.5, 10.12.2, 11.45 Zoster ophthalmicus . . . . . . . . . . . 10.12.6 Hiccups . . . . . . . . . . . . . . . . . . . 20.6 Histoplasmosis . . . . . . . . . . . . . . . . 11.16 Cutaneous . . . . . . . . . . . . . . . . 10.2.3 HIV, PLHIV . . . . . . . . . . . . . . . . . . . 13 Abdominal pain . . . . . . . . . . . . . 10.7a.3 Adolescent considerations . . . . . . . . . 13.12 Anorectal problems . . . . . . . . . . . 10.14.3 Antiretroviral therapy . . . . . . . . . . . 13.4 ART monitoring . . . . . . . . . . . . . . 13.4 CD4 testing . . . . . . . . . . . . . . . . . . 9.3 Cholangiopathy . . . . . . . . . . . . . . 10.8

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Chronic HIV care and prevention . . . . . . . 13 Clinical staging . . . . . . . . . . . . . . . 13.1 Cotrimoxazole prophylaxis . . . . . 13.2.1, 13.8.1 Counselling, provider-initiated . . . . . . . . 9.1 Diagnosis . . . . . . . . . . . . . . . . . . . 9 Diarrhoea . . . . . . . . . . . . . . . . 10.7d.3 Drug resistance . . . . . . . . . . . . . . . ?? Enteropathy . . . . . . . . . . . . . . . 10.7d.3 Eye problems . . . . . . . . . . . . . . 10.12.6 Family planning . . . . . . . . . . . . . . 14.5 Health worker prevention . . . . . . . 6.4, 19.4 Infant feeding . . . . . . . . . . . . . . . 14.4 Isoniazid preventive therapy (IPT) . . . . 13.2.2 Lymphadenopathy . . . . . . . . . . . . 10.5.1 Malaria and HIV . . . . . . . . . . . . . 11.25.5 Malnutrition . . . . . . . . . . . . . . . 10.3.2 Medicines – see individual medicines in 8.4 . 8.4 Mouth problems . . . . . . . . . . . . . 10.17.2 Nephropathy (HIVAN) . . . . . . . . . . 11.31.5 Neurological deﬁcit . . . . . . . . . . . 10.10a Palliative care, special considerations . . . 20.10 Persistent diarrhoea . . . . . . . . . . . 10.7d.3 Positive living . . . . . . . . . . . . . . . 13.11 Positive prevention . . . . . . . . . . . . . 13.10 Postpartum services for HIV-infected and HIV-exposed children . . . . . . . . 14.4 Post-exposure prophylaxis . . . . . . 19.4.1, 19.5 Pregnancy and HIV . . . . . . . . . . . . . 14 Prevention . . . . . . . . . 6.4, 13.10, 19.4, 14.1 Prevention MTCT . . . . . . . . . . . . . . ?? Prophylaxis for positive patients . . . . . . 13.3 Related conditions, management – see opportunistic infections . . . . . . . 13.1 Repeat testing . . . . . . . . . . . . . . . . 9.2 Reproductive choice . . . . . . . . . . . . 14.12 Seizures . . . . . . . . . . . . . . . . . 10.10c Special considerations . . . . . . . . . . . 13.2 Stigma in workplace . . . . . . . . . . . 19.4.3 Transmission . . . . . . . . . . 6.4, 13.10, 14, 19 Testing and counselling . . . . . . . . . . . . 9 Treatment . . . . . . . . . . . . . . . . . 13.12 Tuberculosis . . . . . . . . . . . . . . 13.7, 13.8 Virological testingv13.5, 14.4 Wasting syndrome . . . . . . . . . . . . 10.3.3 HIVAN . . . . . . . . . . . . . . . . . . . 11.31.5 HIV/TB coinfection and co-management . . . 13.10 INH preventive therapy . . . . . . . . . . 13.3 Hookworm . . . . . . . . . . . . . 10.18.1, 10.18.3 Hydradenitis suppurativa . . . . . . . . . . 10.14.3 Hydrocele . . . . . . . . . . . . . . . . . 10.16.3 Hydrosalpinx . . . . . . . . . . . . . . . . 10.15.3 Hyperemesis gravidarum . . . . . . 10.7c.3, 14.1.11 Hypercalcaemia . . . . . . . . . . . . 5.2.3, 10.7b Hyperkalaemia . . . . . . . . . . . . . . . . 5.2.2 Hypernatraemia . . . . . . . . . . . . . . . 5.2.1

Hypersensitivity, antiretroviral . . . . . . . . 13.7 Hyperthermia. . . . . . . . . . . . . . . . 10.1.4 Hyperthyroid . . . . . . . . . . . . . . . . . 10.4 Hypocalcaemia. . . . . . . . . . . . . . . . 5.2.3 Hypoglycaemia . . . . . . . . . QC19, 3.4.2, 10.10c Hypokalaemia . . . . . . . . . . . . . . . . 5.2.2 Hyponatraemia . . . . . . . . . . . . . . . . 5.2.1 Hypothalamic amenorrhoea . . . . . . . . 10.15.2 Hypoxaemia . . . . . . . . . . . . . . . . . 3.2.2 Idiopathic thrombocytopenia purpura . . . 10.19.2 Ileus . . . . . . . . . . . . . . . . . . . . 10.7c.2 Immobilize spine . . . . . . . . . . . . . . . QC21 Immune reconstitution inﬂammatory syndrome (IRIS) . . . . . . . . . . . . . . 13.7 Immunization Adolescents and adults . . . . . . . . . . 19.1 In older adults . . . . . . . . . . . . . . . 18.5 In PLHIV . . . . . . . . . . . . . . . . . . 13.13 Impetigo . . . . . . . . . . . . . . . . . . 10.2.2 Incontinence . . . . . . . . . . . . . . . . 10.15.7 Infection Health care provider, prevention . . . . . . 19.4 Prevention and control . . . . . . . . . QC39, 6.4 Infection prevention and control Acute respiratory diseases – epidemic and pandemic prone . . . . . . . . . . . 6.11 Facility-level activities . . . . . . . . . . 6.1, 6.3 Hand hygiene . . . . . . . . . . . . . . . . 6.2 Isolation precautions . . . . . . . . . . . . . 6.3 PPE . . . . . . . . . . . . . . . . . . . . . 6.3 Standard precautions . . . . . . . . . . . . 6.2 Filovirus haemorrhagic fever . . . . . . . . 6.13 Respiratory hygiene . . . . . . . . . . . . . 6.4 Transmission-based precautions . . . . . . . 6.4 Tuberculosis . . . . . . . . . . . . . 6.12, 19.4.4 Inﬂuenza . . . . . . . . . . . . . . . 11.17, 10.6.3 Inguinal hernia . . . . . . . . . . . . . . . 10.16.3 Inhalation burn . . . . . . . . . . . . . . 3.2, 3.10 Inhalers (see individual medicines in 8) . QC17, 10.6 Injection Safe techniques . . . . . . . . . . . . . . . 6.2 Injecting drug users Harm reduction . . . . . . . . . . . . . . 17.5 Management of complications . . . . . . . 17.8 Opioid substitution therapy . . . . . . . . . 17.4 Insect bite reaction. . . . . . . . . . . . . 10.2.3 Intellectual disability . . . . . . . . . . . . 10.11.3 Intercostal chest drain (chest tube) . . . . . 7.3.1 Intoxication Alcohol . . . . . . . . . . . . . . . . . 3.7, 16 Opioid . . . . . . . . . . . . . . . . . . 3.6, 17 Intra partum services for HIV-infected women . . . . . . . . . . . . . . . . . . . 14.10 Intrauterine device (IUD) Placement . . . . . . . . . . . . . . . . . 7.3.4

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IUD and HIV . . . . . . . . . . . . . . . 14.5.2 Intravenous ﬂuids . . . . . . . . . . . . QC18, 3.1 Intubation Indications, technique . . . . . . QC31-32-33-34 Post-care . . . . . . . . . . . . . . . . . . QC34 IRIS (immune reconstitution inﬂammatory syndrome) . . . . . . . . . . . . 13.7, 10.1,10.5 Irritable bowel syndrome (IBS) . . . . . . . 10.7a.2 Isolation precautions . . . . . . . . . . . . . . 6.3 Isoniazid preventive therapy . . . . . . . . . 13.3 Isosporiasis . . . . . . . . . . . . . 11.18, 10.7d.3 IUD (intrauterine device) placement . . . . . 7.3.4 IV insertion . . . . . . . . . . . . . . . . . . QC18 Jaundice . . . . . . . . . . . . . . . . . . . 10.8 Joints Arthritis . . . . . . . . . . . . . . . . . 10.13.1 Gout . . . . . . . . . . . . . . . . . . . 10.13.2 Osteoarthritis . . . . . . . . . . . . . . 10.13.3 Pain . . . . . . . . . . . . . . . . . . . . 10.13 Rheumatoid arthritis . . . . . . . . . . . 10.13.4 Kaposi sarcoma . . 11.19, 10.2.4, 10.2.5, 10.4, 10.5, 10.12.6, 10.17.3 Keratitis . . . . . . . . . . . . . . . . . . 10.12.2 Keratoconjuncitivis Sicca . . . . . . . . . . . . . . 10.12.2, 10.12.6 Thermal or chemical . . . . . . . . . . . 10.12.2 Ultraviolet . . . . . . . . . . . . . . . . 10.12.2 Kidney problems (see Renal problems) Laboratory Blood counts . . . . . . . . . . . . . . . 10.19.2 Electrolyte abnormalities . . . . . . . . . . 5.2.1 Essential tests – health centre, district hospital . . . . . . . . . . . . . . . 1.2 Result interpretation . . . . . . . . . . . . . 5.1 Labyrinthitis . . . . . . . . . . . . . . . . 10.7c.2 Lactic acidosis . . . . . . . . . . . . 13.9, 10.7a.2 In pregnant women on ART . . . . . . . 14.1.9 Leishmaniasis . . . . . . . . . . . . . . 11.20, 8.4 Cutaneous . . . . . . . . . . . . 11.20.1, 10.2.3 Visceral . . . . . . . . . . . . . . . . . 11.20.2 Coinfection with HIV . . . . . . . . . . . 11.20.3 Leprosy . . . . . . . . . . . . . . . . . . . 11.21 Lepromatous . . . . . . . . . . . . . . . 10.2.5 Leptospirosis . . . . . . . . . . . . . . . . . 11.22 Lethargy . . . . . . . . . . . . . . . . . QC6, 3.4 Leukaemia . . . . . . . . . . . . . 10.5.2, 10.19.2 Leukoplakia . . . . . . . . . . . . . . . . 10.17.3 LGV . . . . . . . . . . . . . . . . . . . . 10.14.3 Lichen planus . . . . . . . . . . . . . . . 10.17.3 Lipoatrophy . . . . . . . . . . . . . . . . . 13.7 Lipodystrophy . . . . . . . . . . . . . . . . 13.7 Liver abscess Amoebic . . . . . . . . . . . . . . . . . 11.1.2 Bacterial . . . . . . . . . . . . . . . . . . 11.23 Liver disease/injury

Alcoholic . . . . . . . . . . . . . . 10.8, 10.9, 16 Ascites . . . . . . . . . . . . . . . . . . . 10.9 Drug-induced . . . . . . . . . . . . . . . 10.8 Hepatitis, viral . . . . . . . . . . . . . . . 11.14 Non-alcoholic steatohepatitis . . . . . . . 10.8 Schistosomiasis . . . . . . . . . . . . . . 11.34 Toxin-induced . . . . . . . . . . . . . 3.8, 10.8 Loaisis . . . . . . . . . . . . . . . . . . . . 11.24 Lumbar puncture . . . . . . . . . . . 7.4.2, 10.10b Lymphatic ﬁliariasis . . . . . . . . . . 10.4, 11.13 Lymphatic obstruction . . . . . . . . . . . . 10.4 Lymph node biopsy . . . . . . . . . . . . . . 7.2.6 Lymphadenopathy and lumps. . . . . . . . . 10.5 Retroperitoneal lymphadenopathy . . . . 10.15.3 Lymphoedema . . . . . . . . . . . . . . . . 10.4 Lymphoma in DDx . . . . . . . . . . . . 10.1, 10.5 Cutaneous . . . . . . . . . . . . . . . . 10.2.5 Primary CNS . . . . . . . . . . . . . . . 10.10b Mycobacterium avium infection (MAC) . 10.1, 11.27 Macular degeneration . . . . . . . . . . . 10.12.6 Maculopapular rash . . . . . . . . . . . . 10.2.6 Malaria Diagnosis . . . . . . . . . . . . 11.25.1, 11.25.2 Malaria and HIV . . . . . . . . . . . . . 11.25.5 Prevention . . . . . . . . . . . . . . . . 11.25.7 Risk . . . . . . . . . . . . . . . . . . . 11.25.2 Severe . . . . . . . . . . QC20, 3.1.5, 3.2.3, 11.25 Treatment . . . . . . . . . . . . . QC20, 11.25 Uncomplicated . . . . . . . . . . . . . . 11.25.3 Malnutrition . . . . . . . . . . . . . . . 10.3, 10.9 Manual ventilation . . . . . . . . . . . . . . QC35 MAO-I toxicity . . . . . . . . . . . . . . . . 3.8.1 Marsupialisation . . . . . . . . . . . . . . . 7.3.3 Massage, uterus . . . . . . . . . . . . . . . QC26 MDR-TB (multidrug-resistant TB) . . . . . . . 15.5 Measles . . . . . . . . . . . . . . . . . . . 10.1 Medicines/therapies Adolescent and adult medicines . . . . . . . 8.4 Analgesics . . . . . . . . . . . . . 8.1, 20.2-20.4 Corticosteroid equivalents . . . . . . . . . . 8.2 Side-effects – see individual medicines . . . 8.4 Summary of medicines/therapies . . . . . . 8.4 Meningitis . . . . . . . . . . . . . . . . . 10.10b Aseptic . . . . . . . . . . . . . . . . 10.10b.2 Bacterial . . . . . . . . . . . . . . . . 10.10b.3 Cryptococcal . . . . . . . . . . . . . . . . 11.5 Meningococcal . . . . . . . . . . . . 10.10b.3 Tuberculous . . . . . . . . . . . . 10.10b.2, 15.3 Meningococcal infection . . . . . . . 10.1, 10.10b.3 Mental health problems . . . . . . . . . . . 10.11 Abnormal behaviour . . . . . . . . . . . 10.11.3 Anxiety . . . . . . . . . . . . . . . . . . 10.11.7 Bipolar disorder . . . . . . . . . . . . . 10.11.5 Delerium . . . . . . . . . . . . . . . 3.4, 10.11.3 Dementia . . . . . . . . . . . . . . . . 10.11.3

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Depression . . . . . . . . . . . . . . . . 10.11.6 Intellectual disability . . . . . . . . . . . 10.11.3 Panic attacks . . . . . . . . . . . . . . 10.11.7 Psychosis . . . . . . . . . . . . . . . . 10.11.4 Sad mood . . . . . . . . . . . . . . . . 10.11.6 Schizophrenia . . . . . . . . . . . . . . 10.11.4 Suicide risk/self-harm . . . . . . . QC30,10.11.2 Metabolic acidosis . . . . . . . . . . . 3.2.2, 10.6 In poisoning . . . . . . . . . . . . . . . . 3.8.1 Methadone . . . . . . . . . . . . . . . . . . 17.4 Microsporidiosis . . . . . . . . . . . 11.26,10.7d3 Mid upper arm circumference (MUAC) . . . 10.3.1 Migraine . . . . . . . . . . . . . . . . . . 10.10b Molluscum contagiosum . . . . . . . . . . 10.2.3 Monitoring Fluid intake . . . . . . . . . . . . . . . . . QC18 Forms and charts . . . . . . . . . . . . . 3.11 Longitudinal monitoring of patients . . . . . 21.1 Inpatient care . . . . . . . . . . . . . . . 21.2 Disease outbreak . . . . . . . . . . . . . 21.3 Mononeuritis multiplex . . . . . . . . . . 10.10a.3 Mononucleosis . . . . . . . . . . . . . . . . 10.1 Motion sickness . . . . . . . . . . . . . . . 10.7b Mouth problems . . . . . . . . . . . . . . . 10.17 Dental caries . . . . . . . . . . . . . . . 10.17.5 Candidiasis . . . . . . . . . . . . 10.17.3, 11.4 Gingivitis . . . . . . . . . . . . . . . . . 10.17.6 Noma . . . . . . . . . . . . . . . . . . 10.17.7 Oral cancer . . . . . . . . . . . . . . . 10.17.4 MSM (men who have sex with men) . . . . . 19.3 Multidrug-resistant TB (MDR-TB) . . . . . . 15.5 Mycobacterium avium complex . . . 10.2.3, 11.27 Myelodysplastic syndromes . . . . . . . . . 10.19 Myelopathy . . . . . . . . . . . . . . . 10.10a.4 HIV-associated. . . . . . . . . . . . . 10.10a.4 Myiasis. . . . . . . . . . . . . . . . . . . 10.2.3 Myocardial infarction . . . . . . . . . . QC8, 3.3 Mycosis fungoides . . . . . . . . . . . . . 10.2.6 Nausea and vomiting . . . . . . . . . . . . . 10.7b Nasogastric tube . . . . . . . . . . . . . . . 7.3.8 Necrotizing fasciitis . . . . . . . . . . 10.2.2, 17.8 Nephropathy, HIV-associated (HIVAN) . . . 11.31.5 Nephritic syndrome . . . . . 11.31.2, 11.31.3, 10.4 Neurocysticercosis . . . . . . . . . 10.10a, 11.7 Nephrotic syndrome . . . . . . . 10.4, 10.9, 11.31 Neurosyphilis Meningovascular . . . . . . . . . 11.37, 10.10a Neurological problems Deﬁcit . . . . . . . . . . . . . . . . . . 10.10a Headache . . . . . . . . . . . . . . . . 10.10b Seizures . . . . . . . . . . . . . . . . . 10.10c Neuropathy- peripheral . . . . . . . 10.10a.6, 13.8 Nicotinic stomatitis . . . . . . . . . . . . . 10.17.3 Nocardiosis . . . . . . . . . . . . . . . . 10.5.2 Noma . . . . . . . . . . . . . . . . . . . 10.17.7

Nosebleed (epistaxis) . . . . . . . . . . . . QC23 Nutrition In sepsis . . . . . . . . . . . . . . . . . . . 3.0 In older adults . . . . . . . . . . . . . . . 18.3 Infant feeding . . . . . . . . . . . . . . . 14.3 In PLHIV . . . . . . . . . . . . . . . . . . 13.13 Prevention malnutrition . . . . . . . . . 10.3.4 Weight loss, malnutrition . . . . . . . . . 10.3.4 Obsessive-compulsive disorder . . . . . . 10.11.7 Oedema Limbs . . . . . . . . . . . . . . . . . 10.4, 20.5 Pulmonary . . . . . . . . . . . . . . . . . 3.2.5 Oesophageal stricture Web, diverticula . . . . . . . . . . . . . . 10.7b Oesophagitis DDx . . . . . . . . . . . . . . . . . . . 10.7b.2 Approach in PLHIV . . . . . . . . . . . . 10.7b.3 Onchocerciasis . . . . . . . . . . . 11.28, 10.2.3 Opioids Analgesic, step 3 pain ladder . . . . . . 20.2, 8.1 Dependence . . . . . . . . . . . . . . . . 17.4 Dyspnoea, difﬁcult breathing . . . . . . . . 20.4 Overdose, use of naloxone . . . . . . QC18, 3.6.1 Substitution therapy (OST) . . . . . . . . . 17.4 Withdrawal . . . . . . . . . . . . . . . . 3.6.2 Opportunistic infections . . . . . . . . . . . 10.5, multiple sections in 11, 13 Optic disk swelling . . . . . . . . . . . . . 10.12.6 Optic neuritis . . . . . . . . . . . . . . . . 10.12.3 Oral hairy leukoplakia . . . . . . . . . . . 10.17.3 Oral problems – see mouth problems . . . . . 10.17 Oral rehydration solution (ORS) . . . . . . . 10.7d2 Orchitis- viral . . . . . . . . . . . . . . . . 10.16.3 Organophosphate intoxication . . . . . . . . 3.8.1 Osteoarthritis. . . . . . . . . . . . . . . . 10.13.1 Osteomyelitis . . . . . . . . . . . . . . . . . 10.1 Overdose Alcohol . . . . . . . . . . . . . . . . . . . 3.7 Opioids . . . . . . . . . . . . . . . . . . . 3.6.1 Medicines, poisons . . . . . . . . . . . . 3.8.1 Stimulants . . . . . . . . . . . . . . . . . 3.6.3 Ovarian cyst Functional . . . . . . . . . . . . . . . . 10.15.3 Ruptured . . . . . . . . . . . . . . . . . 10.15.2 Ovarian torsion . . . . . . . . . . . 10.15.2, 10.15.3 Overactive bladder . . . . . . . . . . . . . 10.15.7 Oxygen Equipment . . . . . . . . . . . . . QC14, QC16 Therapy . . . . . . . . . . . . . . . . QC14, 3.0 Pain Abdominal . . . . . . . . . . . . . . QC8, 10.7b Acute . . . . . . . . . . . . . . . . . . . 20.4 Assessment . . . . . . . . . . . . . . . . 20.1 Chronic, in life-threatening conditions . . . 20.2 Control, analgesia . . . . . . . . 20.2, 20.3, 20.4

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Headache . . . . . . . . . . . . . . . . 10.10b Injecting drug users . . . . . . . . . . . . 17.7 Life-threatening causes . . . . . . . . . QC8-9 Neuropathic . . . . . . . . . . . . 10.10a, 20.3 Pregnancy . . . . . . . . . . . . . . . . . QC8 Palliative care . . . . . . . . . . . . . . . . . 20 Breathing difﬁculty . . . . . . . . . . . . . 20.5 Cancer- special considerations . . . . . . 20.12 Hiccups . . . . . . . . . . . . . . . . . . 20.6 Pain – see Pain PLHIV- special considerations . . . . . . . 20.10 Preventive interventions . . . . . . . . . . 20.9 TB patients- special considerations . . . . 20.11 End-of-life care . . . . . . . . . . . . . . 20.13 Pallor. . . . . . . . . . . . . . . . . . . . 10.18.1 Pancreatitis . . . . . . . . . . . . . . . . 10.7a.2 Panic attack . . . . . . . . . . . . . . . . 10.11.7 PAP smear . . . . . . . . . . . . . . . . . . 7.2.9 Papillomata . . . . . . . . . . . . . . . . 10.12.6 Papular lesions . . . . . . . . . . . . . . . 10.2.3 Papular urticaria . . . . . . . . . . . . . . 10.2.3 Paracentesis (abdominal tap) . . . . . . . . 7.4.3 Paraphimosis, reduction . . . . . . . 7.3.5, 10.16.4 Parenteral ﬂuids . . . . . . . . . . . . . . . QC18 Patient consent . . . . . . . . . . . . . . . . 7.1 Patient monitoring and reporting . . . . . 3.11, 21 PCP (Pneumocystis jirovecii) pneumonia . . . . . . . . . . . . . 3.2.4, 10.6.3 Pediculosis- capitis, corporis, pubis . . . . 10.2.8 Pelvic binder . . . . . . . . . . . . . . . . . QC22 Pelvic mass . . . . . . . . . . . . . . . . 10.15.3 Pelvic examination . . . . . . . . . . . . . . 7.2.8 Pelvic inﬂammatory disease (PID) . . . . . 10.15.5 Pemphigoid . . . . . . . . . . . . . . . . 10.2.4 Pemphigus vulgaris . . . . . . . . . . . . 10.2.4 Penicilliosis . . . . . . . . . . . . . . . . . 11.29 Cutaneous . . . . . . . . . . . . . . . . 10.2.3 Lymphadenopathy . . . . . . . . . . . . 10.5.2 Penile discharge . . . . . . . . . . . . . . 10.16.2 PEP (post exposure prophylaxis- HIV) . . . . 19.4 Peptic ulcer disease (PUD) . . . . . . . . . 10.7a.2 Periodontitis . . . . . . . . . . . . . . . . 10.17.6 Perianal itch . . . . . . . . . . . . . . . . 10.14.2 Pericardiocentesis . . . . . . . . . . . . . . 7.4.5 Pericarditis . . . . . . . . . . . . . 3.3, 10.6, 10.7.3 Peripheral neuropathy . . . . . . . . 13.7,10.10a.6 Peritonitis . . . . . . . . . . . . . . . . . . 10.7b Spontaneous bacterial, in cirrhosis . . . . 10.9 Persistent generalized lymphadenopathy (PGL) . . . . . . . 10.5.2, 13.2 Personal protective equipment (PPE) . . . . . . 6.3 Pharyngeal abscess . . . . . . . . . . . . 10.17.9 Pharyngitis . . . . . . . . . . . . . . . . . 10.17.9 Pharmacovigilance . . . . . . . . . . . . . . 21.4 Phimosis . . . . . . . . . . . . . . . . . . 10.16.5

Phobias . . . . . . . . . . . . . . . . . . 10.11.7 PITC (provider-initiated testing and counselling) . . . . . . . . . . . . . . . 9.1 Pityriasis versicolor . . . . . . . . . . . . 10.2.7 Placenta, manual removal . . . . . . . . . . QC27 Placenta previa . . . . . . . . . . . QC24,10.15.2 Plague Bubonic . . . . . . . . . . . . . . . . . 10.5.2 Pneumonia . . . . . . . . . . . . . . . . 10.6.2 Plaques . . . . . . . . . . . . . . . . . . 10.2.7 Plasmodium falciparum malaria . . . . . . . 11.25 Pleural effusion . . . . . . . . . . 3.2.1, 10.6, 15.1 Pleuritis, pleurisy . . . . . . . . . . . . . . 10.6.2 PMTCT (prevention of mother-to-child transmission) . . . . . . . . . . . . . . . . 14 Pneumocystis jirovecii pneumonia (PCP) . . . . . . . . . . . . . . . . 3.2.3, 10.6.3 Pneumonia . . . . . . . . . . . . . . . 3.2, 10.6.3 Aspiration . . . . . . . . . . . . . . . 10.6.2, 16 Inﬂuenza . . . . . . . . . . . . . . 10.6.3, 11.17 Lobar . . . . . . . . . . . . . . . . . . 10.6.3 Non-severe . . . . . . . . . . . . . . . 10.6.3 Pneumocystis, P. jirovecii, PCP . . . . . . 10.6.7 Severe . . . . . . . . . . . . . . . . 3.2.3, 10.6 Staphylococcal . . . . . . . . . . . . . . 3.2.3 Varicella . . . . . . . . . . . . . . 10.6.3, 11.45 Pneumothorax Tension . . . . . . . . . . . QC22, 3.2.1, 10.6.2 Poisoning . . . . . . . . . . . . . . . . . . . 3.8 Alumimun or zinc phosphide . . . . . . . . 3.8.1 Aspirin . . . . . . . . . . . . . . . . . . . 3.8.1 Antidiabetic agents . . . . . . . . . . . . 3.8.1 Assessment . . . . . . . . . . . . . . . . 3.8.1 Beta-blockers . . . . . . . . . . . . . . . 3.8.1 Calcium-channel blockers . . . . . . . . . 3.8.1 Carbamazepine . . . . . . . . . . . . . . 3.8.1 Chemical . . . . . . . . . . . . . . . . . . 3.8.3 Chloroquine . . . . . . . . . . . . . . . . 3.8.1 Chlorphenoxy herbicides . . . . . . . . . . 3.8.1 Cyanide . . . . . . . . . . . . . . . . . . 3.8.1 Digoxin . . . . . . . . . . . . . . . . . . . 3.8.1 Ethylene glycol . . . . . . . . . . . . . . . 3.8.1 Inhaled . . . . . . . . . . . . . . . . . . . 3.8.2 Iron . . . . . . . . . . . . . . . . . . . . 3.8.1 Lithium . . . . . . . . . . . . . . . . . . . 3.8.1 Management . . . . . . . . . . . . . . . . . 3.8 MAOI drugs . . . . . . . . . . . . . . . . 3.8.1 Methanol . . . . . . . . . . . . . . . . . 3.8.1 Opioids . . . . . . . . . . . . . . QC18, 3.6, 3.8.1 Organophosphates . . . . . . . . . . . . . 3.8.1 Paracetamol (acetaminophen) . . . . . . . 3.8.1 Paraquat . . . . . . . . . . . . . . . . . . 3.8.1 Petrol, kerosene . . . . . . . . . . . . . . 3.8.1 Phenobarbital . . . . . . . . . . . . . . . 3.8.1 Propanil . . . . . . . . . . . . . . . . . . 3.8.1

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Quinine . . . . . . . . . . . . . . . . . . 3.8.1 SSRI medicines (ﬂuoxetine, others) . . . . 3.8.1 Symptoms . . . . . . . . . . . . . . . . . . 3.8 Theophylline . . . . . . . . . . . . . . . . 3.8.1 Tricyclic antidepressants. . . . . . . . . . 3.8.1 Warfarin, anticoagulant rodenticides. . . . 3.8.1 Polycystic ovarian disease . . . . . . . . . 10.15.2 Polyradiculopathy . . . . . . . . . . . . 10.10a.3 Portal hypertension . . . . . . . . . . . . . 10.9 Portal vein obstruction . . . . . . . . . . . . 10.4 Portal vein thrombosis . . . . . . . . . . . . 10.8 Post exposure prophylaxis (PEP)- HIV . 19.4.1, 19.5 Postpartum Bleeding . . . . . . . . . . . . . . . . . . QC25 Services for HIV-infected, HIV-exposed children . . . . . . . . . . . . . . . . . 14.12 Services for mother . . . . . . . . . . . . 14.4 Post-traumatic stress disorder (PTSD) . . . 10.11.7 PPE (personal protective equipment) . . . . . . 6.2 Precautions Health-care worker . . . . . . . . . . 6.2, 19.4 Standard . . . . . . . . . . . . . . . . . 6.2-6.9 Pre-eclampsia . . . . . . . . . . . . . . . . QC28 Pregnancy – see IMPAC tools for management Acute fatty liver . . . . . . . . . . . . . . 10.8 Antiemetic medication . . . . . . . . . . 14.1.6 Ectopic . . . . . . . . . . 10.7a.2, 10.15.2, 10.15.3 Headache . . . . . . . . . . . . . QC8, 10.10b HIV . . . . . . . . . . . . . . . . . . . . . . 14 Hypertensive crisis . . . . . . . . . . . . . 3.2.5 Incomplete abortion . . . . . . . . . . . 10.15.2 Intrahepatic cholestasis . . . . . . . . . . 10.8 Pain . . . . . . . . . . . . . . . . . . . . QC8 Placenta previa . . . . . . . . . . . . . 10.15.2 Placental removal- manual . . . . . . . . . QC27 Postpartum . . . . . . . . . . . . QC25, 14.12 Safety of drugs- see individual medicines . . 8.4 Vaginal bleeding . . . . . . . . . . . . QC24-25 Pretibial myxoedema . . . . . . . . . . . . . 10.4 Prevention of mother-to-child transmission HIV (PMTCT) . . . . . . . . . . . . . . . . . 14 Prevention of HIV with positives . . . . . . . 13.10 Prevention For adolescents and adults . . . . . . . . . 19.1 For health workers . . . . . . . . . . . . . 19.4 Priority signs and symptoms . . . . . . . . . QC10 Procedures Abdominal tap (paracentesis) . . . . . . . 7.4.3 Arthrocentesis (joint aspiration) . . . . . . 7.4.4 Chest tap (thoracentesis) . . . . . . . . . 7.4.1 Chest tube (intercostal chest drain) . . . . 7.3.1 Colposcopy . . . . . . . . . . . . . . . 7.2.11 Crude clotting time . . . . . . . . . . . . 7.2.18 Gastric lavage . . . . . . . . . . . . . . . 7.3.9 Gram stain . . . . . . . . . . . . . . . . 7.2.14

Intercostal chest drain . . . . . . . . . . . 7.3.1 Intubation . . . . . . . . . . . . QC31-23-33-34 IUD placement . . . . . . . . . . . . . . . 7.3.4 Lumbar puncture . . . . . . . . . . . . . . 7.4.2 Manual removal placenta . . . . . . . . . QC27 Marsupialisation . . . . . . . . . . . . . . 7.3.3 Nasogasatric tube placement . . . . . . . 7.3.8 Paracentesis (abdominal tap) . . . . . . . 7.4.3 Paraphimosis, reduction . . . . . . . . . . 7.3.3 Pap smear . . . . . . . . . . . . . . . . . 7.2.9 Pelvic exam . . . . . . . . . . . . . . . . 7.2.8 Pericardiocentesis . . . . . . . . . . . . . 7.4.5 Safety considerations . . . . . . . . . . . 7.1.2 Skin biopsy, snip . . . . . . . . 7.2.1, 7.2.2, 7.2.3 Stool samples . . . . . . . . . . . . . . 7.2.17 Suprapubic catheter insertion . . . . . . . 7.3.7 Thoracentesis (chest tap) . . . . . . . . . 7.4.1 Ultrasound . . . . . . . . . . . . . . . . 7.2.21 Urinalysis . . . . . . . . . . . . . . . . 7.2.16 Urinary catheter insertion – female . . . . 7.3.2 Urinary catheter insertion – male . . . . . 7.3.6 Urinary catheter insertion – suprapubic . . 7.3.7 Wet mount . . . . . . . . . . . . . . . . 7.2.15 Progressive multifocal leucoencephalopathy . . . . . . . . . 10.10a.2 Proteinuria . . . . . . . . . . . . . . . . . 11.31.3 Proctitis . . . . . . . . . . . . . . . . . . 10.14.2 Proctocolitis . . . . . . . . . . . . . . . . 10.14.2 Prostatitis – acute, chronic . . . . . . . . . 10.16.5 Protozoan infections . . . . . . . . . . . . 10.7.1 Provider-initiated testing and counselling (PITC) . . . . . . . . . . . . . . 9.x Pruritis Generalized . . . . . . . . . . . . . . . 10.2.8 Pruritic papular eruption of HIV . . . 10.2.3, 13.2 Psoriasis . . . . . . . . . . . . . . . . . . 10.2.7 Psychiatric problems – see Mental health problems . . . . . . . . . . . . . . 10.11 Psychotherapy . . . . . . . . . 10.11- Appendix 1 Psychosis . . . . . . . . . . . . . . . . . 10.11.4 Pterygium or pinguecula . . . . . . . . . . 10.12.2 Pulmonary oedema . . . . . . . . . . . 3.2.1, 3.2.5 Pulse oximeter . . . . . . . . . . . . . . . . QC14 Pupils, pinpoint Opioid intoxication . . . . . . . . . . . QC18, 3.6 Organophosphate intoxication . . . . . . . 3.8.1 Pyelonephritis . . . . . . . . . . . . 10.7.1, 11.44 Pyomyositis . . . . . . . . . . . . . . 17.8, 10.2.2 Pyrexia . . . . . . . . . . . . . . . . . . . . 10.1 Q fever . . . . . . . . . . . . . . . . . . . . 10.1 Quick check and emergency treatments . . . . . 2 Rabies Disease management, palliative care . . 11.30.1 Rabies vaccine . . . . . . . . . . . . . . 11.30.2 Rape and abuse . . . . . . . . . . . . 4.4, 10.15.2

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Recovery position . . . . . . . . . . . . . . QC19 Red eye . . . . . . . . . . . . . . . . . . 10.12.2 Refractive errors . . . . . . . . . . . . . . 10.12.4 Referral and transport of ill patient . . . . . . QC37 Remove placentavQC27 Renal problems. . . . . . . . . . . . . . . . 11.31 Renal Acute kidney injury . . . . . . . . . . . . 11.31.1 Chronic kidney disease . . . . . . . . . 11.31.2 Hematuria . . . . . . . . . . . . . . . . 11.31.4 Proteinuria . . . . . . . . . . . . . . . . 11.31.3 Stones . . . . . . . . . . . . . . . . . . 10.7a.2 Reproductive choice and HIV. . . . . . . . . 14.12 Retroperitoneal lymphadenopathy . . . . . 10.15.3 Retinal detachment. . . . . . . . . . . . . 10.12.3 Retinitis- CMV . . . . . . . . . . . . 10.12.3, 11.8 Retinopathy Diabetic . . . . . . . . . . . . . . . . . 10.12.6 Sickle-cell disease . . . . . . . . . . . . 10.12.6 Retinal microvasculopathy . . . . . . . . . 10.12.8 Respiratory distress . . . . . . . . . QC2, 3.2, 10.6 Respiratory infections . . . . . . . . . . . . 10.6 Rheumatic fever . . . . . . . . . . . . . . . 11.32 Rib fracture . . . . . . . . . . . . . . 10.6.2, 4.2 Rickettsial diseases . . . . . . . . . . 11.33, 10.1 Ringworm (dermatophytosis) . . . . . . . . 10.2.7 Rodenticide or warfarin toxicity . . . . . . . 3.8.1 Ruptured uterus . . . . . . . . . . . . . . 10.15.2 SAAG (serum-to-ascites gradient) . . . . . 10.9.2 Safe injection techniques . . . . . . . . . . . 6.2 Sarcoidosis . . . . . . . . . . . . . . . . 10.5.2 Scabies . . . . . . . . . . . . . . . . . . 10.2.3 Scalp infections . . . . . . . . . . . . . . 10.2.7 Schistosomiasis . . . . . . . . . . . . . . . 11.34 Fever . . . . . . . . . . . . . . . . . . . . 10.1 Liver . . . . . . . . . . . . . . . . . . . . 11.34 Genital . . . . . . . . . . . . . . 10.15.9, 10.16.6 Schizophrenia . . . . . . . . . . . . . . . 10.11.4 Seborrhoeic dermatitis . . . . . . . . . . . 10.2.7 Second-line antiretroviral therapy . . . . . . 13.6 Sedation For violent or very agitated patients . . . . QC29 Intubation . . . . . . . . . . . . . QC 31, QC34 Ketamine for procedures . . . . . . . . . . QC28 Seizures . . . . . . . . . . . . . . . . 3.5, 10.10c Septic shock/sepsis . . . . . . . . . . . . . 3.1.5 Abortion . . . . . . . . . . . . . . 3.1.5, 10.15.6 Amnionitis . . . . . . . . . . . . . . . . . 3.1.5 Bacterial . . . . . . . . . . . . . . . . . . 3.1.5 Dengue . . . . . . . . . . . . . . . 3.1.5, 11.9 During pregnancy . . . . . . . . . . . . . 3.1.5 Severe inﬂuenza . . . . . . . . . . . 3.1.5, 11.17 Postpartum sepsis . . . . . . . . . 3.1.5, 10.15.6 Severely ill patients . . . . . . . . . . 3.0 to 3.11 Sexually transmitted

infections (STI) . . . . . . . . 11.14, 11.15, 11.16 Gonorrhoea . . . . . . . . . . . . . . . . 11.13 Pelvic inﬂammatory disease . . . . . . . 10.15.5 Syphilis . . . . . . . . . . . . . . . . . . 11.37 Vaginal discharge . . . . . . . . . . . . 10.15.4 Shigella . . . . . . . . . . . . . . . . . . 10.7d.2 Shingles . . . . . . . . . . . . . . . . . . . 11.45 Shock . . . . . . . . . . . . . . . . . . QC4, 3.1 Anaphylaxis . . . . . . . . . . . . . . . . 3.1.3 Haemorrhagic . . . . . . . . . . . . . . . 3.1.1 Hypovolaemic . . . . . . . . . . . . . . . 3.1.2 Differential diagnosis, categories . . . . . . 3.1 Management . . . . . . . . . . . . . . . . . 3.1 Septic . . . . . . . . . . . . . . . . . . . 3.1.5 Sickle-cell disease Anaemia . . . . . . . . . . . . . . . . . 10.18.3 Chest pain . . . . . . . . . . . . . . . . . . 3.3 Jaundice . . . . . . . . . . . . . . . . . . 10.8 Painful crisis . . . . . . . . . . . . QC10, 10.18.3 Renal problems . . . . . . . . . . . . . . 11.31 Retinal detachment . . . . . . . . . . . 10.12.3 Retinopathy . . . . . . . . . . . . . . . 10.12.4 Stroke . . . . . . . . . . . . . . . . . . 10.10a Ulcer, leg . . . . . . . . . . . . . . . . . 10.2.10 Visual loss . . . . . . . . . . . . . . . . 10.12.4 Sinusitis . . . . . . . . . . . . . . . . . . . 11.35 Skin biopsy Scraping, punch, and excision . 7.2.1, 7.2.2, 7.2.4 Skin snip . . . . . . . . . . . . . . . . . . . 7.2.3 Skin problems . . . . . . . . . . . . . . . . 10.2 Cellulitis . . . . . . . . . . . . . . . . . 10.2.2 Cutaneous TB . . . . . . . . . . . . . . 10.2.3 Eczema . . . . . . . . . . . . . . . . . 10.2.7 Folliculitis . . . . . . . . . . . . . . . . 10.2.2 Herpes . . . . . . . . . . . . . . . . . . 10.2.4 Infection . . . . . . . . . . . . . . . . . 10.2.2 Nodular lesions . . . . . . . . . . . . . 10.2.5 Onchocerciasis . . . . . . . . . . . . . 10.2.4 Plaques . . . . . . . . . . . . . . . . . 10.2.7 Psoriasis . . . . . . . . . . . . . . . . . 10.2.7 Scabies . . . . . . . . . . . . . . . . . 10.2.3 Ulcers . . . . . . . . . . . . . . . . . . 10.2.10 Viral warts . . . . . . . . . . . . . . . . 10.2.3 Yaws . . . . . . . . . . . . . . . . . . . 10.2.5 Snake-bite . . . . . . . . . . . . . . . . 3.9, 10.4 Sodium disorders. . . . . . . . . . . . . . . . 5.2 Somatoform disorder . . . . . . . . . . . . . 10.11 Speculum exam . . . . . . . . . . . . . . . . 7.2 Splenomegaly . . . . . . . . . . . . . . . . 10.20 Spinal cord compression . . . . . . . . . 10.10a.4 Spine immobilization . . . . . . . . . . . . . QC21 Splints . . . . . . . . . . . . . . . . . . . . . 4.5 SpO2 . . . . . . . . . . . . . . . . . . . QC14, 3.2 Spondyloarthropathies . . . . . . . . . . . 10.13.1 Spondylosis . . . . . . . . . . . . . . . 10.10a.3

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Staging, WHO for HIV . . . . . . . . . . . . 13.1 Standard precautions . . . . . . . . . . . . . 6.2 Staphylococcal pneumonia . . . . . . . . . 3.2.3 Status epilepticus . . . . . . . . . . . . . 3.5, 8.4 Stevens-Johnson syndrome . . . . . 10.2.3, 10.2.4 Stiff neck, in meningitis . . . . . . . . . . 10.10b Stimulant Intoxication/overdose . . . . . . . . . . . 3.6.3 Withdrawal . . . . . . . . . . . . . . . . 3.6.4 Stool samples . . . . . . . . . . . . . . . 7.2.17 Stop bleeding . . . . . . . . . . . . . . . . QC22 Streptococcal pharyngitis . . . . . . . . . 10.17.9 Stridor . . . . . . . . . . . . . . . . . . . . . 3.2 Strongyloidiasis . . . . . . . . . . . 10.7a.2, 11.36 Strongyloides . . . . . . . . . . 11.36, 10.6, 10.7d Stroke-like syndrome . . . . . . . . . . . . 10.10a Ischaemic or haemorrhagic stroke . . . . 10.10a Subarachnoid haemorrhage . . . . . . . . 10.10b Subconjunctival haemorrhage . . . . . . . 10.12.2 Substance use . . . . . . . . . . . . . . 17, 10.1 Alcohol use . . . . . . . . . . . . . . . . 17.10 Antiretroviral therapy . . . . . . . . . . . 17.6 Family role . . . . . . . . . . . . . . . . . 17.9 Injecting-drug use . . . . . . . . . . . . . 17.8 Opioid dependence . . . . . . . . . . . . 17.4 Pain control . . . . . . . . . . . . . . . . 17.7 Substance dependence . . . . . . . . . . 17.2 Sucking chest wound . . . . . . . . . . . . QC22 Suicide, self-harm . . . . . . . . . . QC30, 10.11.2 Suprapubic catheter insertion . . . . . . . . 7.3.7 Surgical abdomen . . . . . . . 4.2, 10.7a.2, 10.15.2 Surgical problems See Trauma (pre-operative only) Swallowing, painful or difﬁcult . . . . . . . . 10.7b Swelling of limbs . . . . . . . . . . . . . . . 10.4 Syphilis . . . . . . . . . . . . . . . . . . . 11.37 Secondary . . . . . . . . . . 10.2.3, 10.2.6, 11.37 Tertiary. . . . . . . . . . . . . . 11.37,10.10a.3 Tachycardia (fast pulse) . . . . . . . . QC4, 3.1.0 Taeniasis . . . . . . . . . . . . . . . . . . 11.38 Testicular problems . . . . . . . . . . . . 10.16.3 Testicular torsion . . . . . . . . . . . . . . 10.16.3 Tetanus . . . . . . . . . . . . . . . . . . . 11.39 Disease management . . . . . . . . . . . . 11.39 Prevention . . . . . . . . . . . . . . . . . . 19.1 Tetanus spasms . . . . . . . . . . . . . . . 11.39 Thoracentesis (chest tap) . . . . . . . . . . 7.4.1 Thrombocytopenia . . . . . . . . . . . . . . 10.19 Thrombocytopenia, idiopathic purpura . . . 10.19.6 Thrombotic thrombocytopenic purpura (TTP) . . . . . . . . . . . . . . 10.19.2 Thyroid . . . . . . . . . . . . . . . . . . . 10.11.3 Tonsillitis . . . . . . . . . . . . . . . . . . 10.17.9 Toothache . . . . . . . . . . . . . . . . . 10.17.5 Tooth wear . . . . . . . . . . . . . . . . . 10.17.5

Toxic epidermal necrosis . . . . . . . 10.2.3, 10.2.4 Toxicity of antiretroviral drugs . . . . . . . . 13.7 Toxoplasmosis . . . . . . . . . . . 11.40,10.10a.3 Tracheal intubation . . . . . . . . . QC31-32-33-34 Trachoma . . . . . . . . . . . . . . . . . 10.12.5 Transaminases (elevated) . . . . . . . . . . 13.5 Transgender persons . . . . . . . . . . . . . 19.3 Transporting ill patients . . . . . . . . . . . QC37 Transverse myelitis . . . . . . . . . . . . 10.10a.4 Trauma . . . . . . . . . . . . . . . . . . . . . . 4 Emergency triage, assessment, treatment . . . . . . . . . . . . . . . . QC, 4.2 General principles . . . . . . . . . . . . . . . 4 Fractures . . . . . . . . . . . . . . . . . 4.5.2 Managing rape and abuse . . . . . . . . . . 4.4 Suturing . . . . . . . . . . . . . . . . . . 4.5.1 Violence and injury prevention . . . . . . . . 4.3 Wounds . . . . . . . . . . . . . . . . . . 4.5.1 Trichomoniasis . . . . . . . . . . . . . . . 10.15.4 Trigeminal neuralgia . . . . . . . . . . . . 10.10b Trolley, emergency . . . . . . . . . . . . . . QC38 Tropical ulcer . . . . . . . . . . . . . . . 10.2.10 Trypanosomiasis, human African . 11.41, 10.1, 10.5 Trypanosomiasis, American . . . . . . . . . 11.42 Tube placement Endotracheal . . . . . . . . . . QC31-32-33-34 Nasogastric . . . . . . . . . . . . . . . . 7.3.8 Tuberculosis . . . . . . . . . . . . . . . . . . 15 Abdominal or pelvic pain . . . . . 10.7a.3, 10.15.2 Adrenal . . . . . . . . . . . . . . . . . . 3.4.5 Anaemia . . . . . . . . . . . . . . . . . 10.18.2 Arthritis . . . . . . . . . . . . . . . . . 10.13.2 Chest X-ray abnormalities . . . . . . . . 10.6.2 Combination therapy . . . . . . . . . . 15.3, 8.4 Cutaneous . . . . . . . . . . . . . . . . 10.2.3 Diagnosis . . . . . . . . . . . . . . . . . 15.2 Dosing, ﬁrst-line . . . . . . . . . . . . . . 15.3 Drug resistant . . . . . . . . . . . . . . . 15.5 Extrapulmonary (EPTB) . . . . . . . . . 15.1,15.2 Eye problems . . . . . . . . . . . . . . 10.12.7 Focal neurological deﬁcit, tuberculoma, stroke-like syndrome . . . . . . . . . . 10.10a Genital ulcer . . . . . . . . . . . . . . . 10.14.3 Hepatic jaundice . . . . . . . . . . . . . . 10.8 HIV coinfection . . . . . . . . . . . . 15.2, 15.5 HIV testing, retesting . . . . . . . . . . . 9.1, 9.2 HIV–TB co-management . . . . . . . . . . 13.10 Infection prevention and control . . 6.1, 6.12, 19.4 IRIS . . . . . . . . . . . . . . . . . . . . . 13 Isoniazid preventive therapy (IPT) . . . . . 13.3 Lymphadenitis . . . . . . . . . . . . . . 10.5.2 Malnutrition . . . . . . . . . . . . . . . . 10.3 Management . . . . . . . . . . . . . . . . 15.3 Meningitis . . . . . . . . . . . . . . . . 10.10b Miliary, disseminated . . . . . . . 3.1.5, 10.5.2

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Monitoring treatment . . . . . . . . . . . 15.4 Peritonitis . . . . . . . . . . . . . . . . . 10.9 Pericardial effusion or tamponade . . . . . 3.1, 3.3 Persistent diarrhoea in PLHIV . . . . . . . 10.7d Pleural effusion . . . . . . . . . . . . . . 10.6 Prevention in health workers . . . . . . . 19.4.4 Pulmonary TB (PTB) . . . . . . . . . . 10.6, 15.1 Recommended regimens . . . . . . . . . . 15.5 Regimen codes . . . . . . . . . . . . . . 15.3 Resistance . . . . . . . . . . . . . . . . . 15.5 Septic shock . . . . . . . . . . . . . . . . 3.1.5 Severe respiratory distress/pneumonia . . 3.2.3 Smear-positive, smear-negative . . . 3.2.3, 15.2 Treatment . . . . . . . . . . . . . . . . . 15.3 Seizures . . . . . . . . . . . . . . . . . . . 3.5 Spinal . . . . . . . . . . . . . . . . . 10.10a.3 Splenomegaly . . . . . . . . . . . . . . . 10.20 Tubo-ovarian abscess Pyosalpinx . . . . . . . . . . . . . . . . 10.15.3 Typhoid fever . . . . . . . . . . . . 10.7a.2, 11.43 Typhus . . . . . . . . . . . . . . . . . . . . 11.33 Ulcer Skin . . . . . . . . . . . . . . . . . . . 10.2.10 Diabetic . . . . . . . . . . . . . . . . . 10.2.10 Buruli . . . . . . . . . . . . . . . . . . 10.2.10 Trophic . . . . . . . . . . . . . . . . . . 10.2.10 Chronic venous . . . . . . . . . . . . . 10.2.10 Arterial . . . . . . . . . . . . . . . . . . 10.2.10 Tropical . . . . . . . . . . . . . . . . . 10.2.10 Pressure . . . . . . . . . . . . . . . . . 10.2.10 Ultrasound . . . . . . . . . . . . . . . . . 7.2.21 Unconscious patient . . . . . . . . . . . QC6, 3.4 Uraemia . . . . . . . . . . . . . . . . . . 10.7.3 Upper gastrointestinal bleeding . . . . . . . QC23 Urinalysis . . . . . . . . . . . . . . . . . 7.2.16 Urinary catheter insertion Female . . . . . . . . . . . . . . . . . . . 7.3.2 Male . . . . . . . . . . . . . . . . . . . . 7.3.6 Urinary incontinence . . . . . . . . . . . . 10.15.7 Drugs associated with . . . . . . . . . . 10.15.7 Stress . . . . . . . . . . . . . . . . . . 10.15.7 Overﬂow . . . . . . . . . . . . . . . . . 10.15.7 Urinary tract infection . . . . 11.44, 10.7a.2, 10.15.2 Urogenital trichomoniasis . . . . . . . . . 10.15.4 Urticaria . . . . . . . . . . . . . . . . . . 10.2.9 Uterine ﬁbroids . . . . . . . . . . . 10.15.2, 10.15.3 Uterus, massage for PPH . . . . . . . . . . . QC26 Uveitis . . . . . . . . . . . . . . . . . . . 10.12.2

Vaginal bleeding . . . . . . Vaginal candidiasis . . . . . Vaginal discharge . . . . . Varicella . . . . . . . . . . Chicken pox . . . . . . . Herpes zoster . . . . . . Varicocele . . . . . . . . . Venous cut down . . . . . . Ventilation Assess . . . . . . . . . . Assist . . . . . . . . . . Manual (bagging) . . . . Verruca vulgaris See warts, common . . . Vesicular or bullous lesions Violence prevention . . . . Violent patient management Viral gastroenteritis . . . . Viral haemorrhagic fever . . Virological testing . . . . . Visceral leishmaniasis . . . Vitamin B12 deﬁciency . . . Vitreous haemorrhage . . . Vomiting . . . . . . . . . . Blood . . . . . . . . . . In pregnancy . . . . . . . Von Willebrand disease . . Warfarin overdose . . . . . Wart Common . . . . . . . . . Genital . . . . . . . . . . Anal . . . . . . . . . . . Waste management . . . . Containers, colour-coded Disposal . . . . . . . . . Linens . . . . . . . . . . Patient care equipment . Sharps . . . . . . . . . . Weight loss . . . . . . . . Wet mount . . . . . . . . . Wheezing . . . . . . . . . Wounds . . . . . . . . . . Xeroderma . . . . . . . . . Yaws . . . . . . . . . . . . Yellow fever . . . . . . . .

. . . . . . . .

QC5, QC24-25-26 . . 10.15.4, 11.4 . . . . . 10.15.4 . . . . . . 11.45 . . . . . 11.45.1 . . . . . 11.45.2 . . . . . 10.16.3 . . . . . 7.3.10

. . . . QC2, QC12, 3.2 . . . . . . . QC12-13 . . . . . . . . . QC35 . . . . . . . 10.2.3 . . . . . . . 10.2.4 . . . . . . QC10, 4.3 . . . . . . QC29, 3.4 10.7a.2,10.7c.2,10.7d.4 . . . . . . . . . 11.46 . . . . . . . 13.5, 14.4 . . . . . 10.1, 11.20.2 10.10a, 10.18.2, 10.18.3 . . . . . . . . 10.12.5 . . . . . . . . . 10.7c . . . . . . . . . QC23 . . . . . . . . 14.1.11 . . . . . . . . 10.19.6 . . . . . 3.8.1,10.19.7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.3 . . . . 10.14.2 . . . . 10.14.2 . . . . . . . 6 . . . . . . 6.9 . . . . . . 6.8 . . . . . . 6.7 . . . . . . 6.8 . . . . . . 6.8 . . . . . 10.3 . . . . 7.2.15 . . QC17, 3.2.4 QC5, QC22, 4.5 . . . . 10.2.8 . . . . 10.2.5 . . 11.47, 10.1 . . . .

Vol. 2 • Index, Volumes 1 and 2: July 2011

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Abbreviations, acronyms for both Volumes 1 and 2 /r 3TC ABC ACE ACT AFB AIDS AKI ALI ALT ANC ARD ART ARV AST ATS ATV AVPU AZT BMI BP BPM BUN BVM C&S Ca CBT CD4 boosted with ritonavir lamivudine abacavir angiotensin-converting enzyme artemisinin-based combination therapy acid-fast bacillus acquired immune deﬁciency syndrome acute kidney injury acute lung injury alanine aminotransferase antenatal care acute respiratory diseases antiretroviral therapy antiretroviral aspartate aminotransferase amphetamine-type stimulants atazanavir alert, voice, pain, unresponsive azidothymidine (zidovudine) body mass index blood pressure beats per minute (pulse) blood urea nitrogen bag valve mask culture and sensitivity Calcium cognitive behavioural therapy count of the lymphocytes with a CD4 surface marker per cubic millimetre of blood (mm3) congestive heart failure cervical intraepithelial neoplasia DR TB DS DST DTP DVT E EBV ECG EEG EFV CrAg CrCl CRP CSF CT CVA d4T DBS ddI DDx DIC DKA DOTS CKD CMV CNS COPD CPK CPT chronic kidney disease cytomegalovirus central nervous system chronic obstructive pulmonary disease creatine phosphokinase cotrimoxazole prophylaxis (cotrimoxazole preventive therapy) cryptococcal antigen creatinine clearance C-reactive protein cerebral spinal ﬂuid computed tomography cerebrovascular accident stavudine dried blood spot didanosine differential diagnosis disseminated intravascular coagulation diabetic ketoacidosis directly observed therapy short course drug-resistant tuberculosis double strength drug-susceptibility testing diphtheria-tetanus-pertussis vaccine deep vein thrombosis ethambutol Epstein-Barr virus electrocardiogram electroencephalogram efavirenz

CHF CIN

742

Vol. 2 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

ELISA EPTB ESR ETAT Eto FAST

enzyme-linked immunosorbent assay extrapulmonary tuberculosis erythrocyte sedimentation rate emergency triage assessment and treatment ethionamide focused assessment of sonography in trauma (ultrasound exam) full blood count (also known as CBC) ﬁxed dose combination forced expiratory volume in one second fresh frozen plasma ﬁne needle aspiration

HIV HIVAN HONK HPV HR HSV HTC HZ IC IDU IDV IgA IgG IgM IM IMAI IMCI IMEESC

human immunodeﬁciency virus HIV-associated nephropathy hyperosmolar non-ketotic coma human papillomavirus heart rate herpes simplex virus HIV testing and counselling herpes zoster infection control injecting drug user idinavir immunoglobulin A immunoglobulin G immunoglobulin M intramuscular Integrated Management of Adolescent and Adult Illness Integrated Management of Childhood Illness Integrated Management of Emergency and Essential Surgical Care Integrated Management of Pregnancy and Childbirth isoniazid international normalized ratio (to express prothrombin time) infection prevention and control isoniazid preventive therapy intermittent preventive therapy (for malaria in pregnant women) immune reconstitution inﬂammatory syndrome idiopathic thrombocytopenic purpura international unit intrauterine device intravenous

FBC FDC FEV1 FFP FNA

FTA-ABS ﬂuorescent treponemal antibody absorption test FTC FVC G6PD GCS GERD GFR GI GU H Hb HBsAg HBV Hct HCV HDL HELLP emitricatabine forced vital capacity glucose 6 phosphate dehydrogenase Glasgow coma scale gastroesophogeal reﬂux disease glomerular ﬁltration rate gastrointestinal genitourinary (system or urogenital system) isoniazid haemoglobin hepatitis B surface antigen hepatitis B virus haematocrit hepatitis C virus high density lipoprotein haemolysis, elevated liver enzymes & low platelets

IMPAC INH INR IPC IPT IPTp IRIS ITP IU IUD IV

Vol. 2 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

743

JVP K Kcal KCL KJ KOH LAM LDH LDL LEEP LFT LGV LMN LMP LP LPV/r LR MAC MCH MCPC MDI MDR TB MDT mEq Mg MNCH MRI MRSA MSM MTCT MUAC

Na NaCI NFV NG NNRTI NPO NRTI NS NSAID NTD NtRTI NVP OI ORS OST PAS PBS PCP PCPNC PCR PEFR PEP PI PID PITC PLHIV PML PMN

Mycobacterium avium complex maternal and child health Managing Complications in Pregnancy and Childbirth metered-dose inhaler multi-drug resistant tuberculosis multiple drug therapy milliequivalents magnesium maternal, newborn, and child health magnetic resonance imaging methicillin-resistant Staphylococcus aureus men who have sex with men mother-to-child transmission mid upper arm circumference

Pneumocystis jirovecii pneumonia Pregnancy, childbirth, postpartum, and newborn care polymerase chain reaction peak expiratory ﬂow rate post exposure prophylaxis protease inhibitor pelvic inﬂammatory disease provider-initiated testing and counselling people living with HIV progressive multifocal leukoencephalopathy polymorphonuclear neutrophils

744

Vol. 2 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

PMTCT PO PPE PPH PR PRBC PT PTB PTSD PTT PUD PV QC R RAPD RBC RDT RPR RR RTV Rx S SAAG SARS SBP SC SCJ sd-NVP SIADH SJS SLE

prevention of mother-to-child transmission per os (by mouth) personal protection equipment post-partum haemorrhage per rectum packed red blood cells prothrombin time pulmonary tuberculosis post- traumatic stress disorder partial thromboplastin time peptic ulcer disease per vaginal Quick Check (Section 2) rifampicin relative afferent pupillary defect red blood cells rapid diagnostic test rapid plasma reagin (a syphilis test) respiratory rate ritonivir treatment streptomycin serum-to-ascites albumin gradient severe acute respiratory syndrome spontaneous bacterial peritonitis subcutaneous squamocolumnar junction single-dose nevirapine syndrome of inappropriate ADH (antidiuretic hormone) secretion Stevens-Johnson syndrome systemic lupus erythematosis

SMX SP SpO2 spp SQV SS SSRI STB STI T TB TBSA TCA Td TDF TEN TIG TMP TMPSMX TPHA TSH TST TT TTP UMN UO UTI VDRL VIA VL

sulfamethoxazole sulphadoxine-pyrimethamine oxygen saturation species saquinavir single strength selective serotonin reuptake inhibitors Stop TB sexually transmitted infection temperature tuberculosis total body surface area tricylic anti-depressants tetanus-diphtheria toxoid adult vaccine tenoﬁvir toxic epidermal necrosis tetanus immune globulin trimethoprim trimethoprim- sulfamethoxazole (cotrimoxazole) treponema pallidum haemagglutanation assay thyroid stimulating hormone tuberculin skin test tetanus toxoid thrombotic thrombocytopenic purpura upper motor neuron urinary output urinary tract infection venereal disease research laboratory- a syphilis test visual inspection with ascetic acid viral load

Vol. 2 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

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VLDL VT VZV WBC WHO

very low density lipoproteins ventricular tachycardia varicella zoster virus white blood cell count World Health Organization

W/W XDR TB Z ZDV

weight of solute/weight of solution extensively drug resistant tuberculosis pyrazinamide zidovudine (also azidothymidine - AZT)

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Vol. 2 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

Writers and reviewers, Volume 2, and process of development Overall clinical editing and writing of Volume 2 of the IMAI District Clinician Manual Sandy Gove (WHO IMAI team leader), Kirsty McHarry (WHO HIV, now consultant, KwaZulu-Natal, South Africa), Neeri Moodley (WHO HIV, now U KwaZuluNatal Centre for Rural Health, South Africa), Chris Duncombe (WHO HIV, now Gates Foundation), Matthew Chersich (Centre for Health Policy, University of Witwatersrand, South Africa) and Shevin Jacob (University of Washington) Editors: Emily Tuthill, Sarah Johnson, John Liddy, Sandra Woods, Ward Rinehart The process of development, the evidence review, ﬁeld-testing, and ﬁnal external review are as described in the process statement at the end of Volume 1. Final guideline panels: The Palliative Care expert panel met on the 17th of November 2010 in Geneva. It was co-sponsored by MDR TB team in the Stop TB Department. All other guideline panels met by teleconference. Other writers contributing to speciﬁc sections are indicated in bold in lists below. Members of the ﬁnal guideline panels are included in the related expert groups below with a superscript designation. Declarations of interest were received from all contributors to the ﬁnal guideline panels for Volume 2 of this manual and from participants in the ﬁnal external review meeting, held on 20–22 June 2011. Potential conﬂicts of interest were declared by the following individuals participating in the ﬁnal guideline panels: Philip Peters and Barbara Marston, on the hepatitis panel, both working for CDC, USA, declared working for an organization that has an interest in hepatitis. Their working for a public health institution without proprietary interest in the outcome of the discussions was considered an insigniﬁcant conﬂict of interest. Justin Ortiz, on the pulmonary treatment panel, reported having received an award from the American Thoracic Society for lifetime achievement. He was considered unconﬂicted. Natalya Dinat consulted with Pﬁzer Inc. on their trial drug pregabalin for neuropathy in HIV until August 2010. As this drug is not included or considered in the proposed guideline, she was considered substantively unconﬂicted.

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Expert writers and reviewers for Volume 2 Superscript numbers refer to involvement in ﬁnal guideline panels as shown below. Writers’ names appear in boldface. 11 Opportunistic infection 12 Eye panel 13 Oral health 14 Internists 15 Mental health 16 Female GU 17 Palliative care 18 Hepatitis 19 Renal 20 Skin 22 Acute pain 23 Generalist 24 Weight loss 25 MSM

HIV care/OI (OI within Sections 11 and 13) Chris Behrens Robert Colebunders Olivier Koole Maria Zolfo Lut Lynen Sarah Van Rompaey Bateganya Moses Martin Dedicoat14 Corrado Cancedda Ndella Diakhate Mulamba Diese Chris Duncombe11,18 Marco Vitoria Eyerusalem Negussie Jane Ferguson Bruce Dick Robin Flam Lloyd Mulenga Eric Van Praag Pru Ive Nzali Kancheyi Steward Reid11,14 Louise Ivers Chris Matthews11,14 Gisela Schneider Chikholal Thangsing Fikre Woldeamlak Robert Kalyesubula Papa Salif Sow11,14 Jean Nachega11,14 11,14

I-Tech, University of Washington, USA Institute of Tropical Medicine, Belgium

The Africa Centre and Hlabisa Hospital, KwaZulu-Natal, South Africa Partners In Health, Rwanda Centre Hospitalier National Universitaire de Fann, Senegal inistry of ealthEngenderHealth, New York, USA WHO HIV, Switzerland

WHO CAH, Switzerland Columbia University International Center for AIDS Care and Treatment Programs (ICAP), USA Family Health International (Fhi360), Tanzania Consultant, South Africa Center for Infectious Disease Research in Zambia (CIDRZ) Partners In Health University of California San Diego (UCSD) Medical Center, USA Infectious Disease Institute, Uganda AIDS Health, Thailand Consultant, Ethiopia Makerere University, Uganda Centre Hospitalier National Universitaire de Fann, Senegal University of Stellenbosch, South Africa

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Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

Lena Matata Maureen Mutinda Alice Maida Barbara Marston Fareed Ramzi Asfour JH Mukendi Kazadi

Kiliﬁ, Kenya Ministry of Health, Malawi Centers for Disease Control and Prevention (CDC), USA Formerly WHO, now Consultant, USA KITSO AIDS Training Program, Botswana

Pulmonary expert group (10.6) Phil Hopewell2 Janet Diaz Clement Yeh Luke Davis Adithya Cattmanchi Anh Innes Alvaro Cruz Leonard Hudson Shevin Jacob Stephen Gordon Jamie Rylance Patrick Lee Salah Ottmani Allen Cheng Jeremy Farrar Julian Bion 1

University of California San Francisco (UCSF)/San Francisco General Hospital (SFGH), USA

Universidade Federal da Bahia, Brazil Pulmonary and Critical Care Management, University of Washington, USA Liverpool School of Tropical Medicine, UK Partners In Health WHO StopTB, Switzerland School of Health Research, Menzies, Australia Oxford University Clinical Research Unit, Viet Nam University Dept of Anaesthesia & Intensive Care Medicine, Birmingham, UK Anaesthesiology, University of Witwatersrand, South Africa Cambridge University Teaching Hospital, UK University of Sydney, Australia International Union Against Tuberculosis and Lung Disease (IUATLD),, Paris Sunnybrook Health Sciences Centre, Toronto, Canada Partners In Health and Harvard Brigham and Women’s Hospital, USA Médicins Sans Frontières, Belgium Masaka Regional Hospital, Uganda

Satish Bhagwanjee1 Alain Vuylsteke Paul Torzillo2 Anthony Harries Chen Yuen Chaing Neill Adhikari1,2 Kwonjune Seung Natalie Van Meerbeeck Patrick Banura

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Christopher Moore

Department of Medicine, University of Virginia, USA

Internists Martin Dedicoat14 Valerie Asselman Graeme Meintjies Ed Waki Stewart Reid 14

Africa Centre, Hlabisa, South Africa GF Jooste Hospital, South Africa University of Cape Town, South Africa UCSF, USA CIDRZ, Zambia Consultant, USA Makerere University, Uganda UCSD Medical Center, USA Infectious Disease Institute, Uganda Centre Hospitalier National Universitaire de Fann, Senegal I-Tech, University of Washington, USA ICAP, USA CEO of Pangaea and Professor of Clinical Medicine, UCSF, USA WHO Ethiopia Northern Territory Health, Australia Omdurman Teaching Hospital, Sudan Reproductive Health Research Unit, South Africa Ensemble pour une solidarité thérapeutic hospitalièr en réseau (ESTHER), France NAM HATIP, South Africa St John’s Medical College, Bangalore, India Liverpool School of Tropical Medicine, UK Deutsche Gesellschaft für Internationale Zusammenarbeit, Tanzania WHO AFRO AIDS Health, Thailand Management Sciences for Health, USA Family Health International (Fhi360), Tanzania Columbia University ICAP, Ethiopia University of Cape Town, South Africa Basics Project, USA

Fareed Ramzi Asfour14 Robert Kalyesubula Chris Mathews14 David Meya14 Papa Salif Sow Paula Brentlinger Robin Flam Eric Goosby Samuel Habte Melanie Little Omer Nemeri Regina Osih Gilles Raguin Theo Smart John Stephen Miriam Taegtmeyer Rudi Wabitsch Frank Lule Chinkholal Thangsing Diana Silimperi Eric Van Praag Zenebe Melaku Yirsaw Brian Allwood Mary Lyn Field-Nguer 14

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Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

Anaemia and bleeding disorders (10.18, 10.19) Imelda Bates Mulamba Diese Fikre Woldeamlak Ronwyn Tilley Dora Mbanya Noryati Amin Neelam Dhingra Liverpool School of Tropical Medicine, UK Health Action and Social Intervention, USA Gondar College, Ethiopia Consultant, UK University of Yaoundé, Cameroon WHO BTS, Switzerland

Hepatitis (11.14) Phillip Peters18 Barbara J. Marston18 Nick Walsh18 Chris Duncombe18 Annette Verster Stephen Wiersma CDC, USA Consultant, Cambodia WHO HIV, Switzerland WHO HEA, Switzerland

Skin John Stephen20 Toby Maurer Leopold Blanc Anisa Mosam Ncoza Dlova Chris Matthews20 Melanie Little Samuel Habte Robert Colebunders Sian Hartshorne Ramzi Asfour20 Dagnachew Shibeshi20 St John’s Medical College, Bangalore, India UCSF, USA WHO Stop TB, Switzerland University of KwaZulu-Natal, South Africa UCSD, USA Consultant, Australia WHO Ethiopia Institute of Tropical Medicine, Belgium Wits University, South Africa Consultant, USA Consultant, Ethiopia

Malaria (11.25) Andrew Brent7 Nick White7 Malcolm Molyneux7 Jamie Eliades Valerie D’Acremont Peter Olumese Marian Warsame Andrea Bosman KEMRI–Wellcome Trust Research Programme, Kenya Mahidol University, Thailand College of Medicine, University of Malawi Columbia University, USA Swiss Tropical Institute WHO GMP, Switzerland

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HIV testing and counselling (9) Mimi Sabin Elizabeth Marum Alison Schilsky Vincent Wong Donna Higgins Rachel Baggaley WHO HIV, now UNAIDS, Switzerland CDC, USA WHO HIV, now USAID, USA WHO HIV, now consultant, USA WHO HIV, Switzerland

TB/HIV (15) Rolando Cedillos Laura Ciafﬁ Anthony D Harries Louise Ivers Kwonjune Seung Annette Ravaud Jan Van den Hombergh Haileyesus Getahun Delphine Sculier Christian Gunneberg Reuben Granich Phil Hopewell Lisa Nelson Amy Bloom Eyerusalem Negussie El Salvador National Hospital Médicins Sans Frontière, Switzerland, Consultant IUATLD, UK Partners in Health Médecins Sans Frontières Pharmaccess, Tanzania WHO STB, Switzerland

WHO HIV, Switzerland UCSF/SFGH, USA CDC, USA USAID, USA WHO HIV, Switzerland

Neurology (Quick Check, 3.4, 10.10) Corrado Barbui15 Charles Newton Gretchen Birbeck Zenebe Melaku Yirsaw Chris Mathews Elijah Chaila Penny Lewthwaite Theo Smart Martin Dedicoat Kevin Robertson Miriam Taegtmaeyer University of Verona, Italy Kenya Medical Research Institute, Kenya Chikankata Hospital, Zambia ICAP, Ethiopia UCSD, USA The Adelaide and Meath Hospital, Trinity College Dublin Ireland University of Liverpool, UK HIV and AIDS Treatment in Practice, South Africa Africa Centre and Hlabisa Hospital, South Africa University of North Carolina, USA Liverpool School of Tropical Medicine, UK

752

Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

Tarun Dua Ross Carne David Simpson Timothy Steiner Eloise Malan Chris Behrens Chris Duncombe

WHO MSD, Switzerland University of Melbourne, Australia Mount Sinai School of Medicine, USA Imperial Hospital, Division of Neurosciences and Mental Health, UK Consultant, South Africa I-Tech, University of Washington, USA WHO HIV, Switzerland

Mental health (Quick Check, 3.4, 10.11) Francine Cournos15 Mark Halman Julie Maggi 15

Columbia University, USA Saint Michael’s Hospital, University of Toronto, Canada Ministry of Health and Social Welfare, Tanzania Pattison Centre, UK USAID, USA Department of Health, South Africa Johns Hopkins University, USA University of Witwatersrand, South Africa International Training and Education Centre on HIV (I-Tech) London School of Hygiene and Tropical Medicine, UK WHO Mental Health, retired, Switzerland Imperial College, UK Columbia University, USA WHO MSD, Switzerland

Joseph K. Mbatia Helen McColl John Palen Melvyn Freeman Zoe Rush Rita Thom MaryAnn Vitello Vikram Patel Jose Manuel Bertolote Jose Catalan Pamela Collins Milton Wainberg Shekhar Saxena Tarun Dua Alexandra Fleischmann Mohammed Yasamy Corrado Barbui15

France

Eye (10.12) Suneetha Nithyanadam12 Ramachandran Pararajasegaram12 Sophia Pathai12 Millicent Muthoni 12

St John’s Medical School, Bangalore, India Consultant International Centre for Eye Health, UK Cochrane eye group, Kenya WHO PBL, Switzerland

Silvio Paulo Mariotti Simona Minchiotti Ivo Kokur

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Men’s health (10.14, 10.16, 19) Edmond Coleman Evan Collins Don Kilby Sarah Hawkes Kevin Moody Rafael Mazin Reynosa22 Eduard Sanders Jeffrey Stanton Jamie Uhrig Andrew Doupe Kevin O’Reilly Kevin Rebe22 Glenn de Swardt Tudor Kovacs22 Zoryan Kis 22 22

University of Minnesota, USA Global Network for People Living with HIV University of Ottawa, Canada UCL Centre for International Health and Development, Institute of Child Health and Hygiene, UK Global Network of People Living with HIV, Netherlands WHO PAHO Wellcome Trust Research Laboratory, Kenya University of Connecticut, USA United Nations Development Programme (UNDP) WHO HIV, Switzerland ANOVA Health Institute, South Africa

Population Services International, Romania Ukraine CDC, USA Cameroon Johns Hopkins University, USA

Gaston Djomand22 Steave Nemande22 Stefan Baral 22

Weight loss and malnutrition (10.3) Chris Duncombe24 Carmen Casanovas 24

WHO HIV, Switzerland WHO Nutrition, Switzerland Food and Nutrition Technical Assistance, USA WHO HIV- IMAI, Switzerland USAID,USA

Pamela Fergusson24 Eyerusalem Negussie Tim Quick

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Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

Neglected Tropical Diseases Albis Gabrielle Jorge Alvar Bampoe Kingsley Lester Chitsulo Denis Paul Jacques Silvio Paulo Mariotti Francoise Xavier Pedro Jose Ramon Simarro Pere Perez Hugh Taylor Mike Nathan Andre Meheus John Carlos Pinto Dias Kingsley Asiedu Olaf Horstick Raman Velayudhan Daniel Argaw Dagne Lester Chitsulo Albis Francesco GabrielliI Pamela Mbabazi Pierre Cattand Mas Coma Dennis Nordeen Pat Lamy Frank Richards Uche Amazigo Marco Albonico Eloise Meindl John Vorhies WHO NTD, Switzerland

Consultant WHO Intern, Switzerland

Renal (11.31) Robert Kalyesubula14 June Fabian Lut Lynen Eric Gheuens Alfredo Tiu Pat Lee Martin Dedicoat14 Ramzi Asfour Kiran Joshi 14

Makerere University, Uganda University of Witwatersrand, South Africa Institute of Tropical Medicine, Belgium UCSD, USA Partners In Health, Rwanda Africa Centre, South Africa Consultant, USA Consultant, USA

Oral health (10.17) Sudeshni Naidoo13 Peter Berthold Morten Schiodt Poul Erik Petersen University of Western Cape, South Africa University of Minnesota, USA University of Copenhagen, Denmark WHO CHP, Switzerland

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Saman Warnakalsuriya13 Crispian Scully David Reznik Ferbronia Kahabuka13 13

King’s College London, UK Eastman, Uni, UK CDC, USA Muhimbili Centre for Health Sciences, University of Dar es Salaam, Tanzania

Alcohol (3.7, 16) Parvis Afshar Rajat Ray Alex Wodak Emanuele Pontali Mahmud Mazlan Mike Farrell Lubomir Okruhlica Fred Owiti John Saunders Noeline Latt Afarin Rahimi-Movaghar Robert Ali Rick Rawson Annette Verster Jumana Hermez Nico Clark Vladimir Poznyak Vivek Benegal Jonathan Chick Mats Berglund Mark Willenbring Sawitiri Assanangkornchai Maria Lucia Formigoni Sisumru Higuchi Isodore Obot Ministry of Health, Iran All India Institute of Medical Sciences, India Alcohol and Drug Service, St Vincent’s Hospital, Sydney, Australia Genoa Prison, Italy Addiction Medicine Substance Abuse Center,, Malaysia University of New South Wales, Australia Centre for Treatment of Drug Dependencies, Slovakia Arrow Medical Centre, Kenya Sydney Medical School, University of Sydney, Australia Arrow Medical Centre, Kenya University of Adelaide, Australia UCLA, USA WHO HIV, Switzerland WHO EMRO, Switzerland WHO MSD, Switzerland National Institute of Mental Health and Neuro Sciences, India Spire Murrayﬁeld Hospital Edinburgh and Spire Shawfair Park Hospital, UK Lund University, Sweden Treatment and Recovery Research Division of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA Prince of Songkla University, Thailand UDED – Drug Dependence Unit, Federal University of Sao Paulo, Brazil International Society for Biomedical Research on Alcoholism, USA Nigeria

Acute pain Hillary Cohen22 Ayman Yassa22 May Choi22 Rockafeller Oteng22 Maimonides Medical Center, USA Columbia University, USA Komfo Anokye Teaching Hospital, Ghana

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Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

Palliative care (20) Ray Barﬁeld Kevin Bezanson Julia Downing17 K.M. Foley Liz Gwyther Kath Deﬁlippi17 Carla Horne17 Emmanuel Luyirika M R Rajagopal Nick Pahl John Palen Willem Scholten Barbara Milani17 Lameck Thambo Theo Smart Salem Barghout17 Aage Schulz 17

Duke Divinity School, USA Mount Sinai Hospital, Canada African Palliative Care Association, Uganda Death In America Project, USA; Open Society Institute Palliative Care Association, South Africa Family Health International (Fhi360), USA Mildmay Uganda SUT Academy of Medical Sciences, India Help the Hospices, UK USAID, USA WHO EMP, Switzerland Palliative Care Association of Malawi (PACAM) NAM HATIP, South Africa WHO EMRO Cancer Care, Denmark Department of Health, South Africa 17

Norbert Ndjeka17 Ugochukwu Amanyeiwe Hindi Satti17 Michael Rich17 Andreas Ullrich17 Cecilia Sepulveda17 Case Gordon17 Olivia Dix Jorge Eisenchlas Cynthia Goh Akiiki Bitalabeho Rose Kiwanuka Catherine Mears Zipporah Merdin – Ali Lydia Mpanga Sebuyira Sunli Pant Georges Reena Olaitan Soyannwe Francis Tsikai

USAID Partners In Health WHO CHP, Switzerland World Care Council Palliative Care Initiative, UK Udaondo Hospital, Argentina Lien Centre for Palliative Care, Singapore WHO HIV IMAI Palliative Care Association of Uganda British Red Cross Hospice, Kenya Infectious Disease Institute, Uganda Hospice, Nepal Christian Medical College, India Society for Study of Pain, Nigeria Island Hospice, Zimbabwe

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Natalya Dinat17 Aamir Khan 17

University of Witwatersrand, South Africa Centre for Community Development, Pakistan WHO Stop TB, Switzerland Consultant

Ernesto Jaramillo17 Kiran Joshi

Maternal/female GU Jean Anderson16 Adriana Andrade Meg Doherty Francis Ndowa Nathalie Broutet Kelly Curran Jeffrey Smith16 Luc de Bernis Isaac Malonza Thomas Marwa Groesbeck Parham Zahida Qureshi 16

John Hopkins University, USA

WHO RHR, Switzerland Jhpiego, USA UNFPA, USA Jhpiego, Kenya University of Alabama, Birmingham, USA University of Nairobi, Kenya Jhpiego, Madagascar University of Washington, USA Consultant, USA WHO HIV, now UNICEF CDC, now private clinical practice, USA University of Zimbabwe

Richard Hughes Michael Gravett16 Kathy Shapiro Ehounou René Ekpini Fatu Forna Nii Hammond Ruby Ayorsey Matthews Mathai16 Yusuf Ahmed16

WHO MPS, Switzerland University Teaching Hospital, Zambia

PMTCT, family planning (14) Eyerusalem Negussie, Nathan Shaffer Mario Festin Nigel Rollins Matthews Mathai Stanley Luchters Sarah Johnson, Ward Rinehart WHO HIV, Switzerland WHO RHR, Switzerland WHO CAH, Switzerland WHO MPS, Switzerland Ghent University, Belgium Jura Editorial Services, France

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Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

IDU Parvis Afshar Farzad Kasraee Thomas Kresina Emanuele Pontali Robert Ali Lubomir Okruhlica Annette Verster Jumana Hermez Tarak Gawad Afarin Rahimi-Movaghar Alex Wodak Rick Rawson Nico Clark Vladimir Poznyak Penny Miller Michael Farrell Mahmud Maazlan Rajat Ray Fred Owiti Ministry of Health, Iran Substance Abuse and Mental Health Services Administration, USA Prisons of Genoa, Italy University of Adelaide, Australia Centre for Treatment of Drug Dependencies, Slovakia WHO HIV, Switzerland WHO EMRO ISAM, Egypt Iranian Research Center for HIV/AIDS St Vincent’s Hospital, Australia UCLA, USA WHO MSD, Switzerland Family Health International, (Fhi360), Thailand University of New South Wales, Australia Yale University of Medicine, USA All India Institute of Medical Sciences, India Arrow Medical Centre, Kenya

Geriatric care Jean-Pierre Michel John Beard Hôpital Cantonal, Geneva, Switzerland WHO ALC, Switzerland

Medicines/therapeutics: Mona Shah, WHO Consultant, Florida, USA; Kristin Lunghi, UCSF; Julia Lord, The Alfred, Australia; Rohini Fernandopulle. Illustrations: Robert Thatcher X-rays: Harry Shulman, Sunnybrook Health Sciences Centre, Canada; Thienkhai Vu, UCSF/SFGH, USA; Jan van den Hombergh, Pharmaccess, Tanzania; Ruzica Maksimovic, WHO, Switzerland Evidence check: The following contributed to the evidence check for Volume 2, under the direction of Matthew Chersich and Janet Diaz: Laura Diamondstone, Lorna Jenkin, Araya Giday, Helene van Gorsel, Senbeta Guteta, Kiran Joshi, Rudzani Muloiwa, and Priya Shete.

Vol. 2 • Writers and reviewers, Volume 2, and process of development: July 2011

759

WHO acknowledges the specific funding support from USAID towards the development of this manual. This development has also beneﬁted from the active collaboration of HIV/AIDS and other WHO departments. We would like to thank the donors supporting these departments and making this possible. Abbreviations CDC Centers for Disease Control and Prevention, Atlanta, USA CIDRZ Center for Infectious Disease Research in Zambia GIP Global Inﬂuenza Programme, WHO ICAP International Center for AIDS Care and Treatment Programs, Columbia University IDF International Diabetes Federation IMAI Integrated Management of Adolescent and Adult Illness, WHO IUATLD International Union Against TB and Lung Disease PAHO Pan American Health Organization SFGH San Francisco General Hospital UCLA University of California Los Angeles UCSD University of California San Diego UCSF University of California San Francisco UNAIDS Joint United Nations Programme on AIDS UNICEF United Nations Children’s Fund UNFPA United Nations Population Fund USAID United States Agency for International Development WHO ALC WHO AFRO WHO Regional Ofﬁce for Africa WHO BTS WHO CAP WHO EMRO WHO Regional Ofﬁce for the Eastern Mediterranean WHO GMP WHO HEA WHO HIV WHO Department of HIV/AIDS WHO MPS WHO Department of Making Pregnancy Safer WHO MSD WHO NTD WHO Department of Neglected Tropical Diseases WHO PBL WHO RHR WHO Department of Reproductive Health and Research WHO STB WHO Department of Stop TB

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Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

For further information please contact: IMAI Team Department of HIV/AIDS World Health Organisation Avenue Appia, 20 CH–1211 Geneva 27 Switzerland imaimail@who.int www.who.int/hiv/capacity/en

VOLUME 1

IMAI District Clinician Manual: Hospital Care for Adolescents and Adults

G U ID ELIN ES FO R TH E M A N A G EM EN T O F C O M M O N I LLN ES S ES W ITH LI M I TED R ES O U R C ES I ntegrated M anagement of A dolescent and A dult I llness (IMAI)

© World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@ who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of speciﬁc companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. Cover images: © Robert Thatcher (left), Petra Rohr-Rouendaal (right). Production coordination: L’IV Com Sàrl, Villars-sous-Yens, Switzerland. Printed in Switzerland.

VO L U ME 1

Table of contents Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction, assumptions, and principles of this manual . 1.1 1.2 1.3 1.4 1.5 1.6 Target audience and assumptions. . . . . . . . . . . . . . . . . . . . . Essential laboratory tests at the health centre and district hospital Other companion WHO manuals . . . . . . . . . . . . . . . . . . . . . . District network. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Scope of the manual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical reasoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1 3 4 6 7 8 10

2. Quick Check and emergency treatments .

Quick check. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Emergency signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Airway and breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Altered level consciousness/convulsing . . . . . . . . . . . . . . . . . . . . . . . Pain from life-threatening cause . . . . . . . . . . . . . . . . . . . . . . . . . . . . Priority signs and symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to help the choking patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give epinephrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Emergency treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage the airway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give oxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Set up oxygen equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Using a pulse oximeter to monitor SpO2 . . . . . . . . . . . . . . . . . . . . . . . . How to deliver increasing oxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . Respond to drop in SpO2 or increasing respiratory rate on oxygen . . . . . . . Decrease oxygen if patient is stabilizing or improving . . . . . . . . . . . . . . . If wheezing – how to give sequential bronchodilators. . . . . . . . . . . . . . . . . Give salbutamol for moderate – severe wheezing . . . . . . . . . . . . . . . . . Give salbutamol for mild wheezing. . . . . . . . . . . . . . . . . . . . . . . . . . . How to make spacer from plastic bottle . . . . . . . . . . . . . . . . . . . . . . . How to insert IV and give ﬂuids rapidly. . . . . . . . . . . . . . . . . . . . . . . . . . How to give naloxone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give diazepam IV or rectally . . . . . . . . . . . . . . . . . . . . . . . . . . . How to put patient in recovery position . . . . . . . . . . . . . . . . . . . . . . . . . How to give empirical IV/IM antibiotics for emergency management . . . . . . . How to give emergency antimalarial treatment if falciparum malaria is possible. How to give emergency antiviral treatment . . . . . . . . . . . . . . . . . . . . . . . How to immobilize spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage serious head injury . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage tension pneumothorax or massive haemothorax . . . . . . . . . . How to treat sucking chest wound . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to apply pressure to stop bleeding . . . . . . . . . . . . . . . . . . . . . . . . . How to apply pelvic binder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage heavy upper gastrointestinal bleeding . . . . . . . . . . . . . . . . How to manage large haemoptysis . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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13 17 17 17 19 21 23 25 27 28 29 29 33 33 33 34 35 35 37 37 38 38 39 40 41 41 42 42 43 43 44 45 46 46 47 47 48 48

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How to manage large nose bleed (epistaxis) . . . . . . . . . . . . . . . . . . . . . . . Vaginal bleeding in early pregnancy, late pregnancy and during labour . . . . . . . Vaginal bleeding postpartum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to massage uterus and expel clots . . . . . . . . . . . . . . . . . . . . . . . . . . How to inﬂate condom over foley catheter to tamponade uterine bleeding . . . . . How to apply bimanual uterine compression . . . . . . . . . . . . . . . . . . . . . . . How to apply aortic compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give oxytocin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manually remove the placenta if postpartum bleeding . . . . . . . . . . . . . After manual removal of the placenta . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give misoprostol for postpartum bleeding if no response to oxytocin plus ergometrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give magnesium sulfate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Important considerations in caring for a woman with eclampsia or pre-eclampsia How to give ketamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage the violent or very agitated patient . . . . . . . . . . . . . . . . . . . How to manage the suicidal/self-harm patient . . . . . . . . . . . . . . . . . . . . . . Advanced airway management: for district clinicians with training . . . . . . . . . Indications for tracheal intubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to perform tracheal intubation . . . . . . . . . . . . . . . . . . . . . . . . . . . How to conﬁrm endotracheal tube (ETT) placement . . . . . . . . . . . . . . . . . Was intubation successful? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Post-intubation care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to ventilate the intubated patient . . . . . . . . . . . . . . . . . . . . . . . . . How to sedate the intubated patient. . . . . . . . . . . . . . . . . . . . . . . . . . . If patient becomes blue, cyanotic or hypoxic . . . . . . . . . . . . . . . . . . . . . Intubated patients require close monitoring . . . . . . . . . . . . . . . . . . . . . . Manual ventilation (bagging) – how to prepare the health worker, family or other caregivers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . If life threatening upper airway obstruction and unable to ventilate, how to perform cricothyroidotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to refer the severely ill patient to a higher level of care. . . . . . . . . . . . . . How to transport the severely ill patient . . . . . . . . . . . . . . . . . . . . . . . . . . Emergency trolley . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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49 50 51 52 53 54 54 54 55 56 56 57 58 58 59 61 62 62 63 64 65 66 66 66 67 67 68 69 70 71 72

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3. Approach to the severely ill patient (after the Quick Check) . 3.0 3.1 General principles in caring for the severely ill patient. . . . . . . . . . . . . . . . Severely ill patient with shock. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.0 Approach to the patient with shock . . . . . . . . . . . . . . . . . . . . . . 3.1.1 Manage haemorrhagic shock (see Quick Check and Section 4) . . . . . 3.1.2 Manage hypovolaemic shock . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.3 Manage anaphylactic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.4 Manage cardiogenic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.5 Manage septic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Severely ill patient with difﬁcult breathing . . . . . . . . . . . . . . . . . . . . . . . 3.2.1 Assess severely ill patient with difﬁcult breathing . . . . . . . . . . . . . . 3.2.2 Provide initial emergency management for all severely ill patients with difﬁculty breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.3 Manage respiratory distress in patients with suspected severe pneumonia or acute lung injury and without shock . . . . . . . . . . . . . 3.2.4 Manage patients with severe respiratory distress from acute bronchospasm (from either asthma or chronic obstructive pulmonary disease or other causes of acute wheezing) . . . . . . . . . . . . . . . . . . . .

3.2

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73 75 80 80 85 87 88 88 90 99 99 105 108 113

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iii

Manage patients with severe respiratory distress from acute pulmonary oedema or ﬂuid overload . . . . . . . . . . . . . . . . . . 3.2.6 Managing acute decompensated cardiac problems . . . . . . . . 3.3 Approach to the patient with chest pain . . . . . . . . . . . . . . . . . . . . . 3.4 Approach to the patient with altered consciousness (including coma, confusion, intoxication, agitation and convulsions) . . . . . . . . . . . . . . 3.4.1 Clinical approach to the patient with altered consciousness . . . 3.4.2 Manage delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.3 Manage diabetic ketoacidosis. . . . . . . . . . . . . . . . . . . . . . 3.4.4 Manage hypoglycaemia . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.5 Steroid deﬁciency (Addison’s disease; adrenal insufﬁciency) . . . 3.5 Approach to the patient with seizures or status epilepticus . . . . . . . . . 3.6 Manage intoxication or overdose, or withdrawal from injecting or other use of opioids, amphetamine-type stimulants or cocaine . . . . . . . 3.6.1 Opioid intoxication or overdose . . . . . . . . . . . . . . . . . . . . . 3.6.2 Manage opioid withdrawal . . . . . . . . . . . . . . . . . . . . . . . . 3.6.3 Manage stimulant intoxication and overdose . . . . . . . . . . . . . 3.6.4 Manage stimulant withdrawal . . . . . . . . . . . . . . . . . . . . . . 3.7 Acute alcohol withdrawal and intoxication . . . . . . . . . . . . . . . . . . . 3.7.1 Acute alcohol withdrawal . . . . . . . . . . . . . . . . . . . . . . . . 3.7.2 Acute alcohol intoxication . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Poisoning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8.1 Ingested poisons or overdose of medicines. . . . . . . . . . . . . . 3.8.2 Inhaled poisons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8.3 Chemicals on the skin or in the eye . . . . . . . . . . . . . . . . . . . 3.9 Snake-bite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9.1 Snake-bite assessment . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9.2 Snake-bite treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10.1 Initial management and stabilization of burns using Quick Check. 3.10.2 Assess and classify the burn . . . . . . . . . . . . . . . . . . . . . . 3.10.3 Burn management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Severely ill patient monitoring form . . . . . . . . . . . . . . . . . . . . . . .

3.2.5

118 126 127 129 129 134 135 138 140 142 145 145 146 148 149 150 150 159 161 161 187 188 190 190 193 198 198 199 202 206

4. Trauma: approach to the acutely injured patient 4.0 4.1 4.2 General principles of trauma care. . . . . . . . . . . . . . . . Working as a clinical team to care for the trauma patient . Assign responsibilities within the clinical team . . . . . . . . Referral to a higher level of care . . . . . . . . . . . . . . . . Assessing and treating the trauma patient . . . . . . . . . . Oxygen therapy for trauma patients . . . . . . . . . . . . . . First assess and treat immediately life-threatening injuries Resuscitation and stabilization . . . . . . . . . . . . . . . . . Deﬁnitive care and treatment . . . . . . . . . . . . . . . . . . Violence and injury prevention . . . . . . . . . . . . . . . . . Manage rape or abuse in adolescents and adults . . . . . . Provide immediate comfort . . . . . . . . . . . . . . . . . . . . Special considerations for the examination . . . . . . . . . . Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . Wounds (soft tissue injuries) . . . . . . . . . . . . . . . . . . . General approach to wound management. . . . . . . . . . . Suture techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.3 4.4

4.5

. . . . . . . . . . . . . . . . . .

211 . . . . . . . . . . . . . . . . .

213 215 216 217 217 218 219 222 226 226 227 227 227 228 229 230 232

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4.6

Fractures . . . . . . . . . . General principles . . . . Splints and casts . . . . . Compartment syndrome .

. . . .

232 232 233 237

5. Approach to laboratory investigations . 5.1 5.2

Interpreting laboratory results . . . . . . . . . . . . . . . . . . . . . Management of sodium, potassium, and calcium abnormalities 5.2.1 Abnormalities of sodium (Na) concentration . . . . . . . Hypernatraemia (high Na) . . . . . . . . . . . . . . . . . Hyponatraemia (low Na) . . . . . . . . . . . . . . . . . . 5.2.2 Abnormalities of potassium (K) concentration . . . . . . Hyperkalaemia (high K) . . . . . . . . . . . . . . . . . . . Hypokalaemia (low K). . . . . . . . . . . . . . . . . . . . 5.2.3 Abnormalities of calcium (Ca) concentration . . . . . . . Hypercalcaemia (high Ca) . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . .

239 . . . . . . . . . .

241 246 246 246 247 249 249 251 252 252

6. Infection prevention and control . 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 6.10 6.11 6.12 6.13

Principles of hospital infection prevention and control . . . . . . . . . . . . . Health worker role in hospital infection prevention and control . . . . . . . . Standard precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hand hygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appropriate personal protection equipment (PPE) . . . . . . . . . . . . . . . . . Respiratory hygiene and cough etiquette . . . . . . . . . . . . . . . . . . . . . . Prevention of needle-stick and injuries from sharp instruments . . . . . . . . Environmental cleaning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Linens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Waste disposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Patient care equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Select additional infection control interventions including PPE, based on the risk assessment, epidemiology, or likely pathogen . . . . . . . . Special precautions for acute respiratory diseases that are prone to result in epidemics or pandemics . . . . . . . . . . . . . . . . . . . . . . . . . Special precautions for infectious TB patients . . . . . . . . . . . . . . . . . . . Precautions when caring for patient with suspected or conﬁrmed Filovirus (Ebola, Marburg) haemorrhagic fever. . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .

255 . . . . . . . . . . .

257 258 258 259 262 265 266 268 269 269 270 271 273 274 275

. . . . . . . . . . . . . . . . . . . .

7. Procedures 7.1 7.2

General considerations in performing procedures . . . . . . . . 7.1.1 Patient consent. . . . . . . . . . . . . . . . . . . . . . . . 7.1.2 Safety considerations, precautions and anaesthesia . Diagnostic procedures . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 Skin biopsy – shaving or scraping . . . . . . . . . . . . 7.2.2 Skin biopsy – punch . . . . . . . . . . . . . . . . . . . . . 7.2.3 Skin snip for the diagnosis of microﬁlariasis . . . . . . 7.2.4 Skin biopsy – excision. . . . . . . . . . . . . . . . . . . . 7.2.5 Fine needle aspiration (FNA) . . . . . . . . . . . . . . . . 7.2.6 Lymph node biopsy (excisional) . . . . . . . . . . . . . . 7.2.7 Bone marrow aspiration and biopsy . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .

277 . . . . . . . . . . .

279 279 279 281 281 283 284 285 286 287 288

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7.3

7.4

7.2.8 Pelvic examination. . . . . . . . . . . . . . . . . . . . . . . . 7.2.9 Cervical cancer screening: Pap smear . . . . . . . . . . . 7.2.10 Cervical cancer screening: visual screening . . . . . . . . 7.2.11 Colposcopy, cervical biopsy and endocervical curettage 7.2.12 Clinical breast examination . . . . . . . . . . . . . . . . . . 7.2.13 Endometrial biopsy . . . . . . . . . . . . . . . . . . . . . . . 7.2.14 Gram stain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.15 Wet mount. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.16 Urinalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.17 Taking stool samples, including Cary-Blair for cholera . . 7.2.18 Crude clotting time. . . . . . . . . . . . . . . . . . . . . . . . 7.2.19 Thin and thick blood ﬁlms for malaria . . . . . . . . . . . . 7.2.20 AFB (Ziehl Neelsen) . . . . . . . . . . . . . . . . . . . . . . . 7.2.21 Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . Therapeutic procedures . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.1 Chest tube (intercostal chest drain) . . . . . . . . . . . . . 7.3.2 Urinary catheter insertion – female . . . . . . . . . . . . . . 7.3.3 Marsupialization for Bartholin’s cyst or abscess . . . . . . 7.3.4 Intrauterine device (IUD) placement . . . . . . . . . . . . . 7.3.5 Reduction of paraphimosis . . . . . . . . . . . . . . . . . . . 7.3.6 Urinary catheter insertion – male . . . . . . . . . . . . . . . 7.3.7 Suprapubic catheter. . . . . . . . . . . . . . . . . . . . . . . 7.3.8 Inserting a nasogastric (NG) tube . . . . . . . . . . . . . . . 7.3.9 Gastric lavage . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.10 Venous cutdown . . . . . . . . . . . . . . . . . . . . . . . . . Diagnostic and therapeutic procedures . . . . . . . . . . . . . . . . 7.4.1 Thoracentesis (chest tap) . . . . . . . . . . . . . . . . . . . 7.4.2 Lumbar puncture . . . . . . . . . . . . . . . . . . . . . . . . . 7.4.3 Paracentesis (abdominal tap) . . . . . . . . . . . . . . . . . 7.4.4 Arthrocentesis (joint aspiration) . . . . . . . . . . . . . . . . 7.4.5 Pericardiocentesis. . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

290 293 294 295 297 298 299 300 300 301 303 304 305 306 309 309 312 313 315 317 319 321 322 324 325 328 328 330 333 335 336

8. Medicines/therapies 8.1 8.2 8.3 8.4

A guide to the use of different analgesics . . . . . . . . . . . . . . . . . Information on equivalence for interchangeability- corticosteroids . Iron content of different salts. . . . . . . . . . . . . . . . . . . . . . . . . Summary of medicines/therapies in adolescents and adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347 347 347 348 349 350 350 351 352 353 353 354 354 355

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . .

. . . . . . . . . . . . . . . . . . . .

341 . . . . . . . . . . . . . . . . . . .

345 346 349 346 355 355 356 356 357 357 357 358 358 358 359 359 360 360 361

Acamprosate . . . . . . . . . . Acetazolamide. . . . . . . . . Acetylcysteine . . . . . . . . . Acetylsalicyclic acid (aspirin) . Aciclovir . . . . . . . . . . . . Albendazole . . . . . . . . . . Amiloride . . . . . . . . . . . . Amitriptyline . . . . . . . . . . Amoxicillin . . . . . . . . . . . Amoxicillin with clavulanic acid Amphotericin B (conventional) . Amphotericin B (liposomal) . . . Ampicillin . . . . . . . . . . . Antiretrovirals Abacavir (ABC) . . . . . .

. . . . . . . .

Atazanavir + ritonavir (ATV/r) . . . . Didanosine (ddI) . . . . . . . . . . . Efavirenz (EFV) . . . . . . . . . . . . Emtricitabine (FTC) . . . . . . . . . . Lamivudine (3TC). . . . . . . . . . . Nevirapine (NVP) . . . . . . . . . . Lopinavir + ritonavir (LPV/r) . . . . . Saquinavir (SQV) . . . . . . . . . . . Tenofovir (TDF) . . . . . . . . . . . . Zidovudine (ZDV, AZT) . . . . . . . . Artemether . . . . . . . . . . . . . . . . Artemether + lumefantrine . . . . . . . . Artesunate . . . . . . . . . . . . . . . . Artesunate + amodiaquine . . . . . . . . Artesunate + sulfadoxine–pyrimethamine

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Artesunate + meﬂoquine . . . . . . . . . Artesunate + clindamycin . . . . . . . . Aspirin (see acetylsalicylic acid Atropine) Atropine . . . . . . . . . . . . . . . . . Atropine eye drops . . . . . . . . . . . . Azithromycin . . . . . . . . . . . . . . . Beclometasone inhaler . . . . . . . . . . Benzathine benzylpenicillin. . . . . . . . Benznidazole . . . . . . . . . . . . . . . Benzyl benzoate . . . . . . . . . . . . . Benzoyl peroxide . . . . . . . . . . . . . Benzylpenicillin (penicillin G) . . . . . . . Betametasone . . . . . . . . . . . . . . Biperiden. . . . . . . . . . . . . . . . . Buprenorphine . . . . . . . . . . . . . . Calamine lotion . . . . . . . . . . . . . . Calcium gluconate . . . . . . . . . . . . Carbamazepine. . . . . . . . . . . . . . Ceﬁxime . . . . . . . . . . . . . . . . . Ceftriaxone . . . . . . . . . . . . . . . . Charcoal, activated. . . . . . . . . . . . Chloramphenicol . . . . . . . . . . . . . Chloramphenicol eye drops/ointment . . . Chlorhexidine . . . . . . . . . . . . . . Chloroquine . . . . . . . . . . . . . . . Chlorphenamine . . . . . . . . . . . . . Chlorpromazine . . . . . . . . . . . . . Ciproﬂoxacin . . . . . . . . . . . . . . . Clarithromycin . . . . . . . . . . . . . . Clindamycin . . . . . . . . . . . . . . . Clindamycin topical . . . . . . . . . . . Clofazimine . . . . . . . . . . . . . . . . Clomipramine . . . . . . . . . . . . . . Cloxacillin . . . . . . . . . . . . . . . . Coal tar. . . . . . . . . . . . . . . . . . Codeine . . . . . . . . . . . . . . . . . Cotrimoxazole (TMP-SMZ) . . . . . . . . Dapsone . . . . . . . . . . . . . . . . . Deferoxamine . . . . . . . . . . . . . . Dexamethasone . . . . . . . . . . . . . Diazepam . . . . . . . . . . . . . . . . Diethylcarbamazine . . . . . . . . . . . Dihydro-artemisinin + piperaquine . . . . Diloxanide . . . . . . . . . . . . . . . . Dithranol . . . . . . . . . . . . . . . . . Dopamine . . . . . . . . . . . . . . . . Doxycycline . . . . . . . . . . . . . . . Eﬂornithine . . . . . . . . . . . . . . . . Enalapril . . . . . . . . . . . . . . . . . Epinephrine (adrenaline) . . . . . . . . . Ergometrine . . . . . . . . . . . . . . . Erythromycin . . . . . . . . . . . . . . . Erythromycin topical . . . . . . . . . . . Ethambutol . . . . . . . . . . . . . . . . Ethanol . . . . . . . . . . . . . . . . . .

361 361 362 362 363 363 364 364 365 365 366 366 367 367 368 368 369 369 370 372 373 374 374 375 375 376 377 378 379 379 380 380 380 381 381 382 384 384 385 386 386 387 387 387 388 389 391 391 392 392 393 395 395 396

Ferrous sulphate . . . . . . . . . . . . . . Fluconazole . . . . . . . . . . . . . . . . Flucytosine (5-FC) . . . . . . . . . . . . . Fluoxetine . . . . . . . . . . . . . . . . . Fluphenazine . . . . . . . . . . . . . . . . Folic acid . . . . . . . . . . . . . . . . . . Folinic acid . . . . . . . . . . . . . . . . . Furosemide. . . . . . . . . . . . . . . . . Gabapentin . . . . . . . . . . . . . . . . . Ganciclovir . . . . . . . . . . . . . . . . . Gentamicin . . . . . . . . . . . . . . . . . Gentamicin eye drops . . . . . . . . . . . Griseofulvin . . . . . . . . . . . . . . . . Haloperidol . . . . . . . . . . . . . . . . . Hydralazine IV . . . . . . . . . . . . . . . Hydrochlorthiazide . . . . . . . . . . . . . Hydrocortisone . . . . . . . . . . . . . . . Hydrocortisone cream . . . . . . . . . . . Hydroxypropyl methylcellulose eye drops . Ibuprofen. . . . . . . . . . . . . . . . . . Insulin (soluble) . . . . . . . . . . . . . . Ipratropium bromide . . . . . . . . . . . . Isoniazid . . . . . . . . . . . . . . . . . . Isosorbide dinitrate. . . . . . . . . . . . . Itraconazole . . . . . . . . . . . . . . . . Ivermectin . . . . . . . . . . . . . . . . . Ketamine . . . . . . . . . . . . . . . . . . Lactulose. . . . . . . . . . . . . . . . . . Levonorgestrel . . . . . . . . . . . . . . . Lidocaine. . . . . . . . . . . . . . . . . . Magnesium sulfate . . . . . . . . . . . . . Malathion . . . . . . . . . . . . . . . . . Mebendazole. . . . . . . . . . . . . . . . Meglumine antimoniate . . . . . . . . . . Melarsoprol . . . . . . . . . . . . . . . . Methadone . . . . . . . . . . . . . . . . . Methylthioninium chloride (methylene blue) Metoclopramide . . . . . . . . . . . . . . Metronidazole . . . . . . . . . . . . . . . Miconazole. . . . . . . . . . . . . . . . . Midazolam . . . . . . . . . . . . . . . . . Miltefosine . . . . . . . . . . . . . . . . . Misoprostol . . . . . . . . . . . . . . . . Morphine. . . . . . . . . . . . . . . . . . Mupirocin . . . . . . . . . . . . . . . . . Naloxone . . . . . . . . . . . . . . . . . . Naltrexone . . . . . . . . . . . . . . . . . Neostigmine . . . . . . . . . . . . . . . . Nifurtimox . . . . . . . . . . . . . . . . . Nitrofurantoin . . . . . . . . . . . . . . . Omeprazole . . . . . . . . . . . . . . . . Ondansetron . . . . . . . . . . . . . . . . Oseltamivir . . . . . . . . . . . . . . . . . Oxytocin . . . . . . . . . . . . . . . . . . Paracetamol . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

396 397 398 398 399 399 400 400 401 401 402 403 403 404 405 406 406 407 407 407 408 408 408 409 409 410 411 411 412 412 413 414 414 415 416 416 417 417 418 420 420 421 421 422 422 423 423 423 424 424 425 425 426 426 427

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vii

Paromomycin . . . . . . . . . . . . . Pentamidine . . . . . . . . . . . . . . Permethrin . . . . . . . . . . . . . . . Phenobarbital . . . . . . . . . . . . . Phenoxymethyl-penicillin (penicillin V) . Phenytoin . . . . . . . . . . . . . . . Pilocarpine eye drops . . . . . . . . . Podophyllum resin . . . . . . . . . . . Polyvidone iodine (povidone–iodine) . . Polyethylene glycol electrolyte solution Potassium permanganate . . . . . . . Potassium chloride . . . . . . . . . . . Praziquantel . . . . . . . . . . . . . . Prednisolone . . . . . . . . . . . . . . Primaquine . . . . . . . . . . . . . . . Procaine benzylpenicillin G . . . . . . . Propranolol. . . . . . . . . . . . . . . Pyridoxine (vitamin B6) . . . . . . . . . Pyrimethamine . . . . . . . . . . . . . Quinine . . . . . . . . . . . . . . . . . Quinine + clindamycin . . . . . . . . . Rifampicin . . . . . . . . . . . . . . . Rifampicin + isoniazid + pyrazinamide + ethambutol hydrochloride . . . . . Salbutamol . . . . . . . . . . . . . . . Salicylic acid . . . . . . . . . . . . . . Selenium sulﬁde . . . . . . . . . . . . Senna . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . .

427 428 429 430 431 432 433 433 434 434 434 435 435 436 438 438 439 440 440 441 441 442 443 444 444 445 445

Sodium bicarbonate . . . . . . . . . . . . . . 446 Sodium cromoglycate . . . . . . . . . . . . . 446 Sodium nitrite . . . . . . . . . . . . . . . . . 446 Sodium nitroprusside . . . . . . . . . . . . . . 447 Sodium stibogluconate . . . . . . . . . . . . . 447 Sodium thiosulfate . . . . . . . . . . . . . . . 448 Spectinomycin . . . . . . . . . . . . . . . . . 448 Spironolactone . . . . . . . . . . . . . . . . . 448 Streptomycin . . . . . . . . . . . . . . . . . . 449 Sulfadiazine . . . . . . . . . . . . . . . . . . 449 Sulfadoxine with pyrimethamine (SP) . . . . . . 450 Sulfamethoxazole with trimethoprim (TMP-SMX) (see cotrimoxazole) Suramin . . . . . . . . . . . . . . . . . . . . 450 Terbinaﬁne . . . . . . . . . . . . . . . . . . . 451 Tetracaine (amethocaine) eye drops . . . . . . 451 Tetracycline . . . . . . . . . . . . . . . . . . 451 Tetracycline eye ointment . . . . . . . . . . . 452 Thiamine . . . . . . . . . . . . . . . . . . . . 452 Tranexamic acid (TXA) . . . . . . . . . . . . . 453 Tretinoin . . . . . . . . . . . . . . . . . . . . 453 Triclabendazole . . . . . . . . . . . . . . . . 454 Trimethoprim-sulfamethoxazole (see cotrimoxazole) Urea . . . . . . . . . . . . . . . . . . . . . . 454 Valproic acid (sodium valproate) . . . . . . . . 455 Vitamin B6 (see pyridoxine) Vitamin B12 (hydroxocobalamin) . . . . . . . . 456 Vitamin K (phytomenadion) . . . . . . . . . . . 456

Index .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

457 470 475

Abbreviations and acronyms

Process/methods/writers and reviewers

viii

Vol. 1 • Table of contents

Foreword IMAI District Clinician Manual: Hospital Care for Adolescents and Adults The manual is written for clinicians working at the district hospital (ﬁrst-level referral care) who diagnose and manage sick adolescents and adults in resourceconstrained settings. It aims to support clinical reasoning, and to provide an effective clinical approach and protocols for the management of common and serious or potentially life-threatening conditions at district hospitals. The target audience thus includes doctors, clinical ofﬁcers, health ofﬁcers, and senior nurse practitioners. It has been designed to be applicable in both high and low HIV prevalence settings. The manual is divided into two volumes. The ﬁrst covers emergency triage assessment and treatment, and acute care for a severely ill or acutely injured patient for approximately the ﬁrst 24 hours of care. This volume also describes the clinical procedures commonly used in emergency and acute care, and gives a summary of the medicines used and the steps necessary for infection control. Volume 2 provides a symptom-based approach to clinical care for acute and subacute conditions (including mental health). It provides short summaries of the management of diseases that affect multiple systems of the body, focusing on communicable diseases. It also includes the chronic or long-term management of HIV, TB, alcohol, and substance use disorders. Future editions may incorporate the chronic management of non-communicable diseases. The manual was developed to support clinicians in diagnosing and managing adolescent and adult patients at district hospitals with limited essential drugs, laboratory tests, and equipment. It is one component of a broader WHO secondlevel learning programme. It has been developed through a large collaboration of WHO Departments and their experts from many countries and regions across the world working in expert subgroups. Recommendations in the manual are predominately based on recent WHO evidence-based normative guidelines developed by several Departments and disease control programmes, including WHO HIV/AIDS, Stop TB, Global Malaria Programme, Neglected Tropical Diseases (NTD), Mental Health Gap (mhGAP), the Reproductive Health and Research (RHR) STI and cervical cancer and family planning guidelines, Integrated Management of Emergency and Essential Surgical Care (IMEESC) , Integrated Management of Pregnancy and Childbirth (IMPAC) , Global Inﬂuenza Programme (GIP), Global Alert Response (GAR) and others. To put these normative guidelines into operation within an integrated clinical manual supports the implementation of multiple disease-control strategies. Good clinical care is a component of most effective public health approaches. Simpliﬁcation and standardization of case detection and ﬁrst-line treatments support decentralization and expand access to care. Within a district network, the district clinician receives patients in referral who have not responded to ﬁrst-line treatment or who require hospitalization for severe illness. The ability to provide effective emergency care for severely ill patients, to establish a likely differential diagnosis, to provide appropriate management and then monitor the patient’s response to treatment can contribute substantially to the health of the community. Where current WHO guidelines do not exist, selected national guidelines and evidence-based medicine sources, existing systematic reviews of evidence, and randomised clinical trials were reviewed. These evidence checks and updated

Vol. 1 • Foreword

sections of the manual can be accessed on the IMAI second-level EZcollab site. The relevant WHO normative guidelines are listed in footnotes in each Section, including an indication of when these will be revised (when available). The manual will be updated as other WHO guidelines are updated or new WHO guidelines are developed. Within three months of the revision and release of a relevant WHO normative guideline, an updated Section will be posted on the IMAI second-level EZcollab website. Each volume will be reprinted yearly. To request access to this website, or to provide comments or further queries, please send an email to imaimail@who.int. As updates to the manual sections are frequent, readers of the manual are advised to ensure that they are using a current version of the manual. This manual is for country adaptation, to match the national essential medicine list, availability of laboratory tests, and local disease epidemiology. An evolving country Adaptation Guide will be available from the same website. We thank the large number of people who have given valuable input, comments and feedback on this manual to date. Drs Sandy Gove, Kirsty McHarry and Eyerusalem Negussie for the IMAI team.

Vol. 1 • Foreword

1. Introduction, assumptions, and principles of this manual Table of contents 1.1 1.2 1.3 1.4 1.5 1.6 Target audience and assumptions. . . . . . . . . . . . . . . . . . . . . Essential laboratory tests at the health centre and district hospital Other companion WHO manuals . . . . . . . . . . . . . . . . . . . . . . District network. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Scope of the manual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical reasoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3 4 6 7 8 10

1. Introduction, assumptions, and principles of this manual 1.1 Target audience and assumptions Human resource assumptions This manual is aimed at the district clinician who may be a medical ofﬁcer, clinical ofﬁcer, or senior nurse, and other senior health workers working at a district hospital in a resource-constrained setting. The manual assumes that many district hospitals in these settings have general multipurpose practitioners, such as a medical or clinical ofﬁcer, but do not have specialist clinicians, such as an internist, paediatrician, or psychiatrist (although it may be possible to consult with one). Other assumptions are that these settings have: • Limited essential drugs (see the medicine Section 8 at the end of the manual; this is subject to adaptation based on the national essential drug list). • Limited equipment – no mechanical ventilation except for during surgery (see Adaptation Guide for the use of simple ventilators if these are available). • Limited laboratory and other investigations – this manual assumes that there are limited laboratory and other investigations available onsite1, listed in the Table: Essential laboratory tests at the health centre and district hospital, with additional tests available as “send-out” tests to referral laboratory facilities. The diagnostic process and treatment protocols in this manual assume that only the minimum essential laboratory tests are available in the district hospital in resource-limited settings. Additional guidance is provided on using results that may be obtained by sending out specimens or sending patients for additional tests elsewhere. Additional tests that are not usually available at district hospital level are in italics in the text.

1 Consultation on technical and operational recommendations for clinical laboratory testing harmonization and standardization: Helping to expand sustainable quality testing to improve the care and treatment of people infected with and affected by HIV/AIDS, TB, and malaria. WHO, 2008. Available at http://www.who.int/ diagnostics_laboratory/3by5/Maputo_Meeting_Report_7_7_08.pdf

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Target audience

1.2 Essential laboratory tests at the health centre and district hospital2 Table: Essential laboratory tests at the health centre and district hospital At the health centre Essential laboratory tests • Haemoglobin or haematocrit HIV diagnostics • Rapid HIV antibody tests (ﬁrst and second tests) • Infant diagnosis; preparation of dried blood spot (DBS) then send out for virological testing • Blood collection and send-out for CD4 cell absolute count and percentage TB diagnostics • Sputum send-out for smear microscopy (or onsite acid fast bacilli (AFB) smear microscopy) • Sputum send-out for culture and drug susceptibility testing Malaria tests (if in endemic area) • Peripheral blood smear (PBS) preparation and smear microscopy or • Rapid test to detect and discriminate between Plasmodium falciparum and mixed Plasmodium species Other tests • Rapid syphilis test • Rapid pregnancy test • Urine dipstick for sugar and protein (if available, also for leukocytes and ketones) At the district hospital Additional laboratory tests • Full blood count with differential • Erythrocyte sedimentation rate (ESR) HIV diagnostics • Rapid HIV antibody tests (ﬁrst, second and third tests) • CD4 absolute count and percentage TB diagnostics • Acid fast bacilli smear microscopy • Sputum send-out for culture and drug susceptibility testing • WHO-approved molecular testing such as Xpert MTB/RIF Other tests • Serum alanine aminotransferase (ALT) • Serum electrolytes • Amylase • Blood sugar (glucose) • Serum creatinine and blood urea nitrogen (BUN) • Gram stain • Syphilis – rapid plasma reagin (RPR) • Basic microscopy and chemistry for cerebrospinal ﬂuid (CSF), urine, thoracentesis, and paracentesis • Saline and potassium hydroxide (KOH) wet mounts (for bacterial vaginosis (BV) or trichomonas) • Bilirubin determination for neonates • Blood and sputum cultures (may be sent out) • Cryptococcal antigen (CrAg- serum or CSF) or India ink stain of CSF • Lactic acid • Type and cross match for transfusion • Stool microscopy for ova and parasites • Hepatitis B enzyme immunoassay (EIA)

2 Rapid implementation of Xpert MTB/RIF diagnostic test: Technical and operational «How-to» practical considerations. WHO, 2011. Available at whqlibdoc.who.int/publications/2011/9789241501569_eng.pdf

Essential laboratory tests

Vol. 1 • 1. Introduction and assumptions: July 2011

Additional investigations that require special equipment At the district hospital (in addition to health centre equipment) • Oxygen saturation by pulse oximetry (SpO2) • X-ray: chest, plain ﬁlm abdomen, cervical spine, and bone ﬁlms • Ultrasound • ECG • Otoscopy: otoscope • Ophthalmoscopy: ophthalmoscope • Body mass index (BMI) measurement: adult beam scale and height board • Peak ﬂow meter • Snellen eye chart • Colposcopy: colposcope

At the health centre • • • • Mid upper arm circumference (MUAC) tape Blood pressure (BP) measurement: BP machine Auscultation and BP measurement: stethoscope Respiratory rate: timer

Additional tests that may be available at regional or central laboratories (as send-out tests) • • • • • • • • • • • • • Serum aspartate aminotransferase (AST) Serum bilirubin Serum and CSF total protein CSF glucose Serum lipids Sputum AFB culture and drug susceptibility testing HIV viral load (VL) Fungal stains Urine culture Stool culture Toxoplasma serology Cytology (e.g. CSF, cervical) Silver stain or direct ﬂuorescent antibody (DFA) for Pneumocystis jiroveci pneumonia (PCP) diagnosis • General fungal cultures, including blood • Histology (e.g. cervical, lymph node, skin biopsy) Other serological tests, polymerase chain reaction (PCR), other investigations or special cultures may be available at a central laboratory to diagnose brucellosis, dengue, fascioliasis, leishmaniasis, cysticercosis, strongyloidiasis, trypanosomiasis. See Section 11 and the Adaptation Guide.

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Essential laboratory tests

1.3 Other companion WHO manuals This manual assumes that companion WHO manuals are available. The Quick Check and Emergency Treatment sections are intended to support both emergency medical and surgical care, then to link with additional guidance on obstetrical and other surgical interventions found in these other resources: Companion clinical manuals: • IMPAC Managing complications in pregnancy and childbirth (MCPC) (WHO, UNFPA, UNICEF, World Bank 2003)3 • Pocket book of hospital care for children (WHO 2005) with new addendum4 • Manual on paediatric HIV care and treatment for district hospitals IMCI (WHO 2009)5 • Family planning: A global handbook for providers (USAID, John Hopkins, WHO 2011, revised)6 • Surgical care at the district hospital (WHO 2003)7 • Manual for male circumcision under local anaesthesia (WHO, Jhpiego, and UNAIDS 2008)8 Laboratory diagnosis aids: see Section 7 Procedures for list of bench aids.

3 4 5 6 7 8

http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/9241545879/en/index.html http://whqlibdoc.who.int/publications/2005/9241546700.pdf http://whqlibdoc.who.int/publications/2011/9789241501026_eng.pdf http://www.who.int/reproductivehealth/publications/family_planning/9780978856304/en/index.html http://www.who.int/surgery/publications/en/SCDH.pdf http://www.who.int/hiv/pub/malecircumcision/who_mc_local_anaesthesia.pdf

Other companion WHO manuals

Vol. 1 • 1. Introduction and assumptions: July 2011

1.4 District network Relationship to the ﬁrst-level guideline modules Nurses and clinical ofﬁcers in the outpatient department and at health centre level will be using simpler primary health care guidelines, including: • IMAI Acute Care9 • IMAI-IMCI Chronic HIV Care with ARV Therapy and Prevention8 • IMAI General Principles of Good Chronic Care8 • IMAI-IMCI Palliative Care: Symptom Management and End-of-Life Care8 • IMAI-STB Tuberculosis Care with TB-HIV Co-management8 • IMAI-STB-PIH Management of MDR-TB: A ﬁeld guide8 • IMCI Chart Booklet for High HIV Settings10 • IMPAC Pregnancy, Childbirth, Postpartum and Newborn Care11 (PCPNC) • IMEESC toolkit (Integrated Management of Emergency and Essential Surgical Care)12

The district clinician’s role: referral and back-referral The district clinician should understand these simpliﬁed guidelines, and use them to provide primary care for uncomplicated patients on initial presentation, to understand which patients need to be referred for second-level care (based on complications, severe illness or treatment failure), and to supervise and mentor nurse-led clinical teams, both in the hospital outpatient clinic and in health centres. This manual does not address the programme management responsibilities of the district management team (for HIV, TB, maternal and child health, and other programmes). This team provides supportive supervision and important assistance to the health centre, including supplies, laboratory support, hiring health workers, transport, and training. Also, this manual does not address the management and logistical requirements to manage a district hospital.

9 IMAI/IMCI heath centre/primary care guideline modules available at http://www.who.int/hiv/pub/imai/primary/ en/index.html 10 http://www.who.int/child_adolescent_health/documents/9789241597388/en/ 11 http://www.who.int/making_pregnancy_safer/documents/924159084x/en/ 12 IMEESC toolkit that can be accessed at http://www.who.int/surgery/publications/imeesc/en/index.html

Vol. 1 • 1. Introduction and assumptions: July 2011

District network

1.5 Scope of the manual Age 10 and up The manual addresses adolescents from 10 years of age and adults through old age and death. Children under 10 years are addressed in the Pocket book of hospital care for children.13

Addresses people living with HIV (PLHIV) and all acutely ill adolescents and adults The manual was developed to improve acute and chronic care both for PLHIV and others. HIV-infected patients, both immunocompetent and immunocompromised, may have multiple diseases or pathogens involving several systems at once. PLHIV are also at increased risk of drug toxicities and interactions. Common diseases that occur in HIV-negative people are also common in PLHIV. HIV infection does not protect against these. Therefore, the full differential diagnosis for presenting symptoms needs to be considered, and is covered in this manual. As a result, the manual is applicable to all acutely ill adolescents and adults. In addition, the diagnosis of HIV places a huge burden on the psychosocial and economic stability of the patient and the patient’s family. The most sustainable and effective approach is, in partnership with the patient, to enrol PLHIV in chronic care. The strength of a district network can be measured by the quality of chronic care delivered in the district. The role of the district clinician includes supporting primary health care wherever chronic care is delivered, both at health centres and in the outpatient clinic of the district hospital. Long-term care of TB, chronic HIV care, and substance use are included in Volume 2 with plans to add the chronic care of other diseases in the future.

Several symbols appear throughout the manual HIV-related conditions or special considerations in managing HIVpositive people. Some diseases marked with the red ribbon may also occur in HIV-negative people, but less commonly. Special considerations in managing pregnant, postpartum, and breastfeeding women. Notiﬁable diseases. These are communicable diseases that need to be reported to national authorities as their presence has a broader signiﬁcance to the public. These are usually uncommon or even rare, but are included in the differential diagnosis tables because of the importance of early recognition and of the need to report dangerous pathogens and diseases targeted for elimination. See Section 21. Surgery may be needed – call for help.

13 http://www.who.int/child_adolescent_health/documents/9241546700/en/

Scope of the manual

Vol. 1 • 1. Introduction and assumptions: July 2011

The manual has the following sections: Volume 1 Section 1 Introduction, assumptions and principles of this manual Section 2 Quick Check and emergency treatments Section 3 Approach to severely ill patients (acutely ill patients with a lifethreatening condition) Section 4 Trauma: approach to acutely injured patients Section 5 Response to laboratory investigations Section 6 Infection prevention and control Section 7 Procedures Section 8 Medicines and therapies Volume 2 Section 9 HIV diagnosis Section 10 Acute (and subacute) care: organized by the main symptoms. Provides the differential diagnosis and speciﬁc (often empirical) treatment recommendations. Section 11 Multisystem communicable diseases, renal problems, and HIVrelated cancers (in alphabetical order) Section 12 General principles of good chronic care Section 13 Chronic HIV care with ART and prevention at second level Section 14 PMTCT, HIV care and treatment during pregnancy, and family planning Section 15 Long-term care of TB, including MDR-TB Section 16 Management of alcohol use disorders Section 17 Other substance use Section 18 Geriatric care Section 19 Prevention in adolescents and adults Section 20 Palliative care Section 21 Patient monitoring, recording, and reporting of notiﬁable diseases Consult Section 8 for the formulation, dosage, adverse effects, contraindications, and cautions when administering or prescribing medicines.

How palliative care is integrated within the manual It is important that the clinical team addresses both the speciﬁc treatment of the cause of an illness and also the symptoms during both acute and chronic care. In the section on acute care by main symptoms (Section 10), speciﬁc management is summarized and symptom management either summarized or cross-referenced to Section 20. Section 20 on palliative care addresses both the management of pain and other symptoms, as well as end-of-life care. Health workers should be aware of a patient’s quality of life concerns and respect their wishes regarding end-of-life care. Often such discussions are particularly difﬁcult in an emergency setting. For patients with end-stage diseases, “advance directives” should be discussed with the patient and family when the patient’s status is stable. For patients who have a diagnosis of a terminal illness, relief of symptoms should be the priority.

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Scope of the manual

1.6 Clinical reasoning This process involves the health worker being conﬁdent in their knowledge and skills, as well as knowing their limitations, and delivering the best care possible to the patient within the constraints of available diagnostic and therapeutic capacity and resources. First, in every patient, triage for severe conditions and conditions that could potentially deteriorate quickly using the Quick Check (Section 2). Immediately provide emergency treatment and perform emergency laboratory investigations. Thereafter, obtain more information about the presenting complaints and consider the signs and symptoms. Be sure to think again of serious or potentially lifethreatening conditions associated with each symptom. Establish the possibility of such a condition, and keep it near the top of the list until safely excluded. Rapidly do relevant laboratory and other investigations for serious conditions. Initiate early investigations for serious conditions for which relevant tests are available at the health facility. Next, ascertain the likely cause of each presenting symptom. Use the relevant differential diagnosis tables. This involves a process of weighing up the likelihood of one diagnosis over other possible diagnoses by gathering available evidence – history, physical examination, and further investigations. Consider: • patient demographics – age, sex, pregnancy status • risk factors – environmental factors and any others particular to the patient • important negative ﬁndings – remember to actively look to exclude these • combinations of signs and symptoms associated with a particular disease • any history of prior intervention for the current condition. Identify all diagnoses (more than one may be present). Plan treatment and consolidate a combined treatment plan, addressing the several problems an acutely ill patient may have. If there are many unexplained symptoms over time, consider the possibility of a mental health problem (see Section 10.11).

Clinical reasoning and medical uncertainty Health workers in resource-limited settings frequently need to make clinical decisions with incomplete diagnostic support from radiology or the laboratory. The processes of clinical reasoning used, and the knowledge possessed to support decision-making, are critical determinants of the quality of clinical practice. Clinical mentoring and supportive supervision are very important for good clinical decisions and for improving clinical practice over time. In areas with high levels of diagnostic and therapeutic capacity, poor decision-making wastes resources; a large proportion of interventions may be unnecessary while a large number of useful interventions may not be provided. The content of clinical guidelines (such as lists of signs and symptoms, and treatment of common diseases) is very important. However, the process of clinical decision-making is somewhat distinct from these. Reaching an evidence-based clinical decision involves making a systematic health assessment of a patient based on history and physical examination, and linking this with information in the patient’s medical records. Complete and accurate medical records on patients will enable the health worker to make better informed decisions.

Clinical reasoning

Vol. 1 • 1. Introduction and assumptions: July 2011

Each diagnostic process begins with uncertainty but draws upon contextualized and case-speciﬁc knowledge, as well as increasingly on biomedical informatics and support tools. Clinicians transform the information or evidence available to them into a decision with consequent action, based on knowledge, the environmental, socioeconomic, and epidemiological context and the accumulated data on the speciﬁc case. Clinical decision-making is centred on a differential diagnosis (abbreviated DDx throughout the manual). Initially, this should be broad, followed by progressive elimination of possibilities without sufﬁcient evidence. This process of elimination includes both seeking evidence that supports a particular diagnosis and evidence to exclude a possibility. However, solely listing the conditions that could potentially account for the presenting symptoms in a patient is insufﬁcient, especially in PLHIV. It is important to consider other serious diseases or co-morbidities that may be present. Consideration needs to be given to the possibility of disseminated disease affecting multiple organ systems, and diseases with diverse symptomatology (see Section 11). Appropriate context needs to be established by considering the patient’s risk factors, as well as any unmet prevention needs. The frequency and severity of a disease may inﬂuence how diseases within the differential diagnosis table are ranked, and the order in which they are investigated. Differential diagnosis (DDx) tables should be considered in the local context of diseases, both those that are endemic and epidemic in an area. Determining the immunological status of an HIV-infected patient may be useful for ranking the likelihood of a particular infectious agent. Additional or repeated physical examinations, laboratory tests, and other investigations, consultation with clinical mentors, and consideration of the local disease epidemiology, can assist in ruling in or out a diagnosis. It may be important to initiate early investigations for serious conditions for which relevant tests are available at the health facility (see Section 5.1). If it is not possible to conﬁrm a diagnosis at the facility, consider referral or the empirical treatment of common or life-threatening conditions, depending on local guidelines. As for all investigations and therapy, assessment of the risks is required, and of the beneﬁt and cost of investigations versus empirical treatment. At regular intervals, it is necessary to revise an initial diagnosis and reassess clinical progress, particularly whether or not a patient is improving within the expected time frame.

Vol. 1 • 1. Introduction and assumptions: July 2011

Clinical reasoning

Establishing clinical diagnosis using different differential diagnosis tables 1. Use the differential diagnosis tables to establish links between clinical features and possible underlying diagnoses. 2. Prioritize the list of possible diagnoses from the table based on the conditions most likely to exist in the setting or to be life threatening. 3. Request and perform speciﬁc diagnostic tests (such as lumbar puncture, skin scrapings, ﬁne needle aspiration) in order to support or refute diagnoses from the initial differential list. 4. Identify patients who need hospitalization. 5. Determine whether clinical ﬁndings or diagnostic test results support a condition from the initial differential diagnosis list. a. If yes, treat accordingly. i. If treatment was successful, follow the patient as indicated. ii. If treatment was unsuccessful, re-evaluate the patient, modify the differential diagnosis, and return to step 1. b. If no, re-evaluate the patient, modify the differential diagnosis, and return to step 1. 6. If the diagnosis is uncertain: a. Consider initiating empirical therapy for serious or life-threatening conditions. b. Consider initiating empirical therapy for non-severe conditions when a diagnosis is likely and treatment is accessible and likely to be effective.

Improved clinical decision-making comes with experience and knowledge of local patterns of disease. For less experienced staff, supportive supervision and clinical mentoring are important in building conﬁdence. Avoiding errors in clinical reasoning The following principles are often cited to guide the clinical reasoning process. • Try to think of a single disease that accounts for most or all of the clinical ﬁndings (“Occam’s razor”). This principle does not always apply in the elderly and in immunocompromised patients (e.g. patients with advanced HIV infection), where there may be more than one pathological process occurring at the same time, in the same or in different organs. • Even if a clinical presentation looks similar to or is “representative of” a particular illness, this does not prove that the cause is due to that illness. Common diseases sometimes have uncommon presentations, and uncommon diseases can sometimes resemble those that are very common. • An uncommon presentation of a common disease is generally more likely than a typical presentation of an uncommon disease. (Consider “Sutton’s Law,” named after a famous bank robber who explained that he robbed banks because “that’s where the money is”. This suggests that a clinician consider common causes in the local region for a patient’s symptoms before considering uncommon causes.) • Consider what could kill a patient quickly, even if the diagnosis may be uncommon (this counterbalances Sutton’s Law). • Plan the initial empirical or syndromic treatment so as to cover the most common causes and the most serious (life-threatening) possible causes. • Avoid premature closure of the diagnostic process. Start with a broad differential diagnosis so as not to prematurely eliminate possibilities without sufﬁcient evidence. • Do not be overconﬁdent. Seek reasons why decisions may be wrong and consider alternative hypotheses. Ask questions that would disprove, as well as prove the current hypothesis. • Conditions recently seen can be over-diagnosed, especially those that were particularly dramatic, or in which a mistake was made that needs to be avoided in the future. • Avoid “illusory correlation”. This means that just because two ﬁndings occur together, it does not necessarily mean that one caused the other. • Know what you do not know. If you have a knowledge gap, admit it and seek the missing information, e.g. from a book, from your colleagues and co-workers, a clinical mentor, from a warm-line (a phone consultation service that calls users back within a short period of time with relevant information and assistance), or from reputable internet sites.

Clinical reasoning

Vol. 1 • 1. Introduction and assumptions: July 2011

Quick Check and emergency treatments

Table of contents Quick check. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Emergency signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Airway and breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Altered level consciousness/convulsing . . . . . . . . . . . . . . . . . . . . . . . Pain from life-threatening cause . . . . . . . . . . . . . . . . . . . . . . . . . . . . Priority signs and symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to help the choking patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give epinephrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Emergency treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage the airway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give oxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Set up oxygen equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Using a pulse oximeter to monitor SpO2 . . . . . . . . . . . . . . . . . . . . . . . . How to deliver increasing oxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . Respond to drop in SpO2 or increasing respiratory rate on oxygen . . . . . . . Decrease oxygen if patient is stabilizing or improving . . . . . . . . . . . . . . . If wheezing – how to give sequential bronchodilators. . . . . . . . . . . . . . . . . Give salbutamol for moderate – severe wheezing . . . . . . . . . . . . . . . . . Give salbutamol for mild wheezing. . . . . . . . . . . . . . . . . . . . . . . . . . . How to make spacer from plastic bottle . . . . . . . . . . . . . . . . . . . . . . . How to insert IV and give ﬂuids rapidly. . . . . . . . . . . . . . . . . . . . . . . . . . How to give naloxone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give diazepam IV or rectally . . . . . . . . . . . . . . . . . . . . . . . . . . . How to put patient in recovery position . . . . . . . . . . . . . . . . . . . . . . . . . How to give empirical IV/IM antibiotics for emergency management . . . . . . . How to give emergency antimalarial treatment if falciparum malaria is possible. How to give emergency antiviral treatment . . . . . . . . . . . . . . . . . . . . . . . How to immobilize spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage serious head injury . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage tension pneumothorax or massive haemothorax . . . . . . . . . . How to treat sucking chest wound . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to apply pressure to stop bleeding . . . . . . . . . . . . . . . . . . . . . . . . . How to apply pelvic binder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage heavy upper gastrointestinal bleeding . . . . . . . . . . . . . . . . How to manage large haemoptysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage large nose bleed (epistaxis) . . . . . . . . . . . . . . . . . . . . . . Vaginal bleeding in early pregnancy, late pregnancy and during labour . . . . . . Vaginal bleeding postpartum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to massage uterus and expel clots . . . . . . . . . . . . . . . . . . . . . . . . . How to inﬂate condom over foley catheter to tamponade uterine bleeding . . . . How to apply bimanual uterine compression . . . . . . . . . . . . . . . . . . . . . . How to apply aortic compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give oxytocin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manually remove the placenta if postpartum bleeding . . . . . . . . . . . . After manual removal of the placenta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17 17 17 19 21 23 25 27 28 29 29 33 33 33 34 35 35 37 37 38 38 39 40 41 41 42 42 43 43 44 45 46 46 47 47 48 48 49 50 51 52 53 54 54 54 55 56

How to give misoprostol for postpartum bleeding if no response to oxytocin plus ergometrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to give magnesium sulfate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Important considerations in caring for a woman with eclampsia or pre-eclampsia How to give ketamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to manage the violent or very agitated patient . . . . . . . . . . . . . . . . . . . How to manage the suicidal/self-harm patient . . . . . . . . . . . . . . . . . . . . . . Advanced airway management: for district clinicians with training . . . . . . . . . Indications for tracheal intubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to perform tracheal intubation . . . . . . . . . . . . . . . . . . . . . . . . . . . How to conﬁrm endotracheal tube (ETT) placement . . . . . . . . . . . . . . . . . Was intubation successful? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Post-intubation care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to ventilate the intubated patient . . . . . . . . . . . . . . . . . . . . . . . . . How to sedate the intubated patient. . . . . . . . . . . . . . . . . . . . . . . . . . . If patient becomes blue, cyanotic or hypoxic . . . . . . . . . . . . . . . . . . . . . Intubated patients require close monitoring . . . . . . . . . . . . . . . . . . . . . . Manual ventilation (bagging) – how to prepare the health worker, family or other caregivers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . If life threatening upper airway obstruction and unable to ventilate, how to perform cricothyroidotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . How to refer the severely ill patient to a higher level of care. . . . . . . . . . . . . . How to transport the severely ill patient . . . . . . . . . . . . . . . . . . . . . . . . . . Emergency trolley . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . .

56 57 58 58 59 61 62 62 63 64 65 66 66 66 67 67 68 69 70 71 72

. . . . . . . . . .

2. Quick Check and emergency treatments for adolescents and adults The assessment in the Quick Check should be performed for all patients on arrival at the facility. The ABC emergency signs (Airway, Breathing, Circulation, Consciousness, Convulsions) are a special set of emergency signs that are checked rapidly and frequently. Triage is the process of rapidly screening patients soon after arrival in hospital to identify: • patients with emergency signs, who require immediate emergency treatment; • patients with priority signs, who should be given priority and placed at the front of the queue so that they can be assessed and treated without delay; • non-urgent patients, who have neither emergency nor priority signs and can wait in the queue. This section should guide the entire hospital team. The Quick Check should be used both for the immediate, ﬁrst assessment on arrival in hospital and to reassess sick patients in hospital, or waiting in the emergency department. The 4 columns of the Quick Check on pages 17–23 (and on the Quick Check wallchart) are used as follows: 1. The assessment of emergency signs (left column in the Quick Check) should be done by any hospital staff, even the gatekeeper. Emergency signs are circled in red on the Quick Check chart. If any emergency signs are present, call for help! 2. The ﬁrst line emergency treatments (second column) should be given immediately by the nurse or other clinician receiving the patient. 3. If there has been trauma, they should also follow the guidelines in the third, trauma column. 4. The fourth, right-hand column summarizes further urgent medical treatments. This directs the district clinician to continue with other management of the severely ill patient (see Section 3). It also cross-references the IMPAC MCPC 1 (Management of complications in pregnancy and childbirth) and the IMEESC, which are trauma guidelines applicable to all ages.2 Use the IMCI ETAT for Children Less than 5 Years of Age (rather than these guidelines). The version for young children can be found in the Pocket Book of Hospital Care for Children http://www.who.int/child_adolescent_health/ documents/9241546700/en/index.html Several parts of this Section have been adapted from Surgical Care at the District Hospital.1 For additional information on assessment and definitive surgical treatment and inpatient hospital care of the trauma patient, see this manual and the IMEESC toolkit which can be accessed at http://www.who.int/surgery/publications/ imeesc/en/index.html

1 IMPAC Managing Complications in Pregnancy and Childbirth. WHO, 2003. http://www.who.int/making_ pregnancy_safer/documents/9241545879/en/index.html 2 Surgical Care at the District Hospital. WHO, 2003. http://www.who.int/surgery/publications/en/SCDH.pdf

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Quick Check and emergency treatments

QC 15

In addition, use the treatment guidelines in the IMPAC MCPC1 ( Managing Complications in Pregnancy and Childbirth) and PCPNC 3 (Pregnancy Childbirth Postnatal and Newborn Care) when managing women of childbearing age who may be pregnant (referred to on pages 19–24, 50).

Use infection control precautions during triage, Quick Check and emergency treatments • Standard precautions should be followed for all patients. • Add droplet, contact, airborne and special precautions for aerosolgenerating procedures as appropriate (see Section 6). Abbreviations: AVPU oxygen 5 litres Hb LR NS SBP 90 SpO2 90 Alert, Voice, Pain, Unresponsive l = litres 5 litres/minute haemoglobin lactated ringers normal saline (0.9%) RR = respiratory rate ystolic blood pressure 90 mm Hg oxygen saturation 90%

3 IMPAC Pregnancy, childbirth, postpartum and newborn care – A guide for essential practice. WHO, 2006. http:// www.who.int/reproductivehealth/publications/maternal_perinatal_health/924159084X/en/

16 QC

Quick Check and emergency treatments

Vol. 1 • 2. Quick Check: July 2011

Quick Check for adolescents and adults EMERGENCY SIGNS All staff should be able to assess these signs. If any sign is present, patient is severely ill. Call for help. Clinical staff should immediately give emergency treatment(s). FIRST LINE EMERGENCY TREATMENT If any emergency sign is present, nurse and others on clinical team should give the treatments, call for help, and establish IV access. After the Quick Check, test blood for glucose, malaria RDT, haemoglobin. Make sure a full set of vital signs and pulse oximetry are obtained from all patients with emergency signs and these ﬁndings are acted on.

First assess: Airway and breathing Do not move neck if cervical spine injury possible – immobilize spine (see p. 29). If obstructed airway: Check for obstruction (noisy breathing), wheezing, choking, not able to speak ¾ If foreign body aspiration, treat choking patient (see p. 27). ¾ If suspect anaphylaxis, give 1:1000 epinephrine (adrenaline) IM – 0.5 ml if 50 kg or above, 0.4 ml if 40 kg, 0.3 if 30 kg (see p. 28). For all patients: ¾ Manage airway (see p. 30). ¾ Give oxygen 5 litres (see p.34). ¾ If inadequate breathing, assist ventilation with bag valve mask (see p. 31). ¾ Help patient assume position of comfort. ¾ If wheezing, give salbutamol (see p. 37).

Appears obstructed or Central cyanosis or Severe respiratory distress

THEN ASSESS: CIRCULATION

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Airway and breathing

QC 17

Use this chart for rapid triage assessment, then emergency treatments. Assess pregnancy status of women of childbearing age to appropriately manage and refer.

If trauma also CONTINUE WITH URGENT MANAGEMENT OF PATIENTS WITH EMERGENCY SIGNS If head or neck trauma, manage airway and immobilize spine (see p. 44–45). Look for Respiratory distress Trachea deviated Decreased breath sounds Low SBP ¾ Give oxygen 5 litres (see p. 34–36). ¾ If wound to chest wall which sucks air in when patient breathes in —> treat sucking chest wound (see p. 46). ¾ Treat pain (Section 20). ¾ If chest trauma, call for help for possible surgical intervention. Treat tension pneumothorax with emergency needle decompression (see p. 46). Finish remainder of Quick Check then: ¾ Count pulse, RR; measure SBP, SpO2 ¾ Titrate oxygen to SpO2 90 ¾ Give antibiotics if fever and RR >30 (see Section 3.2) ¾ Give antiviral if suspect inﬂuenza ¾ Insert IV and start ﬂuids at 1 ml/kg/hour If... Severely ill patient with difﬁcult breathing: Consider silent chest with bronchospasm If moderate – severe wheeze continues Then... See Section 3.2.

Give salbutamol (another dose) and ipratropium (see p.37). See Section 3.2 for other causes wheezing.

Use standard precautions for all patients. Use droplet precautions if acute respiratory infection of concern. Add aerosol precautions if airway management or intubation. See Section 6.

Pinpoint pupils and suspect organophosphate intoxication Pinpoint pupils and suspect opioid intoxication and RR <10 or SpO2 <90 Suspect other poisoning or snakebite Suspect inhalation burn

Give atropine. See Section 3.8. Assist ventilation and give naloxone. See p. 22 and Section 3.6. See Sections 3.8 and 3.9. See Sections 3.2 and 3.10.

18 QC

Airway and breathing

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First assess: Circulation (shock or heavy bleeding) Do not move neck if cervical spine injury possible – immobilize spine (see p. 44). Weak or fast pulse or Capillary reﬁll longer than three seconds or Heavy bleeding from any site or Severe trauma If SBP <90 mmHg or pulse >110 per minute or heavy bleeding: Check SBP, pulse Is she pregnant? ¾ Give oxygen 5 litres if respiratory distress or SpO2 <90. ¾ Insert IV, give 1 litre bolus crystalloid (LR or NS) then reassess (see give ﬂuids rapidly, see p. 39). ¾ Keep warm (cover). ¾ If in second half pregnancy, place on her side (preferably on the left), not on back. ¾ If anaphylaxis, give 1:1000 epinephrine (adrenaline) IM – 0.5 ml if 50 kg or above, 0.4 ml if 40 kg, 0.3 if 30 kg (see p. 28).

THEN ASSESS: CONSCIOUSNESS/CONVULSING

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Circulation

QC 19

If trauma also CONTINUE WITH URGENT MANAGEMENT OF PATIENTS WITH EMERGENCY SIGNS If trauma and patient in shock (SBP <90, pulse >110) or suspect signiﬁcant internal or external bleeding. ¾ Give oxygen 5 litres if SpO2 <90 or respiratory distress. ¾ Give rapid IV ﬂuids (see p. 39). ¾ Keep warm. ¾ Urgently send blood for type and cross match. If external bleeding: ¾ Apply pressure immediately to stop bleeding (see p. 47). If suspect internal bleeding: Uncontrolled, noncompressible haemorrhage (abdomen, chest, pelvis or around long bone fractures) requires emergency surgical intervention. ¾ If possible femur fracture – splint (see Section 4). ¾ If possible pelvic fracture – apply pelvic binder (see p. 47). ¾ Call for help and plan emergency surgical intervention (see Section 4). ¾ If patient remains in shock after 2 litres of IV ﬂuids – transfuse (see Section 4). Suspect heart failure, cardiogenic shock or severe anaemia Diarrhoea Decide on type of shock and treat accordingly (see Section 3.1). If... Fever, consider septic shock and malaria Then... Give empirical antibiotics (see p. 42), antimalarial and glucose (if blood glucose is low or unknown). Send blood culture if feasible before starting antibiotics. See Section 3.1. Be cautious with giving ﬂuids. See Section 3.2. Classify dehydration. If severe, give rapid ﬂuids for shock and follow Fluid Plan C. See Sections 3.1.2 and 10.7. Vaginal bleeding Assess pregnancy status and amount of bleeding and treat. See p. 50–52. Large nosebleed Vomiting blood See p. 49. See p. 48.

20 QC

Circulation

Vol. 1 • 2. Quick Check: July 2011

Alltered level consciousness/convulsing

Do not move neck if cervical spine injury. For all: Altered level consciousness or Convulsing ¾ Protect from fall or injury. Is she pregnant? ¾ Manage airway and assist into recovery position (see p.29). ¾ Give oxygen 5 litres. ¾ Call for help but do not leave patient alone. ¾ Give glucose (if blood glucose is low or unknown) (see p. 41). ¾ Check (then monitor and record) level of consciousness on AVPU scale. If convulsing: ¾ Give diazepam IV or rectally (see p. 41). ¾ If convulsing in second half of pregnancy or post-partum up to one week, give magnesium sulfate rather than diazepam (see p. 57).4 Then check SBP, pulse, RR, temperature. If convulsions continue after 10 minutes: ¾ Continue to monitor airway, breathing, circulation. ¾ Recheck glucose. ¾ Give second dose diazepam (unless pregnant/post-partum). ¾ Consult district clinician to start phenytoin (see Section 3.5).

4 WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. WHO, 2011. Available at http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/9789241548335/en/index.html

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Altered consciousness/convulsing

QC 21

If trauma also CONTINUE WITH URGENT MANAGEMENT OF PATIENTS WITH EMERGENCY SIGNS Check for signs of serious head and spine trauma: ¾ Immobilize spine (see p. 44). ¾ Give oxygen 5 litres. ¾ Log-roll patient when moving. ¾ Expose patient fully. ¾ Look/feel for deformity of skull. ¾ Look for: • pupils not equal or not reactive to light • blood/ﬂuid from ear or nose • associated traumatic injuries (spine, chest,pelvis) (see Section 4) ¾ Call for help from district clinician/surgeon. Fever Give empirical antibiotics (see p. 42) Give antimalarials if in a malaria endemic area (see Section 11.25). Pinpoint pupils and suspect organophosphate intoxication Pinpoint pupils and suspect opioid intoxication and RR <10 or SpO2 <90 Give atropine. See Section 3.8. Assist ventilation and give naloxone. See p. 31 and Section 3.6. Alcohol intoxication or withdrawal Poisoning Snakebite See Section 3.7.

If... Altered consciousness Convulsions

Then... See Section 3.4. See Section 3.5.

See Section 3.8. See Section 3.9.

22 QC

Altered consciousness/convulsing

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Pain from life-threatening cause Often: ¾ Not able to walk ¾ Sweating ¾ Guarding against pain/abnormal position ¾ Very silent or moaning If these present then checkSBP, pulse, RR, temperature and look for: Severe abdominal pain and Abdomen hard on palpation ¾ ¾ ¾ ¾ ¾ ¾ Nothing by mouth (NPO) IV ﬂuids Give oxygen if respiratory distress or SpO2 <90 Empirical antibiotics IV/IM (see p. 42) Treat pain Suspect surgical abdomen – call for help (see Section 4); send blood for type and cross match

Is she pregnant?

If early pregnancy possible, consider ectopic and check rapid pregnancy test. If late pregnancy, consider abruption or ruptured uterus (see IMPAC MCPC guidelines2).

Severe headache or Stiff neck or Trauma to head/ neck

Is she pregnant?

If current/recent pregnancy, elevated BP and headache, consider severe pre-eclampsia; dipstick urine for protein (see IMPAC MCPC 2). Give magnesium sulfate if diastolic >110 mmHg with proteinuria (see p. 57). If severe headache with stiff neck and fever, consider meningitis: ¾ Give IV antibiotics (call clinician to do LP ﬁrst if can do within 15 minutes). ¾ Give IV or IM antimalarials if in malaria endemic area. If crushing, retrosternal pain (and cardiovascular risk factors)* and no history of trauma, suspect acute myocardial infarction: ¾ Give aspirin (300 mg, chewed). ¾ Give oxygen if SpO2 <90 or respiratory distress. ¾ Insert IV – if no signs of shock, give ﬂuids slowly at a keep-open rate. ¾ Give morphine for pain (see Section 20). ¾ Do ECG. Call district clinician for help. ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾ Manage airway. Consider inhalational burn. Give oxygen if SpO2 <90 or respiratory distress. Insert IV; give ﬂuids rapidly. Treat pain. Apply clean sterile bandages – see Section 3.10. Give oxygen if SpO2 <90 or respiratory distress. Insert IV; give ﬂuids rapidly (see p. 39). Treat pain (see Section 20). See Section 3.9 for antivenom guidelines.

New onset chest pain

Major burn

Snake-bite

* For country adaptation.

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Pain from life-threatening cause

QC 23

After the Quick Check, test blood for glucose and haemoglobin, do malaria microscopy (if not immediately available, a malaria RDT can be performed while waiting for the result of the blood slide). Make sure all patients with positive emergency signs have full set of vital signs and pulse oximetry and that these are acted on.

If trauma also

Do not move neck if cervical spine injury. If trauma with abdominal pain: ¾ Consider possible spleen or liver injury. ¾ If penetrating injuries to abdomen or distended or painful abdomen: • Check Hb. • Send type and cross match. • Consider diagnostic peritoneal lavage or ultrasound to check for internal bleeding.

CONTINUE WITH URGENT MANAGEMENT OF PATIENTS WITH EMERGENCY SIGNS

If... Trauma Pregnant with abdominal pain or severe headache with elevated BP Severe headache

Then... See Section 4. Decide if severe pre-eclampsia. See IMPAC MCPC guidelines. See Section 10.10b. Follow national guidelines. See Section 3.3 for DDx.

If trauma with neck pain or possible cervical spine injury: DO NOT MOVE NECK —> immobilize the neck (see p. 44). ¾ If severe headache, manage as possible head injury (see p. 44). Suspect acute myocardial infarction

If trauma with chest pain: ¾ Palpate chest for rib fractures. • If present, consider pneumothorax (see p. 46).

Major burn Snakebite

See Section 3.10. See Section 3.9.

24 QC

Pain from life-threatening cause

Vol. 1 • 2. Quick Check: July 2011

Priority signs and symptoms After screening for emergency signs, screen all patients for priority signs. Priority signs for infection control: if cough or other signs of respiratory illness, apply source control (use of tissues, handkerchiefs or medical masks) on the patient in the waiting room when coughing or sneezing, and perform hand hygiene. If possible, accommodate patient at least 1 meter away from other patients or in a room, and evaluate as soon as possible – see Section 6. Priority signs for urgent care – these patients should not wait in queue: Any respiratory distress/complaint of difﬁculty breathing Violent behaviour toward self or others or very agitated Very pale Very weak/ill Recent fainting Bleeding: • Large haemoptysis • GI bleeding (vomiting or in stools) • External bleeding Fractures or dislocations Burns Bites from rabid animal Frequent diarrhoea >5 times per day Visual changes New loss of function (possible stroke) Rape/abuse (maintain a high index of suspicion) New extensive rash with peeling and mucous membrane involvement (Stevens-Johnson) Acute pain, cough or dyspnea, priapism, or fever in patient with sickle-cell disease ¾ If any respiratory distress/complaint of difﬁculty breathing – measure SpO2; give oxygen 5 litres if SpO2 <90 (see Sections 3.2 and 10.6). ¾ If wheezing, give salbutamol (see p.38 and Section 3.2.4). ¾ If violent behaviour or very agitated, protect, calm, and sedate the patient as appropriate (see p. 59). Check glucose and SpO2 and consider causes (see Section 3.4). Check SBP, pulse and temperature Initiate interim management if clinician is not available: ¾ Measure haemoglobin if any bleeding, pale, weak, fainting, abdominal pain. ¾ If melena or vomiting blood, manage as on p. 48 and admit. ¾ If large haemoptysis (see p. 48). ¾ If visible deformity, assess and treat possible fractures/dislocations (see Section 4). ¾ Manage burns (see Section 3.10). ¾ If suspect rape or abuse (see Section 4). ¾ If painful vasoocclusive crisis from sicklecell disease – control pain, hydrate and give oxygen if SpO2 <90 (see Section 10.18). The patient needs clinical evaluation and should not wait in queue. Repeat Quick Check if in line more than 20 minutes.

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Priority signs and symptoms

QC 25

In all cases of trauma, consider: ¾ Was alcohol a contributor? If yes, counsel on harmful alcohol use. ¾ Was drug use a contributor? If yes, counsel and arrange for treatment. ¾ Was this a suicide attempt? If possible, ask the patient, were you trying to harm yourself? (See p. 61 and Section 10.11.) ¾ Was abuse or sexual violence involved? (See Section 4.4.) ¾ Was interpersonal violence a contributor? Is there a risk of further violence in retaliation? If yes, get help to interrupt this and prevent further violence.

If no emergency signs and no priority signs, NON-URGENT

Patient can wait in queue Provide routine care and use the appropriate sections Repeat Quick Check if condition changes

26 QC

Priority signs and symptoms

Vol. 1 • 2. Quick Check: July 2011

How to help the choking patient Suspect foreign body obstruction if respiratory distress occurs suddenly while eating, patient is clutching their throat, or when there is silent coughing, cyanosis, stridor or noisy breathing. IN THE CONSCIOUS PATIENT

If patient is able to speak or cough ¾ Encourage patient to cough, and observe carefully until obstruction is removed. If the patient is not able to speak or cough ¾ Tell patient that you are going to help him or her. ¾ Deliver ﬁve abdominal thrusts (if patient is pregnant give chest thrusts): • Go behind patient. • Have patient standing if possible. • Form a ﬁst with one hand and place hand just below the breastbone. • Place the other hand over the ﬁst. • Pull in and up quickly, using hard thrusts, this will force air into the patient’s lungs and help to remove the obstruction. ¾ If still obstruction, give ﬁve back blows. ¾ Repeat abdominal thrusts then back blows until patient speaks or coughs or patient becomes unconscious.

Abominal thrusts

If patient is pregnant, , give chest thrusts usts

IN THE UNCONSCIOUS PATIENT

¾ Lie patient on hard surface, open airway, and give two breaths via bag valve mask (BVM), if available. ¾ If you can see foreign body in mouth, manually remove it (if laryngoscope available may use to look for foreign body). ¾ Deliver ﬁve abdominal thrusts.

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Help choking patient/

QC 27

How to give epinephrine ¾ For anaphylaxis: give 1:1000 epinephrine (adrenaline) IM. 0.5 ml if 50 kg or above, 0.4 ml if 40 kg, 0.3 ml if 30 kg. ¾ Give IM in anterior lateral thigh. ¾ Repeat in ﬁve minutes if no response. ¾ See Section 3.1.3 for further management.

28 QC

Give epinephrine

Vol. 1 • 2. Quick Check: July 2011

Emergency treatments How to manage the airway After only a few minutes, a patient without oxygen can sustain brain damage and die. Most patients can be managed with oxygen and simple manoeuvres, and it is rare for a patient to require advanced airway management and intubation.

STEP 1

ASSESS AIRWAY

¾ Talk to the patient. If the patient is speaking clearly the airway is open. ¾ Look/listen for signs of airway obstruction. • snoring or gurgling. • stridor or noisy breathing. ¾ Foreign body or vomit in mouth.

STEP 2

IF AIRWAY OBSTRUCTED, OPEN AIRWAY AND CLEAR OBSTRUCTION AS FOLLOWS: IF NO OBSTRUCTION, GO TO STEP 4

No trauma ¾ Position patient on ﬁrm surface. ¾ Tilt the head. ¾ Lift the chin. ¾ Remove foreign body if visible. ¾ Clear secretions. ¾ If unconscious, place in recovery position (see p.42).

Trauma ¾ Stabilize cervical spine – do not lift head. ¾ Place ﬁngers behind both sides of mandible and lift up (jaw thrust). ¾ Remove foreign body if visible. ¾ Clear secretions with w suction.

If SEVERE head or neck trauma Patients with severe head or neck trauma often have signiﬁcant associated injuries to airway and cervical spine. When caring for these patients, also: ¾ give oxygen 5 litres. ¾ place oral airway. A deﬁnitive airway including intubation or surgical cricothyroidotomy may be required.

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Manage the airway

QC 29

STEP 3

IF AIRWAY OBSTRUCTED BY TONGUE, INSERT AIRWAY DEVICE TO KEEP AIRWAY OPEN, AND THEN GO TO STEP 4. IF AIRWAY IS NO LONGER OBSTRUCTED, GO TO STEP 4. INSERT AIRWAY

Oropharyngeal airway ¾ Use if patient is unconscious. ¾ Use appropriate size (measure from front of ear to corner of mouth). ¾ Slide airway over tongue. ¾ Give oxygen after placing airway device. ¾ If patient resists, gags, or vomits remove immediately.

Nasopharyngeal airway ¾ Better tolerated if patient is semi-conscious. ¾ Pass well-lubricated airway into one nostril directed posterior towards the throat. ¾ Give oxygen after placing airway device.

STEP 4

ASSESS VENTILATION

¾ If ventilation is inadequate, or patient is cyanotic or unconscious with respiratory distress, then assist breathing via bag valve mask ventilation (go to STEP 5). ¾ If ventilation is adequate, give oxygen and titrate ﬂow (see p. 33–34).

30 QC

Manage the airway

Vol. 1 • 2. Quick Check: July 2011

STEP 5

ASSIST VENTILATION WITH BAG VALVE MASK

¾ Attach the bag valve mask (BVM) to highest available ﬂow oxygen. ¾ Place mask over patient’s mouth and nose (if two people: one person squeezes bag and other holds mask on patient’s face). ¾ Create a seal so that air does not leak out. ¾ If the patient is breathing on their own, deliver breaths during inspiration. Do not attempt to deliver a breath as the patient exhales. ¾ Squeeze bag to give one breath every 6 seconds. ¾ If unable to effectively ventilate, reconsider possibility of foreign body obstruction or air leak. Insert oral or nasal airway device if not already in place (see STEP 3). One person Two people

How to bag patient ¾ Hold the bag in one hand and depress a two-litre bag to about 1/3 of its volume. ¾ After each breath allow the patient to completely exhale before giving another breath. ¾ Watch the chest rising and falling evenly with each breath. ¾ Avoid over-aggressive bagging, as it will result in damage to lungs.

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Manage the airway

QC 31

STEP 6

ASSESS NEED FOR ADVANCED AIRWAY MANAGEMENT

Some patients with easily reversible conditions may quickly improve and be able to ventilate on their own after emergency treatments are given. Others may need continued assistance with ventilation or intubation to protect airway. Look for signs: ¾ Is SpO2 < 90, cyanosis or severe respiratory distress on high ﬂow oxygen therapy? ¾ Is there impending airway failure (e.g. inhalation injury, angioedema)? ¾ Are these basic airway manoeuvres (Steps 1 to 5) failing to maintain or protect airway? ¾ Is prolonged ventilation likely needed (e.g. suspect continued failure from drug overdose, snakebite)? If yes, call for help from district clinician and see advanced airway management (see p. 62).

32 QC

Manage the airway

Vol. 1 • 2. Quick Check: July 2011

How to give oxygen SET UP OXYGEN EQUIPMENT

Either a concentrator with cylinder back-up or a cylinder may be used. ¾ If concentrator, make sure to plug into power source. ¾ Firmly connect the non-crush oxygen delivery tube to the tubing adaptor at the oxygen outlet of the concentrator or cylinder. ¾ Fully open the cylinder by turning the key wheel anti-clockwise. ¾ Turn the knob on the ﬂow controller to adjust the ﬂow based on the ﬂowmeter reading (check manufacture directions for reading). ¾ Check that oxygen is coming out either by holding the end close to your hand and feeling the air ﬂow or holding prongs under water.

USING A PULSE OXIMETER TO MONITOR SpO2

¾ Turn on the pulse oximeter. ¾ Attach the oximeter probe to the ﬁnger or toe. ¾ Wait until there is a consistent pulse signal (this may take 20–30 seconds). ¾ Record the SpO2 on a monitoring chart. ¾ If titrating oxygen down, recheck SpO2 within 15 minutes and record on the monitoring chart. ¾ If problems with the reading or inconsistent with clinical state, remove nail polish.

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Titrate oxygen/pulse oximeter

QC 33

HOW TO DELIVER INCREASING OXYGEN

¾ Start oxygen at 5 litres/minute ¾ Use nasal prongs ¾ Assess response If increasing respiratory distress or SpO2 <90

Place prongs inside the nostril. Hook tubing behind ears. Flow rates higher than 5 litres will dry mucous membranes.

¾ Use face mask ¾ Increase oxygen to 6–10 litres/minute ¾ Assess response If increasing respiratory distress or SpO2 <90

Secure mask ﬁrmly on face over nose and mouth. Pull strap over head.

¾ Use face mask with reservoir ¾ Increase oxygen to 10–15 litres/minute ¾ Make sure bag inﬂates ¾ Call for help from district clinician ¾ Assess response If increasing respiratory distress or SpO2 <90 or If not improving with BVM on high ﬂow oxygen AND Patient has an easily reversible condition (e.g. drug overdose, snakebite) and manual ventilation (bagging – p. 31) possible or Transfer to a hospital with available invasive mechanical ventilator possible. See Referral and transfer of severely ill patients, p. 70.

Make sure bag is full to deliver highest oxygen concentration. An empty bag is dangerous.

¾ Call for help from district clinician for possible tracheal intubation – see advanced airway management, p. 32. ¾ Start manual ventilation (bagging) with high ﬂow oxygen – see p. 31.

34 QC

Give oxygen

Vol. 1 • 2. Quick Check: July 2011

RESPOND TO DROP IN SPO2 OR INCREASING RESPIRATORY RATE ON OXYGEN

¾ Deliver increasing oxygen. See previous page. ¾ Check to make sure oxygen supply and all equipment is working properly: • check that the cylinder still has sufﬁcient oxygen. • check that oxygen is ﬂowing out of the prongs or face mask – hold the end close to your hand and you will feel the airﬂow. • check that there are no leaks in the connections or oxygen tubing. ¾ Exclude pneumothorax, pleural effusion, heart failure, poisoning. ¾ If wheezing, give salbutamol. ¾ Check that antibiotics and antimalarials have been given. ¾ If PLHIV consider PCP – give cotrimoxazole and steroids (see Section 10.6). ¾ Consider TB; check AFB smear.

DECREASE OXYGEN IF PATIENT IS STABILIZING OR IMPROVING

Decrease oxygen ﬂow by 1–2 litres/min. ¾ Observe the patient for at least 2–3 minutes. ¾ If patient does not tolerate less oxygen, then do not titrate oxygen ﬂow until the patient is more stable. ¾ If patient does tolerate less oxygen, then recheck the patient in 15 minutes and measure SpO2. ¾ If patient is in increased respiratory distress or SpO2 <90, then increase oxygen ﬂow to previous ﬂow rate. ¾ If patient remains stable and SpO2 >90, continue to titrate oxygen down as tolerated. Recheck clinical status and SpO2 on patients after 1 hour for delayed hypoxia or respiratory distress.

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Respond to changes on oxygen

QC 35

LITRES IN FULL O2 TANK BY HEIGHT OF TANK/CYLINDER LETTER Rate of oxygen administration: Top row: How long will a tank of this size last. Bottom row: How many tanks required for 24 hours of oxygen administration.

Rate of oxygen administration for one patient 2 litres/min

O2 tank C 170 litres 14 inches 1 hr 25 min 16 tanks 34 min 48 tanks 21 min 72 tanks 17 min 96 tanks

O2 tank D 340 litres 18 inches 2 hr 50 min 8 ½ tanks 1 hr 8 min 21 tanks 42 min 34 tanks 34 min 42 tanks

O2 tank E 680 litres 31 inches

O2 tank F 1360 litres 34 inches

O2 tank G 3400 litres 49 inches

O2 tank J 6800 litres 57 inches 56 hr ½ tank 23 hr 1 tank 14 hr 2 tanks 11 hr 2.2 tanks

5 hr 40 min 11 hr 20 min 28 hr 20 min 4 tanks 2 hr 16 min 10 tanks 1 hr 24 min 17 tanks 1 hr 8 min 21 tanks 2 ½ tanks 1 tank

5 litres/min 8 litres/min 10 litres/min

4 hr 30 min 11 hr 20 min 5 tanks 2 hr 50 min 8 tanks 2 hr 16 min 10 tanks 2 tanks 7 hr 4 tanks 5 hr 40 min 4 tanks

36 QC

Oxygen cylinders

Vol. 1 • 2. Quick Check: July 2011

If wheezing – how to give sequential bronchodilators Also see Section 3.2.4

GIVE SALBUTAMOL FOR MODERATE–SEVERE WHEEZING

Signs of severity: breathless at rest or with talking; speaking in incomplete phrases, single words or not at all; confused, sleepy or agitated; or SpO2 <90 on room air. See Section 3.2.4 to consider other causes of wheezing. ¾ Call for help from district clinician. ¾ By nebulizer: for patient more than 20 kg: place 5 mg salbutamol in 5 ml sterile saline in nebulizer driven by oxygen. Treat until liquid almost all used up. ¾ By metered dose inhaler: prime space with 5 puffs, then give 2 puffs via spacer every 2 minutes. Assess response If incomplete or poor response – signs of severity continue

Give salbutamol by nebulizer, every 10–20 minutes, or if poor response, continuously. ¾ Add ipratropium by metered dose inhaler (2 puffs) in spacer or by nebulizer. ¾ Then continue salbutamol. Assess response If incomplete or poor response – signs of severity continue

Give salbutamol continuously by nebulizer. ¾ For life-threatening wheezing give 2 g of magnesium sulfate IV over 20 minutes or IM. See Section 3.2.4.

Vol. 1 • 2. Quick Check: July 2011

Give salbutamol

QC 37

GIVE SALBUTAMOL FOR MILD WHEEZING

By metered dose inhaler: 100 mcg/puff; 200 puffs/inhaler ¾ Use spacer with inhaler if patient is able to coordinate breathing, if not use mask. ¾ 2 puffs every 20 minutes x 3 times then 2 puffs every 3 to 6 hours. ¾ See Section 10.6.

HOW TO MAKE SPACER FROM PLASTIC BOTTLE

¾ Use a clean plastic 300–500 ml bottle (wash with detergent and rinse well). ¾ Clean monthly and prime with 5 puffs after each cleaning, before using for treatment. ¾ Remove the inhaler cap and trace the shape of the opening of the inhaler on the base of the bottle, directly opposite the mouth of the bottle. ¾ Cut an opening into the base of the bottle exactly (or slightly smaller) than the size traced with a heated paperclip. An alternative is to make a slit in the side of the bottle and place the puffer through the hole. ¾ Insert the inhaler into the spacer to check the size. ¾ For severe attacks or if the patient cannot cooperate, cut off at the neck and use as a mask.

38 QC

Give salbutamol

Vol. 1 • 2. Quick Check: July 2011

How to insert IV and give ﬂuids rapidly ¾ If heavy bleeding or shock, insert two large bore cannulae – at least 16 or 18 gauge. ¾ Attach LR or NS. Give one litre as rapidly with infusion wide open. ¾ Assess response of pulse, SBP and signs of perfusion (urine output, mental status). ¾ If still in shock and no evidence of ﬂuid overload, give another bolus. ¾ If still in shock after 2 litres and suspect ongoing blood loss, start blood transfusion and search again for source of bleeding. ¾ If still in shock after 2 litres, call for help from district clinician and see Section 3.1. ¾ Insert urinary catheter (see Sections 7.3.2 and 7.3.6), and monitor hourly urine output. A urine output of at least 30 ml/hour suggests adequate hydration. See Sections 3.1 (Shock) and 4 (Trauma) for further information on ﬂuid management. If not able to insert peripheral IV, use alternative: ¾ Call for more experienced help, consider: • External jugular vein cannulation. • Femoral vein cannulation (or internal jugular or subclavian vein cannulation, if trained). • Venous cut-down – see 7.3.10.

Vol. 1 • 2. Quick Check: July 2011

IV/Give ﬂuids rapidly

QC 39

How to give naloxone Important: naloxone effect lasts only 40 minutes. Is IV inserted? If IV ¾ Give naloxone 100 mcg IV – repeat dose until patient RR >10/minute. ¾ Response is usually within 30 seconds. May be repeated. If no IV ¾ Give naloxone 400 mcg IM or subcutaneous 800 mcg – repeat 2 minutes later, if necessary.

Second, decide whether opioid was short-acting (heroin) or long-acting (methadone).

If short-acting ¾ Advise to wait two hours. If they go, do not stop them.

If long-acting ¾ If inadequate ventilation assist with BVM using high- ﬂow oxygen. ¾ Call for help from district clinician – see advanced airway management p. 62. ¾ If patient responded to naloxone: • Give naloxone IV infusion – 0.4 mg/hour (for approximately 12 hours). • Try to keep patient until 12 hours after last dose. • Monitor closely: SBP, RR, SpO2 with alarm (if possible). Note: death can occur if the infusion is interrupted or the patient discharges themselves.

• Explain to family or companion beforehand why giving naloxone is necessary. Counsel accompanying person that naloxone wears off quickly and patient could become unconscious again. • Realize that on awakening, the patient may be angry and combative and could injure self or others. • If patient fails to wake up after several doses, rule out other causes of unconsciousness (see Section 3.4 or severe respiratory depression (see Section 3.2). • Explain to patient not to inject again for 12 hours, or overdose might be fatal.

40 QC

Give naloxone

Vol. 1 • 2. Quick Check: July 2011

How to give glucose If symptoms of hypoglycaemia or if glucose low (<3 mmol/l (54 mg/dl)): ¾ Give IV glucose: • make sure IV is running well. • for adolescent or adult, give D50 25 to 50 ml or, if D10 available, give 125 to 250 ml rapidly (D50 is the same as dextrose 50% and glucose 50%). ¾ If no IV glucose is available, give sugar water by mouth (if conscious) or nasogastric tube. • dissolve four level teaspoons of sugar (20 grams) in a 200 ml cup of clean water. ¾ Repeat if necessary.

How to give diazepam IV or rectally ¾ Maximum total IV diazepam dose: 30 mg ¾ Do not give further diazepam if breathing less than 16 breaths per minute. If respiratory arrest develops, ventilate with bag valve mask (see p. 31). ¾ Consider all causes if convulsions continue – see Section 3.5. IV (10 mg/2 ml solution) 2 ml (10 mg) 1 ml (5 mg)

Typical dose for 50 kg adult Initial dose Second dose after 10 minutes

RECTALLY (10mg/2 ml solution) 4 ml (20 mg) 2 ml (10 mg)

¾ If convulsions continue, administer IV antiepileptic drug such as phenytoin (see Section 3.5). ¾ Give phenytoin 15–18 mg/kg IV in normal saline over 1 hour. ¾ Monitor pulse and respiratory rate.

Vol. 1 • 2. Quick Check: July 2011

Give glucose/diazepam

QC 41

How to put patient in recovery position

How to give empirical IV/IM antibiotics for emergency management ¾ Give ceftriaxone 1 gm IV or IM (2 gm if suspect meningitis). ¾ If ceftriaxone not available, give: • ampicillin*† 2 gm IV or IM, and • gentamicin 240 mg IV or IM ¾ For open fractures or wounds, an alternative is a ﬁrst generation cephalosporin or cloxacillin. * If ampicillin is not available, give benzylpenicillin 3 million units. † If patient has penicillin allergy, see Section 8.4 for alternatives.

42 QC

Recovery position/empirical IV/IM

Vol. 1 • 2. Quick Check: July 2011

How to give emergency antimalarial treatment if falciparum malaria is possible5 Preferred treatment is artesunate IV. Use artesunate or artemether rather than quinine, if available. Give artesunate IV in patients in shock, if possible (except for pregnant women in ﬁrst trimester – give quinine). ARTESUNATE IV or IM IV or IM 2.4 mg/kg on admission then at 12 hr and 24 hr then once daily. For each dose, freshly mix 60 mg anhydrous aretesunic acid ampoule with 1 ml of 5% sodium bicarbonate solution

ARTEMETHER IM Subsequent doses 1.6 mg/kg each day until able to take oral medication Initial loading dose: 3.2 mg/kg

QUININE IM or IV Initial dose: 20 mg/kg IM (divide dose equally in 2 and give 1 in each anterior thigh) or IV by rate-controlled infusion not exceeding 5 mg salt/ kg body weight/hour

For IV, further dilute with 5 ml of 5% dextrose (for 10 mg/ml)

For IM, further dilute with 2 ml of 5% dextrose (for 20 mg/ml)

80 mg/ml (in 1 ml ampoules)

150 mg/ml (in 2 ml ampoules)

300 mg/ml (in 2 ml ampoules)

150 mg/ml (in 2 ml ampoules)

es 10 mg/ Subsequent doses ours kg every 8 hours

ALW GLU AYS G COS IVE QUI E WITH NIN E

Weight 30 kg 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg

7.2 ml 9.6 ml 12.0 ml 14.4 ml 16.8 ml 19.2 ml 21.6 ml

3.6 ml 4.8 ml 6.0 ml 7.2 ml 8.4 ml 9.6 ml 10.8 ml

1.2 ml 1.6 ml 2.0 ml 2.4 ml 2.8 ml 3.2 ml 3.6 ml

0.6 ml 0.8 ml 1.0 ml 1.2 ml 1.4 ml 1.6 ml 1.8 ml

4.0 ml 5.4 ml 6.6 ml 8.0 ml 9.3 ml 10.6 ml 12.0 ml

2.0 ml 2.6 ml 3.3 ml 4.0 ml 4.7 ml 5.3 ml 6.0 ml

0.5 ml 0.7 ml 0.8 ml 1.0 ml 1.2 ml 1.3 ml 1.5 ml

¾ If giving quinine by IV, infuse slowly over 4 hours. ¾ If giving large IM dose, divide between 2 thighs. ¾ Give at least 24 hours of parenteral artesunate, artemether or quinine. Start oral as soon as tolerated and complete full course (see Section 11.25).

How to give emergency antiviral treatment6 Oseltamivir Weight 24–40 kg >40 kg Usual dose 60 mg twice daily 75 mg twice daily Severe disease or severely immunosuppressed 60 mg twice daily for 10 days 150 mg twice daily for 10 days

5 Guidelines for the treatment of malaria – 2nd edition. WHO, 2010. Chapter: 8. Treatment of severe P. falciparum malaria. http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html 6 The oseltamivir recommendations are based on the published WHO Guidelines for Pharmacological Management of Pandemic Inﬂuenza A(H1N1) 2009 and other Inﬂuenza Viruses Revised February 2010. http:// www.who.int/csr/resources/publications/swineﬂu/h1n1_guidelines_pharmaceutical_mngt.pdf

Vol. 1 • 2. Quick Check: July 2011

Emergency antibiotics/antimalarials

300 mg/ml (in 2 ml ampoules)

QC 43

How to immobilize spine UNTIL CLEARANCE: NO SPINE INJURY Every patient with a suspected spinal injury should be immobilized until spine can be cleared clinically or with X-ray. It is important to document all examination ﬁndings. Who to immobilize: ¾ every unconscious trauma patient. ¾ every conscious trauma patient with head, face, neck injury. ¾ every trauma patient with posterior neck pain or cervical spine tenderness, and/or neurological signs. How to immobilize cervical spine: ¾ apply cervical collar or stabilize the neck with locally available material. ¾ keep the patient lying on a ﬂat surface. ¾ prevent the neck from moving with locally available materials (towel rolls, newspaper, sandbags, or bags of IV ﬂuids) or cervical collar if available. ¾ if patient vomits, turn whole patient on their side, keeping head in line with the body. ¾ keep someone with patient at all times to watch the airway. How to immobilize thoracic and lumbar spine: ¾ keep patient on a ﬂat surface. ¾ if need to move patient use log roll technique.

Log roll technique

44 QC

Immobilize spine

Vol. 1 • 2. Quick Check: July 2011

How to determine whether cervical spine is clear and collar can be removed: To clear clinically, patient must be conscious, cooperative, not intoxicated and able to concentrate on exam (no other major injuries). If patient is conscious, check for: ¾ posterior neck pain at rest. ¾ tenderness with palpation of posterior cervical spine. ¾ sensory or motor deﬁcit. If patient has none of these symptoms ask them to move neck. If no pain or neurological signs on active range of motion, spine is clear. If patient cannot be cleared clinically, patient should remain immobilized until their cervical spine is cleared by X-ray. Three X-ray views are needed to clear the cervical spine (lateral, AP, open mouth odontoid). The most important view is the lateral X-ray. An adequate lateral X-ray must view to C7/T1. If patient is unconscious, then they must have their cervical spine immobilized until it is cleared by X-ray.

How to manage serious head injury ¾ Monitor airway. Watch for vomiting and aspiration. ¾ Keep head of bed elevated 30° while maintaining spinal precautions. ¾ Log roll patient when moving. ¾ If concern for open skull fracture, give IV antibiotics (e.g. ceftriaxone). ¾ No food or drink by mouth. ¾ Give maintenance intravenous ﬂuids. ¾ Monitor and record: • AVPU scale • ﬂuid input and output • thorough neurologic exam ¾ If possible, urgent referral to a higher level of care (see p. 71). If not possible, continue supportive care.

Vol. 1 • 2. Quick Check: July 2011

Manage head injury

QC 45

How to manage tension pneumothorax or massive haemothorax ¾ Treat tension pneumothorax with emergency needle decompression: • insert large bore (#14) cannula along the upper edge of third rib through second intercostal space in mid-clavicular line • if tension pneumothorax, there will be a rush of expelled air.

¾ Give high ﬂow oxygen. ¾ Call for help from district clinician and see Section 7.3.1. ¾ Chest tube should be placed as soon as possible following needle decompression (even if no rush of air) or for suspected haemothorax ¾ Give IV antibiotics

How to treat sucking chest wound Chest wall wound which sucks air in when patient breaths in (vacuum effect): ¾ Give high ﬂow oxygen. ¾ Cover with petroleum gauze. ¾ Tape three sides of the dressing, leaving one side untaped to act as ﬂap valve. ¾ Deﬁnitive treatment is to insert chest tube (never insert chest tube through wound). ¾ Debride wound and consider closure. ¾ Give IV antibiotics.

46 QC

Pneumothorax/chest wound

Vol. 1 • 2. Quick Check: July 2011

How to apply pressure to stop bleeding ¾ Apply ﬁrm, direct compression. ¾ Reinforce dressings to apply more pressure. ONLY IF all other bleeding control measures have failed AND haemorrhage is life-threatening, consider using tourniquet technique until control by surgery or for transport only. Tourniquet technique: ¾ If available, use pneumatic tourniquet (like BP cuff) over padded skin, inﬂate until bleeding stops. ¾ If not, use elastic band or piece of cloth or belt (the wider, the better), over padded skin. ¾ Apply as close to wound as possible. ¾ Apply enough pressure to make distal pulses disappear and reassess bleeding. If stopped, dress the wound and proceed with surgery or transfer urgently. If not, increase tourniquet pressure until major bleeding (arterial “pumper”) ceases. ¾ Release for 10 minutes every 2 hours, while applying forceful direct pressure over the wound. Do not reapply unless evidence of continued active bleeding. ¾ Never leave a tourniquet on for more than 4 hours. ¾ Make sure tourniquet is clearly visible.

How to apply pelvic binder To pull displaced bones together to tamponade bleeding. ¾ Place bed sheet under the pelvis. ¾ Pull over the great trochanters/iliac wings – cross over anteriorly. ¾ Pull tight and tie.

Vol. 1 • 2. Quick Check: July 2011

Apply pressure/pelvic binder

QC 47

How to manage heavy upper gastrointestinal bleeding Call for help. ¾ Insert IV and give ﬂuids rapidly (see p. 39). ¾ Send blood specimen for type and cross match then transfuse as needed. ¾ Repeat Quick Check and monitor pulse, SBP and haemoglobin. ¾ Insert nasogastric tube to decompress – do not lavage (see Section 7.3.8). ¾ If endoscope and trained provider: locate site and cauterize. ¾ Give proton pump inhibitor in high dose (e.g. omeprazole 80 mg). ¾ Check whole blood clotting time.

How to manage large haemoptysis ¾ Manage airway. ¾ Send blood for type and cross match then transfuse as needed. ¾ Consider antibiotics. ¾ Monitor Quick Check and haemoglobin (see Section 10.6). ¾ Check chest X-ray. If unilateral process, place affected side down.

48 QC

UGI/haemoptysis

Vol. 1 • 2. Quick Check: July 2011

How to manage large nose bleed (epistaxis) 1. Pressure. Have the patient gently blow their nose to remove all clots. ¾ Ask patient to open mouth, then pinch both nostrils tightly between your ﬁngers and thumb. ¾ Hold continuous pressure. Bleeding usually stops within 10 minutes. 2. Consider cautery (i.e. silver nitrate) only if you can clearly identify a bleeding site. For all patients: monitor airway, breathing and circulation (follow Quick Check). Manage in comfortable sitting position with head forward. If patient unstable: insert IV, give LR or NS ﬂuid bolus, and send blood for Hb, type and cross-match. If patient extremely anxious, consider low dose diazepam. For all patients with nasal packing, give antibiotics to prevent toxic shock syndrome.

If bleeding continues

3. Pack the anterior nares – bleeding side. First pack the side that appears to be the main source of bleeding. Use petroleum ribbon gauze (if not available, soak gauze 1 mg of epinephrine diluted in 200 ml saline). 4. Pack both sides. If bleeding continues after both side packed

5. Use a urinary catheter to stop the bleeding from posterior nasopharynx: ¾ Lubricate the catheter, and pass it through the nose until the tip is visible at the oropharynx. ¾ Inﬂate the balloon with 5–10 ml of water. ¾ Gently pull the catheter forward until the balloon is held in the posterior part of the nose. ¾ While holding catheter in place, pack the anterior nares with petroleum or saline soaked gauze. ¾ Tape or tie in place. ¾ Deﬂate the foley catheter after 24 hours, and if bleeding does not recur remove it. ¾ Admit any patient with posterior packing for observation and airway monitoring.

Vol. 1 • 2. Quick Check: July 2011

Nose bleed

QC 49

Vaginal bleeding in pregnant woman or woman of childbearing age2,7 Assess pregnancy status. Assess amount of bleeding.

Heavy bleeding: pad or cloth soaked in <5 minutes. Decide if pregnant.

¾ ¾ ¾ ¾ ¾ ¾ ¾ ¾

EARLY PREGNANCY (uterus NOT above umbilicus; may not be aware of pregnancy) or NOT PREGNANT Light bleeding

Insert an IV line. Give ﬂuids rapidly. Give 0.2 mg ergometrine IM. Repeat 0.2 mg ergometrine IM or IV if bleeding continues. If suspect possible complicated abortion, give appropriate IM or IV antibiotics; see IMPAC MCPC.2 If pregnant, see IMPAC MCPC.2 If not pregnant, consider ﬁbroids, anovulatory bleeding, malignancy, sexual trauma (see Section 10.15). Call for help and admit to hospital.

Examine woman: ¾ Consider ectopic pregnancy (see Section 10.15 and IMPAC MCPC 2). ¾ If pregnancy not likely, see Section 10.15.

LATE PREGNANCY (uterus above umbilicus)

ANT BLEEDING IS DANGEROUS!

DO NOT do vaginal examination, but: ¾ Insert an IV line ¾ Give ﬂuids rapidly if heavy bleeding or shock ¾ Call for help and admit to hospital Call for help from district clinician. See IMPAC MCPC.2 This may be placenta praevia, abruptio placenta, ruptured uterus.

DURING LABOUR Before delivery of baby

BLEEDING MORE THAN 100 ML SINCE LABOUR BEGAN IS DANGEROUS!

7 WHO guidelines for the management of postpartum haemorrhage and retained placenta. WHO, 2009. http:// www.who.int/reproductivehealth/publications/maternal_perinatal_health/9789241598514/en/index.html

50 QC

Vaginal bleeding

Vol. 1 • 2. Quick Check: July 2011

POSTPARTUM2 (BABY IS BORN) bleeding heavy?

Heavy bleeding: • Pad or cloth soaked in<5 minutes • Constant trickling of blood • Bleeding >250 ml or delivered outside hospital and still bleeding

¾ Call for extra help. ¾ Massage uterus until it is hard. Give oxytocin 10 IU IM. ¾ Insert IV line and give IV ﬂuids with 20 IU oxytocin/litre at 60 drops/minute. ¾ Empty bladder, catheterize if necessary. ¾ Check and record SBP and pulse every 15 minutes and treat. ¾ Check and ask if placenta is delivered (continue to follow ﬂowchart). District clinician management: see IMPAC MCPC.1 This may be uterine atony, retained placenta, ruptured uterus, vaginal or cervical tear.

Placenta NOT delivered

Check and ask if placenta is delivered. Placenta delivered

When uterus is hard, deliver placenta by controlled cord traction: ¾ If unsuccessful and bleeding continues. ¾ If bleeding continues, remove placenta manually (see p. 55) and check placenta. ¾ Give appropriate IM/IV antibiotics. ¾ If unable to remove placenta, call for help. Continue IV ﬂuids with 20 IU of oxytocin at 30 drops/minute.

If placenta is complete: ¾ Massage uterus to express any clots. ¾ If uterus remains soft, give ergometrine 0.2 mg IV (DO NOT give ergometrine if pre-eclampsia, eclampsia or known hypertension). ¾ Continue IV ﬂuids with 20 IU oxytocin/litre at 30 drops/minute. ¾ Continue massaging uterus until it is hard. ¾ If bleeding does not respond, give misoprostol7 (see p. 56). ¾ If placenta is incomplete (or not available for inspection): ¾ Remove placental fragments (see IIMPAC MCPC 2). ¾ Give appropriate IM/IV antibiotics. ¾ If cannot remove, call urgently for help from district clinician.

Check for perineal and lower vaginal tears

If present

Examine the tear and determine the degree. controlled cord traction: ¾ If third or fourth degree tear (involving rectum or anus), get district clinician to repair. ¾ For other tears: apply pressure over the tear with a sterile pad or gauze and put legs together. ¾ Check after ﬁve minutes, if bleeding persists repair tear.

Vol. 1 • 2. Quick Check: July 2011

Vaginal bleeding

QC 51

If heavy bleeding

Check if still bleeding Controlled bleeding

Continue IV ﬂuids with 20 units of oxytocin at 30 drops/minute. Insert second IV line. ¾ If can visualize cervix, inﬂate condom over foley catheter7 to tamponade (see p. 53). ¾ Apply bimanual uterine or aortic compression ¾ Give appropriate IM/IV antibiotics B1 5 . ¾ Prepare for surgery Call for district clinician to manage: see IMPAC MCPC 2.

Continue oxytocin infusion with 20 IU/litre of IV ﬂuids at 20 drops/minute for at least one hour after bleeding stops: ¾ Observe closely (every 30 minutes) for four hours. Keep nearby for 24 hours. If severe pallor, refer back to facility. ¾ Examine the woman using MPAC MCPC 2. ¾ Section: Assess the mother after delivery.

How to massage uterus and expel clots If heavy postpartum bleeding persists after placenta is delivered, or uterus is not well contracted (is soft): ¾ Place cupped palm on uterine fundus and feel for state of contraction. ¾ Massage fundus in a circular motion with cupped palm until uterus is well contracted. ¾ When well contracted, place ﬁngers behind fundus and push down in one swift action to expel clots. ¾ Collect blood in a container placed close to the vulva. Measure or estimate blood loss, and record.

52 QC

Vaginal bleeding/massage uterus

Vol. 1 • 2. Quick Check: July 2011

How to inﬂate condom over foley catheter7 to tamponade uterine bleeding If trained and keeping all equipment sterile:

Insert sterile foley catheter up to 3–5 cm below the bulb into a condom.

Tie the condom tightly around the stem of the catheter using sterile gauze ties.

Using a sterile speculum and sponge holding forceps, insert catheter with the condom attached well into the uterine cavity. Clamp the catheter and leave the end inside the vagina.

Connect a bag of sterile ﬂuid to the end of the catheter (ensuring a tight ﬁt) and allow the ﬂuid to run in and ﬁll the catheter. Make arrangements for further treatment as appropriate.

Vol. 1 • 2. Quick Check: July 2011

Tamponade uterine bleeding

QC 53

How to apply bimanual uterine compression If heavy postpartum bleeding persists despite uterine massage, oxytocin/ ergometrine/misoprostol7 treatment and removal of placenta: ¾ Wear sterile or clean gloves. ¾ Introduce the right hand into the vagina, clenched ﬁst, with the back of the hand directed posteriorly and the knuckles in the anterior fornix. ¾ Place the other hand on the abdomen behind the uterus and squeeze the uterus ﬁrmly between the two hands. ¾ Continue compression until bleeding stops (no bleeding if the compression is released). ¾ If bleeding persists, apply aortic compression and transport woman to hospital.

How to apply aortic compression If heavy postpartum bleeding persists despite uterine massage, oxytocin/ ergometrine/misoprostol6 treatment and removal of placenta: ¾ Feel for femoral pulse. ¾ Apply pressure above the umbilicus to stop bleeding. Apply sufﬁcient pressure until femoral pulse is not felt. ¾ After ﬁnding correct site, show assistant or relative how to apply pressure, if necessary. ¾ Continue pressure until bleeding stops. If bleeding persists, keep applying pressure while preparing for surgery or transporting woman to a referral hospital.

How to give oxytocin If heavy postpartum bleeding: Initial dose IM: 10 IU IV infusion: 20 IU in 1 litre at 60 drops/min Continuing dose

MA XIM UM D Not OSE: mor et 3 ﬂuid litres of hat s co IV n t oxy ainin toci n g

IM: repeat 10 IU after 20 minutes if heavy bleeding persists IV infusion: 20 IU in 1 litre at 30 drops/min

54 QC

Uterine/aortic compression/oxytocin

Vol. 1 • 2. Quick Check: July 2011

How to manually remove the placenta if postpartum bleeding2 ¾ If placenta not delivered 30 minutes after delivery of the baby with bleeding, OR ¾ If heavy vaginal bleeding continues despite massage and oxytocin and placenta cannot be delivered by controlled cord traction, or if placenta is incomplete and bleeding continues. Preparation: ¾ Explain to the woman the need for manual removal of the placenta and obtain her consent. ¾ Insert an IV line. If bleeding, give ﬂuids rapidly. If not bleeding, give ﬂuids slowly. ¾ Assist woman to get onto her back. ¾ Give diazepam (10 mg IV) or ketamine sedation (see p. 58) if not comatose. ¾ Clean vulva and perineal area. ¾ Ensure the bladder is empty. Catheterize if necessary. ¾ Wash hands and forearms well and put on long sterile gloves (and an apron or gown if available). How to manually remove placenta: ¾ With the left hand, hold the umbilical cord with the clamp. Then pull the cord gently until it is horizontal. ¾ Insert right hand into the vagina and up into the uterus. ¾ Leave the cord and hold the fundus with the left hand in order to support the fundus of the uterus and to provide counter-traction during removal. ¾ Move the ﬁngers of the right hand sideways until edge of the placenta is located. ¾ Detach the placenta from the implantation site by keeping the ﬁngers tightly together and using the edge of the hand to gradually make a space between the placenta and the uterine wall. ¾ Withdraw the right hand from the uterus gradually, bringing the placenta with it. ¾ Explore the inside of the uterine cavity to ensure all placental tissue has been removed. ¾ With the left hand, provide counter-traction to the fundus through the abdomen by pushing it in the opposite direction of the hand that is being withdrawn. This prevents inversion of the uterus. ¾ Examine the uterine surface of the placenta to ensure that lobes and membranes are complete. If anyplacental lobe or tissue fragments are missing, explore again the uterine cavity to remove them. If hours or days have passed since delivery, or if the placenta is retained due to constriction ring or closed cervix, it may not be possible to put the hand into the uterus. DO NOT persist. Get help; admit or refer. If the placenta does not separate from the uterine surface by gentle sideways movement of the ﬁngertips at the line of cleavage, suspect placenta accreta. DO NOT persist in efforts to remove placenta. Get help; admit or refer.

Vol. 1 • 2. Quick Check: July 2011

Manual removal of placenta

QC 55

After manual removal of the placenta ¾ Repeat oxytocin 10 IU IM/IV. ¾ Massage the fundus of the uterus to encourage a tonic uterine contraction. ¾ Give ampicillin 2 g IV/IM. ¾ If fever >38.5°C, foul-smelling lochia or history of rupture of membranes for 18 or more hours, also give gentamicin 80 mg IM. ¾ If bleeding stops: • give ﬂuids slowly for at least 1 hour after removal of placenta. ¾ If heavy bleeding continues: • give ergometrine 0.2 mg IM • give 20 IU oxytocin in each litre of IV ﬂuids and infuse rapidly • admit to hospital and call for surgical help (see IMPAC MCPC 2). ¾ During transportation, feel continuously whether uterus is well contracted (hard and round). If not, massage and repeat oxytocin 10 IU IM/IV. ¾ Provide bimanual or aortic compression if severe bleeding before and during transport to surgery.

How to give misoprostol7 for postpartum bleeding if noresponse to oxytocin plus ergometrine ¾ Give misoprostol 800 mcg sublingually.

56 QC

Manual removal of placenta/misoprostol

Vol. 1 • 2. Quick Check: July 2011

How to give magnesium sulfate For severe pre-eclampsia and eclampsia:4 Give IV and IM combined dose (loading dose): ¾ Insert IV line and give ﬂuids slowly (NS or LR) 1 litre in 6–8 hours (3 ml/ minute) ¾ Give 4 g of magnesium sulfate (20 ml of 20% solution) IV slowly over 20 minutes (woman may feel warm during injection) AND ¾ Give 10 g of magnesium sulfate IM: give 5 g (10 ml of 50% solution) IM deep in upper outer quadrant of each buttock with 1 ml of 2% lidocaine in the same syringe. If unable to give IV, give IM only (loading dose): ¾ Give 10 g of magnesium sulfate IM: give 5 g (10 ml of 50% solution) IM deep in upper outer quadrant of each buttock with 1 ml of 2% lidocaine in the same syringe. If convulsions recur: ¾ After 15 minutes, give an additional 2 g of magnesium sulfate (10 ml of 20% solution) IV over 20 minutes. ¾ If convulsions still continue, give diazepam. If referral delayed for long, or the woman is in late labour, continue treatment: ¾ Give 5 g of 50% magnesium sulfate solution IM with 1 ml of 2% lidocaine every four hours in alternate

Monitor: ¾ Monitor urine output: collect urine and measure the quantity. ¾ Before giving the next dose of magnesium sulfate, ensure: • knee jerk is present. • urine output >100 ml/4 hours. • RR >16/minute. ¾ DO NOT give the next dose if any of these signs: • knee jerk absent. • urine output <100 ml/4 hours. • RR <16/minute. ¾ Record ﬁndings and drugs given.

Vol. 1 • 2. Quick Check: July 2011

Magnesium sulfate

QC 57

Important considerations in caring for a woman with eclampsia or pre-eclampsia ¾ Do not leave the woman on her own. • help her into the left side position and protect her from fall and injury. ¾ Give IV magnesium sulfate slowly, over 20 minutes. Rapid injection can cause respiratory failure or death. • if respiratory depression (RR less than 16/minute) occurs after magnesium sulfate: DO NOT give any more magnesium sulfate. ¾ Give the antidote: calcium gluconate 1 g IV (10 ml of 10% solution) over 10 minutes. ¾ DO NOT give intravenous ﬂuids rapidly. ¾ DO NOT give intravenously 50% magnesium sulfate without diluting it to 20%. ¾ Consider caesarian section unless delivery is imminent. ¾ If delivery imminent, manage as in childbirth and accompany the woman during transport. • Keep her in the left side position. • If a convulsion occurs during transport, give magnesium sulfate and protect her from fall and injury.

How to give ketamine for a procedure ¾ Prepare: place IV; set up monitoring equipment, suction, oxygen and mask, oral or nasal airway, and BVM at bedside. ¾ Pretreat to prevent emergence reaction (agitation or hallucination) before administering ketamine. • give midazolam 0.05 mg/kg IV over 2 minutes just prior to giving ketamine; OR • alternative, give diazepam 0.05–0.1 mg/kg IV (requires longer observation following sedation): OR • alternative, treat ketamine emergence reaction with midazolam or diazepam only if hallucinations or agitation are observed. ¾ Sedate: • give ketamine 1–2 mg/kg IV over 2 minutes. • repeat 0.5 mg/kg IV every 10 minutes as needed. • alternative to IV: give 4 mg/kg IM. ¾ Monitor: • check BP, pulse, RR, and SpO2 every 2 minutes. • watch for secretions, laryngospasm, and emergence reactions.

58 QC

Eclampsia/ketamine

Vol. 1 • 2. Quick Check: July 2011

How to manage the violent or very agitated patient Calm and protect ¾ Protect patient from harming him/herself, you or others. ¾ Ensure that you are in a quiet area where there is no audience. ¾ Use space to protect yourself. ¾ Get help from colleagues, security, and family members who can help mediate the situation and calm the patient down for the safety of staff and the patient. ¾ Approach in calm and conﬁdent manner. • Speak in a calm and reassuring way. • Be non-confrontational, non-judgemental, and deﬂect criticism. ¾ Keep your own emotions in check. Do not let yourself be affected by verbal abuse or threats. ¾ Be aware of potential weapons and remove unsafe objects. ¾ Consider differential diagnosis: • Check blood glucose and give glucose if low (see p. 41). • Check vital signs including temperature. • Check SpO2 and give oxygen if < 90. • Use the delirium differential diagnosis to consider medical causes including poisoning and substance use (see Section 3.4). • Decide what is the likely cause of the aggression and agitation.

Sedate – as appropriate If suspect agitation is due to ingestion of substances (i.e. alcohol or other sedative withdrawal or stimulant intoxication): ¾ Give diazepam 10–20 mg orally – repeat as necessary (see Sections 3.6 and 3.7). If suspect agitation is due to psychotic disorder, mania, or other psychiatric disorders, consider the use of haloperidol to alleviate the agitation: For most patients: ¾ Give haloperidol 2 mg IM or orally every hour up to 5 doses (max dose = 10 mg). For elderly patients and those with complicating medical illness, including delirium and dementia: ¾ Give haloperidol 0.5–1 mg orally or IM every hour up to 3 doses (max dose = 3 mg). For the most uncontrollable patients at risk to themselves and others: ¾ Seek immediate assistance from security staff or police. Ensure the safety of staff. ¾ If sedation is required give haloperidol 5 mg IM, repeating in 15–30 minutes if necessary (seek specialist advice before using more than 15 mg).

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Violent or very agitated patient

QC 59

Avoid sedatives (diazepam) unless there is a clear diagnosis of alcohol withdrawal or stimulant intoxication. If suspect agitation is due to poisoning with organophosphates or chloroquine ¾ Give diazepam rather than haloperidol (see Section 3.8). See Sections 3.6, 3.7, and 10.11 Mental health. High doses of diazepam can cause problems with respiratory depression. Monitor for signs of respiratory depression for up to 4 hours. High dose of haloperidol can cause dystonic reactions. If acute, treat with biperiden (see Section 8.4). Once the patient is beginning to calm down, wait to see the full effect of any sedative medication before giving any further sedative medication. When the person is no longer acutely agitated, see mental health Section 10.11 for appropriate management. If patient remains agitated despite the above interventions: ¾ Reconsider possible causes including pain. ¾ Recheck SpO2 and glucose. ¾ Seek assistance and advice.

60 QC

Violent or very agitated patient

Vol. 1 • 2. Quick Check: July 2011

How to manage the suicidal/self-harm patient Evaluate whether the person has attempted a medically serious act of selfharm or suicide: ¾ Ask the patient or accompanying friends or family about self harm attempt or recent poisoning. ¾ Look for signs of poisoning or intoxication or signs of self injury. ¾ Medically treat as necessary. ¾ Ensure that the person is closely monitored to prevent further self harm. ¾ Do not leave the patient alone or unsupervised. Evaluate whether there is an imminent risk of self-harm or suicide: ¾ Ask the patient about current thoughts or plans to commit suicide or self harm and about access to means to follow through on those thoughts or plans. ¾ Look for signs of emotional distress, hopelessness, agitation, uncommunicative behaviour, social isolation. If risk is imminent: ¾ Remove access to means of self harm. ¾ Create a secure and supportive environment, ensure that the person is not left alone. ¾ Attend to emotional distress and mental state, solve problems and explore reasons and ways to stay alive. ¾ Assess for presence of a mental health disorder and treat as indicated. ¾ Consult mental health specialist if available. If risk is not imminent but there is a recent history of thoughts of suicide or self harm: ¾ Remove, or advise removal, of access to means of self harm. ¾ Attend to emotional distress and mental state, problem solve and explore reasons and ways to stay alive. ¾ Offer and activate psychosocial support. ¾ Assess for a presence of a mental health disorder and treat as indicated. ¾ Consult mental health specialist if available. In all cases, assess the patient for mental health, neurological, drug use disorders, chronic pain and/or emotional symptoms that require clinical management. See Section 10.11 mental health for more on managing the suicidal patient and for managing mental health disorders.

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Suicidal patient

QC 61

Advanced airway management: for district clinicians with training INDICATIONS FOR TRACHEAL INTUBATION

Tracheal intubation is an advanced airway procedure and should only be attempted if one understands the indications for intubation, is skilled in the technique, and can provide post-intubation care. If you are not skilled with intubation, manage airway in other ways. All intubations are potentially difﬁcult, and a patient should only be intubated if the basic airway interventions (oxygen, head positioning, oral airways, bag valve mask ventilation) are inadequate. Before attempting intubation ask these questions: 1. Does the patient have an indication for intubation? • Failure to maintain or protect airway (risk of aspiration). • Failure to oxygenate or ventilate. • Impending airway obstruction (e.g. inhalation injury, angioedema). 2. Is the intubation equipment in working order? • Laryngoscope with working light. • Appropriate endotracheal tube size. • Use 6.0–7.0 tube in females, and 7.0–8.0 tube in males. • Oxygen source. • Bag valve mask. • Suction. 3. Is there a post-intubation plan? • Is an invasive mechanical ventilator available? If answer is NO, then only consider intubation for the following conditions: ° If you suspect the patient has a rapidly reversible condition and will only require short-term intubation (e.g. snake bite, overdose) and manual ventilation possible. ° If you suspect the patient may need longer intubation and transfer is possible to a hospital with an available invasive mechanical ventilator. • Are sedative drugs available? • Patients often must be sedated during and after intubation. Medications for intubation and sedation should only be administered by clinicians trained to intubate who understand their appropriate use and indication. If the answer to any of these questions is NO, then do not attempt intubation and continue basic airway interventions and bag valve mask ventilation with high ﬂow oxygen. Call for more senior clinician.

62 QC

Advanced airway management

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HOW TO PERFORM TRACHEAL INTUBATION

Tracheal intubation should take no more than 30 seconds. Procedure: ¾ Give high ﬂow oxygen via BVM or face mask with reservoir before the procedure. ¾ Position patient in snifﬁng position (place pillow under neck if no trauma). ¾ Give sedation if required (if not comatose) – midazolam 0.2 mg/kg IV or ketamine 1.5 mg/kg IV.* ¾ Open the patient’s mouth by separating the lips and pulling on the upper jaw with the index ﬁnger. ¾ Hold a laryngoscope in the left hand, insert it into the mouth of the patient with the blade directed to the right tonsil. Once the right tonsil is reached, sweep laryngoscope to the midline, keeping the tongue on the left to bring the epiglottis into view. ¾ Advance the laryngoscope blade until the angle between the base of the tongue and the epiglottis is reached. ¾ Next, lift laryngoscope up and away from you at a 45 degree angle to bring the vocal cords into view. An assistant should press downward and upward on the larynx to help bring the vocal cords in view. ¾ Take the endotracheal tube in the right hand and insert it into the mouth. Insert the tube through the cords to the point that the cuff rests just below the cords. ¾ Inﬂate the cuff to provide a minimal leak when the bag is squeezed. ¾ Attach tube to bag connected to high ﬂow oxygen. ¾ If successful, start post – intubation care (see p. 66–67). ¾ If you are unable to intubate in 30 seconds, perform BVM ventilation with high ﬂow oxygen. ¾ If unable to intubate and unable to ventilate, go to failed airway algorithm (see p. 65). *Skilled clinicians may also add a muscle relaxant such as succinylcholine to facilitate intubation.

Vol. 1 • 2. Quick Check: July 2011

Intubation

QC 63

HOW TO CONFIRM ENDOTRACHEAL TUBE (ETT) PLACEMENT

¾ Give breaths through ETT using manual ventilation with high ﬂow oxygen. ¾ Look for condensation in ETT. ¾ Look for chest rise. ¾ Listen over both lung ﬁelds and stomach for breath sounds. ¾ If breath sounds are heard over stomach, and not in lung ﬁelds, assume oesophageal intubation and immediately remove tube. ¾ Give 6–8 breaths via BVM ventilation with high ﬂow oxygen or until reoxygenated. Re-attempt intubation. ¾ If breath sounds are louder on the right than the left or the left chest not expanding with ventilation consider right mainstem bronchus intubation. Pull ETT out in very small increments (1–2 cm) and listen again – until breath sounds are equal on both sides. ¾ Secure ETT in place (cloth, tape, ribbon gauze). ¾ Continue with manual ventilation, see post-intubation care p. 66–67.

Ten tests of correct tube placement: if in doubt, take it out! Test Look with laryngoscope Listen/feel Tap sternum Inﬂate with self-inﬂating bag Inﬂate with self-inﬂating bag Pass catheter down tube Look Look Listen with stethoscope Listen with stethoscope Result Tube between cords Breathing through tube Puff of air from the tracheal tube Chest rises and falls Gurgling noises Patient coughs (if not paralysed) Patient remains pink after intubation Patient becomes cyanosed after intubation Air entry at apices, axillae and bases Air entry over stomach Signiﬁcance Correct tracheal intubation Correct tracheal intubation Correct tracheal intubation Correct tracheal intubation Oesophageal intubation Correct tracheal intubation Correct tracheal intubation Oesophageal intubation very likely Correct tracheal intubation Oesophageal intubation very likely Reliability Certain Certain Certain Probable REMOVE TUBE Probable Probable REMOVE TUBE Probable REMOVE TUBE

64 QC

Conﬁrm endotracheal tube

Vol. 1 • 2. Quick Check: July 2011

WAS INTUBATION SUCCESSFUL?

Was intubation successful?

YES

Go to postintubation care

Failed airway algorithm ¾ Call for help ¾ Continue bag valve mask ventilation ¾ Reconsider need for intubation

Can patient be ventilated with bag valve mask ventilation? For example, chest rising with each breath.

YES

Optimize conditions and re-attempt intubation ¾ Extend neck ¾ Place pillow under shoulders ¾ Try different laryngoscope blade ¾ Manipulate larynx up and to the right to improve view If still unable to intubate, allow to wake or manage airway with bag valve mask ventilation.

¾ Insert laryngeal mask airway if available and ventilate through airway. ¾ Consider surgical cricothyroidotomy (see p. 69): • This is a specialized procedure and should only be done in lifethreatening circumstances by practitioners who are appropriately trained, and when you cannot ventilate and cannot intubate. As with intubation, only attempt if: ¾ The patient cannot be managed with basic airway techniques. ¾ The equipment is available and in working order. ¾ There is a post-intubation plan for management of ventilation.

Vol. 1 • 2. Quick Check: July 2011

Intubation successful?

QC 65

POST-INTUBATION CARE

How to ventilate the intubated patient Make sure to check all of the following when initiating manual ventilation ¾ Check bag is connected to high ﬂow oxygen source and to ETT correctly. ¾ Check that ETT is properly positioned and secured in place and that cuff is inﬂated. ¾ Make sure you have looked for and treated pneumothorax, ﬂail chest, and sucking chest wounds. ¾ If available, check suction equipment still functioning. ¾ If patient is biting on the tube, insert an oral airway or bite block. ¾ Perform manual ventilation, see next page. How to sedate the intubated patient ¾ Sedate patient with intravenous medication based on local availability (such as midazolam. ¾ 0.02–0.1 mg/kg/hour). ¾ Most patients will require sedation following intubation to treat anxiety or agitation. ¾ Assessing anxiety and agitation can be challenging so use a standardized sedation scale, if possible. ¾ After sedative medication is given, the patient will need to be reassessed at least every 30 minutes to determine if sedation is adequate. ¾ Signs that patient requires more sedation: • patient is biting down on the ETT. • patient is trying to pull ETT out. • increased resistance is felt in the bag when trying to ventilate the patient. • SBP and/or heart rate elevated. • (if patient is on ventilator, high peak pressures are registered).

66 QC

Post-intubation care

Vol. 1 • 2. Quick Check: July 2011

POST-INTUBATION CARE

If patient becomes blue, cyanotic or hypoxic ¾ Conﬁrm placement of ETT (see p. 64). ¾ Check ETT cuff is inﬂated. ¾ Conﬁrm that oxygen source is working. ¾ Suction secretions. ¾ Sedate patient if not adequately sedated. ¾ If wheezing, give salbutamol (see p. 17). ¾ Look for signs of tension pneumothorax – trachea deviated to the side, decreased breath sounds, neck veins distended or crepitus and treat if suspected (see p. 46). ¾ Look for signs of pulmonary oedema, treat if suspected (see Section 3.2.5). ¾ If patient is on ventilator, disconnect patient from ventilator and manually bag patient until patient improves. ¾ If patient remains hypoxic and suspect ETT not in correct position then remove ETT and ventilate via bag valve mask. Intubated patients require close monitoring ¾ Reassess frequently, at least every 30 minutes: do Quick Check, measure vital signs, SpO2. ¾ If available place patient on continuous pulse oximeter monitoring. ¾ Place nasogastric tube (orogastric tube if head trauma suspected; see Section 17.5.1). ¾ Use soft hand restraints. ¾ Record all your observations.

Vol. 1 • 2. Quick Check: July 2011

Post-intubation care

QC 67

MANUAL VENTILATION (BAGGING) – HOW TO PREPARE THE HEALTH WORKER, FAMILY OR OTHER CAREGIVERS

Overaggressive bagging can cause serious harm to a patient’s lungs and also death. It is critical that the health worker or family understands the proper technique, need for continuous bagging and when to call for help. Demonstrate how to bag, then watch them do it ¾ Hold the bag in one hand and depress a 2-litre bag to about 1/3 of its volume. ¾ Give one breath over about one second. ¾ Give about 10 breaths/minute. ¾ Make sure that after each breath, the patient completely exhales before giving another breath. ¾ Watch to make sure that the chest is rising and falling evenly with each breath. The patient’s stomach should not be expanding with each breath. If you are not sure if you are getting a good breath, ask for help from the nurse or doctor. ¾ If the patient is breathing on their own, deliver breaths when the patient is inhaling. Do not attempt to deliver a breath as the patient exhales. ¾ It should be easy to compress the bag and you should feel minimal resistance. If you feel resistance ask for help from the nurse or doctor. When to call for help ¾ If you see the patient vomiting call for help: • stop ventilating the patient for a short period of time while you suction or manually remove all vomit out of the patient’s mouth and the tube. • if there is no concern for a spinal injury, turn the patient’s head to the side to get as much vomit out as possible. • resume ventilation when the vomiting has stopped and as much vomit as possible has been removed from the airway. ¾ If you must take a break, make sure that someone takes over for you and the patient is always being ventilated. ¾ Call immediately for help if: • the patient is turning blue or cyanotic. • the patient is waking up and biting on the tube, or trying to pull the tube out of his or her mouth. • it becomes hard to compress the bag or you feel increased resistance • the patient is vomiting. • you hear gurgling noise when you give a breath or the tube is ﬁlling with secretions. • the patient’s stomach seems to be ﬁlling with air or is expanding. • when you touch the patient’s skin it feels like it is full of air and “crackles” under your ﬁngers. • the patient’s trachea (a hard structure located under the skin in the middle of the neck) seems to move to one side. • if the patient’s oxygen level falls below 90% (only for patients monitored with a pulse oximeter). • you must take a break, and there is no one to relieve you.

68 QC

Ventilating intubated patient

Vol. 1 • 2. Quick Check: July 2011

IF LIFE THREATENING UPPER AIRWAY OBSTRUCTION AND UNABLE TO VENTILATE, HOW TO PERFORM CRICOTHYROIDOTOMY

Surgical cricothyroidotomy should be performed in any patient where intubation has been attempted twice and failed and/or the patient cannot be ventilated. Technique: 1. Hyperextend the neck (unless known or suspected C-spine injury), making the patient comfortable (Figure 1). 2. Clean the area and inﬁltrate with local anaesthetic. 3. Incise through the skin vertically with a 1.5 cm cut and use blunt dissection to ensure that you can see the membrane between the thyroid and cricoid. 4. With a #22 or #23 scalpel blade, stab through the membrane into the hollow trachea (Figure 2). 5. Rotate the blade 90°, insert a curved artery forceps alongside the blade, remove the blade and open the forceps side to side, widening the space between the thyroid and cricoid cartilages (Figure 3). 6. Pass a thin introducer or a nasogastric tube into the trachea if very small access (Figure 4). 7. Run a 4–6 endotracheal tube over the introducer and pass it into the trachea (Figure 5). Figure 1 Figure 2 Figure 3

Figure 4

Figure 5

8. Remove the introducer, if used. ¾ This tube can stay in place for up to 3 days. ¾ This procedure should be performed by an experienced person, with prior knowledge of the anatomy and medical condition of the patient. This procedure should not be undertaken lightly, as wrong placement, bleeding and delay can cause death.

Vol. 1 • 2. Quick Check: July 2011

Cricothyroidotomy

QC 69

How to refer the severely ill patient to a higher level of care Severely ill patients may require referral to a higher level of care for access to personnel, diagnostic testing, equipment or specialty services not available at the district hospital. Patients should only be transported if the receiving hospital has the necessary and appropriate resources to care for the patient and is in agreement. Transport is a very hazardous time for a severely ill patient. In many settings, transport may occur over long distances and is of a signiﬁcant cost to the family. A standard approach to referral in your hospital will help ensure appropriate referrals and minimize patient harm. ¾ Communicate with the receiving hospital. Make a clear agreement that the receiving hospital has the necessary and available resources to care for your patient and will admit the patient for this care. ¾ Prepare a written report that includes the following: vital signs, including those on admission, a brief physical examination, treatments given (e.g. IV ﬂuids, blood transfusion, medications, antimicrobials) and all laboratory and radiographic results. Send this with the patient. ¾ Decide what accompanying caregiver is necessary. ¾ Keep patient comfortable. Treat patient anxiety and pain. Cover patient and keep warm.

70 QC

Referral severely ill patient

Vol. 1 • 2. Quick Check: July 2011

How to transport the severely ill patient Transporting a severely ill patient can be in hospital or inter-hospital. Patient should usually be stabilized before being transported. ¾ Transport requires that resources can be released, including staff to accompany the patient. ¾ Complications range in severity from minor to potentially life threatening and may be related to clinical, equipment or organizational issues. ¾ If indicated: secure airway, immobilize cervical spine, apply manual pressure or pressure dressing to active bleeding, secure IV access, stabilize any injuries that may become life-threatening during transport (e.g. pelvic fracture, pneumothorax). ¾ Use a checklist (see below) to ensure safety and that key supplies, considerations and communication have been taken care of before setting out. Transfer checklist ¾ Airway and NG tube. ¾ Breathing and adequate SpO2. ¾ Circulation, monitoring and IV. ¾ Disability/cervical collar/head injury care. ¾ Exposed, examined and equipment sorted out and secure. ¾ Family informed. ¾ Final considerations: • Ask for notes and X-rays and other results. • Bed conﬁrmed at receiving hospital. • Continuity of care assured? Communication equipment. • Drugs and spare? Documentation, including patient history. • Everything secure? Enough drugs? Enough oxygen? Enough fuel? Enough IV ﬂuids? ¾ Health worker accompanying patient-prepared?

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Transport severely ill patient

QC 71

Emergency trolley Health worker protection Gloves Mask (surgical and N95) Eye protection Gown Sharps box Alcohol based cleansers

Supplies/equipment (in child and adult sizes) Angiocatheters – 14, 16 and 18 gauge Suction catheter Intravenous tubing Nasal prongs Syringes Oxygen mask Needles Oxygen mask with reservoir bag Intraosseus Oxygen mask with nebulizer Alcohol wipe or equivalent antiseptic attachment for skin Oxygen tubing Tourniquet Bag valve mask-hung on side of cart Tubes for blood draw Oral airway Sterile pads and gauze Nasal airway Bandage Pulse oximeter with probes Suture Tongue depressor Tape Laryngoscope Lubricant Magill forceps Spacer

Medication Epinephrine (adrenaline) IV Atropine IV Naloxone IV Salbutamol MDI with spacer Salbutamol ampoules Hydrocortisone IV, oral Furosemide IV, oral Ipratropium MDI LR or NS ﬂuids

Emergency antibiotics Emergency antimalarials Oseltamavir Glucose (dextrose D50) Paracetamol Aspirin Morphine or equivalent* Diazepam IV/PR* Magnesium sulfate IV Haloperidol Ergometrine IM Oxytocin IV

For VAGINAL BLEEDING – see IMPAC MCPC 2

*Lock box.

72 QC

Emergency trolley

Vol. 1 • 2. Quick Check: July 2011

3. Approach to the severely ill patient (after the Quick Check) Table of contents 3.0 3.1 General principles in caring for the severely ill patient. . . . . . . . . . . . . . . . Severely ill patient with shock. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.0 Approach to the patient with shock . . . . . . . . . . . . . . . . . . . . . . 3.1.1 Manage haemorrhagic shock (see Quick Check and Section 4) . . . . . 3.1.2 Manage hypovolaemic shock . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.3 Manage anaphylactic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.4 Manage cardiogenic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.5 Manage septic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Severely ill patient with difﬁcult breathing . . . . . . . . . . . . . . . . . . . . . . . 3.2.1 Assess severely ill patient with difﬁcult breathing . . . . . . . . . . . . . . 3.2.2 Provide initial emergency management for all severely ill patients with difﬁculty breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.3 Manage respiratory distress in patients with suspected severe pneumonia or acute lung injury and without shock . . . . . . . . . . . . . 3.2.4 Manage patients with severe respiratory distress from acute bronchospasm (from either asthma or chronic obstructive pulmonary disease or other causes of acute wheezing) . . . . . . . . . . 3.2.5 Manage patients with severe respiratory distress from acute pulmonary oedema or ﬂuid overload . . . . . . . . . . . . . . . . . . . . . . 3.2.6 Managing acute decompensated cardiac problems . . . . . . . . . . . . Approach to the patient with chest pain . . . . . . . . . . . . . . . . . . . . . . . . . Approach to the patient with altered consciousness (including coma, confusion, intoxication, agitation and convulsions) . . . . . . . . . . . . . . . . . . 3.4.1 Clinical approach to the patient with altered consciousness . . . . . . . 3.4.2 Manage delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.3 Manage diabetic ketoacidosis. . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.4 Manage hypoglycaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.5 Steroid deﬁciency (Addison’s disease; adrenal insufﬁciency) . . . . . . . Approach to the patient with seizures or status epilepticus . . . . . . . . . . . . . Manage intoxication or overdose, or withdrawal from injecting or other use of opioids, amphetamine-type stimulants or cocaine . . . . . . . . . . . 3.6.1 Opioid intoxication or overdose . . . . . . . . . . . . . . . . . . . . . . . . . 3.6.2 Manage opioid withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6.3 Manage stimulant intoxication and overdose . . . . . . . . . . . . . . . . . 3.6.4 Manage stimulant withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . Acute alcohol withdrawal and intoxication . . . . . . . . . . . . . . . . . . . . . . . 3.7.1 Acute alcohol withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7.2 Acute alcohol intoxication . . . . . . . . . . . . . . . . . . . . . . . . . . . . Poisoning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8.1 Ingested poisons or overdose of medicines. . . . . . . . . . . . . . . . . . 3.8.2 Inhaled poisons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8.3 Chemicals on the skin or in the eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.2

75 80 80 85 87 88 88 90 99 99 105 108 113 118 126 127 129 129 134 135 138 140 142 145 145 146 148 149 150 150 159 161 161 187 188

. . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3.3 3.4

3.5 3.6

3.7 3.8

3.9

Snake-bite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9.1 Snake-bite assessment . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9.2 Snake-bite treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10.1 Initial management and stabilization of burns using Quick Check. 3.10.2 Assess and classify the burn . . . . . . . . . . . . . . . . . . . . . . 3.10.3 Burn management . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Severely ill patient monitoring form . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . .

190 190 193 198 198 199 202 206

3. Approach to the severely ill patient (after the Quick Check) 3.0 General principles for caring for the severely ill patient In this section: • Rapid assessment and immediate management • Monitor – record – respond • Give oxygen • Nursing care for severely ill patients • Involving the family in caring for severely ill patients • Limiting therapy and palliative care • Nutrition • Considerations when caring for the pregnant patient with severe illness

Patients with critical illness need careful assessment, timely interventions to correct physiological abnormalities, and close monitoring of responses to interventions. The mortality of severely ill patients is high, and health workers should be mindful of the limits to intervention and the need to preserve dignity and comfort in this difﬁcult situation. This Section addresses severe illness from medical causes. Section 4 addresses trauma.

Rapid assessment and immediate management Severely ill patients require a rapid assessment of their problem and immediate interventions to correct abnormalities that are identiﬁed. The Quick Check should be used both for all patients presenting to hospital and also for severely ill patients who deteriorate after admission. The ABC section of the Quick Check – assessment of airway, breathing, circulation and altered level of consciousness or convulsions – should be used repeatedly in assessing severely ill patients.

Initial management of the severely ill patient Fix the physiology ﬁrst. Focus on correcting physiological abnormalities to stabilize the patient and prevent organ damage. • Rapid breathing or shortness of breath should prompt an assessment of the patient’s airway, administration of oxygen, listening to the chest for wheezing with administration of salbutamol as required, and an assessment for ﬂuid overload. • A fast pulse or low blood pressure should prompt securing intravenous access, administration of a bolus of intravenous ﬂuid, and assessment of causes that may be reversible, such as anaphylaxis, bleeding, or sepsis. Next, assess and treat the underlying cause. For example, give antibiotics for septic shock, pneumonia, or meningitis. For more detailed assessment and management guidelines, see the Sections on shock (3.1), respiratory distress (3.2), coma, convulsions, and altered mental status (3.4). If the diagnosis is not known, treatments can be started for multiple causes, such as antibiotics for bacterial infection together with antimalarials, while results from ongoing assessment and other tests are pending.

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General principles

Monitor – record – respond Close monitoring of critically ill patients is vitally important. Systems should be set up to enable this monitoring. Where possible, severely ill patients should be cared for in a common area close to the nursing station. Nurses should measure vital signs frequently (hourly or even more frequently, depending on acuity), and have speciﬁc instructions on criteria for action. During the ﬁrst 6 hours, monitor the following initially every 30 minutes, and then every 60 minutes once the patient is stable. • SBP (normal – systolic >90) • respiratory rate (normal 12 to 16; use Section 3.2 if >25, Section 10.6 if 20 to 25) • SpO2 (normal: >95%, give oxygen if <90%) • mental status (AVPU scale – alert, responding to voice, responding to pain, unresponsive) • heart rate (normal 60–100). Monitor the following every 6 hours. • temperature (normal 36o–38oC) • urine output (normal >30 ml/hour) – record the quantity if feasible; if not, record whether the patient urinated during this time period. • physical examination of the respiratory and cardiovascular systems In addition, monitor and record treatments as they are given, including medications (antimicrobials, bronchodilators), oxygen ﬂow rate and IV ﬂuid type, volume and ﬂow rate. More speciﬁc guidance on monitoring and appropriate responses is given in each Section. The monitoring process should proceed iteratively; for example, immediately after delivering a bolus of IV ﬂuid check to see if the blood pressure has risen and the pulse has fallen. A failure to respond or only a transient response should prompt an equipment check to see if there is a problem (e.g. IV line extravasation or blockage), reassessment of the diagnosis, administration of another ﬂuid bolus while monitoring the response, and calling for help from a senior clinician. Similarly, administration of oxygen to a breathless and hypoxaemic patient should result in an immediate rise in SpO2. Failure to correct hypoxaemia with oxygen should prompt a check of technical factors (e.g. check to make sure oxygen supply is working properly) and alternative diagnoses (e.g. severe asthma). If ﬂuid overload has been treated with intravenous furosemide, there should be an improvement in shortness of breath and respiratory rate within an hour, associated with increased urine output. A monitoring form for the severely ill patient is in Section 3.11. Once physiological abnormalities have been corrected, patients still require monitoring as problems are likely to recur, but probably less frequently.

General principles

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Give oxygen (see Quick Check pages 33–35) Oxygen should be started immediately for all severely ill patients who have signs of severe respiratory distress or SpO2 <90. Most patients will respond to oxygen with improvement in their respiratory distress or SpO2 within a few minutes. However, some patients will continue to have severe respiratory distress or SpO2 < 90 while on oxygen. For these patients, use a systematic approach to increase oxygen therapy as described in the Quick Check – How to deliver increasing oxygen, page 34. In addition, be systematic in assessing for technical problems and considering alternate causes of respiratory distress as described in the Quick Check – Respond to drop in SpO2 or increasing respiratory rate on oxygen, page 35. Once patient stabilizes or begins to improve, gradually decrease oxygen therapy with close monitoring as described in the Quick Check – Decrease oxygen if patient is stabilizing or improving, page 35. Consider the following when giving oxygen. • Giving oxygen alone will not relieve an upper airway obstruction or inadequate ventilation (see Quick Check – How to manage the airway, pages 29–32). • In patients who are obtunded, placement of an oral or nasal airway can help keep the airway open so that oxygen can be delivered more effectively. • Once oxygen has been given, treat the underlying cause(s) of hypoxaemia, such as severe pneumonia or acute lung injury (see Section 3.2.3), severe bronchospasm (see Sections 3.2.4 and 10.6), or acute pulmonary oedema or ﬂuid overload (see Section 3.2.5).

Nursing care for severely ill patients • Pain control – give analgesia as indicated. • Temperature control – ensure the patient does not get cold or too hot. • Check IV cannula each day and replace if local signs of inﬂammation or infection. Remove IV when no longer required for ﬂuid management. Change to oral antibiotics and ﬂuids as soon as possible. • Consider the possible spread of infections to other patients; integrate infection prevention and control strategies (see Section 6) into treatment planning and delivery of care. • Give special care for the mouth, nose and eyes when patients receive high ﬂow oxygen therapy to prevent irritated or dry mucous membranes, pressure sores behind ears or on the side of the nose, and skin intolerance to mask or nasal prongs. • Pressure care – rotate patient position to prevent development of pressure ulcers. • Comfort care – be attentive to a comfortable position, patient hygiene, respect of the basic needs of the patient and their safety and privacy. • Ensure observation and monitoring with immediate response and rapid notiﬁcation of the district clinician when clinical changes are occurring. • Record observations, procedures performed, procedures planned, and changes in condition. • Ensure continuity of care – keep patient’s chart current to facilitate communication with other team members, and other shifts.

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• Inform patient and family members about the care, how the ward operates, and what behaviour and support is expected.

Involving families in caring for severely ill patients In some hospitals with limited staff and where families are accustomed to caring for their loved ones while in hospital, families can be trained to carry out simple care and monitoring tasks. These tasks may include feeding and washing the patient and rotating the patient from side to side to avoid pressure sores. In some cases, patient attendants may be trained to notify staff when there has been a change in clinical status or when intravenous ﬂuids bags are empty, and in more advanced tasks, such as manual ventilation.

Limiting therapy and palliative care Many patients with critical illness will die; it is an essential professional duty to maintain their comfort and dignity and support the family through this period. It may become evident that treatments are futile, and be appropriate to discontinue active treatments and concentrate on providing comfort (see Section 20). When possible, this decision should be made by a senior clinician after discussion with the family.

Nutrition Once the patient has stabilized, or after 1 to 2 days, pay attention to nutrition. Two groups of patients may not be able to take food orally: • those who have a gastrointestinal disorder or after gastrointestinal surgery (e.g. ileus, pancreatitis); • those who cannot safely swallow due to a risk of aspiration (e.g. alteration in mental status, severe shortness of breath, or ongoing vomiting). All other patients should be provided with food to eat. Most patients lose their appetite when unwell, and may ﬁnd soft foods (e.g. mashed vegetables, soups) and oral ﬂuids (e.g. oral rehydration solution) easier to tolerate. Small frequent meals are often tolerated better. A return of appetite is a good early sign of recovery. Patients who cannot swallow safely may beneﬁt from feeding via nasograstric tube. This may include pureed foods (sufﬁciently thin so as not to block the nasogastric tube). In severely unwell patients, a small amount should be started initially (e.g. 20–40 ml/hour), and the nasogastric aspirates monitored periodically to check for absorption. The rate of feeding can be increased as tolerated.

Considerations when caring for the pregnant patient with severe illness • Treat the pregnant patient with the most effective treatment available. • Place the pregnant patient with shock or severe respiratory distress on their side (preferably the left) to improve uteroplacental blood ﬂow. • When there is a choice of effective drug therapy, choose the drug that is safest in pregnancy. • Monitor the fetus (e.g. fetal heart rate) frequently, according to local practice.

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Clinical decision-making in severely ill patients In an emergency situation, simultaneous assessment and treatment are required and need to be directed at reversing any life-threatening conditions. The initial assessment has already been completed by any hospital staff member within minutes, using the Quick Check. The district clinician now needs to assess the patient (take a brief history and examine) and give additional urgent treatments. Make a list of possible diseases that may account for the patient’s symptoms and signs (the differential diagnosis). Other factors, including environmental exposures, travel history, socioeconomic status, vaccination, other chronic diseases, and local patterns of disease, all have an impact on the differential diagnosis. In particular, the immunological status and use of antiretroviral therapy in PLHIV changes the differential diagnosis considerably. The list should initially be broad; additional evidence may support or eliminate possibilities from the list. It should be based on the most likely diagnoses, but should include less likely but more serious diseases. Investigations and initial treatment in a severely ill patient should be directed towards the most serious, treatable disease. Additional pieces of information, such as changes in symptoms and physical examination ﬁndings on repeat examinations, response to initial emergency treatments, results of investigations, knowledge of other causes of disease, and the opinion of other more senior clinicians, can help make a diagnosis more likely. It should be noted that few investigations are completely accurate; they may not always be positive when a disease is present (not completely sensitive) or not always indicate the correct disease when positive (not completely speciﬁc). Diagnosis and management of severely ill patients often is difﬁcult, and it is important to be systematic in approach. Use the principles of clinical reasoning presented in Section 1. This Section provides guidance on emergency diagnoses and initial treatments, but it may also be necessary to consult Sections 10 and 11, which contain more details on the differential diagnosis and management of speciﬁc diseases. Remember that patients may present with more than one symptom and more than one disease process, and that multiple differential diagnosis tables may need to be consulted for the same patient. The differential diagnosis tables are not exhaustive, but should cover most common and serious conditions. What is the problem (or problems)? • acute low blood pressure (shock) . . . . . . . . . . • airway or difﬁcult breathing (or slow breathing) • chest pain . . . . . . . . . . . . . . . . . . . . . . . . . . . • unconscious, confused or agitated . . . . . . . . . . • seizures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • drug intoxication or withdrawal . . . . . . . . . . . . • alcohol intoxication or withdrawal . . . . . . . . . . • poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . • snake-bite . . . . . . . . . . . . . . . . . . . . . . . . . . . • burn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 3.1 Section 3.2 Section 3.3 Section 3.4 Section 3.5 Section 3.6 Section 3.7 Section 3.8 Section 3.9 Section 3.10

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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3.1 Severely ill patient with shock In this section: 3.1.0 Approach to the patient with shock • General signs of shock common to all causes • Five main categories of shock • DDx shock • General principles of managing shock • Monitor – record – respond 3.1.1 Manage haemorrhagic shock • Identify source of bleeding • Urgent investigations • Stop ongoing blood loss • Restore circulating blood volume 3.1.2 Manage hypovolaemic shock 3.1.3 Manage anaphylactic shock 3.1.4 Manage cardiogenic shock • Table: How to administer peripheral vasopressors • (in cardiogenic or septic shock) 3.1.5 Manage septic shock • Give ﬂuids rapidly • Give empirical IV antimicrobials within ﬁrst hour • Identify the source of infection • Table: Modiﬁed management of septic shock associated with certain infections • Flowchart: Management of septic shock and severe respiratory distress without shock

3.1.0 Approach to the patient with shock Shock is a decrease in blood pressure resulting in poor perfusion and inadequate oxygenation of vital organs (e.g. low urine output, altered level of consciousness). Shock is not a ﬁnal diagnosis. It is important to establish the underlying cause since this determination affects deﬁnitive treatment and supportive care.

General signs of shock common to all causes • • • • • • • • low BP (SBP <90) fast pulse pallor or cold extremities decreased capillary reﬁll dizziness or inability to stand decreased urine output (<30 ml/hour) difﬁculty breathing impaired consciousness, lethargy, agitation, confusion.

Note: Assessment of pulse and BP should be taken in the context of the patient’s pre-morbid state, pregnancy, age, and medication. Some pregnant women, patients with chronic illness, and others may normally have a SBP <90 mmHg and have normal mental status, capillary reﬁll, and urine output; they do not have shock.

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For clinical purposes there are ﬁve main categories of shock Type of shock Haemorrhagic In favour • Trauma • Bleeding – external or internal • Pregnancy complications • • • • History of diarrhoea and vomiting Dehydration Burns Pancreatitis

Hypovolaemia

Septic

• Temperature dysregulation • Infective symptoms • Sepsis can present as “warm shock” (bounding pulse, warm hands) or “cold shock” (vasoconstriction, cold extremities) • Very sudden onset angioedema and wheezing • Urticaria • New medication or known allergy • Older patient • Known cardiac history • Chest pain and difﬁcult breathing, sweaty

Anaphylactic

Cardiogenic

Less common categories and their causes • Obstructive shock occurs when the blood ﬂow into or out of the heart is physically blocked and the heart cannot pump normally due to such conditions as tension pneumothorax, pericardial tamponade, or massive pulmonary embolus. • Endocrine shock occurs when one of the body’s hormone systems is not functioning correctly. Often, the problem will be triggered by a stressful event, such as infection or trauma. • Neurogenic shock occurs when the patient suffers severe spinal cord injury.

History • Predominant symptoms – do they suggest localization to a particular body system, e.g. lungs or heart? • History of any preceding illness or medication use – diarrhoea and vomiting, abdominal pain, fevers? • Speed of onset – if there is a sudden onset, were there any obvious precipitants (e.g. possible exposure to allergen or poison)? • Recent trauma? • Pre-existing disease – HIV, cardiac disease, endocrine problems? • Current or recent pregnancy? • History of surgery?

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Examination Do a focused examination to identify likely causes. Check: • vital signs • signs of anaphylaxis – rash, stridor, wheeze • signs of sepsis – fever, local signs of infection • signs of bleeding – visible bleeding, rigid abdomen (internal), vomiting blood, vaginal bleeding • signs of cardiac disease – distended neck veins, cardiac murmur. DDx: Shock Diagnosis Anaphylaxis In favour • • • • • Swollen neck or tongue Wheeze and stridor Urticaria or red rash Angioedema Exposure to food or medicine just prior to attack

Cardiogenic Arrhythmias Cardiomyopathy Myocardial infarction • Very fast or very slow pulse • Irregular pulse • History of HIV, peripartum, recent viral infection, hypertension • Displaced maximum cardiac impulse, extra heart sounds • Known ischaemic heart disease • Heavy or tight or crushing chest pain associated with nausea or sweating or radiating into arm or neck • Risk factors (smoking, age over 50, hypertension, diabetes) • • • • Risk factors (TB, HIV, malignancy) Sharp sternal pain, worse lying ﬂat Quiet heart sounds Distended neck veins

Pericardial effusion or tamponade see pericardial effusion or tamponade in Section 3.1.4 on cardiogenic shock Valve disease Haemorrhagic Trauma with visible bleeding Trauma with internal bleeding (spleen, liver, femur or pelvic fractures) Gastrointestinal bleeding (peptic ulcer, bleeding varices)

• History of rheumatic fever or heart disease • Murmur

• History of blunt or penetrating trauma • Visible bleeding • • • • • • • • History of blunt or penetrating trauma Major trauma and long bone fractures Localized pain Abdominal pain, tenderness, distension Vomiting blood or melena History of peptic ulcer disease History of cirrhosis Abdominal pain and tenderness

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Ruptured ectopic pregnancy

• Pallor • Vaginal bleeding – mild (usually follows abdominal pain and missed period) • Pelvic or adnexal tenderness • May have mass • Positive pregnancy test (may be too early to detect pregnancy clinically) • • • • • • • • • • Heavy bleeding Dilated cervix Cramping or lower abdominal pain Expulsion of products of conception If septic abortion, purulent cervical discharge or foul-smelling vaginal discharge Late stages of pregnancy Abdominal pain Uterus tender and tense May occur after relatively minor trauma May have fetal distress or fetal death

Incomplete or septic abortion

Abruptio placentae

Placenta previa

• Late pregnancy • Fetal presenting part above the pelvis • May be precipitated by intercourse • Recent childbirth and uterus not contracted (bleeding, usually immediately after childbirth) • Placenta may not be completely expelled • Secondary PPH also can occur from retained products • Consider traumatic PPH • • • • Severe abdominal pain (may decrease after rupture) Bleeding may be vaginal or intra-abdominal Abdominal distension, free ﬂuid Decreased or absent fetal movements, fetal distress, absent fetal heart sounds • Prior caesarean section, prolonged labour, or induction of labour • • • • Sudden, severe onset abdominal pain radiating to the back Pulsatile abdominal mass Peritonitis Asymmetry (left to right) of femoral or distal leg pulses

Postpartum haemorrhage (PPH) see Quick Check page 51 Uterine rupture

Ruptured abdominal aortic aneurysm

Hypovolaemic Severe dehydration due to diarrhoea Severe dengue Haemorrhagic fevers see Section 11.46 Poisoning see Section 3.8 Burns see Section 3.10 • Profuse watery diarrhoea • Known outbreak or travel to area with cholera • Known recent cases of dengue, endemic area • Fever, headache, petechiae • Contact with known outbreak or endemic area • Fever, headache, dizziness • Bruising, bleeding from gastrointestinal or respiratory tracts • History of exposure • Organophosphate (pinpoint pupils, salivation, bradycardia, incontinence, anxiety, coma) • Severe burns

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Pancreatitis

• • • •

Abdominal pain radiating to the back (duration more than 6 hours) Vomiting Known biliary stones (gallstones) or heavy alcohol use Use of didanosine

Septic Septic shock • Fever (temperature more than 38°C) or hypothermia (less than 36°C) • Warm extremities, bounding pulses (often not present) or weak, thready pulse and cold extremities when hypovolaemic from ﬂuid shifts • Signs of infection: headache or neck stiffness (meningitis), severe rash, severe abdominal pain (peritonitis), cough or difﬁcult breathing (pneumonia), painful urination or blood in the urine (pyelonephritis)

Obstructive Tamponade see pericardial effusion or tamponade in Section 3.1.4 on cardiogenic shock Pulmonary emboli • Risk factors (TB, HIV, malignancy) • Sharp sternal pain, worse lying ﬂat • Quiet heart sounds, distended neck veins • • • • • • • • • • Sudden-onset shortness of breath, difﬁcult breathing, pleuritic chest pain Unilateral leg swelling Haemoptysis Tachycardia Risk factor (long travel, prolonged sitting, recent surgery, recent long bone fracture, malignancy, sickle-cell disease) Sudden-onset shortness of breath, difﬁcult breathing, pleuritic chest pain History of trauma or chronic lung disease (e.g. emphysema) Increased resonance on affected side of chest Decreased breath sounds on side of pneumothorax Deviated trachea away from pneumothorax

Tension pneumothorax

Endocrine Hypoadrenalism (Addisonian crisis) • Fatigue, dizziness • Vomiting • Sudden cessation of long-standing steroid medications (or herbal remedies • containing steroids) • Recent precipitant – infection, surgery • Adrenal TB (fever, night sweats, loss of weight) • Hypoglycaemia • Hyponatraemia, hyperkalaemia

Neurogenic Acute spinal cord injury • Acute trauma to the cervical or upper thoracic spine with paraplegia or quadriplegia • Slow pulse • Loss of muscle tone and reﬂexes during acute phase of the injury

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General principles of managing patients with shock • Give oxygen (see Quick Check pages 33–35). • Give IV ﬂuid rapidly (see Quick Check page 39 and speciﬁc ﬂuid recommendations by type of shock in the sections which follow). • Treat underlying cause. • Consider vasopressors if SBP <90 and signs of inadequate perfusion after ﬂuid resuscitation • Monitor – record – respond (see Section 3.0).

Monitor – record – respond In addition to the other clinical parameters that should be monitored in all severely ill patients, as described in Section 3.0, for patients in shock pay particular attention to the signs of perfusion and signs of ﬂuid overload to help guide ongoing management. • signs of inadequate perfusion ° decreased urine output ° altered mental status. • signs of ﬂuid overload: ° worsening crackles (rales) on auscultation ° dyspnoea ° elevated JVP ° peripheral oedema.

Management of speciﬁc types of shock 3.1.1 Manage haemorrhagic shock (see Quick Check page 19 and Section 4) Haemorrhagic shock results from rapid loss of blood. A patient usually ﬁrst will develop tachycardia and tachypnoea (compensated shock) and may not become hypotensive (uncompensated shock) until the condition is immediately lifethreatening. Even with a SBP >90, suspect a patient is in haemorrhagic shock if there is bleeding or if there was a traumatic injury, and if there are signs of poor perfusion (e.g. cool, clammy, or mottled extremities, delayed capillary reﬁll, sweaty, pallor, fast respiratory rate, confusion, restlessness). Do not be falsely reassured that a patient with a normal blood pressure is stable if the patient has clinical signs of shock. In particular, young and previously healthy trauma patients will present in compensated shock, as they are able to maintain a normal blood pressure until they have lost up to 25% of their circulating blood volume. They will often appear very anxious and complain of thirst. It is essential to recognize and treat patients in compensated shock early to avoid increased morbidity and mortality. Call for help from surgical consultant or senior clinician • Manage airway (see Quick Check pages 29–32) • Give oxygen for respiratory distress or SpO2 <90 (see Quick Check pages 33–35)

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Identify source of bleeding Common causes include trauma and postpartum haemorrhage. Patients may present with an obvious source of external bleeding (postpartum haemorrhage or laceration) or with less obvious internal bleeding (abdominal trauma, ruptured ectopic pregnancy). Pain may be referred to the shoulder or back when a patient has free ﬂuid in the abdomen from haemorrhage. Table: Examine the patient to identify the source and signs of bleeding Source Nose and mouth Lung Abdominal Musculoskeletal Rectal Vaginal (do not do vaginal exam in late pregnancy) Signs Epistaxis (nose bleed), haematemesis (vomiting blood) Decreased breath sounds suggests haemothorax Distended, tense, tender abdomen suggests haemoperitoneum Long bone and pelvic fractures Melena, bright red blood suggest lower gastrointestinal bleed or massive upper gastrointestinal bleed (See Quick Check pages 50–52)

Urgent investigations • Hb and type and cross-match • pregnancy in all women of childbearing age • abdominal and pelvic ultrasound (may help to rapidly identify free ﬂuid in the abdomen from abdominal trauma or ruptured ectopic pregnancy but usually cannot identify the source of bleeding; see Section 7.2.21).

Stop ongoing blood loss • Apply direct pressure to stop obvious bleeding (see Quick Check page 47). • Splint long bone or pelvic fracture (see Section 4.5.2 and Quick Check page 47). • Place chest tube if suspect haemothorax (see Section 7.3.1 and Quick Check page 46). • If vaginal bleeding,1 see Quick Check pages 50–52. • When indicated, arrange for immediate deﬁnitive care to stop the bleeding, either in operating theatre (e.g. to stop haemoperitoneum from liver laceration) or with endoscopy (e.g. to stop upper gastrointestinal bleed from ulcer or varices) (see Quick Check page 48).

1 Guidelines for the management of postpartum haemorrhage and retained placenta. WHO (2009). Geneva, Switzerland. Available at http://whqlibdoc.who.int/publications/2009/9789241598514_eng.pdf 2

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Restore circulating blood volume For complete information on blood transfusion, see The Clinical Use of Blood Handbook.2 • During Quick Check (see page 29) the patient with shock was given 1–2 litres of LR or NS rapidly IV. • Check that 2 large-bore (14 or 16 gauge) IVs are in place. • If the patient continues to be in shock (SBP <90) or has signs of poor perfusion, give an additional 1–2 litres LR or NS ﬂuid rapidly. • If the patient fails to improve after 2 litres of IV ﬂuids or there is only a transient improvement, give rapid safe blood transfusion (see Section 4) while arranging deﬁnitive care (if blood not immediately available, continue ﬂuids while waiting). • Place Foley catheter and monitor urine output. • Keep the patient warm. This is very important to slow down the bleeding (for normal clotting factor function).

3.1.2 Manage hypovolaemic shock Patients with shock from severe dehydration (e.g. cholera) will present with other clinical signs of severe dehydration, such as lethargy, depressed consciousness, sunken eyes, or skin pinch that goes back very slowly. Most patients with cholera can be rehydrated with oral rehydration salts (ORS), but those who have developed shock and are weak need intravenous hydration if they are not able to drink or able to drink only very little. Treat patients with severe dehydration and shock from diarrhoeal disease according to Fluid Plan C guidelines (see Section 10.7). • The preferred method of ﬂuid resuscitation is by IV. • During the ﬁrst 30 minutes give 30 ml/kg LR or NS bolus. If still in shock, repeat bolus. (This includes the 1 litre bolus recommended in Quick Check for shock on page 29). Over next 2½ hours give 70 ml/kg. • As in other causes of shock, monitor the patient every 30 minutes and titrate ﬂuids according to response. If the patient remains in shock, give ﬂuids at increased rates. • Start ORS (about 5 ml/kg/hr) as soon as the patient can drink safely. Note: If placement of IV is difﬁcult or delayed, call for help from senior clinician to obtain alternate IV (see Quick Check page 29). While waiting, place a nasogastric tube for rehydration and give ORS 20 ml/kg/hr for 6 hours (total 120 ml/kg/hr). If there is vomiting or increasing abdominal distension, decrease the rate. Other causes of hypovolaemic shock include extensive burns (a result of large insensible losses from burn areas) and severe dengue (a result of generalized leaking from vessels). For detailed guidance, see Section 3.10 for burns management, Section 3.1.5 for septic shock, and Section 11.9 for dengue.

2 The clinical use of blood handbook. WHO, 2002. Geneva, Switzerland. Guidelines are currently in revision. Available at http://www.who.int/bloodsafety/clinical_use/en/

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3.1.3 Manage anaphylactic shock • Give epinephrine (adrenaline) 0.5 ml 1:1000 IM (see Quick Check page 17) – 0.5 ml if 50 kg or above, 0.4 ml if 40 kg, 0.3 ml if 30 kg. May repeat every 5 minutes several times if no or incomplete response (patient remains in shock). • Patients with recurring or persistent shock may require an epinephrine infusion (see the vasopressor table below for the dose). • Give ﬂuids rapidly. • Manage airway. Give oxygen for respiratory distress or if SpO2 <90 (see Quick Check pages 33–35). • Give hydrocortisone IV 200 mg or prednisolone 50 mg orally. • Additional management ° Give antihistamine for itching and rash as available, e.g. chlorphenamine 10–20 mg IV over 1 minute (may be repeated), promethazine 25 mg orally, or diphenhydramine 25 mg orally. (These drugs may cause drowsiness.) ° Other antihistamines or a H2-antagonist (e.g. ranitidine) may provide additional beneﬁt.

3.1.4 Manage cardiogenic shock • Help the patient assume a comfortable position. • Give oxygen for respiratory distress or if SpO2 <90 (see Quick Check pages 33–35). • If there is evidence of pericardial tamponade, the patient will need urgent drainage (refer to pericardiocentesis in Section 7.2.12). • Do an urgent ECG or use a cardiac monitor. ° Assess for ST segment elevation or depression suggestive of myocardial infarction and treat appropriately. ° Treat any serious arrhythmia. • If there is no clinical evidence of ﬂuid overload, give ﬂuids cautiously (250– 500 ml). • If there is clinical evidence of ﬂuid overload, consider vasopressors. See table on next page.

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Table: How to administer peripheral vasopressors (in cardiogenic or septic shock) Mechanism: Vasopressors work by vasoconstriction and increasing the contractility of the heart. Commonly available vasopressor medications include epinephrine (adrenaline) and dopamine. Side-effects: There are many serious side-effects, notably tissue necrosis if the IV inﬁltrates, arrhythmias, and ischaemia to organs (skin, gut, kidneys). To minimize these risks, use the minimum dose possible to maintain the blood pressure (target SBP 90) and discontinue as soon the patient improves. Patients who are on a vasopressor infusion will commonly develop tachycardia. The extremities may become cool or cyanotic due to peripheral vasoconstriction. Delivery: Vasopressors must be given carefully by intravenous infusion and are preferably given via a central venous catheter. However, central venous catheters should be placed only by a doctor who is skilled in the correct technique and at a hospital where this type of IV access is used frequently and personnel are familiar with its care. Central venous catheters are associated with signiﬁcant risks, notably pneumothorax, arterial puncture, and blood infection. See other guidelines and the Adaptation Guide for instructions on using a central venous catheter. If central venous access is not possible, it is acceptable to deliver vasopressor medications through a peripheral line with appropriate precautions. • Use the largest vein possible to deliver a high ﬂow rate. • Always dilute the medication and give by infusion at a strictly controlled rate. • Use a metal gate-clamp in the IV rather than the integral roller device, which can become loose. • Do not use the blood pressure cuff on the same arm through which the medication is infusing. • Inspect the infusion site regularly to detect any extravasation of the medication into the tissues. Stop the infusion if: • the drip has inﬁltrated the tissues (e.g. severe pain and swelling at infusion site) • the patient develops an arrhythmia (irregular pulse or dangerous tachycardia). How to administer and titrate vasopressors 1. Does the patient have adequate perfusion? First, check if vasopressors are indicated. If a patient remains in shock and has clinical signs of poor perfusion (low BP, low urine output, altered level of consciousness) after IV ﬂuid resuscitation, consider the use of vasopressor medications to temporarily support the circulation. Some pregnant women, patients with chronic illness, and others may normally have a SBP <90 mmHg but be awake and alert, with normal mental status, normal capillary reﬁll, and normal urine output. These patients may not need vasopressors to support blood pressure since they have no clinical signs of poor perfusion. 2. Choose a vasopressor and prepare the drip for infusion In most settings the choice of vasopressor is determined by what is available. Become familiar with the dosing and administration of the locally available vasopressor to optimize patient safety and prevent medication errors. For most conditions leading to shock, there is no clear beneﬁt of one vasopressor over the other. In cases of severe malaria, dopamine is preferred. The infusion should be dosed based on the patient’s weight. If the patient cannot be weighed, estimate if the patient is small (50 kg), average (60 kg), large (70 kg). Use the table below to calculate the correct dose. Have a colleague double-check that you are administering the correct medication in the correct dose and to the correct site. 3. Monitor the patient and titrate Frequent monitoring is required, as changes in pulse and blood pressure can occur very quickly. This may mean reducing or increasing the infusion rate within minutes of starting it. Continuous monitoring is preferred, but it is not available in many district hospitals. For the initial administration, start at the lowest rate and monitor pulse every minute and blood pressure every 2 to 5 minutes. If the SBP is still <90 mm Hg, increase the infusion rate. If the SBP is >90 mm Hg, decrease the infusion rate to the minimum dose necessary to maintain the blood pressure and adequate perfusion. For epinephrine, titrate the dose in 0.05 mcg/kg/minute increments. For dopamine, titrate the dose in 2 mcg/kg/minute increments. If the IV site inﬁltrates, stop the infusion and start an infusion in a new IV site, preferably in the opposite arm. Monitor the skin. Keep the limb elevated. Patients whose IV line inﬁltrated while receiving vasopressors may develop skin necrosis and may require surgical debridement several days following the incident.

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4. When to stop vasopressors Vasopressors are intended for short-term use only, to allow other treatments to take effect. Continue to support the patient with intravenous ﬂuids and blood as needed while the patient is on vasopressors. As the patient’s clinical condition improves, titrate the vasopressors down. Discontinue the vasopressor infusion as soon as the patient can maintain an adequate blood pressure, and continue to monitor frequently. How to give vasopressor by peripheral infusion Vasopressor Commonly available concentrations Target infusion concentration Mixing procedure to create target infusion concentration Peripheral epinephrine infusion 1 amp = 1 mg epinephrine (adrenaline) in 1 ml* 10 micrograms per ml Use 2 amps in 200 ml normal saline** OR 10 amps in 1000 ml normal saline** Epinephrine Dose rate*** 0.05 mcg/ kg/ minute 0.2 mcg/kg/minute for very hypotensive 10 mcg/ kg/ minute Peripheral dopamine infusion (preferred for shock in severe malaria) 1 amp = 200 mg dopamine in 5 ml* 1000 micrograms per ml Use 1 amp dopamine in 200 ml normal saline** OR 5 amps dopamine in 1000 ml normal saline** Dopamine 15 mcg/ kg/ minute 20 mcg/ kg/ minute

Infusion rate (ml/hour)**** Patient weight (kg) 50 kg 60 kg 70 kg 15 ml/hour 18 ml/hour 21 ml/hour 60 ml/hour 72 ml/hour 84 ml/hour 30 ml/hour 36 ml/hour 42 ml/hour 45 ml/hour 54 ml/hour 63 ml/hour 60 ml/hour 72 ml/hour 84 ml/hour

* 1 milligram (mg) is equal to 1000 micrograms (mcg). ** Read ampoule label 3 times to conﬁrm concentration before mixing. *** Desired dose rate is weight-based. **** Infusion rate is commonly presented per hour. Infusion rate = desired dose rate or concentration of the infusion.

3.1.5 Manage septic shock CLINICAL DIAGNOSIS of severe sepsis or septic shock Suspected infection plus Hypotension (systolic blood pressure <90 mmHg) plus One or more of the following: • pulse >100 per minute • respiratory rate >24 breaths per minute • abnormal temperature (<36oC or >38oC).

Use the ﬂowchart on the following pages for speciﬁc guidance on the management of septic shock and severe respiratory distress from suspected pneumonia or acute lung injury. It is arranged by hours, starting from patient arrival, and uses a systematic approach, for the recognition of problems, giving oxygen and ﬂuids, and how to monitor, record, and respond to ﬁndings, for both septic shock and

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severe respiratory distress without shock (described in detail in Section 3.2.4). These basic recommendations apply to many etiologies of septic shock. Below is more detailed information about these basic interventions. The Table, Modiﬁed management of septic shock associated with certain infections, below, gives treatment modiﬁcations for speciﬁc causes of septic shock.

Give ﬂuids rapidly • After the initial 1000 ml LR or NS bolus (see Quick Check page 39), continue LR or NS at 20 ml/kg/hour, not to exceed a maximum of 60 ml/kg in the ﬁrst 2 hours (including the initial bolus). • Monitor SBP and clinical signs of perfusion (urine output, mental status). • Consider adding vasopressors if SBP remains <90 and signs of poor perfusion continue after ﬂuid resuscitation (estimated 60 ml/kg) even within ﬁrst 2 hours. • At 2–6 hours, if SBP remains below 90 and signs of poor perfusion continue, continue ﬂuids at 5–10 ml/kg/hour. • At 2–6 hours, if SBP rises above 90, continue ﬂuids at 2 ml/kg/hour. However, if the pulse is still high and there are other signs of poor perfusion, patient may still be volume-depleted and need more ﬂuids. • Watch carefully for signs of ﬂuid overload (increased JVP, increasing crackles or rales on auscultation). If present, decrease the rate of ﬂuid administration. In a pregnant woman with shock, it is particularly important not to delay initiation of vasopressors if ﬂuid resuscitation is failing, to improve perfusion and to maintain fetus perfusion.

Give empirical IV antimicrobials within the ﬁrst hour. This is crucially important (see Quick Check page 43) • Antibiotics: Urgently administer broad spectrum antibiotics by IV. Take blood cultures before antibiotics, but do not delay treatment. ° Choice of antibiotics depends on presence of signs of local infection, local patterns of disease, and availability of antibiotics. ° If community-acquired pneumonia is suspected, refer to your national or institutional guidelines. Common choices include: ceftriaxone (1 gram daily IV) or ampicillin 2 grams every 4 hours plus gentamicin 1.5 mg/kg IV every 8 hours, plus either a macrolide or a respiratory ﬂuoroquinolone. ° If TB is suspected (see below) or if treating a pregnant patient, limit ﬂuoroquinolone use if there are alternative antibiotics available. • Antimalarials: Malaria should be suspected both in areas with malaria transmission and in travellers returning from malarious areas (see Quick Check page 43 and Section 11.25). Start antimalarials immediately and then test for malaria by microscopy as soon as possible (if not immediately available, a malaria RDT can be performed while waiting for the result of the blood slide). • Antivirals: if suspect inﬂuenza, give antiviral. See Quick Check page 43 and Section 11.17.3 3 Guidelines for pharmacological management of pandemic (H1N1) 2009 inﬂuenza and other inﬂuenza viruses. WHO, 2010. Available at http://www.who.int/csr/resources/publications/swineﬂu/h1n1_use_antivirals_20090820/ en/index.html

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Consider TB especially in PLHIV (see Section 15): Patients with HIV-related pulmonary and extrapulmonary TB are at high risk of rapid clinical deterioration and death.4 Perform all appropriate TB investigations (see Section 15) and recommend HIV testing. If available, promptly obtain nationally or WHO-approved molecular testing, e.g. Xpert MTB/RIF, per national guideline recommendations. Otherwise, send sputum for AFB smear and obtain a chest X-ray; if smear negative or suspected MDR/TB send sputum for culture. Perform clinical (and further diagnostic) assessment for extrapulmonary TB (see Section 15). Consider early empirical antituberculous treatment in critically ill PLHIV if, based on suggestive radiograph or clinical judgment, there is high suspicion for disseminated TB-causing shock. Consider disseminated TB especially if there is malnutrition and weight loss. In some PLHIV with septic shock, this may mean simultaneous treatment for TB and bacterial infection. Consult with senior clinician.

Identify the source of infection • Use other sections of this manual organized by main signs or symptoms to identify the source of infection. • Identifying the source of infection should not delay delivery of supportive treatments and empirical antibiotics. • Try to make a microbiological or anatomical diagnosis. Initial laboratory examinations may include: ° urine dipstick or microscopy for leukocytes (see Section 7.2.16) ° malaria test ° AFB smear and culture of sputum ° chest X-ray ° Gram stain ° blood culture. • If a speciﬁc diagnosis is made (e.g. pneumonia, dengue shock syndrome), use established principles for treating those conditions. Other initial laboratory investigations include • Glucose – hypoglycaemia is a manifestation of severe sepsis. • BUN and creatinine – acute kidney injury is also a manifestation of severe sepsis. • Hb or Hct • electrolytes. The ﬂowcharts on the following pages describe speciﬁc management by hours after arrival for recognition of problems, oxygen and ﬂuid administration, and how to monitor, record, and respond to ﬁndings for both septic shock and severe respiratory distress without shock (described in detail in Section 3.2.4). These two clinical pathways have similar interventions but different ﬂuid recommendations. These basic recommendations apply to many etiologies of septic shock, with some differences, as summarized in the following table. 4 Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings. WHO, 2007. Available at http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.379_eng.pdf 92 Shock Vol. 1 • 3. Approach to the severely ill patient: July 2011

Table: Modiﬁed management of septic shock associated with certain infections Suspected etiology Dengue5 see Section 11.9 Modiﬁcations or additions to septic shock guidelines • For dengue patients in shock, ﬂuids differ from the general recommendations for septic shock. Fluid management rate for dengue is lower, at 20 ml/kg in the ﬁrst hour (including the initial bolus), with careful monitoring; then 20 ml/kg in the next hour. This would total 40 ml/kg over the ﬁrst 2 hours, rather than the 60 ml/kg in the ﬁrst 2 hours for other patients with septic shock. • Haematocrit should be monitored frequently. • Watch carefully for signs of ﬂuid overload. If ﬂuid overload develops, see Sections 3.2.5 and 11.9. Note that severe dengue with shock can manifest either as compensated shock (SBP maintained but signs of poor perfusion) or as uncompensated shock (SBP low). Fluid therapy (amount and rate) depends on which type of shock (see Section 11.9). • Give antimalarials. • Severe malaria often is associated with bacteraemic sepsis (in particular Gram-negative bacteria). Give broad-spectrum antibiotics (ampicillin plus gentamicin, or ceftriaxone). • Fluids, other supportive care are the same. Follow ﬂowchart on following pages. • Watch carefully for signs of pulmonary oedema and volume overload (cough, fast respiratory rate, shortness of breath, hypoxaemia, increased JVP, rales on auscultation). • In the calculation of 60 ml/kg total in the ﬁrst 2 hours, include the ﬂuids used to administer antimalarials. • If pulmonary oedema develops, see Section 3.2.5. Stop ﬂuids and use vasopressors to support circulation (dopamine is preferred). • Give antituberculous medications early if patient has TB or high suspicion for TB in severely ill patient. Call for help in this decision from senior clinician. • Fluids, other supportive care are the same. Follow ﬂowchart on following pages. • • • • • • • • Antibiotics may differ depending on suspected etiology; see Section 3.2.3. Inﬂuenza -speciﬁc antiviral if suspect inﬂuenza. If empyaema, drain. Fluids, other supportive care are the same. Follow ﬂowchart on following pages. Add metronidazole to ampicillin and gentamicin. Fetal monitoring; consider delivery. Keep patient on left side. Fluids, other supportive care are the same. Follow ﬂowchart on following pages.

Severe malaria see Section 11.256

Tuberculosis see Section 15

Severe pneumonia see Sections 3.2.3 and 10.6

Suspect amnionitis during pregnancy see IMPAC MCPC7

5 Dengue guidelines for diagnosis, treatment, prevention and control – New edition. WHO, 2009. Chapter 2: Clinical management and delivery of clinical services. Available at http://whqlibdoc.who.int/ publications/2009/9789241547871_eng.pdf 6 Guidelines for the treatment of malaria, 2nd edition. WHO, 2010. Chapter 8: Treatment of severe P. falciparum malaria. Available at http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf

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Suspected etiology Postpartum sepsis or septic abortion see Section 10.15 and IMPAC MCPC7

Modiﬁcations or additions to septic shock guidelines • Add metronidazole (or clindamycin) to ceftriaxone, or give ampicillin plus gentamicin. • Evacuate uterus if there are retained products. • Fluids, other supportive care are the same. Follow ﬂowchart on following pages.

PID8, pelvic or tuboovarian abscess see Section 10.15 and IMPAC MCPC7 Pancreatitis, peritonitis, surgical abdomen or abscess, cholangitis, ruptured appendicitis, etc. see Section 10.7 Viral haemorrhagic fever see Section 11.46

• Give ceftriaxone plus doxycycline; OR clindamycin plus gentamicin. • May need urgent surgery if suspect ruptured tubo-ovarian abscess. • Fluids, other supportive care are the same. Follow ﬂowchart on following pages. • Call for help from surgical consultant to possibly drain abscess or perform other surgical interventions as needed. • Fluids, other supportive care are the same. Follow ﬂowchart on following pages. • IV ribavirin may be effective against arenaviridae (the South American haemorrhagic fevers and Lassa fever) and bunyaviridae (Crimean-Congo haemorrhagic fever, hantaviruses); consult with national programme and experts on its use. • See 6.13 for infection control. • Fluids, other supportive care are the same. Follow ﬂowchart on following pages.

7 Managing complications in pregnancy and childbirth: a guide for midwives and doctors. WHO, 2003. Available at: http://www.who.int/making_pregnancy_safer/publications/archived_publications/mcpc.pdf 8 Guidelines for the management of sexually transmitted infections. WHO, 2003. Updated 2011 version currently in print. Available at http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf

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Flowchart: Management of septic shock and severe respiratory distress without shock Septic shock Clinical diagnosis of severe sepsis or septic shock • Suspected infection • Hypotension (systolic blood pressure <90 mmHg) and 1 or more of the following • Pulse >100 bpm • Respiratory rate >24 • Abnormal temperature (<36°C or >38°C) Oxygen: titrate to SpO2 90 Fix the physiology Fluids: After initial bolus of 1000 ml, continue rapid ﬂuids LR or NS at 20 ml/kg/hour, up to 60 ml/kg within the ﬁrst 2 hours Urgent empirical antimicrobials • Antibiotics • Antimalarials • Inﬂuenza -speciﬁc antiviral if suspect inﬂuenza Severe respiratory distress without shock Clinical diagnosis of severe respiratory distress without shock • If respiratory rate >30 or SpO2 <90, and • SBP >90 mmHg, and • No heart failure, and • Suspected pneumonia or acute lung injury

Recognize

Oxygen: Titrate to SpO2 90 Fluids: Give ﬂuids at 1 ml/kg/hour or orally If wheezing, give salbutamol Identify source of infection • Use signs or symptoms to consider source. • Malaria test • Where available, molecular testing for TB or AFB smear of sputums, if cough • Chest X-ray, Gram-stain sputum • Send blood cultures. Check results of emergency laboratory • If haemoglobin <7 mg/dl (Hct <20), consider transfusion. • If glucose <3 mmol/l (54 mg/dl), then give D50 25–50 ml (see Quick Check page 41).

First 2 hours

Treat infection

Monitor, record

Every 30 minutes until stable; then every 1 hour • SBP, pulse • Respiratory rate • SpO2 • Mental status (AVPU) • JVP, auscultate for crackles (rales) If respiratory function declining SBP <90 (increasing RR, falling SpO2) • Check oxygen supply. • If JVP elevated, increasing crackles,

Respond

If SBP <90, switch to manage as septic shock • If wheezing, give salbutamol. • If suspect ﬂuid overload, slow rate of ﬂuid administration and start Consider ﬂuid overload vasopressors if still in shock.

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Septic shock Reconsider diagnosis if no change in SBP following ﬂuid boluses. Establish source of infection Oxygen: titrate to SpO2 90 Fix the physiology Fluids: • If SBP >90, continue ﬂuids at 2 ml/ kg/hour. • If SBP <90 at 2 hours or later, start vasopressors and continue ﬂuids at 5–10 ml/kg/hour.

Severe respiratory distress without shock If poor response, reconsider pneumothorax, pleural effusion, heart failure, poisoning, TB, and PCP associated with HIV. Oxygen: Titrate to SpO2 90 Fluids: Give ﬂuids at 1 ml/kg/hour or orally If wheezing, give salbutamol

Recognize

Treat infection

Drain surgical infection if required. Every 30 minutes until stable; then every 1 hour • SBP, pulse • Respiratory rate • SpO2 • Mental status (AVPU) • JVP, auscultate for crackles (rales) If respiratory function declining SBP <90 (increasing RR, falling SpO2) • Check oxygen supply. • If JVP elevated, increasing crackles,

Consider source of infection. Review results of investigations. Every 6 hours • Temperature • Urine output • Repeat glucose and Hb if initial values abnormal.

2–6 hours

Monitor, Record

If SBP <90, switch to manage as septic shock and give 1000 ml IV. If respiratory function declining (increasing breathlessness, increasing RR, or SpO2 <90) • Check oxygen supply and increase ﬂow rate if possible. • If wheezing, give salbutamol. • Check that antimicrobials have been given. Consider broader antimicrobial cover. • Consider other diagnoses or infections; see above. • If signs of ﬂuid overload, SBP >100, and shock resolved, stop IV ﬂuids, give furosemide 20 mg IV, and raise head of bed.

Respond

Consider ﬂuid overload

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Septic shock Reconsider diagnosis if no change in SBP following ﬂuid boluses. Recognize Establish source of infection. Consider surgical cause: is drainage required? Oxygen: titrate to SpO2 90 Fluids: • When SBP >90, continue ﬂuids at 2 ml/ kg/hour. If on vasopressors, reduce rate. • If SBP <90, continue or increase vasopressors and continue LR or NS at 2 ml/kg/hour.

Severe respiratory distress without shock If poor response, reconsider • pneumothorax • pleural effusion • heart failure • poisoning • TB • PCP associated with HIV Oxygen: Titrate to SpO2 90 Fluids: • Continue at 1 ml/kg/hour or orally. • If wheezing, give salbutamol.

Fix the physiology

6–24 hours

Treat infection

Continue empirical antimicrobials – next dose • Antibiotics • Antimalarials (if malaria tests are positive) • Antiviral if suspect inﬂuenza Every hour if SBP <90 or on vasopressors; otherwise every 2 hours • SBP, pulse • Respiratory rate • SpO2 • Mental status (AVPU) • JVP, auscultate for crackles (rales) Every 6 hours • Temperature • Urine output • Repeat glucose and Hb if initial values abnormal.

Monitor, Record

Respond

Respond to changes as indicated for 2–6 hours on previous page.

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Septic shock Perform full reassessment. Review available diagnostic data and treat underlying diagnosis. Evidence of a primary cardiac or pulmonary process? Switch to its speciﬁc management. Oxygen: Titrate to SpO2 90 and discontinue when 90 on room air. Fix the physiology Fluids: Reduce to maintenance maximum 2 ml/kg/hour and switch to oral when patient is able to take.

Severe respiratory distress without shock If poor response, reconsider • pneumothorax • pleural effusion • heart failure • poisoning • TB • PCP associated with HIV

Recognize

Oxygen: Titrate to SpO2 90 and discontinue when 90 on room air. Fluids: oral when able to take If wheezing, give salbutamol.

Post-resuscitation

Treat infection

Continue antimicrobials – switch to oral dose • Antibiotics • Antimalarials (give IV antimalarials for at least 24 hours total before switching to oral) • Antiviral if suspect inﬂuenza Procedures to follow once the patient has stabilized, or after 1–2 days • Due to risk of aspiration, do not give food orally if patient cannot safely swallow, (due to, e.g. altered mental status, severe shortness of breath, or severely ill with ongoing vomiting). • All other patients should be provided with food. Most patients lose their appetite when ill and may ﬁnd soft foods and ﬂuids easier to tolerate. Small frequent meals often are tolerated better. • Consider NG feeding using pureed foods if the patient cannot swallow safely. • In severely ill patients give a small amount initially (e.g. 20–40 ml/hour) and monitor NG aspirates to check for absorption. • Increase rate of feeding as tolerated. Every 8 hours (check SBP hourly if weaning off vasopressors); then daily • SBP, pulse • Respiratory rate • SpO2 • Mental status (AVPU) Respond to changes as indicated for 2–6 hours on previous page.

Nutrition

Monitor, Record

Respond

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3.2 Severely ill patient with difﬁculty breathing In this section: 3.2.1 Approach to the severely ill patient with difﬁculty breathing (with DDx tables) • General signs of severe respiratory distress • Four categories of severe respiratory distress • Differential diagnosis of respiratory distress • DDx: upper airway obstruction • DDx: breathing not due to upper airway obstruction • Obtain a chest X-ray to narrow the DDx 3.2.2 Provide initial emergency management for all severely ill patients with difﬁculty breathing • General principles of managing difﬁculty breathing • Manage airway • Give oxygen for hypoxaemia • Assist ventilation if ineffective breathing • Identify and treat underlying cause(s) • Table: Key initial treatments for severely ill patients with respiratory distress 3.2.3 Manage respiratory distress in patients with suspected severe pneumonia or acute lung injury without shock • When to clinically diagnosis • General principles of management • Treat underlying causes • Conservative ﬂuid therapy • Monitor – record – respond • Principles of hospital management for pneumonia 3.2.4 Manage patients with severe respiratory distress from acute bronchospasm • DDx: Acute wheeze • General principles to manage acute bronchospasm • How to give sequential bronchodilator therapy • Investigation to help grade severity • Monitor – record – respond 3.2.5 Manage patients with severe respiratory distress from acute pulmonary oedema or ﬂuid overload • Give diuretic therapy; check response • Treat severe hypertension if present • Treat precipitating cause • Monitor – record – respond • Respond to clinical changes • Flowchart: Severe acute pulmonary oedema or ﬂuid overload 3.2.6 Managing acute decompensated cardiac problems

3.2.1 Approach to severely ill patient with difﬁculty breathing Check again for evidence of life-threatening causes of respiratory failure that may be rapidly reversible. Quick Check identiﬁes emergency signs of airway and breathing difﬁculties, and provides instructions for initial emergency management, including: • choking and upper airway obstruction • anaphylaxis • pneumothorax • overdose of opioids or other sedative drugs • organophosphate poisoning • severe bronchospasm (asthma, COPD). Remember, upper airway obstruction is always an emergency and should be treated immediately.

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Difﬁculty breathing

The instructions for managing the airway, giving oxygen and salbutamol are in Quick Check, pages 33–37. Severely ill patients may present with difﬁculty breathing because of a primary problem with the respiratory system (lung tissue, airways, or respiratory muscles), cardiac system, or a systemic disease.

General signs of severe respiratory distress • • • • • very fast or very slow respiratory rates use of accessory muscles to breathe (neck, intercostal, or abdominal muscles) inability to speak complete sentences cyanosis depressed level of consciousness.

For clinical purposes there are four categories of severe respiratory distress Respiratory Pneumonia • bacterial • inﬂuenza • PCP Pleural effusion COPD Asthma Pulmonary embolism *Pneumothorax Acute lung injury (malaria, severe sepsis, TB) *Tamponade (traumatic, malignancy, TB) Acidosis (malaria, diabetic ketoacidosis) ART (lactic acidosis) Cardiac Pulmonary oedema (acute heart failure) Blood Anaemia Drug toxicity Opioid Organo-phosphate

Common

Less Common

* Although not common, these conditions need to be identiﬁed rapidly because they require an urgent therapeutic procedure.

Carry out a thorough history and physical examination to develop a differential diagnosis and to prioritize treatments and interventions.

History • rapidity of onset (over days or weeks or within minutes) • description of trouble breathing (at rest, with exertion, worse when lying down, wakens from sleep) • associated symptoms (dry or productive cough, fever, chest pain, peripheral oedema, weight loss, night sweats) • pre-existing diseases or medication use ° lung problems (COPD, severe asthma, previous severe pneumonia)

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° heart problems (myocardial infarction, hypertension, cardiomyopathy, heart failure, chest pain) ° systemic illnesses (diabetes, HIV, TB, cancer) ° medications (ART) ° recent opioid drug use ° tobacco use • previous surgical or trauma history ° recent trauma or bite ° recent period of immobility.

Examination Do a focused examination to identify likely causes. Neurological • constricted pupils (opioid overdose) or depressed mental status (suspect intoxication) Respiratory • stridor, swollen tongue, airway oedema (suspect upper airway obstruction) • trachea pushed or pulled to one side (suspect tension pneumothorax) • pattern of breathing ° prolonged expiration time (suspect asthma or COPD) ° deep, laboured breathing (suspect systemic acidosis) ° small, rapid breaths (suspect severe pneumonia, acute lung injury, muscle weakness) • quality and distribution of breath sounds ° decreased air entry on auscultation ° bibasilar crackles (suspect pulmonary oedema) ° bronchial breath sounds (suspect consolidation from pneumonia) ° wheeze (if wheezing, classify severity – see Section 3.2.4) • percussion ° dullness (suspect pleural effusion) ° hyper-resonance (suspect bullae or pneumothorax) Cardiovascular • blood pressure (may be high, low, or normal depending on cause and severity) • pulse (rhythm, rate, and volume) • heart sounds soft or mufﬂed (suspect pericardial effusion) • extra heart sounds (suspect cardiomyopathy) • loud murmurs (suspect valvular heart disease, endocarditis) • distended neck veins and peripheral oedema (suspect ﬂuid overload) Metabolic • sweet breath, smells of ketones (suspect diabetic ketoacidosis) • haematologic • pallor (suspect anaemia).

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Urgent investigations include: • Pulse oximetry to measure SpO2, chest X-ray, haemoglobin, and HIV test (if status unknown). • If fever, send blood cultures and other specimens for culture as clinically indicated. • If suspect malaria, do a malaria test (microscopy with or without RDT). • If suspect TB, do molecular testing with a nationally or WHO-approved technology, e.g. Xpert MTB/RIF, if available. Otherwise, send sputum for AFB smear and culture and other diagnostic assessment if suspect extrapulmonary TB. Send for culture if suspect MDR-TB. • If wheezing, check peak ﬂow. • If suspect volume overload, check creatinine and potassium. • If suspect cardiac problem, check ECG to evaluate ischaemia (ST segment elevations or depressions) or arrhythmias and perform limited echocardiography to evaluate cardiac function, mitral stenosis, or pericardial effusion.

Differential diagnosis of respiratory distress DDx: Upper airway obstruction Requiring urgent treatment Choking see Quick Check page 27 Anaphylaxis see Quick Check page 17 In favour • Very sudden onset • Cyanosed • Grasping at neck, eating just prior to attack • • • • • • • • • Swollen neck or tongue Wheeze and stridor Urticaria or red rash Angioedema Exposure to food or medicine just prior to attack. Gradual onset History of sore throat Swelling and redness visible in lower pharynx Drooling

Severe upper airway infection (pharyngeal abscess, diphtheria, peritonsillar abscess, epiglottitis) Upper airway trauma Inhalation burns see Section 3.10

• History of trauma to face or neck • • • • • • Burns around mouth and nose Singed facial or nasal hair Hoarseness, rasping cough Stridor Soot in the sputum Evidence of glottic oedema

Ingestion of acid or alkaline substance see Section 3.8

• Pain in mouth or throat with swallowing, drooling, vomiting blood • Hoarse voice, stridor • Upper airway obstruction, aspiration pneumonia • Shock, renal failure • Cough, respiratory distress, chest pain • Burning sensation in throat, ocular or nasal irritation • Upper airway oedema, laryngospasm, acute lung injury

Inhalation of airway irritant (e.g. chlorine) see Section 3.8

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DDx: Severely ill patient with difﬁculty breathing not due to upper airway obstruction Requiring urgent treatment Pneumothorax see Quick Check page 46 In favour • • • • • • • • • • • History of trauma, emphysema, or asthma Very sudden shortness of breath Chest pain Increased resonance on one side, normal on the other Decreased breath sounds on one side Suspect tension if deviated trachea, low blood pressure or weak pulse Decreased SpO2 History of tuberculosis (fever, weight loss) or malignancy Distended neck veins (increased JVP) Distant heart sounds, tachycardia, weak pulse Ultrasound can conﬁrm diagnosis

Cardiac tamponade see Section 7.4.5 Common causes Pneumonia (may be viral, bacterial, or opportunistic) see Section 3.2.3

• Fever, cough • Suspect community-acquired pneumonia if pleuritic pain, bronchial sounds • Suspect PCP if dry cough, HIV-infected, chest clear (see Section 10.6) • Suspect TB if productive cough, fever, weight loss, haemoptysis (see Section 15) • Wheeze (or silent chest with cyanosis) • Use of respiratory accessory muscles of prolonged expiration and hyperinﬂation • Altered level of consciousness • Speaks only few words at a time • • • • • Frothy sputum, bilateral crackles Distended neck veins, bilateral lower extremity oedema Known cardiomyopathy, hypertension, recent myocardial infection Peripartum Suspect cardiomyopathy (tachycardia, extra heart sounds, displaced impulse) • Suspect valvular heart disease if loud murmurs • History of renal dysfunction • • • • • • • • Fever Known endemic area or travel to area with malaria Acute lung injury (non-cardiogenic pulmonary oedema) Metabolic acidosis Pale (conjunctivae, palmar creases) Recent heavy blood loss AZT use Severe malaria

Lower airways obstruction (asthma, acute exacerbation of COPD) see Section 3.2.4 Pulmonary oedema (ﬂuid overload from acute heart failure, renal failure)

Severe malaria see Section 11.25 Severe anaemia

Less common causes Pulmonary embolism • • • • • • Sudden onset shortness of breath, difﬁculty breathing Sudden onset pleuritic chest pain Unilateral leg swelling Haemoptysis Tachycardia Risk factors (long travel, prolonged sitting, recent surgery, recent long bone fracture, cancer)

Pleural effusion

• History of tuberculosis • History of cancer

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Requiring urgent treatment Acute lung injury (noncardiogenic pulmonary oedema) see Section 3.2.3

In favour • • • • Bilateral pulmonary inﬁltrates on chest X-ray Severe and rapidly progressive hypoxaemia No clinical evidence of ﬂuid overload from poor cardiac function Known predisposing condition (severe sepsis, pneumonia, pancreatitis, aspiration, blood transfusion) • In pregnancy: tocolytic medication, pre-eclampsia, amniotic ﬂuid, embolism, sepsis, and severe haemorrhage • Clear chest on auscultation • Evidence of an underlying problem resulting in metabolic acidosis (diabetic ketoacidosis, severe sepsis, lactic acidosis, uraemia, intoxication with methanol or ethylene glycol) • • • • Depressed respiratory rate or respiratory arrest Acute lung injury Pinpoint pupils Known opioid user, track marks, or evidence of injecting equipment at the scene • Slurred speech, drowsiness • Unsteady gait • • • • • • • • • • • • • Pinpoint pupils Salivation, excess secretions Bronchospasm, increased respiratory secretions Coarse crackles, aspiration Sweating Bradycardia Incontinence, defecation Anxiety or coma Depressed respiratory rate Slurred speech Unsteady gait Smell of alcohol on breath Evidence of medication containers or bottles of alcohol at the scene

Metabolic acidosis (with hyperventilation to compensate) Opioid intoxication see Sections 3.6 and 17

Organophosphate poisoning see Section 3.8

Alcohol or sedative intoxication see Section 3.7

Poisoning see Section 3.8

• History of exposure (inhalation) or ingestion (e.g. overdose) • If hyperventilation, suspect ingestion that causes acidosis (e.g. pesticides, ethylene glycol, methanol) or aspirin. • If crackles (rales) on auscultation, suspect aspiration (associated with depressed mental status) or acute lung injury (e.g. paraquat, carbon monoxide, chlorine). • If wheezing, suspect inhalation of irritant (e.g. chlorine) or organophosphate. • If slow respiratory rate or arrest, suspect opioid, sedative, carbamazepine. • Kaposi sarcoma lesions – purplish nodules on skin and palate • Recent initiation of new medicine, particularly antiretrovirals (abacavir, nevirapine), cotrimoxazole • Skin rash • • • • • Rapid, shallow breathing History of snake bites, poisoning Ascending weakness (Guillain-Barré syndrome) Decreased reﬂexes If weakness of facial muscles, trouble swallowing (botulism)

Disseminated Kaposi sarcoma see Section 11.19 Drug reaction see Section 10.2 Respiratory muscle weakness (Guillain-Barré syndrome or botulism – see Section 10.10a, snake-bite – see Section 3.9

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Obtain a chest X-ray to assist with narrowing the differential diagnosis

Table: Characteristic ﬁndings on a chest X-ray for common diseases Diagnosis Pneumothorax Cardiac tamponade Chest X-ray ﬁnding • There is a radiolucent area with absence of lung markings and a deﬁned edge to the collapsed lung. • Pericardial effusions are difﬁcult to see on chest X-ray. Most obvious is the shape of the heart—a more rounded, globular shape—and a rapid increase in the cardiac shadow. • Segmental or lobar consolidation • Normal, or ground glass appearance, with nodular elements that can be conﬂuent and consolidate. • Varies from bilateral upper lobe consolidation to widened mediastinum with hilar lymphadenopathy, to cavitation and miliary nodules bilaterally. • Scarring, ﬁbrosis, nodular opacities, pleural effusions, and collapse. • Can be normal or have large-volume lungs, ﬂattening of the diaphragms, bronchial wall thickening, more obvious bronchovascular markings • Cardiomegaly, accumulation of ﬂuid in the lung interstitium (diffuse ﬂuffy opacities) progressing into consolidation, where air bronchogram can be seen. • Upper lobe diversion (dilated pulmonary veins). • May present with effusions bilaterally • Bilateral inﬁltrates, no speciﬁc distribution • Heart size is normal. • Blunted costophrenic angle, curved upper margin of the meniscus • Mediastinal shift • Normal if cause is not pulmonary in origin. • Usually normal. Some may have a wedge-shaped infracted area that might cavitate, a pleural effusion, atelectasis, or paucity of lung markings in the vicinity of the pulmonary embolus.

Bacterial or viral pneumonia PCP Tuberculosis

COPD or asthma exacerbation Pulmonary oedema (acute heart failure)*

Acute lung injury (non-cardiogenic) Pleural effusion

Metabolic acidosis Pulmonary embolism

* Chest X-ray signs of pulmonary oedema may be difﬁcult to interpret when radiographs are of variable quality and projection is an anterior-posterior view (e.g. heart may appear misleadingly large).

3.2.2 Provide initial emergency management for all severely ill patients with difﬁculty breathing General principles of managing a patient with difﬁculty breathing Manage airway . . . . . . . . . . . . . . . . . . . . . Give oxygen . . . . . . . . . . . . . . . . . . . . . . . If wheezing, give salbutamol . . . . . . . . . . . . . . . Position patient in most comfortable position for breathing Identify and treat cause Monitor – record – respond . . . . . . . . . . . . . . . . . . . . Quick Check pages 29–32 . . . . Quick Check pages 33–35 . . . . Quick Check page 37

. . . . Section 3.0

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Manage airway (see Quick Check pages 29–32) Manage upper airway obstruction When the upper airway is blocked, either from swelling of the airway caused by anaphylaxis or trauma, or from aspiration of a foreign object, the obstruction must be relieved. If basic airway interventions and emergency treatments fail to relieve obstruction or if it is likely that swelling will worsen (e.g. trauma, infection), then consider advanced airway management (see Quick Check page 32). If not trained in these interventions, call for help from a more senior clinician. This must be done quickly before progression to complete obstruction. In rare cases, such as direct airway trauma or a massive goitre compressing the trachea, a surgical procedure called a cricothyrotomy (emergent) or tracheotomy may be necessary to bypass the obstruction. If epiglottitis is suspected, antibiotics to cover H. inﬂuenzae (ceftriaxone or chloramphenicol) should be promptly administered after the airway is secured.

Give oxygen for hypoxaemia Oxygen is necessary to maintain normal tissue and organ function. Suspect hypoxaemia (inadequate blood oxygen level) if the patient has respiratory distress or evidence of tissue or organ hypoxia, such as altered mental status or cyanosis. A measured SpO2 of <90 conﬁrms hypoxaemia. Give oxygen to all patients with suspected or conﬁrmed hypoxaemia. Use a systematic approach to deliver increasing oxygen therapy (see Quick Check pages 34–35) and to assess for potential technical problems that may be encountered. Hypoxaemia can result from the abnormal function of any component of the respiratory system. • Bronchospasm (airway constriction and inﬂammation) causes reduced ventilation of lung areas and may result in mild to moderate hypoxaemia that usually responds to oxygen therapy. • Filling of alveolar tissue with inﬂammatory cells (pneumonia) or ﬂuid (pulmonary oedema) can cause an absence of ventilation of lung areas. Blood leaves these areas without the uptake of oxygen resulting in moderate to severe hypoxaemia. The more diffuse the alveolar ﬁlling process, the more severe the hypoxaemia and the less likely it is to respond to oxygen therapy alone. • Abnormalities of the blood supply to the lungs (pulmonary embolus, pulmonary hypertension, or shock) can also cause hypoxaemia. • Weakness of the respiratory muscles (tetanus, botulism, Guillain-Barré syndrome) and other causes of inadequate ventilation (e.g. drug overdose, snake bites) can cause hypoxaemia, which will improve with oxygen therapy, but assistance with ventilation is needed. Most patients with hypoxaemia will improve when they are given oxygen. For those patients who do not respond to high ﬂow oxygen (still in severe distress or SpO2 <90), consider advanced airway management (see below).

Assist ventilation if ineffective breathing Inadequate ventilation occurs when a patient has a low respiratory rate or inadequate breath volumes. A decreased respiratory rate can result from a central nervous system cause, such as an opioid overdose, stroke, or head trauma. Patients with weakness of the respiratory muscles, as seen with tetanus or botulism, also

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can develop inadequate ventilation because breaths are small. In patients with COPD and asthma, severe bronchospasm leads to inadequate ventilation because air cannot be exhaled from the lungs and the patient has to use accessory muscles to breathe. If left untreated, inadequate ventilation will result in the accumulation of carbon dioxide and acid levels in the blood, and the patient will develop an alteration in mental status or depressed level of consciousness. Inadequate ventilation is a clinical diagnosis if you cannot measure carbon dioxide and acid levels in the blood. The patient commonly also has hypoxaemia. If a patient with signs of inadequate ventilation develops an altered mental status or depressed level of consciousness, then assume the patient has progressed to acute respiratory failure but also exclude other rapidly reversible causes (e.g. hypoglycaemia). For patients with inadequate ventilation, temporarily assist with BVM ventilation using high ﬂow oxygen (see Quick Check pages 34). For certain drug overdoses, this can be done temporarily as antidotes are administered (such as naloxone for short-acting opioid overdose) until the patient awakens. For those patients who need continued assistance with ventilation, consider advanced airway management for the following conditions. • For easily reversible conditions (e.g. long-acting opioids, other drug overdoses, poisoning, or snakebite where up to several days of ventilatory problems are anticipated), consider advanced airway management if manual ventilation is possible locally. • For conditions that are not easily reversible and may likely require longer term ventilatory support (e.g. severe bronchospasm, progressive neuromuscular weakness, acute lung injury), intubation should be done if transfer is possible to a hospital where skilled invasive mechanical ventilation is available. Manual ventilation for some of these conditions (e.g. severe bronchospasm) can be challenging because the lungs are very abnormal (see Section 3.2.4).

Identify and treat underlying cause(s) After giving emergency treatments (e.g. oxygen for severe respiratory distress), it is now time to treat the underlying cause(s). To do so, take a more detailed history, perform a physical examination, and use the differential diagnosis table (DDx: Severely ill patient with difﬁculty breathing that is not upper airway obstruction) and clinical reasoning (Section 1.6) to identify the most likely and most serious diagnoses. Speciﬁc treatments for the most likely and most serious diagnoses need to be initiated urgently (if not yet done) and continued. Appropriate laboratory investigations and a chest X-ray may assist in narrowing the differential diagnosis. Do not delay appropriate treatments while awaiting these results. In particular, a chest X-ray can be very useful as many diseases have characteristic radiographic ﬁndings (see Section 3.2.1), but may not be immediately available. Remember, the patient may have more than one disease process (e.g. pneumonia and severe bronchospasm), so it is important to identify the most likely diagnoses, initiate treatments, and reassess frequently.

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Table: Key initial treatments for severely ill patients with respiratory distress Likely diagnosis Upper airway obstruction Anaphylaxis Pneumothorax Pericardial tamponade Pneumonia Initial treatments • Manage airway (see Quick Check pages 39–32). • Give epinephrine (see Quick Check page 17 and Section 3.1.3). • If tension, insert needle or chest tube (see Quick Check page 46). • Drain pericardial ﬂuid (see Section 7). • Non-severe pneumonia (see Section 10.6). • Severe pneumonia (see Section 3.2.3). Give empirical broad-spectrum antimicrobials within 1 hour. If PLHIV, give empirical PCP treatment as well. If suspect inﬂuenza, give antivirals. If TB is suspected, give antituberculosis regimen. • If shock, see Section 3.1.5. • Give salbutamol immediately (see Quick Check page 37 and Section 3.2.4). If suspect asthma or COPD, give hydrocortisone 100 mg IV or equivalent oral dose. • Give furosemide 20 mg IV. • For severe hypertension give vasodilator (see Section 3.2.5). • Treat underlying cause (see Section 3.2.3). • If severe malaria, give antimalarials. • If severe sepsis, give empirical broad spectrum antimicrobials. See Section 10.18. • Give naloxone (see Quick Check page 40). See Section 3.8.

Acute bronchospasm

Acute pulmonary oedema (ﬂuid overload condition) Acute lung injury (e.g. severe malaria) Anaemia Opioid overdose Poisoning

The remainder of Section 2 will cover the management of the following: • severe pneumonia and acute lung injury – see Section 3.2.3 ° If signs of heart failure or other causes of ﬂuid overload, use Section 3.2.5 rather than this Section. ° If shock (SBP<90), use Section 3.1.5. • bronchospasm – see Section 3.2.4 • pulmonary oedema and ﬂuid overload – see Section 3.2.5.

3.2.3 Manage respiratory distress in patients with suspected severe pneumonia or acute lung injury and without shock During Quick Check, patients who had emergency signs of airway and breathing and fever were started on empirical antibiotics. Now it is time to take a more complete history, perform a physical examination, and obtain appropriate laboratory investigations and chest X-ray to prioritize the differential diagnosis and give appropriate additional treatments. Common conditions to consider include primary lung infection (bacterial pneumonia, inﬂuenza,1 advanced tuberculosis) and acute lung injury (ALI). Acute lung injury can be a complication of a severe primary lung infection or can be 1 Some management recommendations are based on Clinical management of human infection with pandemic (H1N1) 2009: revised guidance. WHO, 2009. Available at http://www.who.int/csr/resources/publications/swineﬂu/ clinical_management/en/index.html

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seen resulting from non-pulmonary sources of infections (e.g. severe sepsis from peritonitis), severe malaria, aspiration, pancreatitis, poisoning, or trauma with massive haemorrhage. Suspect clinical diagnosis of severe pneumonia if: • • • • • • Fever or suspected infection Cough Respiratory rate >30 Severe respiratory distress SpO2 <90 Primary lung infections to consider are bacterial (community-acquired), viral (inﬂuenza), TB, and PCP in PLHIV. A chest X-ray may be helpful to distinguish pathogens.

Suspect acute lung injury if: • • • • Rapid progression of severe hypoxaemia (e.g. requiring high-ﬂow oxygen therapy) Chest X-ray shows diffuse inﬁltrates No clinical evidence of ﬂuid overload from poor cardiac function Known precipitating cause, such as infection (pneumonia, severe sepsis, severe malaria, severe dengue) or non-infectious causes (acute pancreatitis, poisoning, transfusion-related, haemorrhage). In pregnant patients, consider additional causes (tocolytic medication, pre-eclampsia or eclampsia).

The remainder of this Section should be used if the patient does not have signs of pulmonary oedema or ﬂuid overload or shock on initial examination • If signs of heart failure or other causes of ﬂuid overload, use Section 3.2.5 rather than this Section. • If shock (SBP <90), use Section 3.1.4. General principles to manage severe pneumonia or acute lung injury • • • • Manage airway . . . . . . . . . . . . . . . . . . . Quick Check pages 29–32 and Section 3.2.1 Give oxygen . . . . . . . . . . . . . . . . . . . . . Quick Check pages 33–35 and Section 3.2.1 Treat underlying cause(s) Conservative ﬂuid management

The ﬂowcharts at the end of Section 3.1.5 provide speciﬁc management by hours for oxygen and ﬂuids and how to monitor, record, and respond to ﬁndings for septic shock and severe respiratory distress without shock. These two clinical pathways have similar interventions but different ﬂuid recommendations.

Treat underlying causes • For severe pneumonia give empirical broad-spectrum IV antimicrobials within the ﬁrst hour. This is crucially important. Refer to national or institutional recommendations. Common choices include: • ceftriaxone 1–2 grams once daily PLUS a macrolide (preferred); OR • ampicillin 2 grams IV 4 times a day PLUS gentamicin PLUS a macrolide. • Macrolides include erythromycin 500 mg 4 times a day, azithromycin 500 mg once a day, clarithromycin 500 mg twice a day. Alternatives to a macrolide include doxycycline 100 mg twice a day (avoid in pregnancy) or an oral respiratory quinolone (for example, levoﬂoxacin; see below for cautions).

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• •

•

Cautions: It is important not to treat patients suspected of having TB with a respiratory quinolone, as it may mask or only partially treat underlying TB. Use of respiratory quinolones should be avoided in high-prevalence TB areas unless TB can be excluded. The safety of respiratory quinolones in pregnancy has not been established. If the patient has a non-anaphylactic allergy to penicillin (for example, skin rash only), then ceftriaxone can be used. If the patient is known to be or suspected of being HIV-infected and has a severe pneumonia, include treatment for PCP in empirical regimen (see Section 10.6) and consider tuberculosis (see Section 15). If suspect tuberculosis, obtain prompt nationally or WHO-approved molecular testing, e.g. Xpert MTB/RIF, where available. Otherwise, send sputum for AFB smear, X-ray chest, send sputum for culture, and perform further clinical assessment.2 Empirical antituberculous treatment may need to be started early in a critically ill PLHIV based on suggestive radiograph or clinical judgment. In those with signs suggesting severe pneumonia, this may mean simultaneous treatment for TB, bacterial pneumonia, and PCP. Consult with senior clinician.

If suspect inﬂuenza, give inﬂuenza-speciﬁc antivirals (see Section 11.17).3 If acute lung injury not from an infectious pneumonia, identify and treat underlying etiology. • If suspect severe sepsis, give broad-spectrum antimicrobials (see Section 3.1.3). • If suspect severe malaria, give antimalarials immediately and send blood for malaria testing (microscopy with or without RDT) (see Section 11.25). • For aspiration, stop oral feedings and observe for development of aspiration pneumonia. • For acute poisoning, see Section 3.8. • For acute pancreatitis, see Section 10.7. • For pre-eclampsia or eclampsia, give magnesium sulfate (see Quick Check page 57) and hydralazine IV (see Section 3.2.5). • For tocolytic-associated acute lung injury, stop medication.

Conservative ﬂuid therapy Patients with severe pneumonia or acute lung injury usually have some degree of dehydration. However, overly aggressive ﬂuid therapy may worsen hypoxaemia and respiratory distress. In addition, hypoalbuminaemia may also worsen oedema; this is seen in severe malaria and pre-eclampsia. • If patient is able to take oral ﬂuids without aspiration risk, oral rehydration is preferable.

2 Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings. WHO, 2007. Available at http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.379_eng.pdf 3 Guidelines for pharmacological management of pandemic (H1N1) 2009 Inﬂuenza and other inﬂuenza viruses. WHO, 2010. Available at http://www.who.int/csr/resources/publications/swineﬂu/h1n1_guidelines_ pharmaceutical_mngt.pdf

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• If patient not able to take oral ﬂuids, give LR or NS at 1 ml/kg/hour. • Monitor closely for worsening hypoxaemia and development or worsening of acute lung injury. • If evidence of volume overload and SBP >100, give furosemide 20 mg IV. Do not give a ﬂuid bolus unless in shock (systolic BP falls below 90) (see Section 3.1) or if speciﬁc cause of acute lung injury requires more aggressive ﬂuid therapy (e.g. acute pancreatitis, massive haemorrhage).

Monitor – record – respond Respond to clinical changes If SBP <90 give 1000 ml IV (see Section 3.1). If respiratory function declining (increasing breathlessness, increasing RR or SpO2 <90) • Manage airway (see Quick Check pages 29–32). • Check oxygen supply and increase ﬂow rate (see Quick Check pages 33–35). • Exclude pneumothorax, pleural effusion, heart failure, and poisoning. • If wheezing, give salbutamol. • Check that antimicrobials have been given (including repeat doses as indicated). Consider broader antimicrobial cover. • Consider TB (in all patients) and PCP in PLHIV (see Sections 15 and 10.6). • If evidence of ﬂuid overload and SBP >100, stop IV ﬂuids and give furosemide 20 mg IV. If respiratory function continues to decline, the prognosis is poor (see Section 3.2.2 and Quick Check page 31). • Reassess patient and reconsider diagnosis and complications as above. If glucose <3 mmoles (54 mg/dl), give D50 25–50 ml (see Quick Check page 41). Monitor closely. Call for help from senior clinician.

• If the patient develops severe hypoxaemia that does not improve on highﬂow oxygen, consider advanced airway management if transfer to centre with available mechanical ventilator is possible (see Quick Check pages 68–69). While awaiting transfer, provide manual ventilation carefully. A patient with respiratory failure from severe pneumonia or acute lung injury may have stiff lungs and require high pressures to inﬂate the lungs, making manual ventilation difﬁcult. During exhalation, the lungs may collapse, and high pressures will again be needed to inﬂate the lungs for the next breath. High pressures, although necessary, may also be harmful. Because manual ventilation may be difﬁcult, patients with severe pneumonia or acute lung injury should be intubated only when transfer to a centre with mechanical ventilation is possible. Mechanical ventilation is able to provide controlled levels of high pressures both during inspiration (to make sure pressures given are in safe range) as well as during expiration, to prevent lung collapse. (Repetitive lung collapse can be harmful.)

Principles of hospital management for pneumonia If patient with pneumonia fails to improve after 3 days, re-evaluate the patient, the differential diagnosis, the diagnostic test results, and alter management as appropriate. Common reasons patients being treated for community-acquired pneumonia fail to improve include: • wrong dose of antibiotic – check that the correct dose of antibiotics are being given;

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• poor penetration of the antibiotic − pulmonary abscess or empyaema, or distant complication such as endocarditis or meningitis; • wrong antibiotic for the causative organism – for example, TB, S. aureus, PCP, and Pseudomonas can cause treatment failures because they are resistant to the usual antibiotics for community-acquired pneumonia; • wrong diagnosis – other processes (e.g. cancer, ﬁbrosis) can cause changes on the chest X-ray that may sometimes look similar to pneumonia. Review all microbiologic data. If not helpful, then obtain another chest X-ray to look for complications such as empyema. Re-send blood culture, full blood count, sputum Gram stain and AFB smear, microscopy, and culture. Look for skin ﬁndings suggestive of fungal infection. Alter treatment plan depending on suspected cause of treatment failure. • Drain empyaema. • Consider ceftriaxone if not already used. When there is concern for S. aureus (e.g. in patients with suspected bacterial coinfection of concurrent inﬂuenza), consider your community epidemiology and the rate of methicillin resistant S. aureus (MRSA). Treat following your current national or institutional recommendation. • When available, vancomycin should be used as a ﬁrst choice for possible MRSA pneumonia. • In areas of high community-associated MRSA prevalence, clindamycin, cotrimoxazole, and doxycycline all have potential activity against MRSA. • Cloxacillin should be added only to regimens that are not already active against methicillin-susceptible S. aureus, and when there is low suspicion for MRSA. • Avoid doxycycline in pregnant women. If no improvement after 3–5 days (or earlier based on clinical judgment)4 • Initiate empirical TB treatment even if sputum is negative for AFB (see diagnosis of smear negative TB, Section 15). In PLHIV with signs suggesting pneumonia, this may mean simultaneous treatment for TB, bacterial pneumonia, and PCP. Choosing a rational antibiotic treatment regimen for community-acquired pneumonia • Intravenous therapy can be switched to oral therapy once the patient has been treated with 24 hours of IV therapy and is tolerating oral intake. • Treat for a minimum of 5 days. Patient should be afebrile for 48–72 hours before discontinuation of therapy. • Narrow antibiotic regimen according to culture results, when available. • See treatment regimens for PCP, inﬂuenza, and tuberculosis in other sections.

4 Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings. WHO, 2007. Available at http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.379_eng.pdf

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Follow-up and discharge of severe community-acquired pneumonia once stable • If HIV-infected and not on cotrimoxazole prophylaxis, start cotrimoxazole prophylaxis. • Discharge when patient is able to walk and eat. • If sputum is positive for AFB, treat for tuberculosis (see Sections 10.6 and 15).

3.2.4 Manage patients with severe respiratory distress from acute bronchospasm (from either asthma or chronic obstructive pulmonary disease or other causes of acute wheezing) A patient with severe respiratory distress from bronchospasm has impaired ventilation. If left untreated, the patient will worsen, develop inadequate ventilation and respiratory failure, and die. This can be prevented with early and aggressive treatment. During Quick Check a patient with emergency signs of airway obstruction with wheezing was given immediate salbutamol treatment. (See Quick Check page 37 for guidance on how to give sequential administration of bronchodilator therapy based on clinical response.) The method of giving salbutamol is determined by the severity of wheezing. For example, for those with moderate or severe wheezing, give nebulized salbutamol. After the initial treatment it is imperative to immediately reassess the patient’s response and to continue to treat severe bronchospasm aggressively if it persists. At the same time, it is important to consider the possible causes of the wheezing, but this should not delay the sequential administration of inhaled salbutamol and other appropriate bronchodilators. Acute bronchospasm can result from many conditions. In a patient with a known history of asthma or COPD, presentation with increased trouble breathing, chest tightness, cough and wheezing would make an exacerbation or acute attack of their chronic airways disease the most likely cause. However, a patient may not yet know that they have asthma or COPD, and this acute presentation may be their ﬁrst presentation. If this is the case, a brief and targeted history may help prioritize the differential diagnosis (e.g. history of long-term exposure to tobacco smoke makes COPD likely; or a history of allergies may make asthma more likely). Other causes of acute bronchospasm include viral pneumonia or inhalation injury. Of note, pulmonary oedema can present atypically with wheezing, so a careful examination for signs of ﬂuid overload should be carried out; if apparent, see Section 3.2.5. The remainder of this section should be used if the patient does not have signs of acute pulmonary oedema or ﬂuid overload. A rapid and targeted clinical history and physical examination will help to classify the severity of wheeze and guide subsequent treatments.

History • • • • • symptoms (chest tightness, shortness of breath, cough, wheezing) onset (acute or subacute) associated symptoms (fever) precipitating factors (cold weather, exercise, strong smell, viral syndrome) medical history (asthma, COPD and previous hospitalizations, allergies such as hay fever)

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• risk factors (tobacco smoke, indoor air pollution) • medications (previous use of salbutamol or steroids).

Examination • respiratory rate (very fast or very slow) • pulse and blood pressure (very severe asthma attacks can cause low blood pressure) • the patient’s level of breathlessness (at rest, with talking, or with walking) • the patient’s ability to speak (silent, speaking in single words, phrases, or full sentences) • accessory muscle use, chest wall excursion • loud wheezing, or is the chest silent as if no air were moving? Urgent investigations include • pulse oximetry to measure SpO2 • peak ﬂow after initial bronchodilator (if available) compared with predicted or personal best • measure pulsus paradoxus • chest X-ray if suspect pneumonia. DDx: Acute wheeze Etiology of acute wheeze Acute bronchitis In favour • Diffuse wheezing or rhonchi • Productive cough • Preceded by viral upper respiratory tract infection (e.g. fever, cough, runny or stuffy nose) • • • • More common in viral pneumonia Diffuse or localized wheezing Usually, acute onset fever and productive cough Chest X-ray with inﬁltrate

Bacterial or viral pneumonia see Section 10.6 Foreign body aspiration Asthma attack see Section 10.6

• Localized wheezing • Acute onset; can have cough and shortness of breath • • • • • Episodic chest tightness, shortness of breath, and diffuse wheezing Night-time symptoms and cough are common Precipitated by exercise, viral syndrome, strong smells Personal history of asthma or allergies Family history of asthma

COPD exacerbation see Section 10.6 Inhalation of airway irritants (e.g. smoke, chemicals, vapours) Ingested poisons see Section 3.8

• Increase in baseline breathlessness, cough, sputum quantity or purulence • Diffuse wheezing and rhonchi • Personal history of COPD or long-term exposure to tobacco smoke or indoor air pollution (e.g. open ﬁre stoves) • Diffuse wheezing and breathlessness • Immediately precipitated by inhalation of large amounts of irritating agent • Organophosphate poisoning (pinpoint pupils, urination, defecation, lacrimation)

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Bronchiectasis

• Wheeze can be diffuse or localized • Increase in baseline or new cough productive of purulent sputum; haemoptysis is common • Personal history of TB infection or severe pneumonia • • • • Localized wheeze Chronic cough, haemoptysis are common Associated with weight loss, anorexia Personal history of exposure to tobacco smoke, exposure to indoor air pollution (e.g. indoor coal stoves)

Cancer

Acute pulmonary oedema see Section 3.2.5

• Atypical presentation with diffuse wheezing and crackles (rales) • Fluid overload (elevated JVP, lower extremity oedema) • History of cardiomyopathy, valvular heart disease, hypertension, ischaemia, renal disease

General principles to manage a patient with acute bronchospasm • Have patient sit upright and assume comfortable position. • Manage airway (see Quick Check pages 29–32). • Give oxygen therapy (see Quick Check pages 33–35). • Give inhaled salbutamol immediately (see Quick Check page 37 for sequential bronchodilator treatment). • Treat underlying causes. Monitor-record and respond (see Section 3.0).

How to give sequential bronchodilator therapy for moderate, severe, or life-threatening wheezing Signs One or more of the following • silent chest • cyanosis • poor respiratory effort • altered consciousness • exhaustion Classify as LIFETHREATENING WHEEZING Treatments • Mange airway (see Quick Check pages 29–32). • Give oxygen (see Quick Check pages 33–35). • Give salbutamol by continuous nebulizer (see Quick Check page 37 for sequential bronchodilators). • If acute asthma or COPD, give steroids (100 mg hydrocortisone IV or 40–60 mg methylprednisolone IV or 40–60 mg oral prednisolone or equivalent). • Reassess immediately (do not leave patient alone). • If no improvement, give salbutamol continuously. Add ipratropium by nebulizer. • If no improvement, give intravenous magnesium sulfate (2 grams over 20 minutes). • If fever, give IM or IV antibiotic. • Give oxygen (see Quick Check pages 29–32). • Give salbutamol by nebulizer (continuous or every 20 minutes) (see Quick Check page 37 for sequential bronchodilators). • If acute asthma or COPD, give steroids (100 mg hydrocortisone IV or 40–60 mg methylprednisolone IV or 40–60 mg oral prednisolone or equivalent). • Reassess immediately (15–30 minutes). • If not improving, give more salbutamol every 20 minutes or, if deteriorating, continuously. Add ipratropium by nebulizer. • If deteriorating, also give magnesium (2 grams over 20 minutes). • If fever, give IM or IV antibiotic.

One or more of the following signs: • breathless at rest • cannot complete sentences in one breath • respiratory rate ≥25 breaths/min • pulse ≥100

SEVERE WHEEZING

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Signs No features of severe asthma

Classify as MODERATE WHEEZING

Treatments • Give oxygen. • Give salbutamol by primed spacer with 5 puffs; then give 2 puffs via spacer every 2 minutes. • If acute asthma or COPD, give steroids – oral prednisolone 40–60 mg (or equivalent). • If fever, give IM or IV antibiotic. • Reassess in 15–30 minutes.

The following investigations help grade severity • SpO2 <90 on room air • Peak ﬂow <33% of predicted or personal best • Absence of pulsus paradoxicus (when respiratory arrest imminent, absence suggests muscle fatigue) • SpO2 >90 • Peak ﬂow 33–50% of predicted or personal best • Pulsus paradoxus >25 mmHg • SpO2 >90 • Peak ﬂow 50–75% of predicted or personal best • Pulsus paradoxus may be present (10–25 mmHg) LIFE-THREATENING WHEEZE

SEVERE WHEEZING MODERATE WHEEZING

If there is no inhaled salbutamol available, consider one of the following for severe bronchospasm • Salbutamol 250 mcg slowly by IV for severe acute bronchospasm. (Be aware that this can lead to hypokalaemia.) • Aminophylline 5 mg/kg slowly over 20 minutes • Epinephrine 0.5 mg (0.5 ml of 1:1000) IM. Note: Aminophylline is not recommended due to toxicity and lower efﬁcacy and is not included on the WHO Model List of Essential Medicines, but it may be effective by slow IV infusion if no other drugs are available.

Monitor – record – respond In addition to the other clinical parameters being monitored for severely ill patients (see Section 3.0), patients with severe wheezing should be monitored very closely as follows. • Initially, patient should be monitored at least every 15–30 minutes, after every salbutamol treatment, to assess response and classify severity until improvement is observed, and then every hour for the initial 6 hours. Do not leave a patient with life-threatening features alone. • Monitoring should cover: ° physical examination ° respiratory rate ° peak ﬂow ° pulse ° pulsus paradoxus.

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Sequential bronchodilator therapy (see Quick Check page 37) Caring for patients with moderate to severe wheezing requires close monitoring, reassessment, and accurate reclassification, as discussed above, and then appropriate administration of bronchodilators. Bronchodilator treatment acts immediately on the airway smooth muscles so that they relax and open up to allow the patient to breathe better. • For any patient with life-threatening features, in addition to giving continuous salbutamol by nebulizer, make sure to give the patient ipratropium (another bronchodilator) by nebulizer and IV magnesium sulfate (2 grams over 20 minutes). • If the patient has severe wheezing that is deteriorating despite salbutamol treatment, treat as if there are life-threatening features with continuous salbutamol, ipratropium every 4–6 hours, and magnesium sulfate. • If patient with severe wheezing has an incomplete response, then continue with salbutamol by nebulizer (continuous or every 20 minutes) and also give ipratropium. • If patient with wheezing is improving, then give salbutamol less frequently (e.g. if on continuous nebulizer treatment, go down to every 20 minutes or, if receiving nebulizer treatments every 20 minutes, go down to every two, then every four hours. If suspect asthma or COPD, give steroids (either 100 mg hydrocortisone IV or 40–60 mg oral prednisolone or equivalent). Steroids should be given immediately, but beneﬁts will take some time to appear. Thus, bronchodilator therapy needs to continue sequentially while awaiting the effects of steroid therapy. Steroids help to reduce airway inﬂammation and swelling so that the airways remain open and the patient can breathe better. If fever, give empirical antibiotics (see Quick Check page 43). On arrival, it may be difﬁcult to know if the patient has a bacterial pneumonia or is having an acute attack of asthma or COPD. Giving empirical antibiotics early is beneﬁcial in case there is a concurrent bacterial infection. Other things to consider if patient is not improving • Check oxygen supply and increase ﬂow rate if SpO2 <90 (see Quick Check pages 34–36). • Reconsider differential diagnosis (pneumothorax, heart failure, poisoning). • If patient develops inadequate ventilation that does not improve on high-ﬂow oxygen and aggressive bronchodilator treatment, consider advanced airway management if transfer to a centre with available mechanical ventilator is possible (see Quick Check pages 37, 62–67). A patient with respiratory failure from severe bronchospasm has severe airﬂow obstruction and is unable to exhale the air from the lungs. As a result, the lungs become hyperinﬂated, which can result in both hypotension and a pneumothorax. Because providing manual ventilation may be difﬁcult and dangerous in patients with severe bronchospasm, these patients should be intubated only if transfer to a centre with mechanical ventilation is possible. Mechanical ventilation will allow greater control of the respiratory rate (enough time to exhale) and size of breaths being delivered (e.g. small breaths so complete exhalation can occur). While awaiting transfer, provide manual ventilation carefully.

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• Use a large-diameter endotracheal tube (7.5 or 8.0 is desired to optimize ventilation). • Allow sufﬁcient time for exhalation to occur; therefore, give breaths at a slow rate (e.g. less than 10 per minute). • If necessary, provide sedation to allow slow breath delivery. • Make sure you continue to deliver bronchodilator treatment through the endotracheal tube. • Monitor blood pressure and pulse for signs of hyperinﬂation (e.g. low SBP, fast pulse). If shock develops, stop ventilation to allow sufﬁcient time for exhalation, give rapid ﬂuids, and assess for pneumothorax.

3.2.5 Manage patients with severe respiratory distress from acute pulmonary oedema or ﬂuid overload Acute pulmonary oedema is the abnormal accumulation of ﬂuid in the lung tissue and airspaces (alveoli), which makes it difﬁcult for oxygen from the air to diffuse into the blood. There are two mechanisms by which this can occur. • Most commonly, pulmonary oedema can form when the ﬁlling pressures of the heart are raised, leading to increased pressures inside the small pulmonary vessels. Fluid is then forced out of the vessels and into the lungs. This is what happens in acute pulmonary oedema from poor cardiac function (congestive heart failure) and from renal failure. • Less commonly, pulmonary oedema can form when there is increased leakiness of the small pulmonary vessels and of the cells lining the alveoli, leading to movement of ﬂuid and protein into the lungs. This is also known as acute lung injury or non-cardiogenic pulmonary oedema. After Quick Check it is important to identify patients with possible pulmonary oedema (presence of respiratory distress, crackles on examination, and chest X-ray with diffuse inﬁltrates) and then to attempt to distinguish between these two forms of acute pulmonary oedema so as to guide early management. This should not delay immediate treatment with oxygen or other emergency treatments as described in Quick Check. Look for clinical evidence of ﬂuid overload. • JVP is elevated, hepatomegaly or ascites, bilateral lower extremity oedema. • Chest X-ray shows ﬂuffy bilateral opacities, perihilar distribution, bilateral effusions. ° If present, consider acute pulmonary oedema from cardiac or renal causes (see Table, Common diagnoses that may present with acute pulmonary oedema, below), and use this section for treatment guidance. ° If not present, then consider acute lung injury (non-cardiogenic pulmonary oedema) and look for other characteristics of ALI (see Section 3.2.3). Perform a history and physical examination to narrow the differential diagnosis. History • rapidity of onset (months, weeks, days, hours) • associated symptoms (fever, cough, abdominal pain) • difﬁculty breathing at rest, during exercise (exertional dyspnoea), when lying ﬂat (orthopnoea), or at night that wakens the person from sleep (nocturnal dyspnoea)

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• precipitating factors – increased intake of salty foods, increased water intake, recent infection, feeling irregular heart palpitations (atrial ﬁbrillation) or chest pain • any chronic diseases – HIV infection, cardiomyopathy, liver disease, renal disease • Pregnancy – women with mitral stenosis will often decompensate in the middle of pregnancy. Peripartum cardiomyopathy develops in the last month of pregnancy or within six months after delivery. Women with pre-eclampsia or eclampsia may have convulsions, high blood pressure. • Medications – if the patient has known heart failure, ask about medication adherence. • The patient’s wishes for intensity of therapy – patients with very advanced heart failure may not want intensive therapies. Physical examination: focused examination to identify likely cause • tachycardia (more than 120/min is common in acute heart failure) • blood pressure (depending on the cause, the patient’s blood pressure may be high, low, or normal). A wide pulse pressure (such as 120/30 mmHg) suggests possible severe aortic insufﬁciency. • fever (may suggest concurrent and/or exacerbating pneumonia or other infection) • weight (compare with previous weights) • poor perfusion (blood ﬂow) – cold extremities • cardiovascular system • displaced point of maximum impulse, extra heart sounds, loud murmurs • distended neck veins, lower-extremity oedema • respiratory • bilateral crackles • decreased breath sounds at bases • gastrointestinal • hepatomegaly, ascites • epigastric tenderness. Urgent investigations include: • creatinine, potassium, haemoglobin • Recommend an HIV test. • If suspect infection, check blood cultures and other cultures as appropriate. • chest X-ray • ECG – evaluate for ischaemia, ventricular hypertrophy, arrhythmias. • Limited echocardiography – assess cardiac function, presence of mitral stenosis, or pericardial effusion. This does not require a cardiologist or a radiologist and can be done with basic ultrasound equipment without Doppler.

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Table: Common diagnoses that may present with acute pulmonary oedema Acute pulmonary oedema with clinical evidence of ﬂuid overload Cardiomyopathy

Symptoms • • • • HIV-infected, peripartum, long-standing hypertension Displaced impulse and extra heart sounds (dilated cardiomyopathy) ECG with left ventricular hypertrophy (hypertensive heart disease) ECG with evidence of ischaemia (ischaemic heart disease)

Valvular heart disease Myocarditis (Chagas disease)

• Loud murmur at apex, in diastole (mitral stenosis) • History of rheumatic heart disease • Endemic area, cardiomyopathy • Syncope, ECG with arrhythmias or conduction abnormalities • Gastrointestinal symptoms • Fever and new murmur • Diabetes, hypertension • HIV-associated nephropathy Symptoms • Fever, pallor, headache, jaundice • Cough, shortness of breath are early signs of pulmonary oedema • Other signs of severe malaria are altered mental status, bleeding, shock, weakness, seizures, hypoglycaemia (see sections 3.2.3 and 11.25). See Section 3.2.3 See Section 3.1.5 See Section 3.8 • Epigastric pain with eating, loss of appetite • Tocolytic medication, pre-eclampsia or eclampsia

Endocarditis Chronic kidney disease Acute lung injury Severe malaria

Severe pneumonia Severe sepsis Poisoning Acute pancreatitis Pregnancy-related

The remainder of this section focuses on the management of patients with acute pulmonary oedema or ﬂuid overload from cardiogenic cause or from renal failure. If severe pneumonia and/or acute lung injury, see Section 3.2.3 instead. General principles to manage a patient with acute pulmonary oedema or ﬂuid overload Immediate diuretic and vasodilator therapy optimizes cardiac output and assists in mobilization of ﬂuids from lungs to the kidneys for excretion. • Have patient sit upright and assume comfortable position. • Manage airway (see Quick Check pages 29–32). • Give oxygen therapy (see Quick Check pages 33–35). • Give diuretic therapy; check response in 30 minutes. • Treat severe hypertension. • Treat precipitating cause(s). • Monitor-record-respond (see Section 3.0).

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Give diuretic therapy; then check response in 30 minutes Diuretic therapy reduces congestion in the lungs. The dose depends on whether the patient has been on this drug before and therefore may have some tolerance. • If the patient has not been on furosemide as an outpatient, give 20 mg furosemide IV. • If the patient has been on furosemide orally as an outpatient, give the oral dose of furosemide IV. For example, if a patient takes 40 mg orally once daily, then give 40 mg IV. IV furosemide is at least twice as effective as the oral dose. • Monitor urine output. Furosemide works fairly quickly, and so a response should be observed within 30 minutes. Monitor also for development of hypotension if urine output is brisk.

Treat severe hypertension if present Give vasodilators to decrease blood pressure. Start with low dose and watch effect. • Start with isosorbide dinitrate 5 mg sublingual. If still hypertensive, can give another dose after 10–15 minutes, not to exceed 10 mg every 2–3 hours. • If isosorbide dinitrate not available, give hydralazine 5 mg IV once. This also can be repeated, if necessary, after 30 minutes. • If patient has good response to vasodilator treatment, start enalipril 5 mg orally within 6–24 hours if creatinine is normal. • Monitor SBP, as combination of diuresis and vasodilators can greatly reduce blood pressure. • In pregnant patient with pre-eclampsia or eclampsia and severe hypertension5, give IV hydralazine or sublingual nifedipine. There is limited experience with the use of isosorbide dinitrate in pregnant women. Enalapril (or other ACE inhibitors) and sodium nitroprusside should be avoided in pregnancy. For continued management, consider oral labetolol, hydralazine, alpha methyldopa, or nifedipine based on cost, availability and experience using the medicine. For other aspects of management of pre-eclampsia or eclampsia, see also Quick Check page 57, and for acute lung injury, see Section 3.2.3.

Treat precipitating cause Patients with cardiomyopathies or renal disease usually decompensate and develop acute pulmonary oedema because of a triggering event. Identify and treat potential triggers. For example: • cardiovascular – ischaemia, arrhythmia, hypertension, pericardial effusion, poorly controlled cardiomyopathy • other – pneumonia (see Section 3.2.3), failure to adhere to medication, increased salt or water intake, pulmonary embolism.

5 WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. WHO, 2011. Available at http://whqlibdoc.who.int/publications/2011/9789241548335_eng.pdf

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Monitor – record – respond In addition to the other clinical parameters (see Section 3.0), monitor patients with acute pulmonary oedema as follows to guide additional diuretic and vasodilator treatment. • Urine output – monitor closely in the ﬁrst couple of hours to assess early response to furosemide and need to increase dose if response is poor. • Weight – monitor daily to assess response to diuresis. • Electrolytes and creatinine – monitor daily to watch for hypokalaemia (see Section 5.2) and rising creatinine (see Section 11.31), which can be side effects of furosemide. Respond to clinical changes If within 30 minutes the patient does not urinate an adequate amount (e.g. 100–150 ml) and is still in distress • Double the initial furosemide dose. If after 1–2 hours the patient is still in distress and there has not been an adequate urine response • Check oxygen supply and increase ﬂow rate if SpO2 <90 (see Quick Check page 35). • Assure precipitating cause is being treated (arrhythmia, ischaemia, infection?). • Reconsider the diagnosis (is there pneumonia, acute lung injury, pleural effusion, pneumothorax?). • Obtain additional diagnostic tests if relevant (chest X-ray, limited echocardiogram). • Call for help from senior clinician (consider doubling the last dose of furosemide). • Check creatinine. If patient has renal failure, then give a higher dose of furosemide (e.g. 80–160 mg) and consider the addition of a thiazide diuretic (e.g. hydrochlorothiazide 25 mg by mouth daily before furosemide dose). • Monitor closely. If SBP <90, give 250–500 ml of LR or NS IV (see Section 3.1.5). • Call for help from senior clinician. • Stop diuresis.

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Flowchart: Severe acute pulmonary oedema or ﬂuid overload Clinical diagnosis of severe acute pulmonary oedema • Respiratory rate >30 or SpO2 <90 and • Bilateral crackles on lung exam • Signs of volume overload: distended neck veins, hepatomegaly, ascites, lower-extremity oedema • History of cardiomyopathy or kidney disease Oxygen: titrate to SpO2 90 Fix the physiology Fluids: Give furosemide 20 mg IV If hypertension: Isosorbide dinitrate 5 mg sublingual If ischaemia: Give aspirin; other management per national guidelines Treat trigger If arrhythmia: Treat per national guidelines If fever: give empirical antimicrobials • Antibiotics • Antimalarials • Antiviral if suspect inﬂuenza Every 30 minutes until stable; then every 1 hour • SBP, pulse, RR, SpO2, mental status (AVPU), urine output • JVP, auscultate for crackles (rales) • Weight on admission • Creatinine, potassium on admission If respiratory distress fails to improve or worsens and urine output is not adequate • Check oxygen supply, increase oxygen ﬂow • Give furosemide IV 40 mg (double dose) • If renal failure, call for help and consider higher doses of furosemide and additional diuretics

Recognize

First 2 hours

Monitor, record

Respond

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Flowchart: Acute pulmonary oedema or ﬂuid overload If poor response, reconsider • Severe pneumonia, acute lung injury, pneumothorax, pleural effusion, poisoning, TB, PCP in PLHIV, malaria Oxygen: titrate to SpO2 90 Fix the physiology Fluids: If urinary response not adequate (150–200 ml), give 40 mg IV furosemide. If adequate response, do not give additional dose. If still hypertension: Give another dose of isosorbide dinitrate SL (5–10 mg). Can repeat every 2–3 hours. Every 30 minutes until stable; then every 1 hour • SBP, pulse, RR • Mental status (AVPU) • Urine output • JVP, auscultate for crackles (rales) If respiratory function declining • Check oxygen supply and increase ﬂow rate If ﬂuid overload unresponsive to escalating diuretic doses • Call for help from senior clinician to give higher dose of furosemide or add another diuretic agent Respond If renal failure • Call for help from senior clinician to assist with diuretic management and consider transfer to a centre with haemodialysis If SBP <90 • Stop diuresis. Give 250 LR or NS bolus. Call for help from senior clinician; if cardiogenic shock, consider vasopressors.

Recognize

Treat trigger

2–6 hours

Monitor, record

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Flowchart: Acute pulmonary oedema or ﬂuid overload If poor response, reconsider • Severe pneumonia, acute lung injury, pneumothorax, pleural effusion, poisoning, TB, PCP in PLHIV, malaria Oxygen: titrate to SpO2 90 Fix the physiology Furosemide: Repeat effective diuretic dose every 6–8 hours Continue to treat hypertension: Start long-acting enalipril 5 mg oral if creatinine normal Continue to treat myocardial ischaemia – next dose

Recognize

6–24 hours

Treat trigger Continue to treat arrhythmia – next dose Continue to treat pneumonia: Empirical antimicrobials – next dose Every hour if SBP <90 or on pressors; otherwise every 2 hours • SBP, pulse • Respiratory rate • SpO2 • Mental status (AVPU) • JVP, auscultate for crackles (rales) Monitor every 6 hours • Temperature • Urine output • Repeat glucose and Hb if initial value abnormal Respond Respond to changes as indicated on previous page for 2–6 hour period

Monitor, record

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Flowchart: Acute pulmonary oedema or ﬂuid overload Perform full reassessment Recognize Review available diagnostic data and treat underlying diagnosis Switch to its speciﬁc management Oxygen: titrate to SpO2 90; discontinue when 90 on room air Fix the physiology Furosemide: Titrate down frequency as tolerated, every 8–12 hours. Change to oral dose. Continue to treat hypertension – next dose Continue to treat myocardial ischaemia – next dose Continue to treat arrhythmia – next dose • Begin once the patient has stabilized and in any case after 1–2 days. • Due to risk of aspiration do not give food orally if patient cannot safely swallow, due, for example. to altered mental status, severe shortness of breath or severely ill, ongoing vomiting. • All other patients should be provided with food. Most patients lose their appetite when ill and may ﬁnd soft foods and oral ﬂuids easier to tolerate. Small, frequent meals are often tolerated better. • Consider NG feeding, using pureed foods, for patients who cannot swallow safely due to risk of aspiration. • In severely ill patients give small amount initially, e.g. 20–40 ml/hour, and monitor NG aspirates to check for absorption. • Increase rate of feeding as tolerated. Every 8 hours (check SBP hourly if weaning off pressors); then daily • SBP • Respiratory rate • SpO2 • Mental status (AVPU) Respond to changes as indicated earlier

Treat trigger

Post-resuscitation

Nutrition

Monitor, Record

Respond

3.2.6 Managing acute decompensated cardiac problems Patients with chronic cardiovascular diseases may present with acutely severe illness and respiratory distress with episodes of decompensation. Section 3.2.5 described the initial management of acute pulmonary oedema from multiple causes. For management of acute and chronic cardiomyopathy, valvular heart disease, arrhythmias, and hypertensive emergencies, refer to national guidelines. The WHO Model Formulary has guidance on many relevant treatments.

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3.3 Approach to the patient with chest pain Chest pain is a common complaint that may be a symptom of serious illness, particularly when associated with shortness of breath, low blood pressure, or fever. Or it may be associated with less serious conditions. A good history and physical examination is important to prioritize the differential diagnosis. The character of the pain is often a helpful clue as to the cause – pleuritic pain (sharp, well localized pain that is worse with breathing or coughing) is usually associated with a primary pulmonary problem such as pneumonia, pleural effusion, or pulmonary emboli. Crushing pain or a tight pain in the chest (that may radiate to the left arm, throat, or jaw) is more suggestive of myocardial ischaemia. See the table that follows for a differential diagnosis that includes common and not so common causes of chest pain. DDx: Chest pain Condition Stable angina In favour • • • • • • • • • • Chest pain with exertion (crushing in nature, radiating to jaw or arm) Associated with nausea and shortness of breath Easily relieved with rest History of cardiac disease Risk factors − hypertension, diabetes, tobacco, hyperlipidaemia, family history

Acute coronary syndrome (unstable angina, non-ST elevation or ST elevation myocardial infarction)

Crushing chest pain (pressure, tightness) radiating to the jaw or arm at rest Clammy, sweaty Associated with nausea and shortness of breath History of cardiac disease Risk factors − hypertension, diabetes, sickle-cell anaemia, tobacco, hyperlipidaemia, family history • ECG changes – Q waves, ST depression or elevation, T wave changes • • • • • Fever and cough Pain exacerbated by breathing (pleuritic) Respiratory distress, hypoxaemia Crackles on auscultation, bronchial breath sounds Consolidation on chest X-ray

Pneumonia see Sections 3.2.3 and 10.6

Pulmonary embolus

• Risk factors – recent immobilization, travel, pregnancy, cancer, recent surgery, long bone or pelvic fracture • Evidence of DVT – swollen leg • May have fever (usually mild) • Difﬁculty breathing • Haemoptysis • Tachycardia • ECG – sinus tachycardia • • • • • Burning epigastric, retrosternal pain Worse at night Worse with food Long history symptoms Relieved by antacids or acid blockers

Oesophageal reﬂux (GERD) See Section 10.7b

Musculoskeletal

• Chest pain that is reproducible on palpation • Pain can be worse with movement or with inspiration • Usually associated with muscle strain or from minor trauma

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Condition Less common causes Oesophageal rupture

In favour

• • • •

Sudden onset central chest and abdominal pain During or following excessive vomiting Vomiting blood Shock

Aortic dissection

• Tearing pain radiating to the back, abdomen or between shoulder blades • Asymmetrical pulses or BP • New stroke • • • • • Difﬁculty breathing Elevated JVP Displaced trachea to opposite side Decreased breath sounds on affected side Hyperresonance on percussion on affected side

Tension pneumothorax see Quick Check page 46

Tuberculosis see Section 15 Panic attack see Section 10.11 Pericarditis

• May involve lungs, pericardium, pleura • Fever, cough, haemoptysis • Common complication of HIV • Hyperventilation • History of anxiety or recent stress • • • • Sharp, posterior pain Relief when leaning forward Acute rheumatic fever, TB pericarditis, chest trauma ECG with diffuse ST elevation

For pneumonia, see Sections 3.2.3 and 10.6. For TB, see Section 15. For oesophageal reﬂux, see Section 10.7. For management of pneumothorax, see Quick Check page 46. For panic attacks and panic disorder, see Section 10.11. For management of acute coronary syndromes and coronary artery disease, refer to national guidelines. The WHO Model Formulary has guidance on several relevant treatments.

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3.4 Approach to the patient with altered consciousness (including coma, confusion, intoxication, agitation, and convulsions) In this section: 3.4.1 Clinical approach to the patient with altered consciousness • Assessment and urgent treatments • DDx: If a patient is unconscious or has a decreased level of consciousness or is confused or delirious 3.4.2 Manage delirium 3.4.3 Manage diabetic ketoacidosis • Clinical presentation of diabetic ketoacidosis • Investigations for DKA • Treatment of DKA • Table: Management of DKA if K measurement or ECG is available and SBP >90 3.4.4 Manage hypoglycaemia 3.4.5 Steroid deﬁciency (Addison’s disease; adrenal insufﬁciency)

3.4.1 Clinical approach to the patient with altered consciousness Assessment and urgent treatments It is important to ensure that, if a patient has an altered level of consciousness, the airway is protected and breathing and circulation are maintained. Ensure that the violent or confused patient is not a danger to himself or to health workers. Assess for coma, convulsions, or other abnormal mental states. Check the level of consciousness on the AVPU scale. • A – alert • V – responds to voice • P – responds to pain • U – unresponsive. If the patient is not able to answer questions, make sure to take a brief, focused history from the people who brought the patient to the hospital before they leave (see below). • If the patient is not awake and alert, try to rouse the patient by talking or shaking an arm. If the patient responds to voice, then the patient is lethargic. If the patient does not respond to voice or pain (squeezing on a ﬁngernail or pressing on the sternum), the patient is in a coma (unconscious) and needs emergency treatment. • Is the patient convulsing (having seizures)? Are there spasmodic, repeated movements in an unresponsive patient? Remember to consider that seizures may present with little movement. • If there are seizures and the patient is a woman, check if she is pregnant or has recently been pregnant (see Section 3.5). Take vital signs – respiratory rate, pulse, temperature, blood pressure • Also, perform emergency laboratory investigations – blood glucose, Hb, malaria test (microscopy with or without RDT), pulse oximetry, and electrolytes.

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A patient may be unconscious because of processes involving the brain (infection, ischaemia, epilepsy), drugs, toxins and poisons, or severe metabolic problems. Patients with pre-existing confusion, such as those with dementia, may become more acutely confused as a result of other problems, such as infection, worsening organ failure, or new medications. An altered state of consciousness may overlap with other syndromes, such as shock or respiratory distress. Shock commonly presents with an altered state of consciousness due to reduced oxygenation of the brain. Severe respiratory distress may present as coma due to retention of carbon dioxide. This Section outlines management of patients with an altered state of consciousness identiﬁed as their primary problem after initial assessment and management. Urgent treatment is required for: • hypoglycaemia (blood glucose <3.0 mmol/l or <50 mg/dl) – give the patient a sweet drink orally (if not at risk of aspirating) or via nasogastric tube, or else 50% dextrose 25–50 ml IV over 2 minutes (see Quick Check page 41 and Section 3.4.2); • infections – meningitis (see Section 10.10b), severe sepsis (see Section 3.1.5), severe malaria (see Section 11.25); • metabolic problems – diabetic ketoacidosis (see Section 3.4.1), electrolyte imbalances (see Section 5.2), hypoxaemia (see Section 3.2); • trauma and head injury (see Quick Check page 44 and Section 4); • poisonings (see Section 3.8) – opioids, organophosphates; • other – hypertension, status epilepticus (see Section 3.5).

History A history obtained from family members or witnesses should focus on the following areas: • onset and duration of illness • injuries – particularly neck trauma and head injury • other medical problems – asthma, diabetes, epilepsy, drug and alcohol use, dementia, HIV, mental health problems • exposures – malaria, typhoid, travel • possible overdose. Examination • If head or neck injury is suspected, do not move neck (see Quick Check page 44). • Exclude additional serious causes – shock (low blood pressure), respiratory failure (cyanosis, difﬁculty breathing). • Abnormal temperature (>38oC or <36oC) • Small pupils (opioids, organophosphate) • Stiff neck (meningitis) • Skull fracture • Focal neurological signs – unequal pupils, asymmetrical tone, abnormal movement (stroke, brain herniation, etc.)

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• Brainstem problem – suggested by abnormal gag reﬂex or absent corneal reﬂex or “doll’s eye” reﬂex • Involuntary side-to-side eye movements.

Differential diagnosis DDx: If a patient is unconscious or has a decreased level of consciousness or is confused or delirious Condition Rapidly reversible causes Hypoglycaemia see Section 3.4.2 • • • • • • Sweating Seizures Confusion Use of hypoglycaemic agents or heavy alcohol use Severe sepsis or malaria Responds quickly to glucose In favour

Severe dehydration see Section 3.1.2 Heat stroke see Section 10.1 Hypoxaemia see Sections 3.2.2 and 10.6

• Signs of shock (elevated pulse, low blood pressure) • Decreased skin turgor • Impaired ability to drink ﬂuids • Prolonged exposure to heat and sun • High temperature (>40.5°C) • Cyanosis (look at nail bed, lips; cyanosis may not be apparent in anaemic patients) • Shortness of breath • Low SpO2

Infection Cerebral malaria see Section 11.25 • • • • • • • • • • • • Endemic area in season Migrant workers Fever, altered mental state Rapid malaria test positive or smear positive Fever Neck stiffness, photophobia, headache Known epidemic of meningitis History or likely to have HIV infection Fever Shock Sometimes: warm extremities, endocarditis Signs of focus of the infection

Meningitis see Section 10.10b

Sepsis from various causes including pneumonia, UTI see Section 3.1.5 HIV encephalopathy see Section 13

• Disabling cognitive or motor dysfunction • Interference with activities of daily living • Progression over weeks or months in the absence of a cause other than HIV • LP excludes other causes • HIV infection with low CD4 count • Endemic areas in Africa • Intermittent fever, headache • Generalized lymphadenopathy, particularly in posterior cervical triangle • Slow onset • Poor concentration and personality changes

Human African trypanosomiasis see Section 11.41

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Condition Encephalitis

In favour • Fever • Altered conscious state, personality change, coma • Seizures • Encephalitic (furious): agitation, hydrophobia (fear of drinking), “fan test” (agitation with breeze on face), pharyngeal spasm, drooling • Paralytic (dumb): paralysis, incontinence • History of animal bite

Rabies see Section 11.30

Metabolic Diabetic ketoacidosis (DKA) or hyperosmolar non-ketotic (HONK) coma see Section 3.4.1 • • • • • • • History of diabetes mellitus (known Type 2 in HONK) Acidotic – deep, laboured breathing (more common in DKA) Ketotic odour (sweet smelling breath) in DKA High glucose in blood or urine (very high in HONK) Dehydrated Focal neurological signs (more common in HONK) Ketones in urine and blood (no or trace ketones in HONK)

Hypernatraemia see Section 5.2.1 Hyponatraemia see Section 5.2.1

• Lethargy, weakness, irritability (early) • Twitching, seizures, coma (late) • • • • Nausea, vomiting, fatigue Apathy Coma Seizures

Hyperkalaemia see Section 5.2.2 Hypokalaemia see Section 5.2.2 Hypercalcaemia see Section 5.2.3

• Twitching, abdominal pain, paraesthesia, seizures • Lethargy, generalized weakness leading to ascending paralysis, ileus • • • • Nausea, vomiting Muscle weakness, bone and joint pain Confusion, fatigue, coma Frequent urination, excessive thirst, nephrolithiasis, acute and chronic renal insufﬁciency • Abdominal pain, constipation, pancreatitis • Bradycardia • Constipation, confusion, chronic generalized pain, bone pain • Seizures, tetany • History of thyroıdectomy (look for scar) • • • • • Hypothyroidism Deterioration in mental status Goitre, swelling of skin/soft tissue Delayed relaxation of reﬂexes Elderly female

Hypocalcaemia

Myxoedema

Toxic Poisoning see Section 3.8 Drug overdose, intoxication, or interactions – prescribed drugs see Section 3.8 • History of exposure • Organophosphate – pinpoint pupils, salivation, bradycardia, incontinence, anxiety, coma • Drug overdose (accidental or deliberate) of prescribed drugs • ARV toxicity: fulminant liver failure from NVP, especially in pregnancy; confusion with EFV toxicity • Drug interactions in AIDS patients taking multiple medications (see Section 13)

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Condition Drug overdose, intoxication – psychoactive substance use see Sections 3.6, 3.7, 17

In favour • • • • • Known hazardous alcohol use or psychoactive drug use Evidence of drug use – injection marks, illicit substances in pockets Alcohol – breath smells of alcohol, reddened face Opioids – sedation, pinpoint pupils Amphetamine-type drugs – dilated pupils, agitation, sweating, fever

Neurotoxic snake bite see Section 3.9 Other causes Status epilepticus see Section 3.5 Post-seizure state

• Snake bite history or bite marks in a setting with neurotoxic snakes

• Ongoing or recurrent stiffening or jerking movements of limbs • Known history of seizures • • • • History of recent seizure (stiffening, jerking movements) Bitten tongue, incontinence Known history of seizures Postictal improvement over minutes or hours from: ° confusion ° poor attention ° poor short-term memory ° cognitive deﬁcits below baseline functioning

Eclampsia see Quick Check page 58 Head trauma see Section 4

• Usually associated with hypertension, oedema • Usually occurs at term, during delivery or immediately following delivery • Bruises, lacerations, other visible injury or history of injury around head or eyes or ears • History of recent trafﬁc accident, fall or violence • Periorbital “racoon eyes” or bruising behind the ears • CSF leaking from nose (rhinorrhoea) or ears (otorrhoea) • Focal neurology (unequal pupils, ﬂaccid limbs) • Seizures • Headache • Nausea, vomiting • Focal neurological signs and symptoms (unequal pupils, cranial nerve ﬁndings, limb weakness, papılloedema) • BP systolic >180 • Known hypertensive • Papilloedema and retinal haemorrhages or exudates • • • • Neurological deﬁcit or impairment Sudden onset Lasting >24 hours (can lead to death) Presumed vascular origin

Intracranial mass

Hypertensive encephalopathy

Cerebral vascular accident (CVA)

Transient ischaemic attack (TIA) Hypothermia Acute liver failure or hepatic encephalopathy

• Focal neurological symptoms or signs • Lasting <24 hours, with full recovery • Decreased core body temperature • Exposure to cold • Asterixis – hepatic ﬂap (ﬂapping tremor when arms are outstretched and wrists are dorsiﬂexed) • History of hazardous alcohol consumption or liver disease • Stigmata of chronic liver disease (spider naevi, petechiae, white nails) • Hepatosplenomegaly, ascites, foetor hepatıcus (musky breath) • Jaundice, hypoglycaemia

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Condition Uraemia see Section 11.31

In favour • • • • • • • • • • • • • • Asterixis – uraemic ﬂap Peripheral oedema, ascites, uraemıc frost History of renal disease Elevated creatinine and BUN Chronic use of alcohol or sedative drugs, with recent discontinuation Tremulousness Confusion Seizures Visual hallucinations Confusion Ataxia Ophthalmoplegia (double-vision, inability to moves eyes to side) Confusion History of hazardous alcohol consumption

Withdrawal from alcohol or other substances see alcohol (Section 16) and other substance use (Section 17) Wernicke-Korsakoff encephalopathy see Section 16

Some mental health problems can present as confusion; however, they do not cause a reduced level of consciousness. Psychosis, dementia, mania, severe learning disabilities see Section 10.11 • See abnormal behaviour, Section 10.11 Mental health

3.4.2 Manage delirium The appropriate treatment of delirium involves determining its underlying causes as well as treating its symptoms. If it is an acute case, health workers should consider the following: • Take measures to prevent the patient from self-harming or harming others due to confusion or agitation. • Assess for dehydration and give ﬂuids as necessary. • Check blood glucose and manage appropriately (see Quick Check page 41). • Decide where treatment should take place. (Hospitalization is usually desirable.) • Coordinate care with all team providers (the district clinician, nurses, medical assistants) who are caring for the delirious patient. This helps ensure appropriate and comprehensive evaluation and care. • Treat the underlying medical conditions. • For delirium due to alcohol withdrawal, give a benzodiazepine (diazepam) (see Section 3.7). Give parenteral thiamine and then glucose. Keep well-hydrated. If delirium persists, consider using antipsychotics such as haloperidol 2.5–5 mg orally up to 3 times daily. • For agitation or psychosis, give the patient low doses of antipsychotic medications (see Quick Check page 59 and Section 10.11 on mental health). The objectives of managing delirium are as follows: • Identify the underlying aetiology of the patient’s delirium and begin medical management. • Ensure that the patient is safe and comfortable. Supervise agitated patients. • Determine the appropriate place for the patient’s treatment (home versus hospital). For cases of severe delirium, treatment should take place in a

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hospital or other health setting. Treatment should involve several clinicians or the equivalent, including a mental health expert. If persons with delirium have milder symptoms, they may be treated in a nursing facility or at home. • Ensure an appropriate environment that does not worsen the delirium, confusion, and misperceptions. • Some environmental considerations include: ° lighting that corresponds with day and night to help reduce sleep disturbances; availability of a window may also assist in orienting the patient to time; ° control of the noise level, making it neither over-stimulating nor too quiet; ° ensuring that individuals who wear eyeglasses or hearing aids wear them, to help lessen confusion and disorientation; ° provision of a clock and calendar in the room to help keep patients oriented to the time and the day of the week. Determine whether management with psychotropic medication is appropriate. If symptoms do not abate, despite addressing medical problems and providing environmental support, consider very low-dose antipsychotics (see Quick Check page 59). If withdrawing from alcohol, see Section 3.7 Acute alcohol withdrawal.

3.4.3 Manage diabetic ketoacidosis Clinical presentation of diabetic ketoacidosis (DKA) The three main features of DKA are hyperglycaemia, ketosis, and acidosis. DKA is characterized by the following: • hyperglycaemia with blood glucose usually more than 300 mg/dl (more than 17 mmol/l); • ketonuria and ketonaemia with total ketones (beta-hydroxybutyrate [βΟΗΒ] and acetoacetate) in serum more than 3 mmol/l; • acidosis with blood pH <7.3 or serum bicarbonate <15 mEq/l; • hyperosmolar dehydration with serum osmolarity >320 mmol/l. DKA is commonly seen in paediatric patients with Type 1 diabetes, both at ﬁrst presentation and in established patients. DKA is also seen in adult patients with Type 2 diabetes at presentation, and in adult patients with established diabetes. This is the case particularly in the presence of infection, myocardial infarction, discontinuation of medications, or long duration of the disease. DKA is a major source of morbidity and mortality; therefore, preventing it should be the primary goal. DKA may cause • Dehydration – ﬂuid loss is generally 3 to 6 litres; expect to give many litres of ﬂuid. • Acidosis with consequent potassium (K) loss – all patients will require potassium replacement. Usual presentations • nausea, vomiting, abdominal pain • polyuria, polydipsia, and weight loss are often early indicators of hyperglycaemia • lethargy

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• a 2−3 day history of deterioration that may be precipitated by infection • apparent shortness of breath (hyperventilation with deep breaths, sighing breaths due to acidosis) • shock (due to dehydration or to sepsis) • coma • characteristic ketotic (sweet-smelling) breath • signs suggestive of a source of infection (pneumonia, urinary tract infection). The acute metabolic problems and dehydration are more dangerous than the underlying high blood sugar and should be addressed immediately

Investigations for DKA Conﬁrm the diagnosis • blood glucose more than 14 mmol/l or 252 mg/dl. If blood glucose is not available, the following investigations should be done: • Urine dipstick with 3+ or 4+ glucose with ketones. • Check electrolytes, creatinine, bicarbonate. Calculate anion gap (serum sodium – (serum chloride + serum bicarbonate). An anion gap of more than 12 mEq/l is abnormal; suspect acidosis. • If available (not required), check arterial blood gas if urine ketones or anion gap is elevated. Blood pH <7.3 conﬁrms acidosis (if venous, then +0.03 less than arterial). • Check an ECG (see Monitoring, below). • Consider precipitating cause for DKA ° urine dipstick and microscopy (for urinary tract infection) ° blood culture (if fever) ° chest X-ray (for pneumonia) ° ECG for chest pain (myocardial infarction).

Treatment of DKA Principles of management include giving IV ﬂuids and insulin, correction of electrolyte abnormalities (K), and treatment of precipitating cause. Use Quick Check pages 17–18 to assess airway and breathing, to protect the airway, and to give oxygen as needed. Use Quick Check page 19 to assess the circulation. If the patient is in shock, insert IV line. • Manage ﬂuids ° Administer 1 litre normal saline immediately – do not add K to this litre. ° Infuse normal saline as quickly as possible. ° If the patient is haemodynamically stable, infusion rate is 10−5 ml/kg body weight per hour in ﬁrst few hours (maximum 50 ml/kg in ﬁrst 4 hours) − generally 1 litre per hour in an average-size person. ° Fluid replacement should be more cautious in elderly or pregnant patients or in heart or renal failure.

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• Manage potassium (see .5.2.2) ° Rapid hydration with normal saline and early initiation of insulin can result in dangerously low K levels. When insulin is given, K moves rapidly into the cells, which can cause a drop in serum K. This is associated with a risk of heart arrhythmias. ° It is important to monitor serum K or ECG hourly for ﬁrst 3 hours if possible (then every 2 hours) and to carefully replace K to avoid hypokalaemia. It is also important to give K by infusion over an hour, never by bolus. ° Potassium chloride supplementation – maintain the K level between 4−5 mEq/l. ° Do not begin replacement until the level is <5.3 and there is adequate urine output (more than 50 ml/h). ° Add 20 mmol to each subsequent litre of saline – unless hyperkalaemia or hypokalaemia is present (see Monitoring below). A litre of normal saline with added K should be infused over 1 hour. ° Hyperkalaemia – if the level is ≥5.3 or there are tall, pointed T waves and a widened QRS complex, then continue NS or Ringer’s solution without K and check the level every 2 hours, or repeat ECG. ° Hypokalaemia – if the level is <3.3, or there are small or absent T waves and a large U wave following the T wave on the ECG, give 20–30 mmol K/hour until the level is higher than 3.3. ° If there is no capacity to measure K and no ECG, consider slowing the rehydration rate and giving empirical K supplementation starting from the second hour (20 mmol K in each litre of ﬂuid). Do not give K supplementation empirically until the patient has produced urine. • Manage glucose with insulin ° Administer soluble (short-acting) insulin IV or IM as soon as you have initiated ﬂuid resuscitation (see the table below). Be aware that children and adolescents younger than 18 years are at increased risk of cerebral oedema, and it is better to wait until ﬂuids have been given for 1–2 hours before starting insulin. ° Continue to monitor blood glucose and adjust insulin according to the table. Table: Management of DKA if K measurement or ECG is available and SBP >90 (If in shock with SBP<90, see Quick Check page 18 and Section 3.1.) Give ﬂuids Give K and insulin according to serum K or ECG result If K <3.3 mEq/l or ECG small (or absent) T waves and large U waves following T waves First hour from time of initiation of IV ﬂuids Give 1 litre NS IV over 1 hour Rapid repletion K: add 40 mEq/l K to one-half NS; run over 1 hour. No insulin therapy until K >3.3 mEq/l. If K 3.3−5.3 mEq/l or normal ECG If K >5.3 mEq/ l or ECG tall, pointed T waves and widened QRS

Do not add K. Give short-acting insulin by IV infusion or IM* • If IV, then bolus 0.15 U/kg body weight followed by infusion at 0.1 U/kg/hour • If IM or SC, 0.4 U/kg given as half IV and half IM or SC

Do not add K. Give insulin as in box to left.

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Give ﬂuids 2 and 3 hours nd rd

Give K and insulin according to serum K or ECG result Rapid repletion K: add 40 mEq/l K to 1/2 NS; run over 1 hour. No insulin therapy until K >3.3 mEq/l. 20 mmol K in each litre ﬂuid Continue insulin and adjust according to decrease in blood glucose. If blood glucose does not decrease by 50 mg/dl or 2.8 mmol/l in ﬁrst hour, increase insulin rate by 50% and repeat same procedure until glucose falls by 50 mg/dl or 2.8 mmol/l over a period of 1 hour. 20 mmol K in each litre ﬂuid Continue insulin and decrease the rate to 0.05 U/kg/hr when blood glucose <14 mmol/l or <250 mg/dl. Do not add K. Continue insulin as above.

Give NS 1 litre/ hour (average-size person)

Over next 4 hours

Give NS 1 litre/ hour (average-size person). Change to 5% dextrose in 0.45% NS when blood glucose <14 mmol/l or <250 mg/dl.

Continue K repletion as above. Delay or reduce rate of insulin therapy until K >3.3 mEq/l.

Do not add K. Continue insulin and decrease the rate to 0.05 U/kg/ hour when blood glucose <14 mmol/l or <250 mg/dl.

* In children and adolescents younger than 18 years, delay initiation of insulin until after the ﬁrst hour of rehydration to avoid cerebral oedema. See speciﬁc paediatric DKA protocols.

Monitoring DKA • Check the patient’s pulse, blood pressure, hydration status, and level of consciousness every hour, and conﬁrm that the ﬂuids are being infused intravenously. • If possible, check blood glucose every hour until it is stable (<12 mmol/l or <216 mg/dl), then maintain on a dextrose infusion and check every 2 hours. • Check K levels on presentation, then every hour for 4 hours, and then after 6 hours. Cease intravenous therapy and hourly insulin when the patient can eat and drink unaided and there are no signs of acidosis (deep sighing, breathing) and, if blood sugar testing is available, when the blood sugar is <12 mmol/l or 216 mg/dl. Patients should receive a maintenance insulin regimen once they are eating and drinking. See guidelines on chronic management of diabetes. Assess for signs of infection and initiate antibiotics as indicated.

3.4.4 Manage hypoglycaemia Hypoglycaemia can be deﬁned as a blood glucose level of <3.1 mmol/litre (<50 mg/dl). However, people with diabetes experience symptoms of hypoglycaemia at varying degrees of blood glucose concentration. Therefore, many people accept Whipple’s triad (symptoms likely caused by hypoglycaemia, low glucose measured at the time of the symptoms, and relief of symptoms when the glucose is raised) as conﬁrmation of hypoglycaemia. The exact level of blood glucose that deﬁnes hypoglycaemia remains a matter of debate. A lack of glucose to supply the brain may result in: • dizziness, confusion, difﬁculty speaking

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• • • • •

decreased consciousness or drowsiness seizures altered behaviour focal neurological deﬁcit sympathetic over-activity – sweating, anxiety, palpitations, hunger, tremor.

Hypoglycaemia should be suspected as a possible cause in all of these presentations, especially in patients being treated with hypoglycaemic agents (oral agents or insulin) for diabetes mellitus or with quinine for malaria, or consuming hazardous amounts of alcohol, as well as in those with severe infections or malnutrition. If hypoglycaemia is suspected, perform a ﬁnger-prick test or carry out laboratory testing immediately to either conﬁrm or rule it out, and urgently give 25–50 ml of 50% dextrose slowly. If glucose testing is unavailable or a delay in obtaining results is expected, treat with glucose empirically.

Some causes of hypoglycaemia Drugs and toxins Organ failure Infections Decreased food intake Insulin, sulphonylureas (e.g. glibenclamide), alcohol, quinine, pentamidine, β-blockers, herbal medicines, cotrimoxazole, haloperidol Liver failure, hypopituitarism, adrenal failure, myxoedema, chronic renal failure, chronic cardiac failure Sepsis, malaria Malnutrition, starvation, unable to eat due to illness, prolonged fasting (religious or otherwise)

Treatment of hypoglycaemia The goal of treatment of hypoglycaemia is to increase the blood glucose to a safe level and prevent sequelae by using an intervention that works fast and relieves symptoms quickly while avoiding rebound hyperglycaemia. • Mild to moderate hypoglycaemia is usually treated with food, oral glucose powder or tablets, or sucrose solutions. The guide is to administer 15–20 g glucose, to raise blood glucose by about 3 mmol/l (65 mg/dl). If the patient is conscious, give sweet drinks (not diabetic or sugar-free), e.g. cola, juice, sweet water. • After the administration of the ﬁrst 15–20 g glucose, patients should wait 15 minutes for symptoms to subside. Administration of glucose can be repeated after that time if the symptoms persist or if the blood glucose level is checked and is still low. • In case of loss of consciousness, give glucose (see Quick Check page 41). The treatment is 20–30 g dextrose IV as 200–300 ml 10% dextrose or 25–50 ml D50 (50% dextrose) slowly, followed by a saline ﬂush to avoid damage to the vein. • When the patient recovers consciousness, food should be provided as soon as the patient can ingest food safely. He or she will need sugary drinks, followed by a long-acting carbohydrate (e.g. bread, rice, maize) to prevent recurrence of symptoms.

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• Monitor blood sugar every 1−2 hours. A continuous infusion of dextrose (1 litre over 8 hours) may be required if blood sugar falls to <3 mmol/l. • Look for and treat the underlying cause. • If there is a possibility of hazardous alcohol consumption or if the patient is malnourished, also give parenteral thiamine (see Section 16).

Prevention of hypoglycaemia • Every person taking anti-diabetic agents (insulin or tablets) should be taught how to recognize the warning symptoms of hypoglycaemia and how to treat them promptly, even if they are subtle, to prevent progression to neuroglycopaenia. • Relatives, friends, teachers, and co-workers also should be taught how to recognize symptoms of hypoglycaemia. In general, they should be suspicious of any unusual behaviour on the part of the person with diabetes. • All hypoglycaemic episodes require treatment, even in the absence of symptoms.

3.4.5 Steroid deﬁciency (Addison’s disease; adrenal insufﬁciency) Patients with a deﬁciency of steroid hormones (cortisol and aldosterone) can present with hypotension, dehydration, and in severe cases: shock and hypoglycaemia.

Causes of adrenal insufﬁciency Adrenal insufﬁciency should be considered in all cases of shock (see Section 3.1). Impaired adrenal gland production of these steroids can result from the following infections. • TB (most commonly) • HIV (opportunistic infections) • disseminated fungal infection • meningococcal sepsis (resulting in adrenal haemorrhage) • human African trypanosomiasis • syphilis. Adrenal insufﬁciency also can be caused by autoimmune adrenalitis, metastatic cancer, and certain drugs, e.g. ketoconazole, or chronic use of prescribed steroids (i.e. for more than 2 weeks) or steroid-containing traditional remedies. An Addisonian crisis can be triggered by the underlying cause as well as by intercurrent infection, acute illness, surgery, abrupt cessation of steroids, or the administration of certain drugs (e.g. rifampicin or phenytoin) that increase hepatic breakdown of cortisol.

Investigations • electrolytes • glucose (ﬁnger-prick or laboratory) • Low Na, high K, and hypoglycaemia support the diagnosis; high calcium may also be present. • chest X-ray (look for TB)

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• abdominal X-ray (look for adrenal calciﬁcation) • blood and urine cultures (can help indicate underlying cause) • ECG, especially if electrolyte imbalances are detected.

Treatment • In hypotensive patients or patients in shock, immediately establish IV access and commence ﬂuid resuscitation with dextrose-containing ﬂuid. Give 1 litre immediately, the next litre over a 1-hour period, and then further ﬂuids at a slower rate determined by the patient’s response and ﬂuid volume status. • If the patient is hypoglycaemic, give 25–50 ml D50 IV slowly (see Quick Check page 41). • Commence urgent steroids. Give 100 mg hydrocortisone IV or 8 mg dexamethasone IV immediately then repeat every 8 hours. If neither is available, give 50 mg oral prednisolone once daily. This is a less effective alternative. See dose equivalents of different corticosteroids in Section 8.2. • Consider general supportive measures, including oxygen and broad-spectrum IV antibiotics for underlying infection, and a Foley catheter to monitor ﬂuid balance. • Regularly monitor pulse and blood pressure, as well as ECG, electrolytes, and glucose as possible. • Investigate and treat the underlying cause. Ongoing care • As the patient recovers and is eating and drinking unaided, IV ﬂuids can be stopped. The IV glucocorticoid should be given in decreasing doses over 3−4 days and then converted to an oral maintenance dose. A typical maintenance regime would be hydrocortisone 10 mg and 5 mg and 5 mg (with meals) or prednisone 5–7.5 mg once daily. • Newly diagnosed patients will need education on long-term steroid use, on the importance of compliance, and on doubling the dose with intercurrent illness. Dietary advice on a salt-rich, low-K diet should be provided when mineralocorticoid replacement is not possible. Gradual dose reduction after chronic steroid use • When steroids are prescribed for other medical conditions for more than 2 weeks, the dose should be reduced gradually.

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3.5 Approach to the patient with seizures or status epilepticus1 Seizures (ﬁts) are manifestations of excessive or abnormal electrical activity in the brain. They are characterized by abnormal movements or, less commonly, transient abnormalities in consciousness or sensation. They usually last for seconds or minutes but may be recurrent. Prolonged continuous seizures or recurrent seizures, where the patient does not recover consciousness between episodes, are known as status epilepticus. Depending on the cause, status epilepticus is associated with high mortality, particularly if seizures last more than 30 minutes. Always check glucose levels if possible. • Eclampsia is associated with pregnancy and should be considered in all female patients presenting with seizures. However, other causes may be possible. • In patients with suspected or known HIV infection, many opportunistic infections, such as toxoplasmosis, tuberculosis, cryptococcus, and lymphoma, may cause seizures. • Infections are a common cause of seizures, including meningitis, malaria, encephalitis, and parasitic infection (Taenia solium, neurocysticercosis).

Diagnosis of seizures and status epilepticus Most seizures are of limited duration, lasting only a few minutes. Symptoms are stereotyped: the same – at least at the start – of each episode. There is usually a period following the seizure in which patients return slowly to their normal mental state, known as the postictal period. Many patients will have a known history of seizures. If a person tends to have recurrent seizures, this is known as epilepsy. There are two types of seizures. Focal (partial) – these start from one part of the brain; the initial symptoms depend on the part of the brain involved. For example, with a lesion in the motor area, a focal seizure will start with involuntary movements on one side of the body (e.g. jerking movements of the left arm). The patient may be conscious. Less commonly, focal seizures may involve recurrent, brief, stereotyped sensory symptoms (tingling or paraesthesia), psychic symptoms (for example, recurring déjà vu), or varying degrees of loss of responsiveness, perhaps with stereotyped movements (e.g. recurrent lip-smacking). Focal seizures may progress to involve other parts of the body (secondary generalization). The affected area may be weak during the postictal period (Todd’s palsy). Generalized – in this type of seizure, the patient is almost always non-responsive. The most common type is known as tonic-clonic seizures, which start with stiffening and collapse (tonic); then jerking movements of the limbs occur (clonic). The patient may be incontinent or bite the tongue.

1 mhGAP intervention guide for mental, neurological and substance use disorders in non-specialized health settings. WHO and mhGAP Evidence Resource Centre, 2010. Available at: http://www.who.int/mental_health/ evidence/mhGAP_intervention_guide/en/index.html. The mhGAP Guidelines and the mhGAP-IG will be reviewed and updated in 5 years. Any revision and update before that will be made to the online version of the document.

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DDx: Seizures Condition Cysticercosis In favour • Endemic area • History of recurrent seizures • May or may not have focal neurological signs • Eclampsia, usually associated with hypertension, oedema • Usually occurs at term, during delivery, or immediately following delivery • Tendency to recurrent seizures, including where the cause is not known • Diabetic patient on treatment • Responds to glucose • History of hazardous alcohol use or use of sedative-hypnotic drugs, with recent cessation or markedly lower level of use • • • • Fever Signs of meningitis (neck stiffness, photophobia) Signs of encephalitis (confusion) Signs of brain abscess (focal neurological signs or septic emboli)

Pregnancy

Epilepsy Hypoglycaemia Alcohol or sedative drug withdrawal see Sections 3.6 and 3.7 CNS infection (meningitis, cerebral malaria)

HIV-related

• Toxoplasmosis, tuberculosis, cerebral lymphoma – all presenting with focal signs • If chest X-ray suggestive of tuberculosis, treat for TB (see Section 15). • If chest X-ray not suggestive of TB, treat for toxoplasmosis (see Section 11.40). • Electrolyte abnormalities (calcium, sodium, potassium) • Pesticides, antidepressants, amphetamines

Poisoning see Section 3.8

Management of acute seizures • Check the patient’s airway, breathing. Place in recovery position (see Quick Check page 42). Give oxygen using nasal prongs. • Give IV glucose D50 25–50 ml slowly (see Quick Check page 41). • Single short seizures that stop on their own (less than 5 minutes) may not require medication. • If seizures have not stopped after 5 minutes, give diazepam 10 mg IV or rectally. If available, lorazepam 4 mg IV is an effective alternative. • Look for the cause of the seizure. In particular, consider pregnancy-induced conditions (such as eclampsia), hypoglycaemia, meningitis (see 10.10b), and malaria (see Section 11.25). • If the seizure is thought to be due to alcohol withdrawal, also give thiamine 100 mg IV. On recovery give diazepam 10–20 mg every 2 hours until the patient is lightly sedated (or has received a total of 120 mg) to manage the withdrawal syndrome and prevent further seizures (see Section 3.7 Alcohol withdrawal).

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Seizures in pregnancy (usually more than 30 weeks, or just after pregnancy) may be caused by severe eclampsia. • For eclampsia, give magnesium sulfate (see Quick Check page 57); consider delivery and anti-hypertensives (see IMPAC MCPC).

Management of ongoing seizures (status epilepticus) Status epilepticus is deﬁned as seizures that last more than 30 minutes, or when successive convulsions occur so frequently that the patient does not recover consciousness between them. This is associated with high mortality. • Give glucose – D50 IV 25–50 ml IV slowly. • Give a repeat dose of diazepam 10 mg IV or rectally. Monitor the patient’s respiratory rate closely. • Give phenytoin 15–18 mg/kg IV (usually 1 g) in normal saline over a 1-hour period through a different line from the diazepam. • Monitor the pulse (preferably via an ECG) and respiratory rate every 15 minutes. • If the patient is already on phenytoin or it is not available, give phenobarbital 10 mg/kg IV over 15 minutes. • Give thiamine 100 mg IV (if seizures due to alcohol withdrawal) if not given previously. In ongoing seizures check the patient’s glucose. If resources (both equipment and staff) for airway management with bag valve mask ventilation or intubation with manual ventilation are available (see Quick Check page 31), then consider giving an additional dose of phenobarbital 10 mg/kg. Respiratory failure is a major risk when using phenobarbital, particularly with a repeat dose. Use with caution, particularly in severe malaria and if other drugs have been given that also cause respiratory depression. Monitor carefully. Apnoea can occur suddenly. Ongoing maintenance treatment of ﬁrst seizure (see Section 10.10c) Adult-onset seizures are more likely to be associated with recurrence and will require further investigation to establish the underlying cause. Treatment is indicated for patients with recurrent seizures. However, ongoing maintenance treatment may not be required for seizures associated with alcohol withdrawal or pregnancy (eclampsia). Anticonvulsant regimens that provide effective maintenance treatment of seizures include: • phenytoin starting at 150–200 mg/day, increasing by small increments of 25–30 mg until maintenance dose of 200–400 mg daily is reached; • carbamazepine 100–200 mg/day, increasing weekly by 100–200 mg; maintenance dose of up to 400–1400 mg daily in divided doses; • phenobarbital starting at 1 mg/kg/day for 2 weeks. If poor response, increase to 2 mg/kg/day for 2 months. If seizures persist, increase to 3 mg/kg/day (180 mg) in divided doses. For patients with HIV, possible treatable causes include TB (see Section 15) and toxoplasmosis (see Section 11.40).

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3.6 Manage intoxication or overdose, or withdrawal from injecting or other use of opioids, amphetamine-type stimulants, or cocaine2,3 In this section: 3.6.1 Opioid intoxication or overdose • Treatment of opioid intoxication or overdose 3.6.2 Manage opioid withdrawal • The effects of acute opioid withdrawal • Manage acute opioid withdrawal 3.6.3 Manage stimulant intoxication and overdose − Standard stimulant intoxication • Complicated stimulant intoxication • Amphetamine and cocaine acute intoxication – initial management • Special features of cocaine intoxication or overdose 3.6.4 Manage stimulant withdrawal • Symptomatic management of withdrawal • Non-pharmacological management of withdrawal

3.6.1 Opioid intoxication or overdose Overdose is a leading cause of morbidity and mortality among injectors of opioid drugs. Up to 80% of heroin users have experienced an overdose while using it. The high risk of overdose is associated with the following: • when 2 or more drugs that have interacting effects are used concurrently (e.g. combined use of opioids, alcohol, and benzodiazepines or other sedatives); • injection methods rather than smoking of opioids; • injecting or other heroin use on one’s own – when no one else is present; • when tolerance is low (e.g. in the ﬁrst few weeks following release from prison, after detoxiﬁcation, or after discharge from a rehabilitation centre). Depressant drugs such as opioids (e.g. heroin) and sedatives (e.g. benzodiazepines and alcohol) slow down the body’s functions. A person who overdoses on a depressant may experience respiratory arrest, i.e. their breathing will become very slow or will stop altogether, leading to death. Death usually occurs 1–3 hours after injection rather than immediately afterwards. Signs and symptoms of opioid intoxication or overdose: • pinpoint pupils and • slow breathing, often with • slurred or interrupted speech • nodding • unsteady gait. Consider also the differential diagnosis for other causes of decreased level of consciousness and confusion (see Section 3.4). Consider that the patient may be using other drugs. 2 Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. WHO, 2009. Available at http://www.who.int/rpc/guidelines/9789241547543/en/ 3 mhGAP Intervention Guide for mental, neurological and substance use disorders in non-specialized health settings. WHO, 2010. Available at http://www.who.int/mental_health/evidence/mhGAP_intervention_guide/en/ The mhGAP Guidelines and the mhGAP-IG will be reviewed and updated in 5 years. Any revision and update before that will be made to the online version of the document.

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Treatment of opioid intoxication or overdose See Quick Check (page 40) for instructions on giving naloxone. Not everyone with pinpoint pupils and the above signs requires naloxone. It is indicated when the respiratory rate is <10/minute, or SpO2 <90. Giving someone who has overdosed an injection of naloxone can precipitate an opioid withdrawal syndrome that can cause temporary but often signiﬁcant agitation and discomfort. The person may become upset that they have lost their «high», refuse to stay in the hospital, and may become aggressive if restrained. To minimize this risk, naloxone should be administered in small doses as indicated in Quick Check. This makes the reversal of overdose more gradual and more controllable. Naloxone is short-acting and wears off within 2–3 hours. This is long enough to reverse the effects of short-acting opioids such as heroin. If a person has used longacting opioids (such as methadone or oral slow-release morphine formulations), they may develop the signs of overdose again when the naloxone wears off. It is therefore important to establish whether the person has used short- or long-acting opioids. An adequate supply of naloxone should be available in district hospitals and staff should be trained in administering it properly. Once the patient has recovered from the overdose, there is an opportunity to talk to the patient. • Establish what drugs were used. • Explain the implications of the overdose. • Consider whether they may need drug detoxiﬁcation or opioid substitution treatment (see Section 17). • Consider that they may have TB or be infected with HIV or viral hepatitis B or C infection. • Recommend HIV testing and counselling (see Section 9), assess for TB and viral hepatitis, and vaccinate for viral hepatitis B. • Counsel about harm reduction (see Section 17). • Counsel about safer sex. Promote and provide condoms, if needed.

3.6.2 Manage opioid withdrawal The effects of acute opioid withdrawal Withdrawal symptoms differ depending on the dose and duration of action of the opioids used, and the patient’s neuroadaptive state. Stopping short-acting opioids leads to withdrawal symptoms at an earlier phase than with long-acting opioids; symptoms peak and resolve earlier. Most opioids have a short duration of action (hours), and the withdrawal syndrome usually lasts 4 to 5 days. The main exceptions are methadone and buprenorphine, and also slow-release preparations of morphine and oxycodone. Signs and symptoms of acute opioid withdrawal: • tremors, shivers • tear formation, rhinorrhoea, yawning • muscle cramps • restlessness

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• • • • • •

gooseﬂesh disturbed sleep or inability to sleep diarrhoea extreme anxiety nausea and vomiting tachycardia.

When assessing withdrawal, examine the patient for both subjective and objective withdrawal symptoms. Subjective withdrawal symptoms are more sensitive measures of opioid withdrawal, but, when they are present, objective symptoms are more reliable.

Manage acute opioid withdrawal (See Section 17.8 for management of withdrawal in hospitalized patients with a medical condition that is causing acute pain.) The management of acute opioid withdrawal depends on the medications available. Buprenorphine (a partial opioid agonist) and methadone (a full agonist) 4 are the most effective for relieving symptoms and ensuring that patients can complete a detoxiﬁcation schedule. • Buprenorphine is given sublingually at a dose range of 4–16 mg/day for 3−14 days. It must not be given while the person has any signs of opioid toxicity because there is a risk that it will precipitate a withdrawal syndrome. • Methadone is given orally at an initial dose of 15–20 mg, increasing to 30–40 mg/day, and then tapering off over 3−28 days. • Care should be taken particularly if the patient is prescribed other sedative drugs. • Treat symptoms as necessary using pharmacological and nonpharmacological care. If the patient has: • muscle cramps and pain Ö give ibuprofen or other NSAIDs • nausea and vomiting Ö give anti-emetics (see Section 10.7c) • restlessness or sleep disorder Ö give mild sedatives such as a sedating antihistamine • diarrhoea Ö see Section 10.7d. Consider giving loperamide. Advise the patient about harm reduction, safer sex, and recommend HIV testing. Consider referral to a drug treatment facility for opioid substitution – see Section 3.6.1 above.

4 If these medications are not available, use oral alpha-2 agonists: clonidine 300 mcg–1.2 mg daily (in doses of 75–300 mcg, 3−4 times daily), or lofexidine 600 mcg–2.4 mg daily (in doses of 150–600 mcg 3−4 times daily). The exact dose depends on body weight, severity of withdrawal, and the patient’s response. Continue for 4−7 days. See Adaptation Guide.

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3.6.3 Manage stimulant intoxication and overdose Stimulant intoxication from amphetamine, amphetamine-type stimulants (ATS), or cocaine can be classiﬁed as “standard” or “complicated”.

Standard stimulant intoxication Signs and symptoms of standard intoxication include dilated pupils associated with any of the following: • irritability, hyperactivity • teeth grinding • restlessness • intermittent paranoia • fast pulse.

Complicated stimulant intoxication Complicated intoxication presents as an acutely disturbed mental state typiﬁed by marked paranoia. Also, it can be associated with a number of other symptoms, such as: • nausea and vomiting • sweating • malaise • abdominal pain • fever • chest pain • arrhythmia (that can lead to myocardial infarction) • progressive psychotic disturbance, including auditory hallucinations • behaviour that is dangerous to the patient or to others • seizures • uncontrolled hypertension.

Amphetamine and cocaine acute intoxication – initial management Patients with acute complicated psychostimulant toxicity should immediately be admitted to the hospital for treatment. Manage the patient as follows: • Ensure the patient is taking ﬂuids and monitor their urine output. • Provide a soothing, non-stimulating and non-threatening environment. • For severe agitation, anxiety and psychosis, give diazepam in titrated doses until the person is calm and lightly sedated. • If there is an inadequate response to diazepam and no other cause of delirium is identiﬁed, give antipsychotics (haloperidol or chlorpromazine). • Periodically monitor the patient’s ECG, BP, and body temperature. For standard (less severe) psychostimulant intoxication, the interventions available are largely social and supportive. • Provide a non-stimulating environment, with support and reassurance. • Prevent the person from harming themselves or others (provide a safe space to “chill out”).

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• Avoid confrontation. • Encourage support from family or sober friends.

Special features of cocaine intoxication or overdose Cocaine overdose is associated speciﬁcally with some potentially lethal reactions, including myocardial infarction, hypertensive crisis, cerebral haemorrhage, aortic dissection and hyperthermia. Arrhythmias may also occur, but are likely to be lethal only in the presence of previous myocardial damage.

3.6.4 Manage stimulant withdrawal Characteristics of psychostimulant withdrawal syndrome include: • fatigue and exhaustion (lack of energy) • hunger • emotional lability and irritability • depressed mood and anxiety • restlessness and agitation • fear • drowsiness and overwhelming desire to sleep (but may sleep poorly) • cravings. The withdrawal syndrome usually lasts 2–4 weeks, although the acute “crash” only lasts for 1–4 days. This syndrome is followed by strong urges to use amphetamines again, which may increase over the following 6 weeks. Symptoms include: • disrupted sleep • headache • body aches • increased appetite • irritability • paranoia • misinterpretations.

Symptomatic management of withdrawal The withdrawal syndrome should be treated sparingly and symptomatically (with extra care if benzodiazepines are used). The person usually becomes symptomfree 1–3 months after stopping amphetamine use, although the cravings may persist for years.

Non-pharmacological management of withdrawal In addition to the symptomatic treatment above, the management of the environment is important. A safe environment includes a safe, secure situation, access to supportive family and other supports, instruction in relaxation, sleep advice with contingency management, and other drug counselling. An inpatient facility or detoxiﬁcation centre may be appropriate, particularly in the presence of polydrug dependence, psychiatric complications, absence of social supports or a previous complicated withdrawal.

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3.7 Acute alcohol withdrawal and intoxication5 3.7.1 Acute alcohol withdrawal Alcohol withdrawal is a neural hyperexcitability syndrome which occurs when an alcohol dependent person suddenly stops heavy alcohol consumption. To make a diagnosis of alcohol withdrawal There must be a recent cessation of or a reduction in drinking after repeated, often prolonged and hazardous alcohol consumption. Symptoms and signs that are compatible with known features of alcohol withdrawal: • tremor of the tongue, eyelids, or outstretched hands • sweating • nausea, retching, or vomiting • tachycardia or hypertension • psychomotor agitation • headache • insomnia • malaise or weakness • transient visual, tactile, or auditory hallucinations or illusions • grand mal convulsions. Symptoms and signs are not accounted for by a medical disorder unrelated to alcohol use, and are not better accounted for by another mental or behavioural disorder. If delirium is present, the diagnosis should be alcohol withdrawal state with delirium (delirium tremens).

Alcohol withdrawal syndrome is often mild and may not require medical intervention. However, when severe, it can be life threatening, and can include tonic-clonic seizures, and a delirium characterized by disorientation and visual hallucinations. The aim of management is to identify patients at risk of alcohol withdrawal and to treat withdrawal symptoms before they become too severe. Alcohol withdrawal usually develops within 24 hours of the last drink, peaks at 2–3 days, and usually resolves within 5 days. When withdrawal seizures occur, this is usually in the ﬁrst 48 hours. Confusion, delirium, and hallucinations occur in severe withdrawal, and can persist for days or (rarely) up to 2 weeks. Sedation with benzodiazepines reduces the severity of delirium and hallucinations due to alcohol withdrawal. However, it must be recognized that other causes of delirium and hallucinations may be present, which will require speciﬁc, additional forms of treatment.

5 mhGAP Intervention Guide for mental, neurological and substance use disorders in non-specialized health settings. WHO and mhGAP Evidence Resource Centre, 2010. Available at http://mental_health/mhgap/evidence/ en/index.html. The mhGAP Guidelines and the mhGAP-IG will be reviewed and updated in 5 years. Any revision and update before that will be made to the online version of the document.

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The following ﬁgure summarizes the progression of the alcohol withdrawal syndrome over time.

Progression of the alcohol withdrawal syndrome

A patient with alcohol withdrawal often has other medical problems. This increases the probability of severe alcohol withdrawal. These other medical problems may include: • urinary tract infections • pneumonia • Wernicke’s encephalopathy • hepatic encephalopathy • gastrointestinal bleeding • head injury with or without subdural haematoma • stroke • hypoglycaemia • metabolic and ﬂuid and electrolyte disturbances • acute psychotic illness. It is important to consider and treat these other medical problems. Use the Quick Check, then the acute care Section 10 for each main symptom. Alcohol-dependent individuals also may be dependent on benzodiazepines. This means that higher doses of diazepam will be needed to treat the alcohol withdrawal.

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Delirium tremens • Occurs in about 5% of patients with alcohol withdrawal. • Onset – usually 24 hours to 96 hours after the last drink. • Seizures may herald the onset of delirium tremens, generally preceded by other alcohol withdrawal features. Clinical features of delirium tremens Symptoms are similar to those of severe alcohol withdrawal, with marked tremor, and the following: • delirium (agitation, disorientation, and confusion) • hallucinations (typically visual, sometimes auditory) • paranoid delusions • autonomic hyperactivity, marked agitation • sweating, dehydration, electrolyte disturbances (hypokalaemia, hypomagnesaemia) • possible cardiovascular collapse. Untreated delirium tremens has a mortality of up to 30%. Patients with severe alcohol withdrawal and, in particular, delirium tremens need to be hospitalized urgently and investigated to identify any aggravating factors.

Treatment of alcohol withdrawal syndrome Treatment of alcohol withdrawal is with a benzodiazepine, typically diazepam. The doses needed may vary from 5–10 mg to several hundred milligrams. The principle of safe treatment is titration of the dose, based on frequent monitoring of the severity of withdrawal symptoms and the response to treatment. The aim of treatment is to keep the patient for 3 days in a state of light sedation. Alcohol withdrawal severity is easily measured clinically. An alcohol withdrawal scale, such as the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-AR), can be used to quantify the severity of alcohol withdrawal, can assist in its early detection and monitoring, and can guide diazepam dosing instructions for nursing staff (see example below). Adequate sedation reduces anxiety and agitation and helps to prevent hallucinations, seizures, and delirium tremens. A patient with alcohol withdrawal that progresses to a severe syndrome and delirium tremens may need a high level of medical and nursing attention.

The following regime is suitable for patients who have no complicating medical disorders 1. Sedation If there are no contraindications, a benzodiazepine should be given. Diazepam is the most commonly used. If the patient presents in an alcohol withdrawal state, give diazepam 10–20 mg orally every 2 hours until the patient is calm and mildly sedated. Titration of diazepam can be delegated to non-medical staff with the assistance of a withdrawal scale. Use extreme caution in using diazepam if the patient has a head injury or other medical cause of confusion or delirium (such as hepatic encephalopathy). Patients can have a tendency to abuse benzodiazepines; therefore, they should not be prescribed for more than 1 week. The diazepam regime for a simple withdrawal should be ﬁnished within a week to avoid risk of benzodiazepine dependence.

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Following delirium tremens, up to 10 days of sedation reduction may be required. Patients should not be discharged with a prescription for benzodiazepines. 2. Antipsychotic medication There is no place for antipsychotics in the management of simple alcohol withdrawal. In alcohol withdrawal delirium, diazepam is the preferred medication (see below for dose schedule). Antipsychotic drugs, such as haloperidol 2.5–5 mg orally 3–4 times daily, can be used in addition to benzodiazepines to manage delirium that persists after tremor and sweating have subsided. The use of antipsychotic drugs early in withdrawal increases the likelihood of seizures. 3. Thiamine and multivitamin supplements Administer thiamine 100 mg daily orally for 5 days for all patients. If the patient is malnourished or unable to take oral medication, give thiamine 100 mg daily IM for 5 days, then switch if possible to oral medication. Continue thiamine 100 mg daily long term. Consider other vitamin supplementation when indicated. Ensure that the patient is well-hydrated and eats well. 4. Oral or intravenous ﬂuids If a patient is dehydrated, the condition needs to be corrected. Use ORS if there are signs of dehydration (see Section 10.7 on diarrhoea). Use IV ﬂuids if the patient has a delayed recovery from a seizure. 5. Potassium Correct hypokalaemia with appropriate potassium supplements 80–240 mmol daily (see Section 5.2). 6. Magnesium Correct hypomagnesaemia, e.g. magnesium aspartate 500 mg orally 2–4 times a day, taken with meals (contraindicated in cases of renal failure). 7. Supportive care If patient has hypoglycaemia, give glucose (see Quick Check page 41) but only after the patient has received thiamine 100 mg IV or IM. If there have been periods of prolonged immobility which may cause rhabdomyolysis and acute renal failure, check CPK. Turn the patient regularly. 8. Skilled nursing Skilled nursing is vital in managing alcohol withdrawal. Manage the environment, nurse the patient in a quiet dimly lit room, constantly reassure and reorientate the patient, and check the alcohol withdrawal scale regularly, e.g. every 2−4 hours in the hospital. 9. Close monitoring Close monitoring (every 2–4 hours) of the alcohol withdrawal is recommended for all patients (CIWA-AR should be <10). If the patient has a seizure • Use Quick Check and Section 3.5. • Ensure a responsible person remains with the patient at all times. • Place the patient in a quiet room without bright lights.

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• Every 30–60 minutes monitor BP, pulse, temperature, respiratory rate, and record the alcohol withdrawal score. • If recovery of consciousness is slow, ensure adequate IV ﬂuids. Following recovery from the seizure, give diazepam 10–20 mg every 2 hours until the patient is lightly sedated (or has received 80 mg) to manage the withdrawal syndrome, prevent further seizures, and reduce the likelihood of delirium. There is no need for ongoing anticonvulsant therapy after an alcohol withdrawal seizure. If the patient has alcohol withdrawal delirium • Use Quick Check and Section 3.4. • Insert an IV cannula. • Give 5 mg diazepam IV, repeated if necessary every 15 minutes until the patient is in a state of light sedation or can take oral diazepam. • Exclude other causes of confusion, e.g. hypoxia, infections, subdural haematoma, metabolic and electrolyte imbalance, CVA, or decompensated liver disease. • Ensure skilled nursing care is available. • Place the patient in a quiet room with adequate but not bright lights. • Every 30 minutes monitor BP, pulse, temperature, respiratory rate, and record the alcohol withdrawal score. • Give thiamine 100 mg IV or IM daily. • Give adequate ﬂuids IV. Following recovery from the delirium, diazepam should be given according to the severity of the residual withdrawal state.

Precautions in patients who have complicating medical disorders If patients have chronic airﬂow limitation without respiratory failure, the dose of diazepam should be reduced and carefully titrated. Monitor SpO2 before and after each dose of diazepam. If there is respiratory failure, DO NOT sedate. Use Quick Check airway management instructions (page 29) and obtain help urgently to maintain a clear airway. Give oxygen cautiously and assist with ventilation. In patients with liver disease with hepatic decompensation (encephalopathy, ascites, jaundice), benzodiazepines may worsen hepatic encephalopathy. In these cases, often the patient is already drowsy and no diazepam is necessary. If patients are exhibiting signs of autonomic hyperactivity consistent with alcohol withdrawal, give them a small dose of diazepam, and wait to see what effect it has and how long it lasts. Often, one dose is sufﬁcient. An example alcohol withdrawal scale follows – the CIWA-AR alcohol withdrawal scale.6 The scale is used to monitor and treat all patients who might be alcoholdependent and have ceased alcohol consumption in the previous 72 hours.

6 Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). British Journal of Addiction, 1989;84:1353-7.

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Is the patient at low risk of alcohol withdrawal? • drinking <6 drinks per day, and • no previous history of alcohol withdrawal.

Treatment as usual

Is the patient currently experiencing severe withdrawal (CIWA >20) or likely to experience severe alcohol withdrawal? • cessation of heavy alcohol within the last week, and • previous severe alcohol withdrawal episodes, or • previous alcohol withdrawal seizures or alcohol withdrawal delirium.

Treatment of withdrawal symptoms as they emerge with 20 mg diazepam every 2 hours until patient is lightly sedated. Monitor with CIWA for 1 week and treat reemergence of withdrawal.

Monitor for emergence of alcohol withdrawal with CIWA. Treat withdrawal symptoms if and when they emerge.

• 10–20 mg diazepam if CIWA ≥10, and repeat CIWA in 2 hours. • 5–10 mg diazepam if CIWA <10, for mild withdrawal symptoms. Repeat CIWA in 4–8 hours. • Continue until CIWA <10 for 24 hours after the last dose of diazepam. • Do not give diazepam if the patient is sedated, no matter what the CIWA score. • Do not base treatment on CIWA score if it is elevated for other reasons (i.e. other medical problems).

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CIWA-AR alcohol withdrawal scale (AWS) Record observations according to the following scale. Transfer the scores to the summary sheet on the following page. Nausea and vomiting Ask “Do you feel sick to your stomach? Have you vomited?” 0 1 2 3 4 5 6 7 No nausea and no vomiting Mild nausea and no vomiting Tactile disturbances Ask “Have you any itching, pins and needles sensations, any burning, any numbness, or do you feel bugs crawling under your skin?” 0 None 1 Very mild itching, pins and needles, burning or numbness 2 Mild itching, pins and needles, burning or numbness 3 Moderate itching, pins and needles, burning or numbness 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations Auditory hallucinations Ask “Are you more aware of sounds around you? Are they harsh? Do they frighten you? Are you hearing anything that is disturbing to you? Are you hearing things you know are not there?” 0 1 2 3 4 5 6 7 Not present Very mild harshness or ability to frighten Mild harshness or ability to frighten Moderate harshness or ability to frighten Moderately severe hallucinations Severe hallucinations Extremely severe hallucinations Continuous hallucinations

Intermittent nausea with dry heaves

Constant nausea, frequent dry heaves and vomiting

Tremor Observe patient’s arms extended and ﬁngers spread apart.

0 1 2 3 4 5 6 7

No tremor Not visible, but can be felt ﬁngertip to ﬁngertip

Moderate, with patient’s arms extended

Severe, even with arms not extended

Paroxysmal sweats Record observations.

Visual disturbances Ask “Does the light appear to be too bright? Is its colour different? Does it hurt your eyes? Are you seeing anything that is disturbing to you? Are you seeing things you know are not there?” 0 1 2 3 4 5 6 7 Not present Very mild sensitivity Mild sensitivity Moderate sensitivity Moderately severe hallucinations Severe hallucinations Extremely severe hallucinations Continuous hallucinations

0 1 2 3 4 5 6 7

No sweat visible Barely perceptible sweating, palms moist

Beads of sweat obvious on forehead

Drenching sweats

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Anxiety Ask “Do you feel nervous?”

Headaches, fullness in head Ask “Does your head feel different? Does it feel like there is a band around your head?” Do not rate for dizziness or light headedness. Otherwise rate severity. 0 1 2 3 4 5 6 7 Not present Very mild Mild Moderate Moderately severe Severe Very severe Extremely severe

0 No anxiety, at ease 1 Mildly anxious 2 3 4 Moderately anxious, or guarded, so anxiety is inferred 5 6 7 Equivalent to acute panic states as seen in severe delirium or acute schizophrenic reactions Agitation 0 1 2 3 4 5 6 7 Normal activity Somewhat more than normal activity

Orientation and clouding of sensorium Ask: “What day is this? Where are you? Who am I?” 0 1 2 3 4 Orientated and can do serial additions Cannot do serial additions or is uncertain about date Disorientated for date by no >2 calendar dates Disorientated for date by >2 calendar dates Disorientated for place or person

Moderately ﬁdgety and restless

Paces back and forth during most of the interview, or constantly thrashes about

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Estimated date and time of last drink Date: Time: Nausea and vomiting Tremor Paroxysmal sweats Anxiety Agitation Tactile disturbances Auditory hallucinations Visual disturbances Headaches, fullness in the head Orientation and clouding of sensorium Score

Vital signs: Temperature Pulse Respiratory rate BP

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3.7.2 Acute alcohol intoxication This Section summarizes interventions for acute alcohol intoxication and other acute syndromes related to acute alcohol consumption. People with alcohol intoxication, or who are suffering acute problems from its use, may present to services such as health posts, the police, ambulance services, emergency departments, and acute care clinics. Ensure the patient is in a safe environment. Use Quick Check and monitor vital signs. Repeat Quick Check regularly. Conduct a brief overall assessment. a. Is the person aggressive or hyperactive? If yes, then: • consider whether the person has used psycho-stimulants, or has a psychiatric disorder; • beware of giving sedation if the intoxication is due to alcohol alone as this may increase the degree of aggression or cause sudden loss of consciousness; • medical back-up may be needed. b. Is the person slow, confused or do they have a reduced conscious level? If yes, then: • ensure that vital signs are stable by regularly monitoring airways, breathing, circulation. c. Is the person unconscious? If yes, consider the following: • Place the patient on their side (in “coma position”) to avoid aspiration. Consider the need to use assisted respiration in patients with severe respiratory depression. • Check for evidence of a head injury, other injuries, fever and other causes of confusion and reduced conscious level. • If the patient is confused, give parenteral thiamine. • Protect the patient from falls and avoid prolonged immobility to prevent rhabdomyolysis. • Check blood glucose. Repeated use of intoxicating amounts of alcohol places a person at high risk of acute harm and of long-term damage (see Section 16 on alcohol).

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Place the person in a safe environment and conduct a brief overall assessment Ask about alcohol use

If the person is aggressive or hyperactive and a danger to self or others Seek medical back-up (the patient may have used psychostimulants or have a psychiatric illness and may need sedation or antipsychotics)

If the person is slow, confused or has reduced consciousness Use Quick Check (repeat): Airway Breathing Circulation Monitor vital signs

If the person is unconscious Place on their side in coma position to avoid aspiration. Use Quick Check (repeat): Airway Breathing Circulation Monitor vital signs Manage airway (see Quick Check p.12)

Check for evidence of head injury, other injuries, fever, and other causes of confusion and reduced consciousness Protect from falls and avoid prolonged immobility in order to prevent rhabdomyolysis Call for medical back-up

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3.8 Poisoning In this section: 3.8.1 Opioid intoxication or overdose • Ingested poisons or overdose of medicines • Prevent aspiration of gastric contents • Assess airway and breathing • Assess circulation • Assess neurological impairment • Assess the need for antidotes • Risk assessment • Common agents • Management principles for ingested poisons • Important considerations in resuscitation and stabilization that may differ from management of nonpoisoned patients • Differences with standard guidelines for management of arrhythmias and advanced cardiac life support • Criteria for inpatient hospital admission • Removal of the poison from the gastrointestinal tract (gut decontamination) • Induction of vomiting (emesis) to treat poisoning should usually not be used • Very limited role for gastric lavage • Activated charcoal may be useful in the ﬁrst 1–2 hours after ingestion for some poisons • Very limited role for whole bowel irrigation (WBI) for gut decontamination • Management of speciﬁc poisons • Table: Poisons or toxins, symptoms of toxicity in overdose, and brief guidance on speciﬁc management 3.8.2 Inhaled poisons • Table: Inhaled poisons or toxins, symptoms of toxicity, and brief guidance on speciﬁc management 3.8.3 Chemicals on the skin or in the eye • Health worker protection • Manage chemicals in the eye • Manage chemicals on the skin • Manage organophosphates or carbamate on skin • Manage exposure to tear gas (e.g. CN or CS gas)

Suspect poisoning if a previously healthy patient presents with any unexplained illness. Poisoning can occur with pharmaceutical agents, recreational drugs, commercial and household chemicals, agrochemicals, plants and fungi. Traditional medicines and contaminated food and water can also be sources of poisoning. Ingestion is the most common route of exposure, but poisoning can occur through inhalation and skin exposure, as well as from venomous bites and stings (see Section 3.9 Snakebite). Possible poisoning from alcohol, opioids, and other recreational drugs is discussed in Sections 3.6 and 3.7.

3.8.1 Ingested poisons or overdose of medicines Poisoned patients can present to a medical facility in a multitude of clinical scenarios. They may walk in, be brought in a drowsy state with stable vital signs, or brought in unconscious with upper airway obstruction and unstable cardiovascular status (shock or arrhythmia). All patients who present with a possibility of poisoning should be evaluated immediately for life-threatening conditions such as hypotension, hypoxia, hypoglycaemia, and electrolyte abnormalities, followed by a risk assessment. • Use Quick Check to assess emergencies of airway, breathing, circulation, coma or convulsions, and to deliver emergency treatments.

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Prevent aspiration of gastric contents This is one of the most important aspects of the management of poisoning with either central nervous system depressants or those causing signiﬁcant vomiting. Preventing aspiration is also important during transport of the patient from the site of poisoning to the nearest medical facility. • Patients who are drowsy should be managed in the recovery position (see Quick Check page 42) to prevent gastric aspiration.

Assess airway and breathing Use Quick Check for guidance on the assessment of airway and breathing emergencies and how to deliver emergency treatments, such as how to manage the airway (e.g. head manoeuvres), how to give oxygen, how to give salbutamol for wheezing, and advanced airway management (e.g. indications for intubation, manual ventilation, transferring a patient). Also, see Section 3.2.3 for more detailed discussion of caring for the severely ill patient with respiratory distress. Patients with poisoning can present with severe respiratory distress from multiple causes, such as the inability to protect the airway, poor respiratory effort, upper airway obstruction, bronchospasm, aspiration, or acute lung injury. Look for signs of severe respiratory distress in the poisoned patient, such as: • a rapid or very slow respiratory rate • cyanosis, SpO2 <90 • abnormal auscultatory ﬁndings (e.g. bronchospasm, crackles, or rales) • Sluggish chest movement with compensatory abdominal movement suggests severe diaphragmatic muscle weakness and is an indication of inadequate ventilation. • Low AVPU score (P or worse) suggests the patient may not be able to protect their airway and is at high risk for aspiration. If the patient does not cough during suction of secretions in the pharynx, it is unlikely that they can protect their airway. It is difﬁcult to generalize a safe rate of breathing in a patient with poisoning. In assessing the airway, it is paramount to remember the above-mentioned clinical features and monitor the patient closely to see if symptoms worsen or improve. A respiratory rate of <8 warrants action as soon as possible. For example, in patients with opioid toxicity, give naloxone and assist ventilation with a bag valve mask (BVM) (see Quick Check page 31) until the patient recovers and can breathe unassisted. A rate of 12 (normal) may indicate the need for further assessment of other clinical parameters and close monitoring to see if breathing becomes abnormal. If the patient has a respiratory rate greater than 25 or other signs of respiratory distress, look for the cause. Fast breathing can be caused by many factors, for example: • hypoxia secondary to excessive secretions from respiratory mucosa, as in cases of organophosphorous self-poisoning. This should be conﬁrmed by auscultation for crackles (rales) or wheezing, followed by the administration of atropine. • hypoxia due to aspiration of gastric contents. Auscultation will reveal coarse crepitations in a single lung in most cases. This can lead to acute lung injury, with diffuse crackles and inﬁltrates on chest X-ray (see Section 3.2.3). • changes in acid-base status, such as metabolic acidosis or primary stimulation of the respiratory centre (causing respiratory alkalosis), as in salicylate

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toxicity. It is very important to think of this possibility if the patient has a normal peripheral saturation and clear lungs. (Analysis of arterial or venous blood gas is useful.)

Assess circulation If the patient is talking and alert, serious cardiovascular abnormality is unlikely. In most cases of poisoning, hypotension can be treated with the administration of IV ﬂuids (see Quick Check page 39 and Section 3.1). In addition, some cases may require administration of antidotes. Determine further ﬂuid requirements based on the clinical response (look for signs of adequate perfusion and signs of ﬂuid overload). See Section 3.1 for further details regarding management of shock. For shock that is unresponsive to ﬂuid resuscitation and antidotes, consider vasopressors early, as many poisons can cause depressed myocardial contractility. The presence of hypertension following overdose is rare, and should alert to the possibility of cocaine, amphetamine, or other sympathomimetic agents (see Section 3.6.3).

Assess neurologic impairment Neurological status should be assessed using the AVPU scale (see Section 3.4). If the score is P or worse and the patient has no cough reﬂex, the patient is at high risk for aspiration. Failure to protect the airway is an indication for advanced airway management with tracheal intubation. This should be considered when it is feasible to perform manual ventilation for short-term conditions, or if transfer to another hospital with mechanical ventilation is possible. See Quick Check pages 29–32 for further details on advanced airway management. Patients who are drowsy should be managed in the recovery position (see Quick Check page 42) to prevent gastric aspiration.

Assess the need for antidotes After resuscitation, the patient’s need for antidotes should be assessed.

Risk assessment Try to determine what was taken (name of drug, product, plant), whether multiple substances were taken (ethanol is often a co-ingestant), how much (strength of tablets, volume, and concentration of liquids), when it was taken (time elapsed since exposure) and the duration of exposure, whether the patient has vomited, and whether any ﬁrst aid has been given (obtain a description of the ﬁrst aid). It is also important to ﬁnd out why the poisoning occurred: was it accidental or deliberate? If the latter (suicide or homicide attempt), then the overdose may be more severe. If this was a suicide attempt, see also Quick Check page 70 and Section 10.11.2. The route of exposure is important since this may determine the speed of onset of toxic effects. Multiple routes of exposure are possible (e.g. inhalation and dermal). • Ask for the container, bottle, or plant sample to be brought in with the patient (it may be found near the patient or in a rubbish bin). • Check whether another person was involved. • Check the medical and occupational history of the patient since these factors may inﬂuence the risk of toxicity, e.g. chronic illness such as diabetes, cardiovascular disease, drug dependency, occupational exposure to chemicals, or psychological and familial problems. Nutritional status is

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also important, e.g. malnourishment may increase the risk of toxicity in paracetamol overdose. • Check what other medications the patient is taking, including traditional medicines, because these may interact with the substance that has been taken in overdose, resulting in faster onset of toxic effects, or more prolonged or severe toxic effects. The co-ingestion of two serotinergic drugs, for example, increases the risk of serotonin syndrome. An important group of medicines are antiretroviral protease inhibitors, which are metabolised by hepatic P450 enzymes. Ritonavir, for example, inhibits metabolism of dextropropoxyphene resulting in a greater risk of toxicity and a number of protease inhibitors inhibit metabolism of benzodiazepines such as diazepam.1

Common agents • Medicines: pain killers (e.g. paracetamol [acetaminophen], opioids, salicylates), antidepressants, anticonvulsants, sedatives, antimalarials, iron salts, antihypertensives, hypoglycaemic agents, bronchodilators, and drugs of abuse. • Plants: e.g. Datura stramonium (thorn apple, jimson weed), datura merel (angel’s trumpet), ricinus communis (castor bean), thevetia peruviana (yellow oleander), atropa belladonna (deadly nightshade), gloriosa superba (glory lily). • Fungi: e.g. Amanita phalloides, gyromitra species. • Herbal preparations: e.g. pennyroyal, bitter melon, arnica, aristolochia. • Pesticides: e.g. rodenticides (rat or mouse killers), (e.g. anticoagulants, aluminium, and zinc phosphide), insecticides (e.g. organophosphate and carbamate compounds), herbicides (e.g. paraquat, 2, 4-D, glyphosate, propanil, bispyribac sodium). • Household products: e.g. detergents, bleach, drain cleaner, disc batteries. • Common chemicals: e.g. acids, alkalis, kerosene or parafﬁn, ﬁre lighters, paints, methanol, ethylene glycol, arsenic, lead. Diagnosis and treatment decisions should be based on a combination of the history (identity of the poison, quantity taken), physical examination (assessment of vital signs, presence of characteristic symptoms and signs, i.e. toxidromes), simple bedside laboratory tests (e.g. urine colour tests and SpO2) and general laboratory examinations (blood glucose, ECG, and arterial or venous blood gas). In the case of opioids, a challenge dose of naloxone is diagnostic, but should be given cautiously, especially in opioid-dependent patients (see Quick Check page 40 and Section 3.6). The treatment table below is a guide to toxic doses of medicines. However, it is important to note that a number of factors affect the risk from poisoning, such as body weight, age, pre-existing health problems, chronic use of medications, and genetic factors. Therefore, the patient should be assessed as a whole, rather than relying on the history of the overdose alone. If a toxicology laboratory is available to measure serum levels, these provide helpful indicators of the need for treatment for certain drugs and toxic substances.

1 Medicine interaction information can be found in the WHO Model Formulary. WHO, 2008. Available at http:// apps.who.int/emlib/ModelList.aspx?Language=EN&MdType=FORMULARY or the British National Formulary (BNF), available through HINARI at http://extranet.who.int/hinari/en/journals.php. The BNF also includes a short section on poisoning.

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If there is no clear history of the agent ingested, the diagnosis of the agent involved should be based on symptoms and signs and a limited number of investigations. If this is not possible, patients should be given supportive care and vital parameters should be stabilized, such as blood pressure and SpO2. • Use Quick Check to check for emergency signs and to provide emergency treatments as appropriate (e.g. airway management, oxygen, IV ﬂuids, glucose, naloxone). • Look in the patient’s mouth and smell the breath. • Feel the pulse and do an ECG to check for arrhythmias. • Examine the patient from head to toe: look for trauma, cyanosis, blisters, burns in or around the mouth, and check for stridor (laryngeal damage from corrosives).

Management principles for ingested poisons • Perform Quick Check to assess for emergencies of airway, breathing, circulation, or coma or convulsions. • Manage the airway (see Quick Check pages 17–18). • If inadequate ventilation, assist ventilation with BVM (see Quick Check pages 17–18). • If signs of severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If wheezing, give salbutamol (see Quick Check page 37). • Is there an indication for advanced airway management with tracheal intubation (see Quick Check pages 62–67)? ° Failure to maintain or protect airway? ° Failure to oxygenate or ventilate? ° Impending airway obstruction? • For patients who have indications for tracheal intubation and continued assistance with ventilation, consider advanced airway management taking into account these requirements (see Quick Check pages 62–67 and Section 3.2.2): ° for easily reversible conditions (e.g. long-acting opioids, other drug overdoses, or poisoning where several days of ventilatory problems are anticipated), manual ventilation may be possible; ° for conditions that are not easily reversible and that may require longer term ventilatory support (e.g. paraquat-associated acute lung injury or upper airway obstruction from corrosive ingestion), transferral to a hospital where skilled invasive mechanical ventilation is possible must be arranged. • If shock, give rapid IV LR or NS ﬂuids (see Quick Check page 39 and Section 3.1). If not in shock, give ﬂuids more slowly (100 ml per hour). Monitor closely for signs of adequate perfusion (urine output) and signs of ﬂuid overload. Titrate accordingly. • If consciousness is altered, check glucose and treat if low (<3 mmol/54 mg/dl) or unknown (see Quick Check page 41). • If consciousness is reduced, place in the recovery position. • Manage seizures with diazepam or lorazepam (see Quick Check page 41 and Section 3.5). If poisoning is suspected, phenobarbital should be the secondline antiepileptic (phenytoin is usually considered the anticonvulsant of last choice for drug-induced seizures since it may be ineffective or may worsen cardiac toxicity).

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• Check Hb, Hct, and urinalysis. • If the patient is hypothermic (use a low-reading rectal thermometer), wrap them in warm blankets and administer warm IV ﬂuids if necessary. • If the patient is hyperthermic, see Section 10.1 and guidance below for speciﬁc agents. • Check for focal neurological signs or any asymmetry (see Section 10.10a). • Manage agitation with diazepam (see Quick Check page 59 and Section 3.4). Avoid haloperidol and chlorpromazine, especially in haemodynamically unstable patients. • Few patients require active removal of the poison or the use of antidotes. • Frequently monitor vital signs, neurological and respiratory status (see Section 3.0 on the general principles for caring for severely ill patients).

Important considerations in resuscitation and stabilization in clinical toxicology that may differ from management of non-poisoned patients • Caustic ingestion may lead to severe upper airway injury (mucosal inﬂammation and necrosis), stridor, and obstruction, and requires advanced airway management (see Section 3.2.2). Call for help from a senior clinician immediately as progression to complete obstruction can happen rapidly. This type of injury can make tracheal intubation very difﬁcult. Ensure an experienced senior clinician is present and be prepared for surgical airway management, if necessary. If the airway is already obstructed, proceed to emergency cricothyroidotomy (see Quick Check page 69) or surgical tracheotomy to bypass obstruction. • Fixed dilated pupils are not necessarily an indicator of poor prognosis in comatose patients with tricyclic antidepressant or other anticholinergic poisoning, or who are receiving atropine. • Intubation and insertion of a nasogastric tube in beta-blocker poisoning may worsen concurrent bradycardia. Use prophylactic atropine (0.6 mg for adults) prior to the procedure.

Differences with standard guidelines for management of arrhythmias and advanced cardiac life support (such as the ACLS protocol) • Resuscitation with IV ﬂuids and vasopressors may be needed for a longer period than in non-poisoned patients. • Higher doses of atropine may be needed in patients with organophosphateinduced cholinergic symptoms. • Class 1a agents such as procainamide, quinidine, and disopyramide are contraindicated for ventricular dysrhythmias in overdose with cyclic antidepressants and other myocardial sodium channel-blocking agents. • Class Ia and Class III antiarrhythmics should be avoided in sotalol-induced cardiac arrhythmias. • Intravenous calcium is indicated in poisoning with hydroﬂuoric acid, calcium channel-blocking agents, and magnesium (see Quick Check p. 28). • Calcium salts should be avoided in digoxin toxicity. • Synchronized electrical cardioversion for atrial tachyarrhythmias may precipitate asystole in digoxin poisoning. • Sodium bicarbonate should be given to treat ventricular tachycardias caused

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by toxic agents (see individual guidance on management) and those with salicylate poisoning. • Insulin-dextrose should be used early in managing severe hypotension following calcium channel blocker poisoning, and may have a role in betablocker poisoning.

Criteria for inpatient hospital admission These include patients who: • have intentionally poisoned themselves; • may have been given the drug or poison intentionally by another person; • are at risk of recurrent self-harm or homicide; • present with a reduced level of consciousness; • present with hypotension or other cardiovascular impairment; • have ingested pesticides, methanol, iron, paracetamol, aspirin, narcotics, antidepressant drugs, chloroquine, antiarrhythmic drugs, or other highly toxic agents associated with serious morbidity or mortality; • have taken poisons that have a delayed action, even if they appear well. Delayed-action poisons include aspirin, iron, lithium, paracetamol, paraquat, tricyclic antidepressants, and anticoagulants. The effects of modiﬁed-release or prolonged-release preparations can also be delayed. • have ingested corrosives or petroleum products. These patients should be admitted or observed for at least 6 hours. Corrosives can cause oesophageal burns that may not be immediately apparent. Petroleum products, if aspirated, can cause pulmonary oedema that may take several hours to develop. If personnel and resources are inadequate to manage the severely ill patient with poisoning, and there is a referral hospital with available resources to treat the patient (see Quick Check pages 70–71), safely transfer the patient after ensuring that the airway is protected. Transferring unstable patients may lead to adverse events during transfer. Consult a poisons expert. Some countries have a poison centre warm or hot line. If not, these services can be reached by telephoning a poison centre in another country.2 A directory of poisons centres can be found at http://www.who.int/ipcs/ poisons/centre/directory/en/.

Removal of the poison from the gastrointestinal tract (gut decontamination) Gut decontamination should not be attempted in a drowsy or unconscious patient with an unprotected airway due to the risk of pulmonary aspiration.

Induction of vomiting (emesis) to treat poisoning should usually not be used There is no evidence that vomiting reduces absorption of the poison, and it may increase the risk of aspiration. Furthermore, the effects of the substance given to

2 Insert phone numbers of cooperating centres; insert warm or hot line number, if available, during country adaptation.

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induce vomiting may complicate the diagnosis. In particular, vomiting should not be induced following ingestion of corrosives and hydrocarbons, as it increases the risk of complications.

There is a very limited role for gastric lavage Gastric lavage is rarely required, and should be considered only if the patient has ingested, within the last hour, a life-threatening amount of a substance that cannot be removed effectively by other means (e.g. iron). Gastric lavage is unnecessary if the risk of toxicity is small, or if the patient presents too late. The main risk is pulmonary aspiration of stomach contents and trauma to the uncooperative patient. The prerequisites for gastric lavage are: • patient consent • the patient is conscious and able to protect the airway, or is intubated • the patient has been adequately resuscitated and has a stable cardiovascular status. The contraindications to gastric lavage are: • a patient with an unprotected airway, such as a patient with a depressed level of consciousness and without endotracheal intubation; • a patient who has ingested corrosives (likely to increase the risk of injury to the oesophagus and stomach during gastric lavage); • if its use increases the risk and severity of aspiration (e.g. a patient who has ingested a hydrocarbon with high aspiration potential); • a patient at risk of haemorrhage or gastrointestinal perforation due to pathology, recent surgery, or other medical conditions. Gastric lavage should be performed by a qualiﬁed and experienced clinician and the procedure MUST be explained to the patient. The patient’s pulse and blood pressure should be monitored throughout the procedure. Never use force to introduce the tube. Place the patient in the left lateral position, with the head tilted down. Insert a orogastric tube (36 to 40 French gauge or 30 English gauge in adults, with an external diameter of 12 to 13.3 mm; and 24 to 28 French gauge in children, external diameter 7.8 to 9.3 mm). Introduce 200 to 300 ml (10 ml/kg in children) of normal saline or water (preferably warmed to 38°C – avoid water in children to prevent hyponatraemia). Remove the volume introduced before giving further ﬂuid. If the patient becomes restless or if the blood pressure drops, abandon the procedure. Give a dose of activated charcoal (50 g) to an adult and 1 g/kg to a child after the lavage (see below).

Activated charcoal may be useful in the ﬁrst 1–2 hours after ingestion for some poisons Activated charcoal acts by adsorbing the poison and preventing it from being absorbed by the patient. • It is ineffective in poisoning due to alkalis, acids, heavy metals, iron, lithium, toxic alcohols, glycols, and hydrocarbons such as kerosene. Activated charcoal is contraindicated: • if the patient has an unprotected airway, such as in a patient with a depressed level of consciousness and without endotracheal intubation;

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• if its use increases the risk and severity of aspiration (e.g. a hydrocarbon with a high aspiration potential); • in patients who are at risk of gastrointestinal haemorrhage or perforation due to pathology, recent surgery, or medical conditions that could further be compromised by single dose of activated charcoal. How to prepare activated charcoal Activated charcoal should be mixed with water according to manufacturer’s instructions and well-shaken. • For adolescents and adults: give 50–100 g as a single dose (children 1–12 years: give 1 g/kg, maximum 50 g). • The solution can be administered via a nasogastric tube if the airway is protected and the patient is compliant.

The presence of activated charcoal in the gastrointestinal tract may obscure endoscopic visualization. However, a corrosive is not a contraindication when charcoal is used for co-ingested agents that are systemic toxins.

There is a very limited role for whole bowel irrigation (WBI) for gut decontamination This aims to clear the entire gastro-intestinal tract using an osmotically balanced polyethylene glycol-electrolyte solution. NB: WBI should only be performed using this solution, which is carefully formulated to prevent development of electrolyte and ﬂuid imbalance. • The indications for WBI are potentially toxic ingestion of sustained-release or enteric-coated drugs, iron, and packets of illicit drugs. • WBI is contraindicated in the presence of ileus, bowel obstruction, bowel perforation, clinically signiﬁcant gastrointestinal haemorrhage, haemodynamic instability, uncontrollable intractable vomiting, and an unprotected, compromised airway. A 12 French nasogastric tube is passed into the stomach (gastric location should be conﬁrmed by auscultation during air injection). The tube is then attached to a reservoir bag of irrigation solution that is hung from an elevated site. The patient should be seated or the head of the bed elevated to at least 45°. The irrigation ﬂuid is given at a rate of 1500–2000 ml/h for adults and adolescents. The patient should be placed on a commode or similar receptacle to collect the efﬂuent. WBI should be continued at least until the rectal efﬂuent is clear.

Management of speciﬁc poisons Brief guidance on the management of speciﬁc poisonings is given in the table on the next page, Poisons and agents, symptoms of toxicity in overdose, and brief guidance on speciﬁc management. This does not cover all aspects of management or complications, and the reader is advised to consult additional sources. Some agrochemicals and medicines do not lead to serious adverse clinical outcomes and should only be treated with supportive care (see Table: Agrochemicals and pharmaceuticals that are unlikely to lead to adverse clinical outcomes).

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Table: Poisons or toxins, symptoms of toxicity in overdose, and brief guidance on speciﬁc management Poison or toxin Drugs Aspirin (acetylsalicylic acid) Toxic dose: >150 mg/kg or 6.5 g aspirin equivalent (whichever is less) Ingestion of >4 ml of oil of wintergreen (98% methyl salicylate) or more than a lick or taste for <6 years of age Vomiting, deafness, tinnitus, confusion, hyperventilation, fast pulse, low SBP, dehydration, hypoglycaemia, coma Prolonged or delayed absorption possible • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). Target adequate urine output. • Give activated charcoal, followed by a second dose 4 hours later. • Monitor electrolytes and bicarbonate 2 hourly. • Correct hypokalaemia. Maintain serum K between 4 and 4.5 mmol/l. • Check and monitor the serum salicylate concentration. • Correct metabolic acidosis with sodium bicarbonate 1–2 mmol/ kg as IV bolus, followed by maintenance infusion. • If salicylate level is >500 mg/l, give sodium bicarbonate to alkalinize the urine (pH>7.5). Give sodium bicarbonate 225 mmol (225 ml of an 8.4% solution) intravenously over 1 hour. Give additional boluses of intravenous sodium bicarbonate to maintain urine pH in the range of 7.5–8.5. Note: Urinary alkalinisation should only be done if there are facilities to monitor plasma bicarbonate and urine pH. • Regular monitoring of urine pH, serum bicarbonate, and potassium. • Refer for haemodialysis if salicylate concentration >700 mg/l, renal failure, pulmonary oedema, progressive deterioration of vital signs, coma, convulsions, severe acid base or electrolyte imbalance, despite appropriate treatment, or hepatic compromise. Symptoms Management

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Poison or toxin Beta-blockers Toxic dose: variable response to overdose

Symptoms Hypotension and bradycardia, AV block, electromechanical dissociation, intraventricular conduction delays and asystole CNS depression and seizures with propranolol

3 Calcium chloride 10% – 0.2 ml/kg to a maximum of 10 ml over 5 minutes.

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Poison or toxin Calcium-channel blockers Toxic dose: any overdose is potentially serious

Symptoms Hypotension and bradycardia, cardiogenic shock Reﬂex tachycardia with nifedepine

Management • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 41 and Section 3.1). Be cautious for signs of ﬂuid overload in patients with cardiac disease. • Give activated charcoal if patient presents within 2 hours and is stable. • For sustained-release preparations, give multiple doses of activated charcoal and consider the use of whole bowel irrigation. • Cardiac monitoring and perform 12-lead ECG. • If no response to IV ﬂuids, give IV calcium salts (calcium chloride 10% – 0.2 ml/kg to a maximum of 10 ml over 5 minutes; OR calcium gluconate 10% – 0.6 ml/kg up to a maximum of 30 ml over 5 minutes). Can be repeated every 10–20 minutes up to 4 doses. • If there is bradycardia, give atropine: 0.5 to 1 mg IV. Repeat every 3 to 5 minutes to a total dose of 0.04 mg/kg. • Monitor calcium, arterial blood gases, glucose, and potassium. • If SBP is unresponsive to calcium salts, initiate insulindextrose treatment as follows: loading dose of short acting insulin 1–2 U/kg with 50 ml of 50% dextrose followed by 0.5–1 U/kg per hour and an infusion of dextrose titrated to blood glucose level. • Closely monitor blood glucose (check every 3–60 minutes) and serum potassium. Note: With insulin therapy, hypokalaemia may occur because of redistribution from plasma into cells, so take care not to overcorrect. • Hypotension unresponsive to the above treatment should be treated with vasopressors starting with epinephrine (see Section 3.1.4). Large doses may be needed. If nifedipine taken, give dopamine. • If necessary, follow with glucagon: loading dose IV 5 to 10 mg in 5% dextrose solution and 1 to 10 mg/hour in 5% dextrose in water, titrated against response, as maintenance dose for no more than 48 hours. • If unresponsive to other measures and this is available, consider intravenous lipid emulsion (1.5 ml/kg of 20% emulsion bolus followed by 0.5 ml/kg/minute for 30 to 60 minutes). • Manage airway and assist ventilation as needed (see Quick Check pages 29–32 and 31). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). Be cautious for signs of ﬂuid overload in patients with cardiac disease. • Give repeat dose of activated charcoal provided that bowel sounds are present and the airway is protected. • Cardiac monitoring and perform 12-lead ECG. • If still in shock after ﬂuid resuscitation, give vasopressors (see Section 3.1.4). • Administer sodium bicarbonate at a dose of 50 ml of 8.4% or 1–2 mmol/kg to treat a patient who has metabolic acidosis or arrhythmias, or progressive widening of QRS (or QRS longer than 120 millisecond). • For a patient who develops seizures, give diazepam as a ﬁrstline treatment, followed by phenobarbital if necessary (see Quick Check page 41 and Section 3.5). Do not give phenytoin.

Carbamazepine Toxic dose: >20 mg/kg

Nystagmus, dilated pupils, ataxia, slurred speech, ﬂuctuating level of consciousness, hypotension, tachycardia, urinary retention In severe poisoning: seizures, coma, respiratory depression, and arrhythmias

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Poison or toxin Tricyclic antidepressants, e.g. amitriptyline, imipramine Toxic dose: despiramine, trimipramine, and nortriptyline >2.5 mg/kg Protriptyline >1 mg/kg All others >5 mg/kg

Symptoms Cardiovascular: hypotension, dysrrythmias, cardiac arrest Central nervous system: excitation, restlessness, myoclonus, hyperreﬂexia, disorientation, confusion, hallucination, coma, seizures Anticholinergic: hyperthermia, urinary retention, paralytic ileus, mydriasis, dry mouth, ﬂushing of skin

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). • Give activated charcoal if patient presents within 2 hours after ingestion, provided airway is protected. • Monitor blood gases, correct hypoxia. • Cardiac monitoring and perform 12-lead ECG, measure the QRS width. • If shock persists, give vasopressors (see Section 3.1.4) – norepinephrine is preferred or give epinephrine. • Correct acidosis if can measure bicarbonate. • Sodium bicarbonate (50 ml of 8.4% or 1–2 mmol/kg) should be given to all patients with QRS prolongation (>120 millisecond) or arrhythmias. Give repeated boluses of sodium bicarbonate to keep QRS at <120 millisecond and arterial pH between 7.45–7.55. • Seizures should be treated with diazepam (see Quick Check page 19 and Section 3.5). Avoid the use of phenytoin. • Following seizures, a dose of bicarbonate is suggested to correct acidosis and reduce risk of further toxicity. • Manage airway and assist ventilation, as needed (see Quick Check pages 29–32). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). • If shock persists, give vasopressors (see Section 3.1.4) – epinephrine is preferred. • Give activated charcoal if airway is protected and within 1 hour of ingestion. • Observe for a minimum of 12 hours, monitor vital signs. • Monitor blood glucose, urea, electrolytes, blood gases. • Cardiac monitoring and perform 12-lead ECG, and measure the QRS width. If >120 millisecond, give sodium bicarbonate (50 ml of 8.4% or 1–2 mmol/kg). Give repeated boluses of sodium bicarbonate to keep QRS at <120 millisecond and arterial pH between 7.45–7.55. • Correct hypokalaemia if <3 to no more than 3.5 (beware of rebound increase in potassium). • Seizures should be treated with diazepam (see Quick Check page 41 and Section 3.5). Avoid barbiturates as these may precipitate cardiac arrest. Avoid phenytoin.

Chloroquine Toxic dose: >20 mg/kg is toxic

Nausea, vomiting, diarrhoea, and abdominal pain, dizziness, convulsions, coma, hypotension, arrhythmias, sudden cardiac arrest

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Poison or toxin Quinine Toxic dose: >15 mg/kg could be toxic

Symptoms Tinnitus, deafness, abdominal pain, visual changes, blindness, ataxia, coma, convulsions, arrhythmia, torsade de pointes, hypoglycaemia

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). • Give activated charcoal if airway is protected. • In severe cases, provided airway is protected, give repeat doses of activated charcoal. • Monitor urea, electrolytes, blood glucose, blood gases. • Cardiac monitoring and perform 12-lead ECG and measure the QRS width – if >120 milliseconds there is a risk of cardiac arrhythmias. • If shock persists, give vasopressors to treat hypotension (see Section 3.1.4). • Treat cardiotoxicity (hypotension, wide QRS complexes, and QTc prolongation) with sodium bicarbonate (50 ml of 8.4% or 1–2 mmol/kg). Give repeated boluses of sodium bicarbonate to keep QRS at <120 millisecond and arterial pH between 7.45–7.55. • Treat torsade de pointes with magnesium sulfate 1–2 grams IV. • Seizures should be treated with diazepam (see Quick Check page 41 and Section 3.5). Avoid barbiturates and phenytoin. • Give a dose of activated charcoal if presenting within 1 hour. • Multiple doses of activated charcoal (every 4 hours for 24 hours) may be considered in the absence of digoxin antibodies. • Monitor ECG. • Monitor electrolytes at least every 6 hours and correct if necessary (particularly potassium). • Monitor blood gases and pH and correct metabolic acidosis with sodium bicarbonate. • Digoxin antibodies should be given, if available, for the following indications: ° serum potassium >6 mmol/l ° bradycardia or heart block with hypotension ° tachyarrhythmia with hypotension. • Treat hyperkalaemia: if K >5.5 mmol/l give sodium bicarbonate (1mmol/kg), glucose (0.5 g/kg IV), PLUS insulin (0.1 U/kg IV) (see Section 5.2.2). Note: Do not use calcium, furosemide, or salbutamol as these may worsen toxicity. • Give atropine for bradycardia or heart block associated with hypotension. • If readily available, consider referral for insertion of a temporary pacing wire if there is evidence of signiﬁcant bradycardia or AV block with haemodynamic compromise. • Ventricular tachyarrhythmia – give magnesium sulfate 2 g IV over 20 minutes in an adult initially. If no response consider lidocaine.

Digoxin, oleander (Thevetia peruviana, Nerium oleander, Digitalis spp) Toxic dose digoxin: ≥3 mg (produces toxic level in adults). Note: ≥10 mg is often lethal. Patients on digoxin therapy are more susceptible in overdose.

Nausea, vomiting, abdominal pain, visual changes, headache, fatigue, coma, Heart block and tachy – or brady– arrhythmias

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Poison or toxin Antidiabetic agents: hypoglycaemic agents (if metformin see separate entry) Toxic dose: for suphonylurea and insulin, more than the usual recommended dose

Symptoms Sweating, agitation, giddiness, confusion, coma. Delayed onset of hypoglycaemia possible, also recurrent hypoglycaemia

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If unconscious, give 25–50 ml D50 (see Quick Check page 41). A continuous infusion of 10% dextrose (1 litre over 8 hours) may be required if blood sugar falls to <3 mmol/l (see Section 3.4.2). • When the patient recovers consciousness, give sugary drinks and food, followed by a long-acting carbohydrate (e.g. bread, rice, maize) to prevent recurrent symptoms. • Give activated charcoal if airway is protected and it is within 1 hour of ingestion of an oral hypoglycaemic. • Check blood sugar and monitor every 1 to 2 hours. • Continue monitoring for at least 24 hours. • Monitor level of consciousness using AVPU. • Correct asymptomatic hypoglycaemia with sweet drinks (not diabetic or sugar-free), e.g. cola, juice, sweet water, oral glucose powder or tablets (see Section 3.4.2). • Do not give prophylactic dextrose without symptoms or a low blood glucose. • Octreotide, if available, could be given to patients whose blood sugar does not normalise after above measures. • Give activated charcoal if airway is protected and it is within 2 hours of ingestion. • Monitor blood gases and lactate. • If acidotic, ensure that patient is adequately ventilated and perfused and give IV sodium bicarbonate. • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • Give naloxone (see Quick Check page 40 and Section 3.6). • Give activated charcoal if within 2 hours of ingestion and airway is protected. • Cardiac monitoring and perform 12-lead ECG if dextroproxyphene taken. If QRS >120 millisecond, give sodium bicarbonate (50 ml of 8.4% or 1–2 mmol/kg). • For serotonin syndrome, see SSRIs.

Antidiabetic agents: metformin Toxic dose: variable response Opioids e.g. morphine, diamorphine (heroin), raw opium, codeine, methadone, dextropropoxyphene, oxycodone, tramadol Toxic dose: variable

Lactic acidosis (does not cause hypoglycaemia)

Respiratory depression, central nervous system depression (drowsiness to coma), miosis, hypotension, hypothermia, ataxia, respiratory arrest, non-cardiogenic pulmonary oedema Tramadol: seizures, serotonin syndrome Dextropropoxyphene: cardiac dysrhythmias

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Poison or toxin Paracetamol (acetaminophen) Note: Risk of toxicity is increased in patients taking enzyme-inducing drugs, e.g. carbamazepine, phenobarbital, phenytoin, primidone, rifampicin.

Symptoms Vomiting, right upper quadrant abdominal pain, hepatic encephalopathy

Management • Give activated charcoal if less than 2 hours after ingestion. • Obtain blood level if possible; however, the sample should be taken at 4 hours or more after the ingestion. • Efﬁcacy of antidote declines from 8 hours post-ingestion, so give antidote based on history only if there is a delay in getting the paracetamol level or it cannot be obtained. • See paracetamol nomogram below. • If paracetamol level not available, base treatment on ingested dose: ° 75 mg/kg if high risk (nutritionally deﬁcient, acute starvation, AIDS, alcoholic, on enzyme-inducing drugs); ° 150 mg/kg if not high risk. • Give acetylcysteine IV or orally: ° IV acetylcysteine: initially 150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. Administration: dilute requisite dose in glucose intravenous infusion 5% as follows – initially 200 ml given over 15 minutes, then 500 ml over 4 hours, then 1 litre over 16 hours. ° Oral acetylcysteine (acetylcysteine solution intended for antidotal use, not granules for mucolytic use) – administer a loading dose of 140 mg/kg body weight. Four hours after administration of the loading dose, initiate a maintenance dose of 70 mg/kg administered at 4-hourly intervals for 17 doses. The acetylcysteine solution should be given until 72 hours post-ingestion – continue for longer if LFTs abnormal. Dilute to a 5% solution in soda pop, juice, or water prior to oral or nasogastric administration. ° Check liver function tests, INR (prothrombin time), creatinine and BUN, and electrolytes. • Give activated charcoal within 2 hours of ingestion. • Perform 12-lead ECG. • Manage serotonin syndrome: ° Monitor urea, electrolytes, CK, and renal function. ° Cardiac monitoring and perform 12-lead ECG. ° Give IV ﬂuids to maintain good urine output. If in shock, give rapidly (see Quick Check page 39). ° If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). ° Sedate with diazepam if agitated or if having seizures (see Quick Check pages 41, 59). ° Hyperthermia (>40.5°C) should be treated with rapid cooling (see Section 10.1). ° Cyproheptadine can be considered if available, and no response to above measures. Give 4 to 8 mg every 1 to 4 hours. Repeat until therapeutic response is achieved. Maximum dose of 32 mg over 24 hours. ° In cases of severe hyperthermia (>41°C) not improving despite sedation and cooling measures, consider deeper sedation and paralysis, provided advanced airway management is possible – either manual ventilation or transfer to a hospital with a mechanical ventilator..

Selective serotonin reuptake inhibitors (SSRI) e.g. ﬂuoxetine, paroxtine, sertraline Toxic dose: variable

Nausea, vomiting, dry mouth, tachycardia, drowsiness, coma Serotonin syndrome may occur: agitation, confusion, delirium, drowsiness, coma, tremor, teeth grinding, myoclonus and hyperreﬂexia, hypertension or hypotension, seizures, hyperthermia, rhabdomyolysis, renal failure, coagulopathies may develop

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Poison or toxin Monoamine oxidase inhibitors (MAOI), e.g. phenelzine, tranylcypromine Toxic dose: In adults >5 tablets of any preparation can be toxic

Symptoms Anxiety, vomiting, restlessness, confusion, ﬂushing, sweating, hypertension, hyperthermia, seizures Note: MAOIs interact with a wide range of drugs and some foods to cause severe hypertension. They have a life-threatening interaction with pethidine. Serotonin syndrome may occur.

Management • Give activated charcoal if airway is protected and within 2 hours of ingestion. • If symptomatic, monitor pulse, blood pressure, temperature, respiratory rate, and AVPU every 30 minutes. • Check urea and electrolytes and full blood count. • Check creatine kinase activity in all symptomatic patients. • Hypertension: give IV diazepam (0.1–0.2 mg/kg). If ineffective, then treat with IV nitrates, e.g. sodium nitroprusside. Beta blockers are contraindicated. • Give diazepam for agitation or seizures (see Quick Check pages 41, 59). • Hyperthermia (>40.5°C) should be treated with rapid cooling (see Section 10.1). • In cases of severe hyperthermia (>41°C) not improving despite sedation and cooling measures, then consider deeper sedation and paralysis, provided advanced airway management is possible, either manual ventilation or transfer to a hospital with mechanical ventilator. • If convulsions unresponsive to ﬁrst- and second-line antiepileptics (see Quick Check page 41 and Section 3.5), and advanced airway management is feasible, consider anaesthetic (e.g. thiopental or propofol). • See also management of serotonin syndrome under SSRIs. • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). • If more than 40 mg/kg body weight of elemental iron ingested then: ° do abdominal X-ray (if possible) to check if tablets are visible in gut (Note: A negative X-ray does not necessarily exclude iron ingestion.) • If within 4 hours of ingestion, initiate whole bowel irrigation with osmotically balanced polyethylene glycol-electrolyte solution (2 litres per hour for adults and 0.5 litres/hour in children – see above). • If WBI is not available, give gastric lavage (with a wide-bore tube) within 1 hour of ingestion or if radiography reveals tablets in the stomach. • Monitor urea and electrolytes, WBC, blood glucose, LFTs, whole blood clotting time, renal function, and blood gases. • If possible, check iron level 4 hours post-ingestion and give deferoxamine if the serum iron level is over 90 µmol/l. • If iron levels are not available, give deferoxamine if patient has: ° taken 60 mg/kg elemental iron (see table of elemental iron content or check label), or ° any of the following: metabolic acidosis, hypotension, shock, coma, convulsions. • Give deferoxamine by slow IV infusion: initially 15 mg/kg/hour, reduced after 4–6 hours so that total dose does not exceed 80 mg/kg in 24 hours.

Iron (ferrous salts) Toxic dose: >40 mg/kg elemental iron, or if there is persistent vomiting or diarrhoea Approximate elemental iron content of ferrous salts is: • ferrous fumarate 210 mg (68 mg iron) • ferrous gluconate 300 mg (35 mg iron) • ferrous succinate 100 mg (35 mg iron) • ferrous sulfate 300 mg (60 mg iron) • dried ferrous sulfate 200 mg (65 mg iron) Note: Check label to make sure.

Vomiting and diarrhoea – often bloody; drowsiness, lethargy, coma, shock, convulsions, liver failure Delayed pyloric stenosis. Note: Initial symptoms may be followed by apparent recovery, then a relapse. Therefore all symptomatic patients should be observed for minimum of 12 hours.

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Poison or toxin Lithium Toxic dose: Acute overdose is >2 g in adults Note: Acute overdose is usually welltolerated. Acute-on-chronic: any amount more than the usual daily dose could be toxic Phenobarbital Toxic dose: variable response

Symptoms Mild toxicity: nausea, vomiting, diarrhoea, ﬁne tremor Moderate toxicity: confusion, fasciculation, and hyperreﬂexia Severe toxicity: coma, convulsions and cardiac arrhythmias

Management • Acute overdose with normal renal function – no gut decontamination is needed. • Overdose in patient on lithium therapy (taking sustainedrelease) or with impaired renal function – consider the use of whole bowel irrigation. All: • If hypotension or shock, give rapid IV ﬂuids (see Quick Check page 39 and Section 3.1) – NS preferred. Titrate to ensure good urine output. • Cardiac monitoring and perform 12-lead ECG. • Monitor renal function. • Monitor and correct electrolyte imbalance. • Seizures should be treated with diazepam (see Quick Check page 41 and Section 3.5). • Haemodialysis for patients with coma, convulsions, respiratory failure, or acute renal failure. • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). • If symptomatic, give repeat doses of activated charcoal provided bowel sounds are present and airway is protected. • Manage hypothermia. • Give supportive care. • Monitor pulse, respiratory rate, BP, temperature, AVPU. • Haemodialysis if ileus, failure to respond to supportive care. • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 39 and Section 3.1). • Give multiple dose activated charcoal. • Give antiemetic such as metoclopramide (may need large dose) or ondansetron. • Monitor electrolytes and cautiously correct hypokalaemia if <3 to no more than 3.5 (beware of rebound increase in potassium). • Monitor vital signs. • Cardiac monitoring and perform 12-lead ECG. • Treat SVT if it is causing haemodynamic compromise. Give a beta-blocker (preferably beta-1 selective blockers, such as esmolol, metoprolol, but beware of bronchospasm in asthmatics and those with COPD – in these cases consider verapamil or adenosine). • For ventricular arrhythmias causing haemodynamic compromise, use magnesium or lidocaine. If severe, treat with DC cardioversion. • Diazepam for seizures (see Quick Check pages 41, 59). If unresponsive, follow with phenobarbital. If convulsions are unresponsive to ﬁrst-line antiepileptics (see Section 3.5), and advanced airway management is feasible, consider anaesthetic (e.g. thiopental). Do not use phenytoin. • Consider haemodialysis, if available, for life-threatening toxicity.

Drowsiness, lethargy, slurred speech, nystagmus, coma, respiratory depression, hypotension, tachycardia, hypothermia

Theophylline Toxic dose >20 mg/kg

Vomiting (may be protracted), haematemesis, agitation, tachycardia, hypertension, hypotension, hyperventilation, cardiac dysrhythmias, seizures, acid-base disturbance, hypokalaemia, rhabdomyolysis, respiratory arrest

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Poison or toxin Warfarin

Symptoms See anticoagulant pesticides further down.

Management

Pesticides Aluminium or zinc phosphide Retrosternal burning, persistent vomiting, hypotension, shock, bradycardia or tachycardia, myocardial depression, refractory hypotension, headache, dizziness, restlessness, hypoglycaemia, metabolic acidosis, non-cardiogenic pulmonary oedema, acute respiratory distress syndrome, acute renal failure, hepatic damage Bleeding: spontaneous bruising, haematomas, haematuria, rectal bleeding and haemorrhage into any internal organ Delayed onset and may be prolonged • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1). • If shock persists after ﬂuid resuscitation, start vasopressors (see Section 3.1). • Cardiac monitoring and perform 12-lead ECG. • Monitor for and correct hypoglycaemia. • Monitor for and correct electrolyte imbalance. • Give sodium bicarbonate (1–2 mmol/kg) for metabolic acidosis. • Magnesium sulfate may improve cardiac output – give 1 g 6 hourly. • Other supportive care as required. • Monitor renal and hepatic function.

Anticoagulant rodenticides (raticides, rat and mouse killers) or anticoagulant therapy (warfarin

• Monitor INR at 24 and 48 hours. • If poisoning and INR mild to moderately elevated without major bleeding, give oral vitamin K 10–20 mg. • If patient is on anticoagulant therapy and there is no active bleeding but the INR is prolonged (INR 5.0–9.0), omit 2 doses of warfarin, then repeat the INR. Further doses may be missed as needed, titrated to INR. Restart at lower maintenance dose once the INR is in the therapeutic range. • If patient is on anticoagulant therapy and there is no active bleeding but the INR is dangerously prolonged (INR ≥9.0), warfarin should be stopped and give vitamin K 2.5 to 5 mg orally. Further doses may be given as necessary, titrated to the INR. • If serious or life-threatening bleeding, stop warfarin and give vitamin K 10 mg IV by slow infusion (over 20 to 60 minutes), supplemented by transfusions of fresh frozen plasma (FFP) 2-3 units initially, or prothrombin complex concentrate. • In case of long-acting anticoagulant rodenticides, vitamin K therapy may be needed for several weeks. The dose should be titrated to response.

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Poison or toxin Chlorphenoxy herbicides e.g. MCPA, 2, 4-D

Symptoms Burning pain in the mouth and epigastrium. Muscle pain and rigidity, muscle twitching, agitation, seizures, hyperpyrexia, rhabdomyolysis leading to renal failure. Metabolic acidosis, hyperventilation, tachycardia, hypotension, ECG abnormalities, prolonged coma

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1). Titrate to maintain adequate urine output. • Monitor blood gases, renal and liver function, creatine kinase. • Look for dark-coloured urine (check for myoglobin). • Cardiac monitoring and perform 12-lead ECG. • In symptomatic cases, alkalinise the urine to pH>7.5 with IV sodium bicarbonate. Suggested regimen: sodium bicarbonate 225 mmol (225 ml of an 8.4% solution) intravenously over 1 hour. Give additional boluses of intravenous sodium bicarbonate to maintain urine pH in the range 7.5–8.5. Urinary alkalinisation should only be done if there are facilities to monitor plasma bicarbonate and urine pH. • Treat rhabdomyolysis with ﬂuid replacement to maintain good renal output together with urinary alkalinisation. • In severe poisoning use haemodialysis, if available. • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1). Titrate to maintain adequate urine output. • Give atropine 1–3 mg intravenously as a bolus. • Listen to lungs, take pulse, and measure blood pressure. • Aim for clear lungs, stable blood pressure • (>90 mmHg systolic), dry mucous membranes, and oxygen saturation of >95%. • Recheck at ﬁve minutes. If no improvement, give double the initial dose of atropine. Dilated pupils and tachycardia alone should not be considered as end points. • Continue to give doubling doses of atropine every • 5–10 minutes until the patient is stable. If the lung crepitations persist after 3 to 5 boluses of atropine (doubling doses), consider that the patient may have aspirated. • If blood pressure does not improve with atropine, consider giving ﬂuid boluses and exclude metabolic acidosis. • Once the patient has been atropinized, initiate an infusion of atropine (20% of the total dose required to atropinize) as an hourly infusion. • Monitor signs of atropine toxicity (agitation, confusion, hyperthermia) every 4 to 6 hours. If atropine toxicity develops, stop the infusion and restart at 70% of the last infusion rate once the toxicity settles. • Monitor respiratory rate, pulse rate, and blood pressure. Prepare to intubate and if necessary ventilate. • Give diazepam 5–10 mg IV for agitation, seizures, and fasciculations (see Quick Check pages 41, 59 and Section 3.5). Repeat dose as necessary. • For organophosphates ONLY, give pralidoxime, if available.4

Organophosphates and carbamates

Muscarinic effects: DUMBBELS (defecation, urination, miosis, bronchospasm, bronchorrhea, emesis, lacrimation, salivation) Nicotinic effects: weakness, fasciculation, paralysis, mydriasis Other: agitation, confusion, lethargy, convulsions, coma

4 Pralidoxime chloride or mesylate: 30 mg/kg IV over 5–10 minutes, followed by the same dose every 4–6 hours, or by IV infusion of 8 mg/kg/hour, maximum of 12 g in 24 hours. Most useful within 24–48 hours. Pralidoxime is not on the WHO EML..

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Poison or toxin Paraquat

Symptoms Early stages (hours to a few days): burning pain of the mouth, lips, and tongue. Gastrointestinal corrosion leading to painful swallowing (odynophagia), nausea, vomiting, abdominal pain. Following large ingestions: coma convulsions, cardiovascular collapse, and shortness of breath. Burning sensation of the skin. Later (few days): ulceration of the tongue and oral cavity with contact bleeding, shortness of breath due to acute alveolitis, pulmonary oedema, pneumothorax, and pneumomediastinum. Acute renal failure and hepatitis. Acute pancreatitis. Later (weeks). Chronic hypoxia due to progressive lung ﬁbrosis. Renal failure.

Management • If shock, give rapid IV ﬂuids (see Quick Check page 40 and Section 3.1). Titrate to maintain adequate urine output. • Avoid giving supplemental oxygen if possible as this worsens lung injury. Oxygen may be needed in late stage as ﬁbrosis develops. • Give activated charcoal or Fullers earth for patients presenting within 2 hours. • Insert a nasogastric tube as early as possible to facilitate feeding. • Conﬁrm systemic absorption with urine dithionite test, if available. • Assess baseline electrolytes, creatinine, FBC, and blood gases, and correct all reversible abnormalities. • Screen and treat for sepsis – monitor temperature, check WBC, blood cultures when indicated. Start empirical antibiotics (see Section 3.1.5). • Give IV ﬂuids to maintain good renal output. • Liberal pain relief and sedation with opioids and benzodiazepines as needed.

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Poison or toxin Propanil

Symptoms Causes methaemoglobinaemia. Nausea, vomiting, diarrhoea, dizziness, cyanosis, headache, tachycardia, hypotension, respiratory depression, lactic acidosis, chest pain, confusion, coma, and convulsions. Dark brown or reddish urine.

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40). • Give activated charcoal. • Monitor blood gases with co-oximeter (Note: A pulse oximeter will give a misleading result in the presence of methaemoglobin). • Cardiac monitoring until patients maintain stable cardiovascular status. • Check haemoglobin level to detect anaemia due to haemolysis. • Patients who present with depressed level of consciousness tend to have poor prognosis. These patients should be closely observed. • Check methaemoglobin concentration, if possible. • A qualitative test for methaemoglobin is to place 1 to 2 drops of the patient’s blood on white paper. Normal blood will be dark red or violet and will brighten on exposure to oxygen. Methaemoglobin will appear “chocolate” brown and will not change colour. • If the patient has a methaemoglobin level of >20–30% or is symptomatic (confusion, tachycardia, hypotension, chest pain, cyanosis) in the absence of methaemoglobin level, treat with methylthioninium chloride (methylene blue). ° Give a loading dose of methylthioninium chloride 2 mg/kg IV of 1% solution (10 mg/ml) over 5 minutes. Assess after 15 minutes. If no improvement, give a further dose of 1 mg/kg and transfer if possible for further treatment with methylthioninium chloride. ° After 6 hours recheck methaemoglobin level, clinical status, and blood gases. Then, if necessary repeat the dose of 1 mg/kg. Continue to repeat 6 hourly while patient is symptomatic or methaemoglobin level remains >30%. ° May need methylthioninium chloride for 2–3 days. ° If patient is deteriorating on this therapy, consider possibility of G6PD deﬁciency or haemolysis. ° If methylthioninium chloride is not available or patient has G6PDD, give IV or oral ascorbic acid 500 mg every 12 hours. ° If patient continues to deteriorate consider exchange transfusion.

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Poison or toxin Other chemicals Corrosive substances

Symptoms

Management

Pain in mouth, throat, epigastrium, or abdomen. Dysphagia, hypersalivation (drooling), hoarse voice, and stridor. Gastrointestinal bleeding and haematemesis. Perforation, shock. Aspiration pneumonia, airway obstruction. Acids cause coagulation necrosis. Strong acetic acid also causes haemolysis and renal failure. Alkalis cause liquefaction necrosis, which may result in extensive penetration of tissue.

• Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If stridor, consider advanced airway management (see Quick Check pages 62–65) and surgical airway (see Quick Check page 69 and Section 3.2.2). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1). • Do NOT induce vomiting or give gastric lavage or activated charcoal. • Do NOT attempt neutralization. • Give adequate pain relief with IV opioids. • Refer all patients for assessment of gastrointestinal injury by cautious endoscopy between 6–24 hours of ingestion. • If grade III injury, put nasojejunal tube under endoscopy or perform feeding jejunostomy. • Monitor pH, ﬂuid, and electrolyte status, haemoglobin and clotting time. • If possible perform abdominal and chest X-ray to assess for aspiration and perforation. • Patients with acid ingestion: correct metabolic acidosis with sodium bicarbonate. • Consider surgical intervention for any signs of perforation.

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Poison or toxin Ethylene glycol

Symptoms Drunken-state, nausea, vomiting, metabolic acidosis, renal failure, calcium oxalate crystals in urine, hypocalcaemia, seizures, coma, tetany

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1) and titrate to maintain good urine output. • Give strong alcoholic drink (e.g. brand-named vodka or whisky, not informally distilled spirit) to block metabolism. Oral loading dose (by PO or by NG tube) – 1.8 ml/kg of a 40–43% alcohol drink over 15–30 minutes (diluted). Patient should be managed at tertiary facility. Transfer at this stage if necessary. • Continue oral administration of alcohol drink as follows. • Maintenance dose: ° 0.2 ml/kg/hour (non-drinker) ° 0.46 ml/kg/hour (heavy alcohol user). • Maintenance dose during dialysis: ° 0.5 ml/kg/hour (non-drinker) ° 0.77 ml/kg/hour (heavy alcohol user). • May need to give alcohol for 2–3 days. • Correct metabolic acidosis with sodium bicarbonate (may need high doses) and ﬂuid replacement. Important to monitor electrolytes for hypernatraemia and hypokalaemia. • To conﬁrm diagnosis, if possible, check osmolar gap, anion gap, and serum ethanol. In the early stages a gap of >19 mOsm/kgH2O may be indicative of ethylene glycol poisoning if serum ethanol is 0 (if not, subtract 24 mOsm/kgH2O per 100 mg/dl of ethanol). Later a raised anion-gap metabolic acidosis develops. • Haemodialysis if there is a severe metabolic acidosis (pH <7.25 or base deﬁcit >15 mm despite buffer) or renal failure. Consider peritoneal dialysis if haemodialysis is not available. • Fomepizole is an alternative to ethanol. Give a bolus dose of 15 mg/kg followed by 10 mg/kg twice daily for a maximum of 4 doses; followed by 15 mg/kg IV every 12 hours thereafter. • If hypocalcaemia – cautious correction with calcium gluconate. • If readily available, pyridoxine 50 mg IV or IM every 6 hours for 6 doses, and thiamine 100 mg IV or IM every 8 hours for 6 doses. These may be beneﬁcial if the patient is alcoholic.

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Poison or toxin Methanol

Symptoms Non-speciﬁc features: GI symptoms (nausea, vomiting, abdominal pain), chest pain, dyspnoea. More speciﬁc features: metabolic acidosis, visual disturbances of all kinds leading to blindness, coma.

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1) and titrate to maintain good urine output. • Give strong alcoholic drink (e.g. brand-named vodka or whisky, not informally distilled spirit) to block metabolism. Oral loading dose (by PO or by NG tube): 1.8 ml/kg of a 40–43% alcohol drink over 15–30 minutes (diluted). Patient should be managed at a tertiary facility. Transfer at this stage if necessary. • Continue oral administration of alcohol drink as follows. • Maintenance dose: ° 0.2 ml/kg/hour (non-drinker) ° 0.46 ml/kg/hour (heavy alcohol user). • Maintenance dose during dialysis: ° 0.5 ml/kg/hour (non-drinker) ° 0.77 ml/kg/hour (heavy alcohol user). • May need to give alcohol for 2–3 days. • Correct metabolic acidosis with sodium bicarbonate and ﬂuid replacement. • To conﬁrm diagnosis, if possible, check osmolar gap, anion gap and serum ethanol). In the early stages a gap of >19 mOsm/kgH2O may be indicative of ethylene glycol poisoning if serum ethanol is 0 (if not subtract 24 mOsm/kgH2O per 100 mg/dl of ethanol). Later a raised anion-gap metabolic acidosis develops. • Haemodialysis if there is a severe metabolic acidosis (pH <7.25 or base deﬁcit >15 mm despite buffer) or signs of end organ toxicity, coma and seizures, renal failure, or signs of visual disturbances. Consider peritoneal dialysis if haemodialysis not available. • Folinic acid 50 mg IV every 4 hours for 6 doses. • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • If severe respiratory distress or SpO2 <90, give oxygen (see Quick Check pages 33–35). • If hypotension or shock, give IV ﬂuids rapidly (see Quick Check page 40 and Section 3.1). • Do NOT induce vomiting, attempt gastric lavage, or give activated charcoal. • If acute lung injury, see Section 3.2. • Observe for at least 6 hours for respiratory symptoms. If asymptomatic, discharge. • Immediate chest X-ray if symptomatic.

Petrol, kerosene and other volatile hydrocarbons – ingestion

Nausea, vomiting, abdominal pain, haematemesis, coughing, shortness of breath, tachypnoea, pulmonary oedema, coma.

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Paracetamol nomogram5

Table: Agrochemicals and pharmaceuticals that are unlikely to lead to adverse clinical outcomes Agrochemicals • • • • • • • • • • • • • • acephate acetamiprid azadirachtin beta-cyﬂuthrin bispyribac carbendazim chlorﬂuazuron chlorothalonil cyhalothrin cypermethrin deltamethrin d-trans allethrin edifenphos etofenprox • • • • • • • • • • • • • fenoxaprop-ethyl fenvalerate hexaconazole imidacloprid mancozeb permethrin propiconazole propineb pyrethroids (others) tebuconazole tebufenozide thiophanate thiram Pharmaceuticals antibiotics diuretics and ACE inhibitors oral contraceptive pills nonsteroidal anti-inﬂammatory agents (excluding salicylates and mefenamic acid) • acid suppressants (proton pump inhibitors, H2 receptor blockers • lipid-lowering agents • • • •

5 Used with permission from All Wales Therapeutics and Toxicology Centre, Cardiff, UK..

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3.8.2 Inhaled poisons Inhaled poisons may take the form of gases, vapours, or aerosols. These may cause systemic toxicity (e.g. carbon monoxide, mercury vapour) or respiratory irritation (e.g. chlorine). Table: Inhaled poisons or toxins, symptoms of toxicity, and brief guidance on speciﬁc management Poison or toxin Carbon monoxide Symptoms Mild to moderate toxicity: dizziness, headache, nausea, vomiting, weakness, and confusion. Severe toxicity: syncope, tachypnoea, dyspnoea, respiratory failure or pulmonary oedema, coma, seizures, cerebral oedema, cardiac dysrhythmias, myocardial ischemia, bullous lesions of the skin, muscle necrosis, rhabdomyolysis, compartment syndrome. There may be delayed neuropsychiatric complications. Chlorine Mild to moderate poisoning: cough, shortness of breath, chest pain, burning sensation in the throat and substernal area, nausea or vomiting, ocular and nasal irritation, choking, muscle weakness, dizziness, abdominal discomfort, headache. Severe poisoning: upper airway oedema, laryngospasm, severe non-cardiogenic pulmonary oedema, pneumonia, persistent hypoxemia, respiratory failure, acute lung injury. Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • Give high-ﬂow oxygen aiming at 100% for 6–24 hours (see Quick Check pages 33–35 and Section 3). Give regardless of oxygen saturation and do not titrate. • Cardiac monitoring and perform 12-lead ECG. • Monitor urea, electrolytes and renal function, blood gases, and pH. • Measure carboxyhaemoglobin level, if possible. • Treat seizures (see Section 3.5). • Give supportive care. • If cerebral oedema is suspected, consider advanced airway management for hyperventilation (see Quick Check page 62). • The beneﬁts of hyperbaric oxygen therapy in preventing neurological complications are uncertain. • Check if there are other victims. • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • Consider early intubation if stridor is present. • If severe respiratory distress or SpO2 <90, give oxygen. • Give salbutamol for wheezing (see Quick Check page 37). • Irrigate the eyes. • Check peak ﬂow. • Do chest X-ray if symptomatic. • Monitor SpO2 and electrolytes. • Treat non-cardiogenic pulmonary oedema (see Section 3.2.3).

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Poison or toxin Cyanide

Symptoms Headache, dyspnoea, confusion, coma, convulsions, cardiovascular collapse, metabolic acidosis

Management • Manage airway and assist ventilation as needed (see Quick Check pages 29–32, 62). • Give high-ﬂow oxygen aiming at 100% (see Quick Check pages 33–35 and Section 3). Give regardless of oxygen saturation and do not titrate. • Measure lactate. • Correct persistent metabolic acidosis with sodium bicarbonate. • Severe toxicity (comatose patients): ° Give sodium nitrite: 300 mg (10 ml of 3% solution) by slow IV injection over 5–20 minutes. ° Then give sodium thiosulphate: 12.5 g (50 ml of 25% solution) by slow IV injection over 10 minutes. ° If no response after 30 minutes, give further dose of sodium nitrite 150 mg followed by sodium thiosulphate 12.5 g. • Alternatively, hydroxocobalamin 5 grams IV over 15 minutes can be given, if available. • Moderate toxicity (recovered from a period of unconsciousness, convulsions, cyanosis), smoke inhalation victim, or a presumed cyanide poisoning: ° give sodium thiosulphate 12.5 g (83 ml of 15% solution) by slow IV injection over 10 minutes.

3.8.3 Chemicals on the skin or in the eye Health worker protection It is very important that the person administering ﬁrst aid wears appropriate protective clothing, e.g. gloves and apron to avoid exposing themselves to the chemicals. Remember, emergencies of the airway, breathing, and circulation take precedence.

Manage chemicals in the eye • Hold the eyes open (the patient may need a local anaesthetic to prevent blepharospasm). • Wash any chemicals out with cool, clean water for 15–20 minutes. Take care that run-off does not enter the other eye. In the case of acids or alkalis, check the pH of the conjunctival ﬂuid and continue irrigation until the pH is 7.4. • Do not let the patient rub the eyes. • Treat pain. • If light causes pain, cover the eye with a sterile pad. • Examine the eye (see Section 10.12).

Manage chemicals on the skin • Remove the patient’s clothing or ask the patient to do it. Avoid pulling clothes over the head. Cut clothing off if necessary. • Rinse the skin for about 15 minutes with large amounts of water.

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• • • •

In the case of alkali burns, rinse with water until the pH of the skin is neutral. Watch for signs of poisoning from an absorbed chemical. Consult a poison reference or a poison centre for advice on speciﬁc chemicals. Put contaminated clothes in a sealable bag to protect against secondary contamination.

Manage organophosphates or carbamate on skin • Prevent further absorption by moving the patient to fresh air, removing contaminated clothing, and washing contaminated skin with soap and water.

Manage exposure to tear gas (e.g. CN or CS gas) • Tear gas is also called a ‘lacrimator’ because it irritates the mucous membranes of the eyes, causing a stinging sensation and tears. It may also irritate the upper respiratory tract , causing coughing, choking, and general debility. • Contaminated clothing may continue to emit gas for some time, affecting other people nearby. Therefore, if possible, have the victim remove clothing before entering the treatment area. • Follow the advice above for decontaminating eyes and skin. However, wash the skin with soap and water and then rinse with tepid water for 15 minutes.6 Soothing lotions such as calamine can be applied to irritated skin once decontamination has been done.

6 Public health response to biological and chemical weapons. WHO Guidance, 2004. Available at http://www.who. int/csr/delibepidemics/biochemguide/en/

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3.9 Snake-bite1,2 In this section: 3.9.1 Snake-bite assessment • Establish the circumstances of the bite • Clinical features and diagnosis • Table: Some snakes of medical importance and major features of envenomation 3.9.2 Snake-bite treatment • Treatment of systemic envenomation • Manage complications • Manage local necrosis and compartment syndrome • Snake venom ophthalmia (cobra-spit) • Manage muscle weakness (neurotoxicity) • Manage bleeding from clotting factor defects • Important myths

Snake venoms vary considerably in their effect, ranging from venoms that produce no effects or minimal effects to venoms that are potentially life-threatening. Usually, there is a history of snake-bite, but snake-bite should also be considered in any patient with severe pain or swelling of a limb of unknown origin and when a patient with any unexplained illness presents with bleeding or abnormal neurological signs.

3.9.1 Snake-bite assessment Establish the circumstances of the bite In most snake-bite victims the bite marks are obvious, and the majority of patients will experience signiﬁcant local pain. However, bites by neurotoxic snakes may be virtually painless and, in some cases, the bite site may be difﬁcult to detect. In addition, not all snake-bites lead to signiﬁcant envenoming: 10–50% of bites may be “dry bites”, i.e. insufﬁcient venom was injected to cause clinical effects. If there is any doubt, observe the patient closely. If a bite occurred, consider the following: • Time since the bite • Can the snake be identiﬁed? Local knowledge is important to help identify the correct species. Also, some snakes change considerably in appearance during their life cycle. If there is any doubt, treat the bite as if it is from an unknown species. • Are there any obvious symptoms of envenoming? In some regions particular species may be associated with characteristic clinical syndromes (see Table: Some snakes of medical importance and major features of envenomation).

1 Guidelines for the prevention and clinical management of snake-bite in Africa. Chapters 10, 12, 15. WHO Regional Ofﬁce for Africa, 2010. Available at http://www.afro.who.int/en/clusters-a-programmes/hss/essentialmedicines/highlights/2731-guidelines-for-the-prevention-and-clinical-management-of-snake-bite-in-africa.html 2 Guidelines for the management of snake-bites. WHO Regional Ofﬁce for South-East Asia, 2010. Available at http://www.searo.who.int/LinkFiles/BCT_snake_bite_guidelines.pdf

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Clinical features and diagnosis Clinical assessment should be directed towards determining whether envenoming has occurred. Clinical features may not be apparent until many hours after the bite. Therefore, repeat serial assessment is required. Serial assessment includes the following: • Perform the Quick Check looking at Airway, Breathing, and Circulation (see Quick Check pages 17–19). • Examine the site of the bite for signs such as fang marks, local necrosis, blister formation, or bleeding. • Regional lymph nodes may be tender or enlarged. • Local swelling may gradually extend up the bitten limb. This may lead to a compartment syndrome. • Non-speciﬁc symptoms of systemic envenomation include nausea, vomiting, abdominal pain, dizziness, and headache. • Assess for bleeding ° external, from gums, wounds, or ulcers, needle puncture sites; ° internal, especially intracranial, haematuria, and a prolonged whole blood clotting time. The 20-minute whole blood clotting time test (see below) should be performed routinely. Also see Sections 7.2.18 and 10.19. • Assess for signs of neurotoxicity, including: ° ophthalmoplegia (ptosis), double vision, difﬁculty swallowing (bulbar palsy) and talking, muscle weakness, difﬁculty breathing, and ﬂaccid paralysis with respiratory failure. • Assess for signs of muscle breakdown, including muscle pains and black urine (a urine dipstick test positive for blood is indicative of muscle breakdown resulting in myoglobinuria). It is difﬁcult to give advice that can be generalized to all regions and situations, and local knowledge and adaptation of the management plan are important.3 Note: Due to the wide spectrum of toxic components in snake venoms, a combination of clinical syndromes is common in individual snake-bite victims. See the table below with some snakes of medical importance and the major features of envenomation).

Twenty-minute whole blood clotting test 2−3 ml of whole blood should be collected into a new, clean, dry, glass tube and allowed to stand at room temperature for 20 minutes. Tilt the tube gently to see if a clot has formed. The test is positive if blood has not clotted. The vessel must be glass rather than plastic in order to activate blood coagulation. Glass vessels may not activate coagulation, however, if they have been cleaned with detergent or are wet.

3 Updated snake distributions maps are available at http://apps.who.int/bloodproducts/snakeantivenoms/ database/

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Table: Some snakes of medical importance and major features of envenomation4

South America • Bothrops spp (lance-headed vipers) • Crotalus durissus terriﬁcus (South American pit viper) North America • Crotalus spp (pit vipers) • Micrurus spp (coral snakes) Australia and the Paciﬁc • Pseudonaja spp (brown) • Notechis spp (tiger) • Pseudechis australis (mulga) • Pseudechis porphyriacus (red-bellied black) • Acanthophis spp (death adders) • Oxyuranus spp (taipan) • Sea snakes East and South-East Asia • Daboia russelii (Russell’s viper) • Naja spp (cobras) • Naja philippinensis (Philippine cobra) • Echis carinatus (saw-scaled viper) • Bungarus spp (Kraits) • Hypnale spp (hump-nosed vipers) • Sea snakes Africa • Bitis arietans (puff adder) • Echis ocellatus (carpet viper) • Naja spp (African spitting cobras) +++ ++ +++ ++ +++ + + +++ ± + +++ ++ +++ + +++ +++ ++ + +++ + + ++ +++ ± +++ +++ +++ ++(+) ++ + + + ++(+) ± + ++ + ± + ± +++ +++ +++ ++ + +++ +++ +++ + +++ + ++ ± +++ ± ++ +++ + ± + ++ ± ++ + ++ + ++ ++ ± + +++ ± ++ ++ ++ + +++ + ++ +++

4 Adapted from Meier J, White J. Clinical toxicity of animal venoms and poisons, 1995. CRC Press. Boca Raton FL. and http://www.toxinology.com/

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Renal failure

Local effects

Muscle breakdown

Weakness

Clotting disorders

Low BP

• Naja spp (African neurotoxic cobras) • Atractaspis spp (burrowing asps) • Dendroaspis polylepis (mamba) Europe • Vipera spp (European adders)

+++ ++ +

± ± +++ + +

Note: This table provides a general guide only since there may be interspecies differences in the spectrum and severity of clinical effects. Key: + mild, ++ moderate, +++ severe, ± may or may not be present

3.9.2 Snake-bite treatment Snake-bite victims are generally extremely anxious and restless. First aid measures include reassurance of the victim, immobilization of the bitten limb, and rapid transport to a medical facility. Some snake-bites lead to rapid onset of respiratory failure and cardiovascular collapse. Use Quick Check pages 17–18 for regular assessment of airway, breathing, and circulation. It is important to remove rings and bangles, as the swelling of limbs may worsen. Once the patient is in a medical facility, the most important aspect of management is to determine the need for antivenom and, if indicated, to administer it as soon as possible.

Treatment of systemic envenomation Antivenom is required if there is evidence of systemic envenomation (clinical or biochemical) from a venomous snake. Such evidence may include: • neurotoxicity • clotting disorder (spontaneous bleeding or a positive 20-minute whole blood clotting time) • muscle breakdown – muscle pains or black urine or a 3+ result for blood on a urinary dipstick • hypotension, shock, arrhythmia that persists • local necrosis or extensive swelling (more than half the bitten limb), rapidly progressive local swelling, bites on ﬁngers and toes. If these symptoms and signs are not present, continue to observe the patient closely. On an hourly basis check the patient for weakness (including droopy eyelids and difﬁculty swallowing), muscle strength, any breathing difﬁculty and for signs of bleeding. Carry out a 20-minute whole blood clotting test if there is suspected bleeding or in suspected haemostatic snake-bite. In general, antivenom administration should not be started until there is evidence of systemic envenomation or local necrosis. If antivenom is not available, consider transferring the patient to a facility where antivenom is available (see Quick Check page 70). In the interim ﬂuid replacement, administration of fresh frozen plasma or initiation of dialysis (see Section 11.31) should be considered in such situations. If the patient is in severe respiratory distress, see Quick Check pages 17−18 and consider advanced airway management (see Quick Check pages 62−67).

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Administration of antivenom Clinical points • The dose required depends on the quantity of venom injected; therefore, the dose is not related to whether the patient is an adult or a child. • Antivenom should always be given intravenously. • Epinephrine (adrenaline) should be available for use immediately in case of anaphylaxis. For management of anaphylaxis, see Quick Check page 17 and Section 3.1.3. • Antivenoms are more effective if given early (within hours of envenomation). However, improvement is possible even days after envenomation from some snakes. Expected response to an antivenom • Systemic symptoms usually improve over hours. • Clotting usually corrects itself over a number of hours (depending on the type of snake). Repeat a 20-minute whole blood clotting test after 3−6 hours. • Weakness tends to stop worsening, but may not immediately get better. • Local necrosis will not be reversed but should not progress. • Muscle breakdown may stop progressing, but kidney failure may still occur. Reasons for a patient’s failure to respond to an antivenom • It could be the wrong type of antivenom (particularly if monospeciﬁc). • The antivenom could be inactive or not efﬁcient. • There was an insufﬁcient dose. • There was an excessive delay after envenomation in administration of the antivenom.

Manage complications All patients with snake-bite envenomation should be monitored for development of complications. This requires regular clinical examination (respiratory rate, breath volumes by observation or with spirometry, pulse and blood pressure; signs of compartment syndrome and gangrene), review of charts (urine output and urine colour, temperature) and biochemical investigations (serum potassium, creatinine, and clotting proﬁle). Prevention of renal failure requires adequate ﬂuid intake. A deteriorating level of consciousness may be an indicator of intracerebral haemorrhage.

Manage local necrosis and compartment syndrome The degree of local necrosis depends on the type of venom. Early administration of antivenom is the best way to prevent muscle damage. Compartment syndrome is rare and is difﬁcult to distinguish from local tissue necrosis. • Give analgesia for pain. • It is important to involve a surgeon if there is signiﬁcant swelling of digits or a limb. • Fasciotomy should be considered only if: ° there is clinical evidence of compartment syndrome (disproportionately severe pain, weakness of intracompartmental muscles, pain on passive stretching of intracompartmental muscles, hypoaesthesia of areas of skin supplied by nerves running through the compartment, and obvious tenseness of the compartment on palpation); and ° the intracompartmental pressure has been measured and is >40 mmHg (in adults); and ° clotting disorders have been corrected with antivenom. • Infection is uncommon ° Antibiotics should be given only if there is a necrotic wound or signs of an established infection (e.g. local area is red, hot, swollen, and ﬂuctuant). • Tetanus toxoid vaccine should be given routinely to unvaccinated patients.

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Snake venom ophthalmia (cobra-spit) Following venom contact with the eye, the cornea should be irrigated with large volumes of clean water, and a clean pad and topical antibiotic ointment (e.g. tetracycline) applied. If necessary, use a single dose of a topical local anaesthetic to help open the eyelid so as to properly cleanse the eye. Consider the use of 0.1% epinephrine eye drops to relieve the burning sensation. Diluted antivenom is not recommended.

Manage muscle weakness (neurotoxicity) The use of polyvalent antivenom usually will not prevent the progression of neurotoxic effects in the acute phase, in particular respiratory paralysis, and the patient will not survive without life support. Late administration of antivenom may reverse weakness after envenomation by some snakes. If antivenom is not available, respiratory failure should be managed with assisted ventilation until spontaneous recovery occurs. Monitor the patient closely for signs of progressive muscle weakness • Early signs of neurotoxicity include droopy eyelids, double vision, difﬁculty swallowing, and drooling of saliva. These may indicate impending respiratory paralysis. • Late signs of neurotoxicity include generalized weakness and weakness of the respiratory muscles. As the respiratory muscles become weak, the patient will breathe at a faster rate, take small shallow, and eventually use accessory muscles to breathe. • Hypoxaemia is an ominous sign; usually, it is due to inadequate ventilation or oxygenation (see Section 3.2.1). When SpO2 is <90, give oxygen (see Quick Check pages 33−35). This is a temporary measure, as giving oxygen alone will NOT improve ventilation. If ventilation is inadequate, assist ventilation with BVM (see Quick Check page 31). For cases that are easily reversible, BVM can continue until antivenom takes effect. In neurotoxic snake-bite, anticipate a prolonged course of weakness and consider advanced airway management with tracheal intubation (see Quick Check pages 62−67) if local manual ventilation is feasible or transfer to a hospital where mechanical ventilator is available. Advanced airway management should be considered if there are signs of bulbar palsy (drooling, difﬁculty swallowing, aspiration), as these are signs that the patient can no longer properly protect the airway. Patients with neurotoxic symptoms, except those thought to have been bitten by mambas, should be given an anticholinesterase test. Ideally, edrophonium is used for this because it is short-acting; however, edrophonium is rarely available, and neostigmine can be used as an alternative. Neostigmine is widely used by anaesthetists to reverse non-depolarizing (competitive) neuromuscular blockade. Steps in the anticholinesterase test 1. Take baseline observations for comparison. 2. Then give atropine sulphate (0.6 mg for adults) by slow intravenous injection to block the unpleasant and potentially serious muscarinic effects of acetylcholine (such as colic).

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3. Then give edrophonium chloride (10 mg in adults) by slow intravenous injection, or, if edrophonium is not available, use neostigmine bromide by intramuscular injection – 0.02 mg/kg for adults. 4. A convincing response is increased muscle power or improvement in ptosis. If the patient has a convincing positive response, maintain on neostigmine, 0.5–2.5 mg every 1−3 hours up to 10 mg/24 hours maximum for adults by IV/IM or SC injection, together with atropine as above.

Manage bleeding from clotting factor defects (See Section 10.19 Abnormal bleeding and bruising) • Spontaneous systemic bleeding usually stops within 15–30 minutes, and blood coagulation is restored within about 6 hours if an adequate dose of antivenom has been given. The 20 minute whole blood clotting test should be used to monitor the dose of antivenom in patients with coagulopathy. If the blood remains uncoagulated 6 hours after the ﬁrst dose, the dose should be repeated every 6 hours until blood coagulation is restored. • If the patient starts bleeding excessively, correct with fresh frozen plasma, platelets or cryoprecipitates in addition to antivenom. If these blood products are not available, use fresh whole blood (see Section 10.19). • Heparin should not be given. • Central venous lines and surgery should not be attempted unless clotting has been corrected with antivenom.

Manage muscle breakdown (rhabdomyolysis) • An early sign includes muscle pain and a positive urine dipstick test for blood (cross-reacting with myoglobin from muscle). • Late signs include dark urine and renal failure. • Give IV LR or NS ﬂuids (more than 3 litres per day). Keep patient very well hydrated by maintaining the JVP (visually) to be slightly higher than normal, and use furosemide when appropriate (see Section 11.31). • Urine output should be monitored, and the rate of ﬂuid administration adjusted accordingly. • Correct acidosis and electrolyte disturbances. • Haemodialysis or peritoneal dialysis may be required to treat acute renal failure and associated complications such as hyperkalaemia and acidosis (see Section 11.31).

Important myths 1. “Any antivenom will do” – FALSE. Antivenoms are very speciﬁc to the type of snake. For example, antivenom made for snakes in India will not be effective for snakes in Papua New Guinea. However, many antivenoms are polyvalent. This means that the venoms of more than one snake (there may be 10 or more) are used in their preparation. 2. “Cut the bite out” – FALSE. This may result in more extensive injuries than caused by the snake. If clotting problems are present, the patient may bleed to death.

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3. “Tying a tourniquet stops the poison spreading” – FALSE. Cutting off the blood supply may not stop the venom spreading, and it may endanger the limb through lack of blood. 4. “Snake-bite pills” and other herbal remedies are effective in treating snakebites – FALSE. Intravenous antivenom is the only speciﬁc treatment for snake-bite. No oral tablets, plant extracts, or treatments applied directly on the skin have been shown to reverse the effects of venom. This includes the use of special “black stones”, coals, or ash. Other false myths include the use of scariﬁcation, injection of the wound with Condy’s crystals, the use of electric current, and sucking on the wound.

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3.10 Burns1 In this section: 3.10.1 Initial management and stabilization of burns using Quick Check • Airway and breathing • Circulation • Remove all burned clothing, and cool skin with water. • Manage associated trauma. • Cover the burn to reduce pain, and provide appropriate analgesia. 3.10.2 Assess and classify the burn • Determine the degree of the burn • Estimate the extent of the burn • Types of burns • Classify the burn to decide how to manage it 3.10.3 Burn management • Manage inhalation injury • Fluid resuscitation in patients with severe burns • Burn skin care

Burns are a severe form of trauma that can cause signiﬁcant soft tissue injury as well as metabolic changes affecting ﬂuid balance. Extensive burns are a lifethreatening emergency. The extent of the burn, extremes of age, co-morbidities, and the circumstances surrounding the injury all will inﬂuence patient outcome.

3.10.1 Initial management and stabilization of burns using Quick Check Airway and breathing • Consider early intubation or tracheotomy for any burns of the face, anterior neck, and upper chest to protect from laryngeal swelling. • Administer oxygen to all patients with Quick Check emergency signs, severe burns (>15% of total body surface area (TBSA) or airway involvement), altered mental status, SpO2 <90, or suspicion of carbon monoxide poisoning (smoke inhalation, ﬁre in enclosed space).

Circulation • Insert IV. Calculate amount of ﬂuids according to the Parkland formula for patients with severe burns and Quick Check emergency signs. Parkland formula calculates the amount of ﬂuid to be administered over the ﬁrst 24 hours post-burn; 4 ml x body weight in kg x percentage burns per TBSA

1 Surgical care at the district hospital. WHO, 2003. Available at www.who.int/child_adolescent_health/ documents/9241545755/en/index.html and Integrated management for emergency and essential surgical care. WHO, 2003. Available at www.who.int/surgery/publications/imeesc/en/index.html

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Remove all burned clothing, and cool skin with water. • If the burn is acute, apply cool, wet towels for 30 minutes to cool the burn. • Beware of hypothermia.

Manage associated trauma. Cover the burn to reduce pain, and provide appropriate analgesia.

3.10.2 Assess and classify the burn Determine the degree of the burn The degree of the burn indicates its depth and severity and determines if surgery will be required. 1st degree 2nd degree 3 degree rd

superﬁcial superﬁcial or deep partial thickness full thickness

red or pink, painful, skin intact, no blisters red, blisters, wet, painful, blanches white or black/leathery, no sensation, dry

Experienced burn doctors often reserve judgement on the deﬁnitive classiﬁcation of the burn until they have examined the wounds at 72 hours after the injury. • First-degree burns usually will heal with minimal sequelae, even without treatment. • Second-degree burns will heal, but often with signiﬁcant scarring and contractures. • Third-degree burns will heal (if at all) by contracture and cause severe scarring and disability. Third-degree burns also may include injury to the muscles or tendons. Skin grafting is indicated for deeper second-degree burns and third-degree burns to improve cosmetic and functional outcome. If the wound is not epithelialized by 21 days, it should be grafted.

Estimate the extent of the burn (relative to TBSA) • Determine the percentage of area burned using the “rule of 9s”, whereby the body is divided into 9 areas or parts. • If the burns do not fully cover a body part or cover more than one part, the percentage can be calculated by using the patient’s palm as approximately equal to 1% of the TBSA. • If a second- or third-degree burn involves the face, neck, hands, feet, or perineum or is circumferential (encircles a limb), it should be treated as a severe burn, and surgical referral is indicated, even if the TBSA is small.

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Estimating the burned surface area in adults The rule of 9s

Types of burns Flame burns are the most common. A history of a ﬂame burn in an enclosed space suggests inhalation injury. Look for soot in the mouth and burned hairs in the nose. Strongly consider airway protection before laryngeal swelling makes intubation too difﬁcult. Flame burns often are deep, with feathered edges of partial-thickness burn. Clean off soot and loose skin with soap and water. Scald burns. It can be very difﬁcult to assess the full depth of a scald burn in the ﬁrst few hours. It may not be apparent until the third day. Contact burns usually are small but very deep, down to muscle, and likely to require excision and grafting. Grease burns. Cooking oil is usually very hot. These are typically deep, partialthickness or full-thickness wounds. Electrical ﬂash burns. These occur when a screwdriver or other conductive tool is inserted into a live electrical box. There is an extremely hot ﬂash, but electricity does not travel through the body. Such burns typically involve the face and hands. Examine the patient’s eyes with ﬂuorescein and blue light for corneal damage. If corneal damage is present, treat with antibiotic eye drops or ointment. Even if there is no smoke involved, electrical ﬂash burns can cause laryngeal swelling, and airway protection needs to be considered. Otherwise, treat as a thermal burn. Electrical conduction burns. These result from conduction of high voltage electricity through the body. If the patient is conscious, there may be a history of the “can’t let go” phenomenon: The patient was unable to let go of the electric wire or other source. On the surface, burns are typically only small entrance and exit wounds, but suspect massive underlying tissue injury. Look for cardiac arrhythmias and fractures. Destruction of muscle leads to myoglobinuria and renal

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failure (see Section 11.31). In all cases insert a urinary catheter. If the urine is dark, raise the pH of the urine by giving large volumes of 5% dextrose with 150 mEq sodium bicarbonate per litre. (Putting bicarbonate in normal saline will yield a very hypertonic solution.) Give mannitol boluses and furosemide. Assess compartment pressures in the affected limbs and perform early fasciectomy. Remember that compartment pressures will rise with ﬂuid resuscitation, and so re-examine the patient frequently. Chemical burns. While caused by a wide variety of chemicals, acid and alkali burns are the most common. Always protect staff ﬁrst! First, dust off any dry chemical, then wash the whole body for 40 minutes or more in running water to dilute the chemical. Irrigate the eyes thoroughly.

Classify the burn to decide how to manage it SIGNS • Any full-thickness burn • Partial-thickness burn ° ≥15% TBSA in adults ° ≥10% TBSA in children ° Special regions (hands, face, feet, perineum) • Any circumferential burn • Inhalation injury • Signiﬁcant associated trauma OR • Any burn in the very young or elderly OR • Signiﬁcant pre-burn illness (diabetes, HIV) CLASSIFY AS SEVERE BURN TREATMENTS • Protect airway (consider laryngeal oedema with or without inhalation injury). • Cool burn if acute. • Fluid resuscitation ° Give ﬂuid according to Parkland formula, and insert urinary catheter to monitor urine output. • Consider escharotomy for circumferential burns. • Give tetanus toxoid. • Burn skin care (see below) • Prophylactic antibiotics are not recommended. Reserve antibiotics for clinical indications of infection. • Manage acute pain (see Section 20). • Place a nasogastric tube for feeding and give medication for gastric acid suppression (H2 blocker or proton pump inhibitor). • Admit to hospital. • Burn skin care (see below) • Give tetanus toxoid. • Some will require admission for pain control and dressings. Others may be managed at home with close follow-up. ° Change dressing daily. ° Mobilize joint twice daily and especially at each dressing change (move through range of motion). ° Manage acute pain: pre-medicate for dressing changes • Schedule follow-up the next day and regularly thereafter. The burns must be seen by a doctor on the third day to determine full extent of the burn and whether surgical referral is required for skin grafting. • • • • • Burn skin care (see below) Give tetanus toxoid. Manage acute pain. Patient can be managed at home. Advise to return if fever, purulent drainage, or increased pain or redness.

Second degree burns • <15% of body (adults) First degree burns • >50%

MODERATE BURNS

Small burns of non-critical areas

MILD BURN

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3.10.3 Burn management Manage inhalation injury Suspect airway injury in all those who were burned in an enclosed space. Look for facial burns, soot in the mouth, and singed nasal hairs. Airway oedema may progress rapidly in the ﬁrst hours to days after injury; frequent re-assessment is required for any patient with suspected airway injury. There are 3 components to consider in inhalation injury. 1. Laryngeal oedema may be caused by inhalation of hot gas or by any burn involving the face, anterior neck, and upper chest, including scald and electrical ﬂash burns. Burns larger than 30% TBSA, so called “metabolic burns”, will likely swell; it is prudent to protect the airway. 2. Carbon monoxide poisoning should be suspected in anyone who lost consciousness in a ﬁre. Intubate and provide 100% oxygen where possible if patient is confused or unconscious. 3. True smoke inhalation causes a pneumonitis that may not become apparent on chest X-ray until 72 hours after the injury. Protect the airway before stridor develops. Stridor is a very late sign of lifethreatening airway oedema. Where there is no capacity to manage the patient on a ventilator, consider early tracheotomy. Call for help if not skilled in airway management. WARNING SIGNS: face and neck burns, black sputum, wheezing, hoarse voice, burned hair in the nose.

Fluid resuscitation in patients with severe burns Patients with signiﬁcant burns will require intravenous hydration. • Place a large-bore IV X 2 in an area away from the burned skin. • Use lactated Ringer’s solution or normal saline. • Consider using a bladder catheter to follow urine output. • Use the Parkland formula to estimate ﬂuid needs: ° half in the ﬁrst 8 hours and remainder in the next 16 hours (starting from the time of the burn, not the time at which ﬂuid resuscitation is begun) • Monitor urine output in all burn patients and adjust intravenous ﬂuids to ensure adequate urine output (0.5–1 cc/kg/hour). Do not over-resuscitate. Example: Parkland calculation using 4 ml 60 kg adult with 30% partial-thickness burns. ml x kg x % = ml ﬂuid required 4 x 60 x 30 = 7200 ml (7.2 litres) The patient requires a total of 7200 ml of IV ﬂuid in ﬁrst 24 hours. Give 3600 ml over the ﬁrst 8 hours and 3600 over the next 16 hours.

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Burn skin care • Use sterile techniques for cleaning and debridement. • Remove loose, necrotic skin and broken, tense, or infected blisters. • Apply a non-adherent dressing and provide a moist healing environment. ° In resource-limited settings topical antibiotics may need to be reserved for infected wounds. Bland dressings, such as parafﬁn gauze or honey and ghee (clariﬁed butter), are an acceptable alternative for uninfected burns. Make honey and ghee dressings by mixing equal parts honey and either ghee or oil and spread the mixture over sterile gauze in a ﬂat pan. ° If infection of the burn is suspected, apply a topical antibiotic (for example bacitracin, silver sulfadiazine). IV or IM antibiotics may also be indicated if there is evidence of a wound infection. • Change the dressing daily. • Mobilize any burned joints twice a day and at dressing changes (move through range of motion, medicate for pain as needed). • If a burn encircles a limb, there can be marked swelling and decreased circulation. ° Elevate any burned extremity and monitor it frequently. ° Escharotomy is indicated for limb cyanosis, decreased pulses, or worsening neurological status. • Consider escharotomy in the severe burn patient with difﬁculty ventilating secondary to burned skin that limits chest movement.

Special issues For all burns investigate any suspected cases of domestic or child abuse. Large burns. Patients with large burns (>30% TBSA) should be referred to a specialized burn centre as soon as possible. But ﬁrst: • cool the burn to stop ongoing tissue destruction, but preserve and monitor body temperature - beware of potential hypothermia; • protect the airway; • start resuscitation ﬂuid; • place a urinary catheter and a nasogastric feeding tube; • give tetanus toxoid; • give omeprazole2; • do escharotomy if indicated; • dress the burns. Then transfer the patient promptly to a burn centre. Delayed presentation. Many patients will present late. Carefully assess hydration and nutritional status. Give ﬂuid to restore euvolaemia. Debride the wound (with adequate analgesia). Treat infection and malnutrition. Hand burns are common and can be severely disabling. After cleaning the hand and considering escharotomy of the dorsum and ﬁngers, apply topical antibiotic

2 Ranitidine is an alternative.

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and cover with either a plastic bag or loose-ﬁtting surgical glove taped or wrapped above the wrist. Splint the hand in the “safe position” (see ﬁgure below), elevate the arm, and range the joints twice a day, with adequate analgesia. Blisters. Small blisters may be left intact, but those that are large, ﬂaccid, blood- or pus-ﬁlled, and those restricting joint movement should be un-roofed and the base covered with a dressing. Bathing. It is helpful to thoroughly wash the patient with soap and water at the time of admission. Showering is a good way to help remove debris from the wound. However, the routine immersion of burn patients in non-sterile bathtubs is unhelpful and spreads infection. Face burns. It is difﬁcult to keep dressings on the face. Open, uncovered treatment is preferred, with frequent, gentle cleaning and the application of topical antibiotic ointment. Shave facial hair every 2 days to prevent accumulation of exudate and infection. Examine eyes with ﬂuorescein and, if keratitis or corneal ulceration is found, apply antibiotic eye ointment frequently. Eyelid contractures expose the surface of the eye; early surgical referral should be made for grafting of the lids. Keep the eye well protected with ointment. Blepharoplasty (suturing together the lids) is seldom indicated, as the sutures pull out, compounding the problem. Circumferential, partial-, and full-thickness burns. Burned skin does not stretch and, thus, as the underlying tissue swells, pressure may cut off circulation to the extremity. This may not be apparent at the time of presentation; the swelling will increase as ﬂuid is given, however. Escharotomy is performed by cutting through the burned skin in the mid-lateral and mid-medial axes of the extremity. A fullthickness burn has no sensation, but the edges of the burn may have exquisitely tender partial-thickness burn, so a local anaesthetic is helpful. Cut through the burn down to fat, and you will see the skin spread apart. Put a little “T” at the end of the incision where burn meets normal skin to allow more expansion. Never cut un-burned skin. Cover with dressings. Surgical referral. All signiﬁcant burns should be evaluated by a surgeon. Burns heal by a combination of re-epithelialization and contraction. The appearance of white epithelial pearls in the wound indicates re-epithelialization from nests of un-burned epithelium at the bottom of hair follicles and sweat glands. Red granulation tissue, however, clean as it may be, is granulating dermis and fat; if it ever heals, it will be by wound contraction. Any burn that does not heal by 3 weeks needs a skin graft. Nutrition. Patients with a major burn may require more than twice their normal protein and calorie intake. Large amounts of protein are lost through the burn, and healing requires a lot of protein as well. The metabolic rate is elevated, and carbohydrate requirements are elevated as well. Because of pain and associated illness, few burn patients feel hungry. The best strategy is to insert a nasogastric feeding tube and give enteral feeds. Standard feeding solutions are good but expensive. Perfectly adequate solutions can be made from commonly available local foods and administered by the patient’s relatives. In limited-resource settings good nutrition may be the most important intervention that can help a burn patient survive and heal. Oral rehydration solution (ORS) may be given by nasogastric tube instead of IV ﬂuid resuscitation where IV access is difﬁcult. ORS should be given freely to patients who are able to tolerate oral intake. Analgesia. Burns are exceedingly painful, and so adequate analgesia is very important. Use a multimodal approach with different classes of analgesic.

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Paracetamol and morphine provide good basal analgesia but should be supplemented with short-acting agents for dressing changes and daily physiotherapy. Splinting and positioning. It is vitally important to splint burned hands in a position with the wrist dorsiﬂexed, the metacarpophalangeal (MCP) joints ﬂexed at 90°, and the ﬁngers straight. Splints can readily be fashioned from plaster of Paris and secured with a rolled bandage outside the plastic bag or glove. In general, splint other joints against the force of contracture. Do not let someone with a neck burn sleep with a pillow (which ﬂexes the neck); take away the pillow so that the neck remains extended as much as possible. Position a burned shoulder at 90°. It is easier to prevent contractures than to treat them later.

Figure: The “safe position” for splinting a burned hand

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3.11 Severely ill patient monitoring form Careful monitoring of critically ill patients is important. After initially assessing the patient for emergency signs using Quick Check and giving appropriate emergency treatments, reassess the patient for response and respond accordingly. Throughout Section 3 there is an emphasis on how to monitor–record–respond. Section 3.0 describes the clinical parameters that should be monitored and recorded as well as the frequency of monitoring. This section provides a sample patient monitoring form that can be used to record the patient’s clinical parameters by time since arrival. A patient monitoring form gives quick access to clinical information required to track the patients’ progress (Are they getting better, or are they getting worse?) and to easily review a patient’s status at a point in time. Also, it allows the clinician to see what medications or other interventions have been given so that further treatments can be given at the appropriate times. The form includes is an area for laboratory tests that allows the clinician to keep track of what tests have been done, what are the results (if completed), and what tests are pending. The clinician should start ﬁlling out this form as soon as the patient arrives. However, emergency treatment should not be delayed to ﬁll out the form. Complete the form as follows: 1. Fill in the patient’s name, age, sex, patient clinic number, admission date and time. 2. 3. 4. 5. 6. Fill in the working diagnosis. Fill in investigations. Circle the appropriate tests, if sent, and record the results. For all women check if pregnant and, if so, note expected date of delivery (EDD). Record any history of drug allergy and type of reaction. Record the time of day at each monitoring point, starting with the time of arrival. The form speciﬁes time monitoring intervals in minutes, starting at time 0. Alternatively, if the patient monitoring form is started after a patient has already been admitted, record the time of day at the start of the resuscitation. Record the following clinical parameters every 30 minutes until stable, then every 60 minutes; • SpO2 • systolic BP in mmHg • pulse • respiratory rate per minute • consciousness level – use AVPU scale: Alert – Responds to Voice – Responds to Pain – Unresponsive. If trauma patient, ﬁll in an initial Glasgow Coma Scale; repeat if head injury.

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Record the following every 6 hours in column corresponding to time since arrival: • temperature in degrees Celsius • urine output** in ml per hour. Record volume if Foley catheter used. If not, just enter checkmark (9) if noted. • Repeat glucose and haemoglobin if initial values abnormal.

8. 9.

Record results of glucose, haemoglobin. Exam – record ﬁndings of patient examination.

10. Assess – record clinical assessment of major problems plus likely or differential diagnosis. 11. Response − indicate which treatment was given and at what time. 12. Initials − always write your initials after recording patient information. 13. Any additional notes − document any additional information about clinical history, examination, interventions, and response as necessary to communicate clinical course to other health workers. 14. Benchmarks achieved − these are a targeted list of interventions that should be completed within certain time frames. They serve as markers of delivering high-quality care to severely ill patients. For example, a patient with septic shock should be given empiric antimicrobials within 1 hour. Using a checklist like this can help health workers to deliver high-quality care.

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208 Birth date: ___/___/___ Circle if test sent Electrolytes _______________________ Urine dipstick ________________ and record result: Malaria ________ AFB _______ Blood culture _______ Gram stain _______ CXR ________ Other ________________________________________________________ Allergies: Age: Sex: M / F Admission date: Admission time: 0 30 60 (1 hr) 90 120 (2 hrs) 150 180 (3 hrs) 210 240 (4 hrs) 270 300 (5 hrs) 330 360 (6 hrs) 390

Name:

Patient No.:

Diagnosis:

Pregnant:

Yes/No

EDD:

Time of day

Monitoring interval (minutes) from arrival or start SpO2

Q30 – 60 min (until normal)

Heart rate

Systolic BP

Severe illness monitoring form (ﬁrst 6 hours)

Monitoring form

Respiratory rate

Conscious level (AVPU)

Temperature (°C)

Q1 – 6 hours, repeat if abnormal

Glucose

Urine output*

Haemoglobin

Exam

Assess

Response

Fluids (type, rate)

Oxygen (method/ﬂow)

Salbutamol

Vasopressor (type/rate)

Glucose

Antibiotics

Antimalarial

Antiviral

Furosemide

Blood

Other

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Clinician (initials)

Name: Circle if sent and record result: Allergies: 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Patient No.:

Birth date: ___/___/___

Age:

Sex: M / F

Time of transfer:

Ward:

Diagnosis:

Electrolytes _______________________ Urine dipstick _________________ Malaria ________ AFB _______ Blood culture _______ Gram stain _______ CXR ______ Other _________________________________________________________

Pregnant:

Yes/No EDD: Time of day

Monitoring interval (hours) SpO2

Heart rate

Systolic BP

Q 1 hour if SBP<90 or if on pressors, otherwise Q 2 hours

Respiratory rate

Conscious level (AVPU)

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Q 6 hours

Urine output*

Temperature (°C)

Glucose Repeat if initial value Haemoglobin abnormal

Exam

Assess

Response

Fluids (type, rate)

Oxygen (method, ﬂow)

Severe illness monitoring form (hours 7-24)

Monitoring form

Salbutamol

Vasopressor (type, rate) Glucose

Antibiotics

Antimalarial

Antiviral

Furosemide

Blood

Other

Clinician (initials)

209

210 If acute pulmonary oedema, within 30 minutes: Oxygen started SpO2 measured Furosemide 20 mg IV given If hypertensive, isosorbide dinitrate given If ischaemia (chest pain), aspirin given If wheezing, within 30 minutes: Salbutamol given If asthma/COPD, steroid given If shock, within 30 minutes: IV line and rapid ﬂuids started 1000 ml ﬂuid bolus given Within 1 hour, if fever or suspect septic shock: Antibiotics given If malaria possible, antimalarial given If inﬂuenza possible, antiviral given Within ﬁrst 2 hours: 3 litres IV ﬂuids given If altered level of consciousness/ convulsing: Oxygen started Oxygen saturation measured Recovery position Glucose checked and given If convulsing, diazepam given If convulsing and pregnant, magnesium sulphate given If trauma, within 30 minutes: Oxygen started Oxygen saturation measured Spine immobilized until clear If shock, IV line and rapid ﬂuid bolus If shock, surgical consult Hb and type and cross sent

Additional notes (please note any changes from standard protocol).

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Monitoring form

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

BENCHMARKS – circle the relevant condition(s), then check if achieved

If severe respiratory distress, suspect pneumonia, or acute lung injury, within 30 minutes: Oxygen started SpO2 measured IV started If wheezing, salbutamol given Appropriate infection control

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Within 1 hour: Broad-spectrum antibiotics If malaria possible, antimalarial given If inﬂuenza possible, antiviral given

4. Trauma: approach to the acutely injured patient Table of contents 4.0 4.1 4.2 General principles of trauma care. . . . . . . . . . . . . . . . Working as a clinical team to care for the trauma patient . Assign responsibilities within the clinical team . . . . . . . . Referral to a higher level of care . . . . . . . . . . . . . . . . Assessing and treating the trauma patient . . . . . . . . . . Oxygen therapy for trauma patients . . . . . . . . . . . . . . First assess and treat immediately life-threatening injuries Resuscitation and stabilization . . . . . . . . . . . . . . . . . Deﬁnitive care and treatment . . . . . . . . . . . . . . . . . . Violence and injury prevention . . . . . . . . . . . . . . . . . Manage rape or abuse in adolescents and adults . . . . . . Provide immediate comfort . . . . . . . . . . . . . . . . . . . . Special considerations for the examination . . . . . . . . . . Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . Wounds (soft tissue injuries) . . . . . . . . . . . . . . . . . . . General approach to wound management. . . . . . . . . . . Suture techniques . . . . . . . . . . . . . . . . . . . . . . . . . Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General principles . . . . . . . . . . . . . . . . . . . . . . . . . Splints and casts . . . . . . . . . . . . . . . . . . . . . . . . . . Compartment syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.3 4.4

4.5 4.6

213 215 216 217 217 218 219 222 226 226 227 227 227 228 229 230 232 232 232 233 237

4. Trauma: approach to the acutely injured patient1 This manual covers only the initial emergency assessment and management of an acutely injured adolescent or adult patient, prior to surgery. See Surgical Care at the District Hospital for additional information on deﬁnitive surgical treatment and inpatient hospital care.

4.0 General principles of trauma care Correct management of the trauma patient in the ﬁrst few hours is critical. Many deaths can be prevented if rapid care is given, including treatment of pneumothorax, abdominal haemorrhage, and pelvic and long bone injuries. Early identiﬁcation and treatment of injuries can prevent late complications and death from infection or multiple organ failure. Hospitals with limited resources face additional challenges when caring for the trauma patient. Patients often must travel long distances to reach the hospital, and delays in presentation can lead to increased morbidity from untreated wounds, abdominal injuries, and fractures. Other challenges include a lack of trauma care specialists, equipment, and supplies. In addition, prolonged transport times may undermine safe transfer to a higher level of care.1,2 Despite these obstacles, an organized team approach will greatly improve the care of trauma patients in resource-limited settings. Practice frequently using the team system during routine care, and during scheduled training drills. Use the Quick Check to identify and treat patients with immediately life-threatening injuries leading to emergency signs. Early priorities for the trauma patient include managing airway emergencies, stabilizing the spine, controlling haemorrhage, and treating shock. Trauma patients identiﬁed using Quick Check emergency signs (airway and breathing, circulation, altered consciousness or convulsions) are seriously ill and may rapidly deteriorate. Any trauma patient with abnormal vital signs (SBP <90, pulse >110, SpO2 <90) is considered unstable. Common mechanisms causing serious trauma include motor vehicle accidents, falls from a signiﬁcant height, and gunshot or stab wounds. As with all seriously ill patients, frequent monitoring, recording, and responding to clinical changes is of vital importance.

When caring for the seriously ill trauma patient: • Identify and immediately treat airway obstruction, tension pneumothorax, or haemorrhagic shock. • Immediately immobilize the cervical spine. Only move the patient using the log roll technique until a spinal injury is excluded clinically or by X-ray. See page 44 Quick Check. • Stop any visible haemorrhage with manual pressure or a compression dressing. • Insert at least 2 large bore IVs (14 or 16 gauge), and send blood for haemoglobin and type and cross-match. Blood may be needed quickly and in large quantities for some trauma patients. 1 Adapted from Surgical Care at the District Hospital. WHO, 2003. Available at http://www.who.int/surgery/ publications/scdh_manual/en/index.html with updates based on the evidence review 2 For additional information on assessment and treatment of the trauma patient, see this manual and the IMEESC toolkit that can be accessed at http://www.who.int/surgery/publications/imeesc/en/index.html

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• Only use isotonic crystalloid ﬂuid (normal saline (NS) or Lactated Ringer’s solution (LR)) for resuscitation in the trauma patient. If possible, warm IV ﬂuids are preferred. • If signiﬁcant haemorrhage is ongoing, or there is a risk of signiﬁcant haemorrhage, give tranexamic acid.3 Administer an intravenous loading dose of 1 g of tranexamic acid over 10 minutes, followed by an intravenous infusion of 1 g over 8 hours. Tranexamic acid should be given as soon as possible. The effect of tranexamic acid depends on the time interval between injury and the onset of treatment. A new analysis of the 2010 CRASH-2 study shows that tranexamic acid should be given to bleeding trauma patients as early as possible. If treatment is not given until 3 hours or later after injury, it is less effective.4 • If after 2–3 litres of IV ﬂuids the patient is still in shock (SBP <90), identify and control source of haemorrhage and transfuse packed red blood cells. Blood transfusion protocols should follow national or regional guidelines. Safe blood transfusion procedures should be followed for all patients, including emergency patients. • As soon as possible after any emergency signs are treated, examine the patient thoroughly from head to toe to identify any other injuries. Fully expose all trauma patients on arrival (all clothing removed, and look at both front and back of patient) to identify injuries. After the complete assessment, cover and keep the patient warm. • Reassess the patient frequently in the ﬁrst few hours, and after any treatments are given. Monitor and record vital signs (BP, HR, RR, SpO2) and mental status (both Glasgow Coma Scale (GCS) and AVPU) on arrival, and at least every 15 minutes for the ﬁrst hour. Continue to check Glasgow Coma Scale for patients with head injury. For other patients with major trauma, recheck the GCS until stable, then use AVPU. • If the patient deteriorates, repeat Quick Check and perform a thorough examination to identify any missed injuries. If the patient is in shock (SBP <90 mm Hg) and no visible bleeding is present, assume the patient has internal bleeding. • Treat pain as soon as possible. • If the patient requires referral for specialized care, and if the patient has been stabilized to the extent possible within the local capabilities for safe transfer, transport the patient without delay. Note the special considerations in Quick Check for trauma patients. Knowledge of the mechanism of injury can help identify at risk patients who require immediate assessment and treatment. In addition to the presence of obvious visible trauma or emergency signs, triage patients as a Quick Check emergency if there is a high-risk mechanism of injury or speciﬁc injury patterns present that indicate the patient was injured by a considerable force. Patients who initially appear uninjured may have life-threatening occult injuries, such as internal bleeding. Monitor trauma patients

3 Added to WHO Essential Medicine List at the March 2011 expert meeting http://www.who.int/selection_ medicines/committees/expert/18/applications/TRANEXAMIC_ACID_10_2.pdf based on the clinical trial Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with signiﬁcant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. Available at www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60835-5/ abstract 4 The CRASH-2 collaborators. CRASH-2: tranexamic acid and trauma patients. Lancet, 2011. Available at http:// www.thelancet.com/crash-2

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frequently, at a minimum for the ﬁrst hour, and until life-threatening injuries have been excluded. If unstable, continuously monitor the patient until the condition is stabilized and deﬁnitive care is arranged. High-risk mechanism of injury Fall more than 3 metres Road trafﬁc accident at speed more than 30 km/hour or with signiﬁcant damage to vehicle Thrown from a vehicle or trapped in a vehicle Pedestrian or cyclist hit by a car Motorcycle crash with separation of rider from bike Death of another person in the same accident Injury from a high- or low-velocity weapon High-risk injuries Penetrating injuries to head, neck, torso, and extremities proximal to elbow and knee Flail chest Combination of trauma with burns Two or more proximal long-bone fractures Pelvic fractures Limb paralysis Amputation proximal to wrist or ankle

Patients with chronic medical conditions or at the extremes of age are at increased risk for complications from traumatic injuries. Have a high index of suspicion for occult injury in patients with high-risk co-morbid conditions. These patients often will require admission for observation, even in the absence of signiﬁcant obvious injuries. High-risk co-morbid conditions Age <5 years or >55 years Cardiac or respiratory disease Insulin-dependent diabetes Cirrhosis Morbid obesity Pregnancy Immunosuppression Known bleeding disorder or on anticoagulants

4.1 Working as a clinical team to care for the trauma patient Preparation It is important to check that the resuscitation area is ready at all times, before a trauma patient arrives. • Emergency trolley in the resuscitation area with necessary emergency medications and equipment (Quick Check page 72) • Adequate supply of resuscitation ﬂuid (LR or NS) and safe blood for transfusion • Equipment to stabilize the cervical spine and a spinal board to move the patient, if necessary • A plan and equipment to transport the patient to the operating theatre, if required.

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Assign responsibilities within the clinical team Caring for a critically injured trauma patient requires multiple tasks to occur simultaneously, such as protecting the airway and cervical spine, completely undressing the patient, checking vital signs, obtaining IV access and starting IV ﬂuids, obtaining the history and performing a physical examination, and sending laboratory investigations and documentation. Keeping the situation calm and controlled is important for delivering quality care. If possible, designate tasks ahead of time. Regardless of how many people make up the clinical trauma team, treating emergency signs of airway, breathing, and circulation will always take ﬁrst priority. During all trauma resuscitations, one person should be in charge as the “team leader.” The team leader is usually the most senior member present. The team leader’s responsibilities include coordinating and controlling the resuscitation, ordering any procedures and diagnostic tests, and deciding on transfer to the operating theatre or a higher level of care. Although in many district hospitals there may only be 1 or 2 people to care for the patient, all hospitals should develop a trauma team plan ahead of time based on their available personnel and resources. This plan may vary depending on the time of day if there are fewer health workers available during night hours or weekends.5 Sample division of roles on the clinical team caring for a trauma patient at a district hospital5 Team leader Coordinate and control resuscitation Designate tasks for others Ensure treatment of any Quick Check emergency signs Ensure protection of the cervical spine and appropriate movement of the patient Order all medications, IV ﬂuids, blood Order all procedures and diagnostic tests Perform any specialized procedures if necessary (i.e. securing the airway, treating tension pneumothorax, splinting fractures) or delegate to another skilled team member Monitor progress Decide on referral to the operating theatre or a higher level of care Primary nurse Obtain IV access Monitor and record vital signs and urine output Give IV ﬂuids, blood, and medications Nursing assistant Completely undress patient Help with obtaining vital signs Assist with moving patient and patient transport Transport blood to lab Help gather any necessary equipment and supplies

Following a trauma resuscitation, restock any used equipment, medications, and intravenous ﬂuids. Check the emergency trolley and oxygen cylinder at least twice daily and record all supplies on a log.

5 Adapted from: Krantz B. Field triage in resources for optimal care of the injured patient. Chicago: American College of Surgeons, 1993.

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Referral to a higher level of care It may be necessary to refer critically injured trauma patients to a higher level of care for specialty treatment. Agreed patterns of referral should be worked out ahead of time between facilities and include written criteria for when a patient should be referred and the referral procedure. Communication between the hospital referring the patient and the receiving hospital is critical to quality patient care. In addition to the general recommendations for referral for all patients (see Quick Check p. 71), do not delay transport for additional diagnostic testing if the testing can be performed at the receiving facility. For example, if a patient needs transport to a hospital with an operating theatre based on a high suspicion of an intra-abdominal injury, do not delay transport to obtain a conﬁrmatory ultrasound of the abdomen. A follow-up system that relays the outcome of referred trauma patients should be established between facilities as a means of continuing education and quality improvement. Many critically injured patients may not be stable enough for transport and all reasonable efforts should be made to stabilize patients. Patients with serious injuries to the head and neck may develop a life-threatening compromise of the airway. If skilled personnel and appropriate equipment are available and it is clinically indicated, secure the airway with endotracheal intubation prior to transport. Transport critically injured patients with a health worker who is appropriately trained to assess the patient and respond to emergency conditions. If it does not delay care, give the ﬁrst dose of IV antibiotics for open fractures prior to transport. Treat pain prior to transport. Document all treatments given and send any reports or diagnostic tests with patient.

4.2 Assessing and treating the trauma patient Assessment of the trauma patient includes the following: • Quick Check (triage and primary survey) • secondary exam (secondary survey) • ongoing assessment and monitoring. Simultaneously with the assessment, management steps should be initiated including: • emergency treatments • resuscitation and stabilization • deﬁnitive care and treatments. Time 0–10 minutes (repeat if patient deteriorates) After 10 minutes Assessment Quick Check Secondary survey Monitor using patient monitoring form Assess and record every 15–30 minutes until stable Management Emergency treatments Resuscitation Ongoing resuscitation Stabilize Deﬁnitive care and treatments (transfer for diagnostic testing, operating theatre, referral to a higher level of care)

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Speciﬁc emergency treatments for trauma patients are described in Quick Check including: • airway management (page 29–32) • management of tension pneumothorax or massive haemothorax (page 46) • management of sucking chest wound (page 46) • spine immobilization and clearance of the cervical spine (page 44) • management of serious head injury (page 45) • management of visible haemorrhage (page 47) • initial management of suspected intra-abdominal injury (page 20). Oxygen therapy for trauma patients Patients with traumatic injuries may have multiple mechanisms that result in deﬁcient oxygen transport. For example, a patient involved in a motor vehicle accident may have an obstructed airway due to coma, impaired gas exchange due to lung contusion, pneumothorax or rib fractures, or inadequate oxygen delivery due to anaemia or hypotension. During the initial assessment (primary survey), give oxygen to all patients with signiﬁcant trauma, particularly in suspected head injury patients. Increasing the inspired oxygen concentration reduces the risk of tissue hypoxia while diagnosis and treatment of the underlying injuries is carried out. Some injuries, such as bruising to the lungs, will get worse as time progresses and there is more tissue swelling and damage. These patients may have increasing oxygenation requirements from hours to days after the injury (delayed hypoxia). Oxygen therapy in major trauma normally should be started at a high concentration, and then titrated as a result of frequent reassessment (Quick Check pages 33–35).

Immediately following Quick Check and the initiation of any emergency treatments, complete a full secondary examination (also known as a secondary survey) looking from head to toe for any other injuries. Obtain further information including: • detailed history of the injury • past medical history • medications • drug allergies • social history.

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First assess and treat immediately life-threatening injuries Quick Check and emergency treatments for trauma patients (do not move neck if cervical spine injury possible) Assess Airway Look, listen and feel for Airway obstruction (risk factors include obtundation, obvious trauma to airway, expanding neck haematoma) Suspect injuries and treat Open airway using jaw thrust. Place oral or nasal airway (avoid nasal airway if suspected mid-face fracture). Secure airway with endotracheal tube if clinically indicated and appropriate equipment and personnel are available (Quick Check page 30). Give oxygen. Treat suspected tension pneumothorax or haemothorax. Treat sucking chest wound. Give bag valve mask ventilation, if ventilation inadequate. Insert 2 large IV cannulas and give 1 litre bolus LR (or NS). Keep warm. If pregnant, place on side (preferably left). Apply pressure to stop any active bleeding. Send Hb and Hct, and type and cross-match. Splint suspected femur or pelvic fracture. Arrange for surgery if suspected intraabdominal injury or occult haemorrhage. If the patient remains hypotensive after 2 litres bolus (LR or NS) or suspect ongoing heavy blood loss, transfuse blood as per national or local guidelines and consider giving tranexamic acid. Perform ultrasound exam (focused assessment of sonography in trauma – FAST) to assess for free ﬂuid in abdomen (see Section 7.2.20). Protect from further injury. Manage airway. Give oxygen. Give glucose. Give diazepam if convulsing. Suspect spinal injury or closed head injury and treat (see emergency treatments). Suspect intra-abdominal injury. Nothing by mouth (NPO). Give IV ﬂuids. Send blood for type and cross-match. Surgical consult Treat pain. Perform ultrasound – FAST exam to assess for free ﬂuid in abdomen (see Section 7.2.20)

Breathing

Central cyanosis Severe respiratory distress Tracheal deviation Decreased breath sounds

Circulation

Weak or fast pulse Capillary reﬁll longer than 3 seconds Heavy bleeding from any site Severe trauma – systolic BP <90, HR >110

Altered consciousness and convulsions

Altered level of consciousness Convulsing Deformity of skull Pupils not equally reactive to light Blood or ﬂuid from ear or nose

Life-threatening causes of pain

Severe abdominal pain or abdomen hard on palpation (distended, tense, guarding, rebound) Penetrating wound to abdomen

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Assess

Look, listen and feel for Trauma to head or neck

Suspect injuries and treat Suspect head and spinal injury. Immobilize cervical spine. Monitor airway. Call for help. Suspect pneumothorax or haemothorax. Suspect rib fractures. Treat pain. If available, obtain upright chest X-ray.

Chest pain Ecchymosis to chest wall Air under the skin

Then look for and treat other injuries (see over). Secondary exam: Check the patient from head to toe and look for the following Assess Consciousness Look, listen and feel for Confusion, agitation, coma, convulsions Suspect injuries and treat Head injury If decreasing level of consciousness, agitation or seizures, suspect and manage serious head injury (see Quick Check). Manage airway. Record AVPU . Record Glasgow Coma Scale. Give glucose if known or suspected hypoglycaemia. Manage seizures. Head injury Monitor mental status and manage airway. Treat any soft tissue injury, open fracture, or laceration. If patient is confused, agitated, seizing, or vomiting, manage as a serious head injury (see Quick Check page 45). Eye injury Protect eye. Check visual acuity. If suspect globe penetration, call for surgical help. Maxillofacial Visual deformity Mid-face stability Malocclusion Palpate for crepitus Facial fracture Monitor airway. Check and document cranial nerves. Avoid nose blowing. Give antibiotics for open facial fracture. If major facial trauma or malocclusion, call for surgical help. Injury to larynx, trachea or oesophagus Manage airway. NPO. Call for surgical help. Vascular injury Manage airway. NPO. Control any active bleeding. Call for surgical help. Cervical spine injury Immobilize cervical spine (Quick Check page 44). Arrange for radiographic evaluation.

Head and pupils

Size, shape, and reactivity of pupils Inspect scalp for lacerations and skull fractures Palpable defects

Neck

Visible trauma Subcutaneous emphysema Haematoma Pain or tenderness of cervical spine

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Assess Thorax

Look, listen and feel for Bruising, deformity Uneven chest wall movement Subcutaneous air Decreased breath sounds Mufﬂed heart tones Severe back pain

Suspect injuries and treat Pneumothorax or haemothorax, ﬂail chest, sucking chest wound (see Quick Check page 46) Rib fracture Treat pain. Check for associated pneumothorax. Deep breathing exercises. If sub-acute, check for secondary pneumonia. Vascular injury Manage airway. Send Hb, and type and cross-match. Call for surgical help. Pericardial tamponade If haemodynamically unstable (SBP <90 mm Hg), emergent pericardiocentesis. FAST ultrasound to conﬁrm diagnosis if patient stable and equipment and personnel available. For all serious injuries to thorax obtain chest X-ray.

Abdomen or ﬂank

Abdominal pain or tenderness Abdominal distension Abdominal rebound or guarding Visible abdominal wound Ecchymosis back or abdomen, mark of seatbelt across lower abdomen Look for ecchymosis Palpate bony pelvis for tenderness. Palpate pubic symphysis for widening. If no obvious injury, check pelvis for stability. Inspect perineum and look for blood at urethral meatus. Perform rectal and vaginal exam.

Liver or spleen injury, pancreatic injury, bowel injury, retroperitoneal haemorrhage, aortic injury NPO. Give IV ﬂuid bolus. Send Hb, and type and cross-match. Give pain medication. Call for surgical help. Perform FAST ultrasound if diagnosis equivocal and equipment and personnel immediately available. Pelvic fracture If suspect unstable pelvic fracture, wrap tightly with pelvic binder or bed sheet (Quick Check page 47). NPO. Give IV ﬂuid bolus. Send Hb and Hct, and type and cross-match. Give pain medication. Obtain pelvic X-ray. Call for surgical help. GU tract, rectal, vaginal, perineal injury If the patient is conscious and if can void spontaneously, check for gross blood. Do not place Foley catheter if high-riding prostate or blood at urethral meatus. Catheter should pass easily, do not force. Vertebral injury or spinal cord injury Keep spine immobilized (see Quick Check page 44). Monitor airway. Treat pain. Document and monitor neurovascular exam. Obtain radiographic evaluation. Call for surgical help.

Pelvis or GU

Spine

Palpate for any bony tenderness of spine or step offs. Motor function Rectal tone, saddle anaesthesia Pain and sensation

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Assess Extremities

Look, listen and feel for Swelling, bruising, or tenderness Deformity Open fracture (open wound in the vicinity of a fracture) Absent or diminished pulses Pallor or cold extremities Neurological deﬁcits Tense muscular compartments

Suspect injuries and treat Fracture Check and document neurovascular status. If any neurovascular compromise, reduce immediately. Splint. Treat pain. If open fracture, also: • give antibiotics and tetanus toxoid • copiously irrigate and splint • call for surgical help. If femur fracture, also: • send Hb and type and cross-match • NPO • IV ﬂuid bolus • call for surgical help. Compartment syndrome Perform decompressive fasciotomy. Vascular injury Document exam. NPO. Call for surgical help.

Skin

Bruising, abrasion, laceration

Laceration, abrasion Irrigate wound Suture and splint, if indicated. Give pain control. Give tetanus toxoid. Contusion Give pain control, elevation, and ice, if available.

Following the secondary survey and the initiation of urgent treatments, document all ﬁndings, investigation results, medications, or treatments given.

Resuscitation and stabilization Assume that any trauma patient in shock (SBP <90 mmHg, pulse >110) is haemorrhaging. The priority is to rapidly identify and stop any ongoing blood loss. Control visible bleeding with manual pressure. Immediately send blood for type and cross-match and Hb. Keep the patient warm. Place a Foley catheter and monitor urine output. A rapid FAST ultrasound exam can be used to identify free ﬂuid in the abdomen or pericardial effusion (see Section 7.2.21). If the patient is unstable with suspected internal bleeding, do not delay treatment for these diagnostic tests. Transport the patient to the operating theatre for an exploratory laparotomy. If no source of bleeding is identified, and the patient remains hypotensive after intravenous ﬂuids and blood, consider other sources of shock, such as septic, cardiogenic, and neurogenic shock. Intravenous ﬂuid • Only isotonic ﬂuids should be used (LR or NS). • Administer IV ﬂuids rapidly in response to abnormal vital signs. • If the SBP <90 mm Hg, HR >110, or there is suspected ongoing blood loss, administer 1000 ml LR or NS rapidly and monitor vital signs. • Monitor urine output.

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Blood (for complete information on blood transfusion see WHO’s The Clinical Use of Blood Handbook.6) If 2 litres of IV ﬂuids are given, or if signiﬁcant blood loss is suspected, arrange for a blood transfusion as soon as possible. If the patient requires a transfusion, continue resuscitation with IV ﬂuids until the blood is available to keep the SBP >90 mm Hg. • Use national or local guidelines when transfusing blood. • Blood should be warmed when possible. Cross-matched blood is always preferred, but may not be immediately available in an emergency situation: ° uncross-matched blood (O-negative) generally available in 0–5 minutes ° uncross-matched group-speciﬁc blood generally available within 10–20 minutes ° cross-matched blood generally available within 60 minutes. • If the patient has severe ongoing haemorrhage and is very unstable (SBP <90 mmHg, signs of poor perfusion), start a transfusion of packed red blood cells (PRBC) within 5 minutes and infuse the blood as fast as possible. Give O-negative blood to women of childbearing age, or if male, give O-positive or O-negative. • If the patient has severe ongoing haemorrhage, but the SBP is >90 and the patient is not yet showing any signs of poor perfusion, it is acceptable to wait for uncross-matched group-speciﬁc blood to be available. A transfusion of PRBC should be started at least within 30 minutes and infused as quickly as possible. Frequently re-assess the patient. If the patient becomes very unstable and group-speciﬁc blood is not yet available, give O-negative (women), and if male, give O-positive or O-negative. • If the patient is stable or cross-matched blood is available, give cross-matched blood. • Observe for transfusion reaction (see Section 10.18). • If the patient requires a massive blood transfusion, deﬁned as replacement of blood loss equivalent of greater than the patient’s total blood volume (70 ml/ kg) in less than 24 hours, then transfusion of other blood products (e.g. fresh frozen plasma and platelets) should be given to help the blood clot. • Calcium is depleted when multiple transfusions are given and should be replaced. Tranexamic acid Treatment with tranexamic acid has been shown to safely reduce the number of deaths in bleeding trauma patients. The indications for treatment include evidence of signiﬁcant haemorrhage (SBP <90, HR >110) or those considered by the clinician to be at risk for haemorrhage. Because the effect of tranexamic acid on death due to bleeding depends importantly on the time interval between injury and the onset of treatment, it should be given as early as possible and within 3−4 hours of the injury. Monitoring For any unstable patient, frequently monitor vital signs, mental status, and urine output, and perform frequent physical examinations. Patients who are stable but have been injured by a high-risk mechanism, such as a fall from a signiﬁcant 6 The Clinical Use of Blood Handbook. WHO, 2002 (in revision). Available at http://www.who.int/bloodsafety/ clinical_use/en/

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height, also should be monitored closely for the ﬁrst few hours. Use the patient monitoring form, introduced in Section 3.11, to monitor trauma patients. For the ﬁrst hour, monitor patients, including vital signs and mental status, at least every 15 minutes. After the ﬁrst hour, use the same monitoring intervals as when caring for other seriously ill patients, such as patients in septic shock. Continue resuscitation until the patient is stabilized or transferred for deﬁnitive operative management. Initial and every 15 minutes for 1st hour then every 30–60 minutes until improved Pulse (normal: 60–100 bpm) BP (normal: systolic >90) Urine output Respiratory rate (normal 12–16; respond if >20) SpO2 (normal >95, give oxygen if <90) Physical exam: lungs, CV, peripheral circulation Mental status: AVPU (repeat GCS if head injury)

Initial laboratory and diagnostic examinations Glucose Hb and Hct Blood type and crossmatch Urine for pregnancy (if indicated) Urinalysis AVPU and, if head injury, Glasgow Coma Scale If indicated and available: • X-ray: chest, pelvis, spine, suspected longbone fractures • diagnostic peritoneal lavage • abdominal ultrasound (FAST – see Section 7.2.20)

Initial then every 1–2 hours Temperature (normal <38oC)

Repeat every 4 hours Hb and Hct if initial value abnormal or suspect ongoing blood loss

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Glasgow Coma Scale Use the Glasgow Coma Scale to assess and monitor patients with head injury. The patient is assessed for eye opening, verbal response, and motor response. The lower the score, the more severe the head injury: • severe head injury – GCS 8 or less • moderate head injury – GCS between 9 and 12 • minor head injury – GCS between 13 and 15. Glasgow Coma Scale (GCS) Function Eyes (4) Response Open spontaneously Open to command Open to pain None Verbal (5) Normal Confused talk Inappropriate words Inappropriate sounds None Motor (6) Obeys command Localizes pain Flexes limbs normally to pain Flexes limbs abnormally to pain Extends limbs to pain None Score 4 3 2 1 5 4 3 2 1 6 5 4 3 2 1

If at any point the patient deteriorates, reassess the patient using Quick Check and give any necessary emergency treatments. Repeat a secondary survey to look for occult or missed injuries. Normal vital signs and improving mental status may suggest that the patient is stabilizing. Some critically injured trauma patients will not stabilize until their injuries are repaired in the operating theatre. The decision whether to rush a patient to the operating theatre needs careful consideration and good communication between the trauma team, surgeon, anaesthetist, and the patient’s family. Once the decision is made that the patient requires emergency surgery it should not be delayed. If a patient remains unstable despite resuscitative efforts, or the patient has a nonsurvivable injury, consider whether further treatment is futile.

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Deﬁnitive care and treatment Following Quick Check, secondary examination and initial resuscitation, transfer the patient to where they can receive deﬁnitive care (ward, operating theatre, referral to higher level of care). If stable, the patient may also be transferred at this time to the radiology department for any necessary tests. Major trauma patients are at a high risk of complications during their hospitalization, such as pulmonary infections, pressure ulcers, gastric ulcers, and deep vein thrombosis (DVT). See Section 3.0 for more details regarding the general principles in caring for the severely ill patient. Trauma patients have high nutritional requirements early in the hospital course, and nutrition should be started within 1−2 days. If the patient is unable safely to take food by mouth, start nasogastric feeds slowly and advance as tolerated if there is no contraindication (e.g. severe ileus). For multi-trauma patients, begin gastric ulcer prophylaxis with a proton pump inhibitor or H2 antagonist (blocker) within 1−2 days. Major trauma patients with spinal cord injury, or pelvic or long-bone fractures are at high risk for the development of DVT. Start prophylaxis within the ﬁrst 24 hours: • If not bleeding and not at high risk of a bleeding event, give heparin 5000 units subcutaneously 3 times daily to prevent DVT. When available, enoxaparin 30 mg subcutaneously twice daily should be used as it has been shown to be more effective. • For patients who are bleeding or at high risk of a bleeding event, place graduated compression stockings or intermittent pneumatic compression devices to prevent DVT. See IMEESC for complete management of traumatic injuries.7

4.3 Violence and injury prevention Interpersonal violence Once emergency conditions are identiﬁed and stabilized, obtain a thorough history of the events surrounding the injury. Interpersonal violence is a common cause of injuries. Health workers should always be aware of possible injuries caused by interpersonal violence. In cases of domestic abuse, counsel the patient and make sure that, if discharged, the patient has a safe place to stay. Enquire about other victims who may be at risk in the home, particularly children. Many patients may be reluctant to volunteer information about interpersonal violence. Interview the patient in a private, comfortable, and safe place. Sometimes the abuser may come to the hospital with the patient. Be cautious in these situations. Directly confronting the abuser or accusing the abuser may put the patient at additional risk, particularly if the patient chooses to return to the home. Try to get some time alone to talk with the patient and to develop a plan so that the patient will be safe. Violence and injury prevention The best way to treat trauma is to prevent it. Medical and nursing teams are in a unique position to educate patients and health workers about effective ways of 7 Integrated Management for Emergency and Essential Surgical Care (IMEESC) tool kit. WHO, 2009. Available at http://www.who.int/surgery/publications/imeesc/en/index.html

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preventing injury. Preventive strategies include: • improvements in road safety • pedestrian and cyclist awareness • wearing of seatbelts in cars or helmets for motor cyclists • preventing drivers from drinking alcohol • promoting safety in the workplace • identifying and treating victims of inter-partner violence • teaching about ﬁrearms safety • violence interruption programmes. Ask in all cases of trauma: • Was alcohol a contributor? If yes, counsel about harmful alcohol use. • Was drug use a contributor? If yes, counsel and arrange for treatment. • Was this a suicide attempt? If possible, ask the patient, were you trying to harm yourself? • Was sexual abuse or violence involved? • Was interpersonal violence a contributor? Is there a risk of further violence in retaliation? If yes, get help to interrupt this and prevent further violence.

4.4 Manage rape or abuse in adolescents and adults8 Provide immediate comfort • Do not leave a woman alone. • Encourage contact with a friend who can come and help. • Conduct yourself in a compassionate, calming, and professional manner (“You are safe now”). • If possible, the health worker should be of the same sex as the patient. A male health worker should have a female attendant if the patient is female. • Try to create a climate of trust. • Do not display curiosity, do not moralize, and avoid statements that blame the victim. • Assure conﬁdentiality.

Special considerations for the examination • Examine in private. • Obtain verbal consent before the examination. • Assure the patient that information given and examination ﬁndings will be kept conﬁdential. • Explain what you are going to do as you go through the examination – the patient needs to feel in control.

8 Clinical management of rape survivors. WHO, UNFPA and UNHCR, 2004. Available at http://www.who.int/ reproductivehealth/publications/emergencies/924159263X/en/

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• Allow the patient to keep covered areas of the body that already have been examined. • Try to understand the patient’s emotional state. Talk to the patient before starting the examination. • Look for complications of abuse (head to toe) such as: ° bites, punch marks, haematomas, marks of restraints on the hands or wrists; ° trauma to the genital region (tears, bruises, abrasions, redness, swelling) and rectal region (look for ﬁssures and bleeding), head, chest or abdomen; ° check for internal injuries (introitus, hymen, cervix) if trained, and it is acceptable to the patient. • There may be no physical injuries. • For country adaptation • If trained, collect forensic evidence following local legal requirements and involve suitably trained and legally recognized staff. • Follow reporting requirements and document notes thoroughly: ° record details of injuries and actual or attempted sexual activity. ° use the victim’s words in quotes in the record. ° advise the patient to go to speciﬁc forensic services, if available.

Management Manage any injuries • If there are breaks in the skin or mucosa: ° give wound care. ° give tetanus toxoid or immunoglobulin following local protocols. • Give pain relief and manage symptoms. • Give presumptive treatment for sexually transmitted infections.9 Recommended medications should be adapted based on the country. For example, give (for presumptive treatment of gonorrhoea, syphilis, and Chlamydial infection) in a woman: Option 1: ° ceﬁxime 400 mg orally or ceftriaxone 250 mg IM; PLUS ° azithromycin 1 g orally; PLUS ° metronidazole 2 g orally single dose, if trichomonas is prevalent (avoid alcohol when taking metronidazole). Option 2: (if not pregnant and not allergic to penicillin) ° ceﬁxime 400 mg or ceftriaxone 250 IM: PLUS ° benzathine benzylpenicillin 2.4 million IU IM; PLUS ° doxycycline 100 mg orally, twice daily for 7 days or azithromycin 1 g orally; PLUS ° metronidazole 2 g orally single dose, if trichomonas is prevalent (avoid alcohol when taking metronidazole). • Give HIV post-exposure prophylaxis within 72 hours. • Recommend baseline HIV testing and counselling. • Offer emergency contraception if new pregnancy possible (see Section 14.5 – 9 Guidelines for the management of sexually transmitted infections. WHO, 2003. Available at http://whqlibdoc.who. int/publications/2003/9241546263.pdf

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the regimen is the same for HIV-positive and HIV-negative women). • Inform women that: ° emergency contraception can decrease the risk of pregnancy if taken within 3−5 days of the assault (depending on the regimen); ° the medication is not 100% effective; ° (if she is concerned) emergency contraception pills do not cause abortion (they delay or prevent ovulation or implantation); ° to avoid nausea and vomiting, eat before taking the pills and, if vomiting occurs within 1 hour, take an antiemetic pill and repeat the dose; ° the IUD is very effective, as both as emergency and ongoing contraception, if a woman is interested in ongoing contraception. • Admit or refer as needed. • Arrange follow up if discharged home.

4.5 Wounds (soft tissue injuries) Wounds and lacerations are common injuries and all health workers should be familiar with the basic principles of wound management. The goals of wound management are to: • avoid infection • achieve normal function of the injured area • achieve a cosmetically acceptable result (minimize scarring). Avoiding infection is the single most important principle of wound care, and will directly affect the ability to achieve a good, functional, and cosmetic result. Table: Factors that increase the risk of infection and poor healing Host factors Extremes of age Diabetes mellitus Anaemia Immunosuppression • HIV • cancer, chemotherapy, and radiation therapy • chronic steroid use Chronic renal failure Malnutrition Inability to care for wound at home Wound factors Location of wound • area with limited blood supply (e.g. hands and feet) • involvement of joint or open fracture • tendon involvement Mechanism of wound • crush injury • bite • puncture wound Duration of the injury (how long ago did the injury occur) Likelihood of contamination • foreign body • dirt or debris in wound

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General approach to wound management This is the same for all patients with wounds and lacerations. • Stabilize the patient and assess and treat any life-threatening injuries (Quick Check). • Apply pressure to any active bleeding. • Check and record perfusion distal to the wound (distal pulse, capillary reﬁll). Call for help if circulation is compromised. • Treat pain (see Section 20). • Take a history and identify factors that increase the risk of infection or poor healing (see table above). • Examine the wound. ° Document ﬁndings (often it is helpful to draw a picture of the wound). ° Explore and remove any foreign body. ° Document any motor or sensory deﬁcit. If there is a deﬁcit, the patient may require consultation or referral. • Give tetanus toxoid or immunoglobulin for a tetanus-prone wound according to local protocols (see Section 11.39). • Thoroughly ﬂush the wound with normal saline or clean water. This is the critical step in managing a wound. Irrigation reduces the chance of infection by washing bacteria and debris out of the wound. It is important to use a large volume of ﬂuid to remove all visible dirt and debris from a wound. For contaminated wounds, use at least 2 litres of ﬂuid to irrigate the wound. • Debridement: if wound edges look dead, remove the dead tissue. Healthy skin should look pink, moist, and bleed easily. Dead skin will be black or grey, may have a white ﬁlm, and will not bleed easily. Dead skin makes it difﬁcult for the wound to heal and increases the risk of infection. ° Call for help if not familiar with debridement technique. ° Inject local anaesthesia. Debridement of a large area of necrotic skin may need to be performed under general anaesthesia in the operating theatre. ° Using aseptic techniques and scissors or blade, cut dead skin away in thin layers until pink, bleeding tissue is visible. ° Re-assess the wound. • Determine ﬁnal wound care based on the location and extent of the wound, available resources, and the likelihood of infection (see table above). ° Primary closure ◊ This method is indicated for clean wounds less than 8 hours old with a low risk of infection. If clean, a wound on the face or scalp may be closed up to 24 hours. ◊ Close the wound with sutures to bring wound edges together, preventing wound contamination and facilitating healing. ◊ The goal is to bring the sides of the wound close together (good approximation) and limit tension or pulling on the skin. It may be necessary to use both deep sutures (the lower skin level and muscle) and superﬁcial sutures (at the surface) to reduce tension on the wound. ° Delayed primary closure ◊ This method may be chosen if the patient presents with a wound that is more than 8 hours old, or there is concern for contamination. ◊ Clean and debride the wound as described above. ◊ Pack the wound with damp saline gauze. ◊ Give oral antibiotics for 5−7 days (e.g. ﬁrst generation cephalosporin).

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◊ Have the patient return in 2 days to evaluate for closure. Alternatively, for patients who are being admitted, lay down closure sutures at the time of debridement, but do not tie them; tie the closure sutures at the bedside during the ﬁrst dressing change 48–72 hours later, if the wound is clean. ° Secondary healing ◊ This method should be used for: • grossly contaminated or infected wounds • wounds with large gaping holes when there is not enough skin at the edges to close the wound • puncture wounds • gunshot wounds • bite wounds. ◊ The wound remains open and is packed with saline soaked gauze. ◊ The gauze is removed every 48–72 hours and the wound is copiously irrigated, reassessed, and the dressing replaced. ◊ The wound gradually becomes smaller, and heals from “inside-out”. Key points • Not all wounds will need to be closed. After cleaning, small wounds and abrasions can be treated with topical antibiotic ointment and a clean dressing. • Before closing a wound with sutures, determine that wound closure will not increase the risk of infection based on the patient’s co-morbidities, the timing and mechanism of the wound, contamination, and location. • NEVER close an infected wound with sutures. Pus will accumulate under the closed skin and the infection will worsen. If there is concern about the risk of infection, conservative management is recommended. Allow the wound to close by secondary healing. • Educate all patients on appropriate wound care including the signs and symptoms of infection and when they should return for follow-up care. • Consider suturing a wound if: ° the wound is large (usually greater than 1 cm); ◊ large wounds may need to be considered for eventual consultation or referral for skin grafting; ° the wound continues to bleed; ° the wound is over a joint; ° the wound is in a location where the cosmetic result is important (e.g. face). • Antibiotic use ° Antibiotics are not routinely indicated for all wounds. ° Consider antibiotics if there is a risk of infection (see Table: Factors that increase the risk of infection and poor healing). ° If there is a suspected open fracture or joint or tendon involvement, give an initial dose of IV or IM antibiotics (e.g. ﬁrst generation cephalosporin). Consider consultation or referral if a higher level of care is necessary. ° All patients with wounds should receive appropriate discharge instructions to recognize signs and symptoms of infection. If a wound appears infected, or there is a high risk of infection, or an infected wound is worsening when the patient is already on oral antibiotics, consider admission for IV antibiotics and observation. Reconsider the possibility of a retained foreign body.

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Suture techniques Before debridement and suturing, provide adequate pain control using local anaesthesia. When using local anaesthesia: • Ask about any medication allergies. • Give the anaesthesia solution through a small needle and inject slowly to minimize pain. • Inject the solution through the edges of the wound where there is no or minimal contamination. • Do not use a solution containing epinephrine on the ﬁngers, toes, ears, penis, or tip of nose. Refer to IMEESC guidelines for wound management, burns, suturing techniques, tendon injuries, management of speciﬁc lacerations, gunshot wounds, and land mine injuries.

4.6 Fractures Refer to Surgical Care at the District Hospital manual1 (Sections 17 and 18) for speciﬁc splinting techniques, cast application, and traction methods.

General principles • In the multiple-injured trauma patient, address all life-threatening injuries before any non-critical orthopaedic injuries. • A fracture is a break in the continuity of a bone or cartilage. • Fractures can take from 2−4 months to heal. Healing is affected by the type of bone, age, and other co-morbidities. Treat severe sprains and strains as fractures. • Goals of fracture management ° Treat and reduce pain. ° Prevent infection. ° Re-align bony fragments so that healing and union can take place and normal function is restored. • Diagnosis of fractures ° Suspect a fracture if there is loss of function, pain, swelling, discoloration, or deformity following trauma. ° Most fractures can be diagnosed clinically. ° If X-rays are available, at minimum 2 views perpendicular to each other should be obtained prior to reduction. ◊ If there is any compromise of circulation, the limb should be immediately reduced before X-rays. ° If X-rays are not available and a fracture is suspected, treat the patient as though a fracture is present. ° Even if X-rays do not show a fracture, if a fracture is suspected clinically, the patient initially should be treated for a fracture with immobilization. • Treatment ° Always assess and record vascular status of the limb distal to the fracture. ◊ If no perfusion (limb cold, pale, no pulse, slow or no capillary reﬁll),

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urgent correction (reduction) of gross deformities is required to restore circulation. ◊ If still no perfusion after re-alignment of the limb, splint and consider urgent orthopaedic consultation or referral. ◊ If perfusion is now good following re-alignment, splint the injured segment and obtain X-rays, if available. ° Reduction (bones are manually re-aligned to put the limb back into its normal position). ◊ Reduction initially causes pain, and a patient should always be told what is happening and treated for pain. ◊ Fractures that are not properly reduced will result in non-union and a poor functional outcome. ◊ Always check neurovascular status before and after any reduction. ◊ Relocate any dislocated joints as soon as possible. ° Immobilization (keep the fracture site from moving). ◊ Splints and casts are used for immobilization. ◊ Splints are usually more appropriate for acute injuries because they allow for continued swelling. ◊ Splints prevent the motion of broken bone ends, decrease pain, and minimize further damage to soft tissue, nerves, and blood vessels. ◊ Generally, the joint above and below the fracture site should be immobilized. ◊ Skeletal traction is required for temporary stabilization of certain fractures, such as the hip or femur. Deﬁnitive treatment will be dependent on the environment, resources, and other injuries. • Consider any patient to have an open fracture if there is a wound (more than just a skin abrasion) near a fracture site. ° Open fractures are orthopaedic emergencies. ° If an open fracture is suspected: ◊ control haemorrhage with a sterile pressure dressing ◊ perform immediate reduction if any neurovascular compromise ◊ treat pain ◊ carefully remove any gross debris ◊ splint ◊ irrigate with saline and cover the wound with saline soaked gauze ◊ begin IV antibiotics (example ﬁrst generation cephalosporin) ◊ administer tetanus prophylaxis based on immunization status and local protocols ◊ consider consultation or referral for irrigation and fracture repair in the operating theatre.

Splints and casts Key points about splints and casts • Splints and casts support and protect injured bones and soft tissue, reducing pain, swelling, and muscle spasm. • Splints are rigid material used to immobilize acutely injured extremities (fractures, strains and sprains, soft tissue injuries). Splints (usually only on one side of the arm or hand) offer less support and protection than a cast and may not be a treatment option in all circumstances, but may be useful for initial management while there is acute swelling. • Casts are usually made of plaster and are wrapped circumferentially around the extremity, moulded to support and protect the extremity, providing more

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• • •

rigid ﬁxation than splints, but allow less room for swelling than splints. They are often used for deﬁnitive treatment of a fracture, and usually applied a few days after the injury when some of the swelling has resolved. Construct splints with plaster. ° If necessary, wood and cardboard will serve as temporary splints. As a general rule, immobilize joints in their “functional position” (i.e. 90° ﬂexion at the elbow, neutral position at the ankle). Metacarpophalangeal joints (where ﬁngers attach to the hand) should always be immobilized in ﬂexion, never straight. Apply plaster when the joint is held in the desired position. Avoid moving the joints once the plaster has been rolled, as this movement may cause ﬂexion creases inside the casts and result in pressure sores. Always re-assess circulation and perfusion once the plaster is hard.

Splint application • Materials ° stockinette and padding – protect the skin and allow swelling ° support material – plaster, pre-formed splints, modiﬁed local materials ° elastic bandages secure the splint in place ° adhesive tape ° knife or scissors to cut the splint to the proper length: ° bucket or pail of wet plaster ° apron and gloves. • Procedure 1. Always explain to the patient what you are doing and why. 2. 3. 4. 5. 6. 7. 8. 9. Treat pain prior to applying a splint. Remove clothing to adequately visualize the injured extremity. Check and document neurovascular status (circulation, motor, sensory) before and after application of the splint. Cover open fractures or joints with saline moistened sterile gauze. Apply a splint to immobilize a joint above and below the suspected fracture site. If the injured extremity is visibly deformed, ﬁrst straighten (reduce) prior to the application of the splint. Place the joint in the desired position prior to splinting. If the injury involves the digits, apply padding between the ﬁngers and toes.

10. If available, place a stockinette over the skin: • the stockinette should extend 10–15 cm beyond the area to be splinted at each end; • make sure the stockinette is smooth and there are no wrinkles; • it may be necessary to cut a slit to avoid wrinkling at the bony prominences.

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11. Wrap padding around the entire area to be splinted: • wrap at least 2−3 layers thick • each turn should overlap the previous turn by 25% • extend 5 cm beyond the edge of the splint at each end • use extra padding over the bony prominences • avoid wrinkling. 12. Measure the length of material needed to secure the limb: • the plaster width should be slightly greater than the diameter of the limb to be splinted; • use 6–12 layers depending on the area to be splinted.

13. Soak the plaster roll in a pail containing water at room temperature. Do not use warm water as the heat given off by the plaster as it sets may burn the patient. Leave the plaster in the water until it is completely soaked and the air bubbles cease to rise.

14. Grasp the plaster layer at each end. Smooth the wet plaster with the palm into a homogeneous layer. Always hold wet plaster with the palm of the hand, not the ﬁnger tips, as this may create pressure points and subsequent sores: • plaster becomes hot when wet and can cause skin burns; • apply plaster quickly, or it will dry.

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15. Place the plaster splint over the area to be immobilized. Keep the area to be splinted steady and in the desired position. 16. Fold the padding and stockinette back to secure the splint in place and form smooth rounded edges. 17. While still wet, mould the plaster to the limb contours and secure with an elastic bandage or gauze wrap.

Patient instructions Give oral and written instructions to the patient or to accompanying relatives or other attendants. Use non-technical language that the patient can understand. Explain the following instructions. • Keep the splint dry at all times. • Do not try to scratch your skin under the cast or splint with any object, sharp or blunt. • For acute injuries, elevate the injured part for 24–48 hours and wiggle your ﬁngers or toes frequently. • Return to the health clinic immediately if: ° your splint gets wet or becomes soft or broken; ° you have increasing pain; ° you experience numbness or tingling, or have difﬁculty moving your ﬁngers or toes; ° you see a change in skin colour of the extremity; ° your cast or splint has a foul odour. Complications Most problems are caused by improper initial application. Pressure sores result from skin necrosis caused by localized pressure. They occur over prominent bony areas, from ridges formed during improper application and from foreign bodies placed under the cast. Common sites are: • heel • ankle • dorsum of the foot • distal ulna at the wrist. Areas under pressure begin as painful spots but, if ignored, the underlying skin becomes anaesthetised as an open wound develops. Drainage follows, often with

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a foul smelling odour. Patients who complain of pain under their splint, particularly if away from fracture site or over a known bony prominence, should have their splint removed, the skin under the area examined, and the splint re-applied.

Compartment syndrome This is a serious acute emergency caused by swelling in the compartments of an injured limb, which cannot expand. The increasing pressure in the compartment can result in reduced circulation to the limb and nerve and muscle damage. If you suspect compartment syndrome, and are not comfortable with the management, call for assistance. Increased compartment pressure is commonly caused by: • tight casts or dressings • external limb compression • burn eschar • fractures • soft tissue crush injuries • arterial injury The most common areas involved are the anterior and deep posterior compartment of the leg and the volar forearm compartment. Other areas include the thigh, the dorsal forearm, the foot, the dorsal hand, and, rarely, the buttocks. Diagnostic physical ﬁndings include: • tense muscle compartments to palpation • weakness of the involved muscle groups • pain with passive stretch of the involved muscle • pain out of proportion to the injury • decreased sensation (late ﬁnding) • pallor and decreased capillary reﬁll (late ﬁnding) • elevated compartment pressure (if measurement is possible). Compartment syndrome is a surgical emergency and requires decompression. See IMEESC7 for further management of compartment syndrome. Considerations when caring for the pregnant patient with severe illness and trauma • The priorities of trauma management are the same as with non-pregnant patients. • Treat the pregnant patient with the most effective treatment available. • Place the pregnant patient with shock or severe respiratory distress on their side (preferably the left) to improve uteroplacental blood ﬂow. (Log roll if suspected spine injury – see Quick Check page 44.) • Watch for trauma-related complications such as premature labour, uterine rupture, placental separation. • Monitor the fetus (e.g. fetal pulse) frequently, according to local practice.

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5. Approach to laboratory investigations Table of contents 5.1 5.2 Interpreting laboratory results . . . . . . . . . . . . . . . . . . . . . Management of sodium, potassium, and calcium abnormalities 5.2.1 Abnormalities of sodium (Na) concentration . . . . . . . Hypernatraemia (high Na) . . . . . . . . . . . . . . . . . Hyponatraemia (low Na) . . . . . . . . . . . . . . . . . . 5.2.2 Abnormalities of potassium (K) concentration . . . . . . Hyperkalaemia (high K) . . . . . . . . . . . . . . . . . . . Hypokalaemia (low K). . . . . . . . . . . . . . . . . . . . 5.2.3 Abnormalities of calcium (Ca) concentration . . . . . . . Hypercalcaemia (high Ca) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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5. Approach to laboratory investigations 5.1 Interpreting laboratory results Evidence-based medicine: steps to using laboratory results After taking a pertinent history and performing a physical examination, use your knowledge and the appropriate differential diagnosis tables to develop a relevant differential diagnosis, ranked both by what can be common causes and by what can be life-threatening causes. • Laboratory tests are useful to conﬁrm or rule out a diagnosis (or differential diagnoses); to establish the severity of disease (e.g. CD4 cell count); to monitor treatment outcomes; or to screen for disease (active TB case ﬁnding). The tests you choose to order are based on evidence-based health care, national guidelines, and your clinical judgement. • Order the “best tests” you have available in your setting to either “rule in” or “rule out” a diagnosis that you are considering. Very few tests in medicine are perfect, so it is important that, as the clinician you know how accurate a test is before interpreting a result. For example, how accurate is a single expectorated sputum to diagnose pulmonary tuberculosis in someone with a lung cavity? How accurate is this test in someone without a lung cavity? • The accuracy of a test can be described by its sensitivity, speciﬁcity, and predictive value: ° Sensitivity refers to the ability of the test to correctly identify individuals who truly have the disease. If you perform a test that is highly sensitive for a particular disease and the result is negative, it is very unlikely that that disease is present; hence, the test has been helpful in ruling out the disease in question. Example: the malaria Rapid Diagnostic Test (RDT) is a very sensitive test. Therefore, if the result is negative, the possibility of malaria has been ruled out. The patient does not have malaria. ° Speciﬁcity refers to the ability of the test to correctly identify individuals who do not have the disease. If you perform a test that is highly speciﬁc for a given disease and the result is positive, you can now be more certain that you have made the correct diagnosis; hence, the test has been helpful in ruling in the disease in question. Example: an AFB smear on CSF is a very speciﬁc test. Therefore, if the result is positive, the possibility of tuberculous meningitis has been ruled in. The patient has tuberculous meningitis. ° The predictive value of a test (also called the post-test probability of disease) refers to the ability of the test to correctly identify the disease. Unlike sensitivity and speciﬁcity, which do not vary within populations, the predictive value of a test depends on age, gender, geographic location, and disease prevalence.

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Test your knowledge of evidence-based decision-making by considering a clinical case. • A 36-year-old man started ART (AZT + 3TC + EFV) in April. • His pre-treatment CD4 was 15. He is at WHO clinical stage 3, with oral thrush. • In June, two months after starting ART, he presented with severe headache, confusion, a stiff neck, and fever. • His chest X-ray was normal. • The CSF indicated: ° 19 polys, 253 lymphs ° protein 0.92 ° glucose 2.6 ° Gram stain – no bacteria Question: • What is your differential diagnosis for meningitis? Differential diagnosis: • Tuberculous meningitis • Cryptococcal meningitis • Bacterial meningitis (partially treated) • Lymphomatous meningitis You decide to perform an AFB smear on the CSF. What is the probability that the meningitis of this patient is due to tuberculosis 1) if the test is positive? 2) if the test is negative? These probabilities depend on the sensitivity and speciﬁcity of the test, as described above, and also on how frequent the disease is in your region (prevalence of the disease in the general sick population, also called “pre-test probability”, as it is the probability that the patient has the disease before any testing). Situation A Let us say that evaluation of a cohort of AIDS patients living in your region has shown that 20% of meningitis is due to tuberculosis. You can draw the following 2-by-2 table: Step 1: Among 1000 patients, 200 (20%) have the disease and 800 do not have the disease. Tuberculous meningitis Present Result of AFB smear of CSF Positive Negative Total patients 200 800 1000 Absent Total patients

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Step 2: The sensitivity of AFB smear on CSF is 60%. Thus, among 200 patients having the disease, 120 tests (60%) will be positive. The speciﬁcity of AFB smear on CSF is 99%. Thus, among 800 patients not having the disease, 792 tests (99%) will be negative. Tuberculous meningitis Present Result of AFB smear of CSF Positive Negative Total patients 120 80 200 Absent 8 792 800 Total patients 120 + 8 = 128 80 + 792 = 872 1000

Ø 120 200 = sensitivity = 60%

Ø 792 800 = speciﬁcity = 99%

Step 3: (a) The Positive Predictive Value (PPV) is 120/128 = 0.94. Thus, if the AFB smear on CSF is positive, the (post-test) probability that the patient has tuberculous meningitis is 94%. (b) The Negative Predictive Value (NPV) is 792/872 = 0.91. Thus, if the AFB smear on CSF is negative, the (post-test) probability that the patient actually has tuberculous meningitis is only 9% (100%−91%). Tuberculous meningitis Present Result of AFB smear of CSF Positive Negative Total patients 120 80 200 Absent 8 792 800 Total patients 128 872 1000

Ö120/128 = 94% = PPV Ö792/872 = 91% = NPV

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Situation B If the cohort of AIDS patients living in your region has shown that in fact only 2% of meningitis is due to tuberculosis, the 2-by-2 table will change in the following way: Tuberculous meningitis Present Result of AFB smear of CSF Positive Negative Total patients 12 8 20 Absent 9 871 880 Total patients 21 879 1000

Ö12/21 = 57% = PPV Ö871/879 = 99% = NPV

Ø 12 20 = sensitivity = 60%

Ø 871 880 = speciﬁcity = 99%

In this situation: (a) If the AFB smear on CSF is positive, the (post-test) probability that the patient has tuberculous meningitis is only 57%. Hence, the etiology of the meningitis might be tuberculosis, but it might also be a disease other than tuberculosis. Further investigations are necessary. (b) If the AFB smear on CSF is negative, the (post-test) probability that the patient has tuberculous meningitis is only 1% (100−99%). The possibility of tuberculous meningitis is thus fully excluded.

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Table: Sensitivity and speciﬁcity for selected diagnostic tests Disease HIV HIV Malaria Syphilis Pulmonary tuberculosis – culture positive Cryptococcal meningitis Test HIV ELISA HIV rapid tests Malaria smear RPR/VDRL FTA-ABS 3 expectorated sputum smears1 Antibiotic trial to rule out pulmonary TB in smear negative2 CSF India ink3 CSF cryptococcal antigen4 Serum cryptococcal antigen5 Sensitivity 100% 99% 52.5% 91% 92% 70% 55% 72.6% 94.1% 91.4% Speciﬁcity 98% 98% 77% 95% 96% 96% 77% 99% 99% 83.3%

1 Crampin AC, et al. Comparison of two versus three smears in identifying culture-positive tuberculosis patients in a rural African setting with high HIV prevalence. International Journal of Tuberculosis and Lung Disease, 2001, 5(11):994–9. 2 Wilkinson D et al. Trial-of-antibiotic algorithm for the diagnosis of tuberculosis in a district hospital in a developing country with high HIV prevalence. International Journal of Tuberculosis and Lung Disease, 2000, 4(6):513–8. 3 Chen S et al. Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Clinical Infectious Diseases, 2000, 31(2):499–508. 4 Antinori S et al. The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis. Journal of Clinical Microbiology, 2005, 43(11):5828–9. 5 Asawavichienjinda T, Sitthi-Amorn C, Tanyanont V. Serum cyrptococcal antigen: diagnostic value in the diagnosis of AIDS-related cryptococcal meningitis. Journal of the Medical Association of Thailand, 1999, 82(1):65–71.

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5.2 Management of sodium, potassium, and calcium abnormalities 5.2.1 Abnormalities of sodium (Na) concentration Hypernatraemia (high Na) Hypernatraemia is an electrolyte disturbance that is deﬁned by an elevated sodium level in the blood. It may occur in patients who are unwell from other causes (such as diarrhoea, diabetic ketoacidosis, or sepsis). The patient may present with symptoms of thirst, fatigue, weakness, or those of the underlying cause. In severe cases, hypernatraemia may present with emergency signs such as confusion, coma, or convulsions (see Section 3.5). Always consider hypernatraemia in each of these situations. A history and a clinical evaluation and, in particular, an assessment of the patient’s hydration or volume status will help establish the cause of hypernatraemia and guide initial management. Diagnosis Serum sodium >145 mmol/litre. Causes • Hypernatraemia usually is not caused by an excess of sodium, but rather by a relative deﬁcit of free water in the body. It may occur in the following cases: ° excessive water loss ◊ gastrointestinal losses − diarrhoea, vomiting ◊ cutaneous losses − high fever, sweating, burns ◊ renal losses − hyperglycaemia (by osmotic diuresis), diabetes insipidus (low ADH secretion that may occur with meningoencephalitis or from drugs such as lithium). ° insufﬁcient water intake ◊ lack of availability ◊ decreased intake due to decreased level of consciousness. ° excessive sodium administration ◊ excessive IV normal saline (NS) replacement in hospitalized patients. Management • Avoid rapid correction of serum sodium as this can result in cerebral oedema and permanent neurological damage. • Assess the volume status (hydration) of the patient. • Calculate volume of ﬂuid to be replaced. In the dehydrated hypernatraemic patient, the volume of water required to correct the deﬁcit can be calculated from the following equation. Water deﬁcit (in litres) = (serum Na concentration – 140) x 0.5 x body weight (kg) 140

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• •

•

E.g. if the serum sodium is 160 mmol in a 70 kg patient, then the total water deﬁcit is (160–140)/140 x 0.5 x 70 = 5 litres. This volume should be replaced over 48–72 hours. Ongoing losses also need to be factored into ﬂuid replacement. Give water orally if the patient is haemodynamically stable and alert, or by nasogastric tube. If unable to give water orally, use IV ﬂuid replacement. This is required if the patient is hypovolaemic (increased heart rate, low BP, or postural drop, low JVP, cool peripheries, dry mucosa, decreased skin turgor, or low urine output) or unable to take ﬂuids orally due to decreased level of consciousness. Use normal saline (0.9%) until the patient is haemodynamically stable, then change to 5% dextrose to replace the water deﬁcit. Stop IV ﬂuids when adequate oral intake is established. Monitor sodium and other electrolytes twice daily initially, if possible. The serum sodium concentration should be lowered by a maximum of 10 mmol/ litre over the ﬁrst 24 hours. Diagnose and treat the underlying cause when possible, and correct other electrolyte abnormalities.

Hyponatraemia (low Na) Hyponatraemia is an electrolyte disturbance in which the sodium concentration in the blood is lower than normal. It can be a manifestation of a variety of disorders. It is usually only symptomatic when it is severe, or if the onset has been rapid, leading to the development of cerebral oedema. Hyponatraemia may present with nausea, lethargy, confusion, muscle weakness and cramps, and in extreme cases seizures and coma. The signs and symptoms of the underlying cause are likely to be apparent. Diagnosis Mild: Moderate: Severe: Na 130–135 mmol/litre Na 120–129 mmol/litre Na less than 120 mmol/litre

Causes Hyponatraemia can be caused by many conditions and an assessment of the patient’s volume status, used in combination with the calculated osmolality (using the equation below), can indicate the underlying cause and guide management. Osmolality (mmol/l) = 2 x (Na + K) + urea/2.8 mg/dl + glucose/18 mg/dl) (normal range = 280–300 mmol/l)

See summary table below for more details on causes and management. Most causes of hyponatraemia will be associated with a low serum osmolality.

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Table: Assessment and management of hyponatraemia according to volume status and serum osmolality Volume status Dehydrated or hypovolaemic (increased pulse rate, low BP, or postural drop, low JVP, cool peripheries, dry mucous membranes, decreased skin turgor, low urine output) Classify dehydration according to section 10.7d.2. Possible causes Renal losses Diuretics (especially thiazides) Hyperglycaemia (due to osmotic diuresis) Addison’s disease Non-renal losses: Gastrointestinal losses (vomiting, diarrhoea, bowel obstruction) Burns Serum osmolality <260 mmol/l Syndrome of inappropriate ADH release (SIADH)* Chest disease: TB, pneumonia, abscess CNS disorder: head injury, meningoencephalitis, brain abscess, stroke Malignancy Nephrotic syndrome Cirrhosis Congestive cardiac failure Treat the underlying cause if possible, and restrict total ﬂuid intake to 50–60% of daily ﬂuid requirement (500–1000 ml on average). Management Cautious intravenous hydration using the principles below, and treatment of the underlying cause when possible.

Euvolaemic (normal pulse rate, BP, JVP, peripheries, and urine output)

Hypervolaemic (raised JVP, peripheral oedema)

Treat the underlying cause if possible, and restrict total ﬂuid intake to 50–60% of daily ﬂuid requirement (500–1000 ml on average). May require diuresis.

*Syndrome of inappropriate ADH release (SIADH) is an important cause of low Na but is frequently overdiagnosed; many patients are inappropriately ﬂuid-restricted due to this misdiagnosis. Patients with SIADH are euvolaemic (not dehydrated or oedematous, and not on diuretics). Investigations of a concentrated urine (urine Na >20 mmol/l) in the presence of hyponatraemia (<125 mmol/l) or low plasma osmolality (<260 mmol/kg) conﬁrms this.

Management Management should be guided by: • the volume status of the patient • the likely duration (chronic hyponatraemia is usually symptomatic) • symptom severity. Correct Na abnormalities slowly to minimize the risk of permanent neurological deﬁcits or death, which may occur as a consequence of rapid ﬂuid shifts. The increase in serum sodium should be <10 mmol/litre in the ﬁrst 24 hours and <18 mmol/litre in the ﬁrst 48 hours. • In all cases, treat the underlying cause if possible. No further treatment measures are required for asymptomatic or mild hyponatraemia. • Repeat electrolytes every 12 hours initially to monitor sodium rise, as well as to check for other electrolyte abnormalities. • In hypovolaemic patients, cautiously hydrate with 0.9% NS to replace the ﬂuid deﬁcit. Use the table in Section 10.7d.2 as a guide to estimate the degree of dehydration. Discontinue ﬂuids when the blood pressure is restored and the patient is euvolaemic.

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• In the euvolaemic patient, consider giving a low dose of furosemide (e.g. 40 mg IV) in order to prevent ﬂuid overload while treating the hyponatraemia • In hypervolaemic patients, treat with 500–1000 ml a day ﬂuid restriction and IV furosemide (40–80 mg). Recheck electrolytes at 4 hours, and then every 6 hours. In emergency presentations of seizures or coma, the initial correction should be aggressive. Consider using hypertonic saline. If this is not available, use normal saline. Aim for an initial correction of 6 mmol/litre over 4 hours, then a more gradual correction as described above. The rate at which ﬂuid should be given in the initial 4 hours can be calculated from the formula below. The rate of replacement should not exceed 70 mmol/hour. Emergency infusion rate (ml/hour) = 4 x weight (kg) / Na concentration of infusion ﬂuid (%)

E.g. the infusion rate of 0.9% normal saline in a 70 kg patient should be 4 x 70/0.9 ≈ 300 ml/hour. However, do not exceed 70 mmol/hour. 1 litre of normal saline (0.9%) contains 154 mmol/l NaCl, i.e. the maximum amount of normal saline that can be given in 1 hour is approximately 450 ml. Hypertonic saline, 3%, has 513 mmol/l of NaCl.

5.2.2 Abnormalities of potassium (K) concentration Similar to most other electrolyte abnormalities, mild hyperkalaemia and hypokalaemia are often asymptomatic, and are clinically undetectable without a blood test. Severe potassium disturbance may manifest as severe arrhythmia necessitating urgent correction, and may be associated with general lethargy and muscle weakness. Always consider concurrent electrolyte abnormalities.

Hyperkalaemia (high K) Hyperkalaemia is high serum potassium. It is usually asymptomatic and may be encountered in patients unwell from other causes (diabetic ketoacidosis, septic shock), and is usually diagnosed on routine blood tests or ECGs. Severe hyperkalaemia may be associated with muscle weakness, and can cause sudden serious cardiac arrhythmias and death. Diagnosis Mild to moderate: Severe: K 5.5–6.5 mmol/l K more than 6.5 mmol/l or symptomatic or ECG changes

Causes • Falsely high K reading: haemolysed sample commonly causes an elevated reading as potassium leaks from the cells. Repeat the blood test. • renal failure • shock (from any causes) • diabetic ketoacidosis (hyperglycaemia, insulin deﬁciency) • medications: potassium supplements, potassium-sparing diuretics (e.g. spironolactone), ACE inhibitors, non-selective beta-blockers (e.g. atenolol), NSAIDs, heparin • other: rhabdomyolysis (muscle breakdown), metabolic acidosis, Addison’s disease.

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Management • If available, obtain an ECG. Changes occur most markedly in lead V6 and S1. Consider cardiac monitoring or serial ECGs if any of the changes shown below are present. ECG changes: peaked T waves, prolonged PR interval, small or loss of P waves, widening of the QRS complex progressing to sinusoidal wave, and potentially ventricular tachycardia (VT) or ventricular ﬁbrillation (VF).

• Obtain a repeat sample to check the result, especially if there are no ECG changes. Treat urgently if ECG changes are present, or if K more than 6.5 mmol/litre. • Give IV calcium gluconate 1000 mg (10 ml of 10% solution) or calcium chloride 500–1000 mg (5–10 ml of 10% solution) over 2 minutes, to stabilize the cardiac membrane ﬁrst if ECG changes are present. This can be repeated after 5 minutes if ECG changes persist. • Give short-acting insulin 10–15 units IV in 50 ml D50 (50% dextrose water) infused over 2 hours, to activate intracellular transfer of K, followed by a dextrose infusion and regular blood glucose monitoring. • Give salbutamol 10-20 mg by nebulizer or 0.5 mg (500 micrograms) IV. IV administration should be slow, over 15-20 minutes. ° If these are not available, give salbutamol 1200 micrograms by metereddose inhaler with spacer (this is 12 puffs). ° Repeat if necessary, especially if other options are not available. • Hyperkalaemia associated with severe oliguric renal failure may only be correctable with dialysis, in patients with acute or end-stage renal failure (see Section 11.31), and when the above measures fail. These patients may not have any ECG changes as the increase has been over a long period of time. • Treat the underlying cause. • Re-check the serum K to monitor response every 12 hours. • Repeat all above if necessary. Note: Most treatment options mentioned here will have little effect in cases of advanced or oliguria renal failure. Ongoing management and management of mild hyperkalaemia • Investigate and treat the cause. • Stop drugs that increase serum K concentration. • Diuretics, e.g. 20–40 mg furosemide once daily, or a thiazide diuretic, will increase K excretion, and gradually lower K levels over days. Higher doses will be required in renal failure. Except for those who are ﬂuid overloaded, ﬂuid losses should be replaced.

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• Kayexelate 15–30 g in 50–100 ml of 20% sorbitol orally or rectally. Be aware of excess Na absorption. • Avoid potassium-rich foods (e.g. bananas, oranges, mangoes, potatoes, yams, beans, peas, cabbage, and spinach).

Hypokalaemia (low K) Hypokalaemia is low serum potassium. It is usually asymptomatic but may be symptomatic if the fall in serum potassium is sudden. It may be encountered in patients unwell for other reasons (e.g. diarrhoea, diabetic ketoacidosis, septic shock), and is usually diagnosed on routine blood tests or ECGs. It may also present with muscle weakness and cramps. Severe hypokalaemia may cause sudden serious cardiac arrhythmias and death. Diagnosis Mild: Moderate: Severe: K 3.0–3.5 mmol/litre K 2.5–3.0 mmol/litre K <2.5 mmol/litre, symptoms or ECG changes

Causes • gastrointestinal losses (diarrhoea, vomiting) • medications: diuretics (e.g. furosemide) and chloroquine intoxication • diabetic ketoacidosis • other causes: stress response (increased β adrenergic activity), metabolic alkalosis. Management • If available, obtain an ECG to help determine the severity ECG changes: ST depression, ﬂattened or absent T waves, U waves (positive deﬂection after the T wave), prolonged PR interval, variety of atrial or ventricular arrhythmias.

Mild to moderate hypokalaemia: • Oral potassium supplements in any preparation (salts, tablet, liquid) should be given at a dose of 10–20 mmol every 6–12 hours. If available, potassium chloride is preferable to citrate or bicarbonate preparations. • If potassium supplements are not available, encourage the patient to eat potassium-rich foods such as tomatoes, bananas, oranges, melons, mangoes, potatoes, yams, beans, soya beans, peas, cabbage, or spinach.

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Severe hypokalaemia: • Consider cardiac monitoring, especially in patients with ECG abnormalities. • Use higher doses of oral potassium preparation such as 40 to 60 mmol/l every 6–8 hours. • In addition, in patients with worrying symptoms, or those who are unable to take oral supplements, give intravenous potassium in saline (dextrose can worsen hypokalaemia initially). NEVER give a bolus dose of intravenous K as this can cause death. In most cases, concentrations of 20–40 mmol/l should be used. Caution: more concentrated solutions 100–200 mmol/litre can be used in small volume preparations e.g. 100 ml in patients who are unable to tolerate large infusion volumes. (Particular care should be taken, including ECG monitoring, when concentrated solutions are being infused, as errors in calculating infusion rates may be fatal.) • The maximal rate of infusion should not exceed 10–20 mmol/hour. • In all cases, regularly re-check the serum potassium when giving replacements, and look for and treat the underlying cause.

5.2.3 Abnormalities of calcium (Ca) concentration Hypercalcaemia (high Ca) Hypercalcaemia is a high serum calcium level. It is most commonly associated with malignancy or parathyroid disease. In mild cases, it is usually asymptomatic; however, when severe, it can present with confusion, coma, or a cardiac arrhythmia. The patient may also present with any of the following symptoms: • gastrointestinal – abdominal pain, dysphagia, constipation, nausea, vomiting • renal – dehydration, polyuria, renal stones and renal failure • neuropsychiatric – anxiety, depression, confusion, seizures, coma • musculoskeletal – bone pain, weakness. Diagnosis If serum albumin can be measured, calculate the more physiologically relevant ionized calcium. Ionized calcium = Ca + (40 – serum albumin (g/l) x 0.02

Mild: Moderate: Severe:

2.65–3 mmol/litre 3–3.5 mmol/litre and asymptomatic >3.5 mmol/litre or >3.0 and symptomatic or dehydrated

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If available, obtain an ECG. ECG changes: shortened QT interval, widened QRS, ﬂat T waves, AV block, occasional fatal arrhythmias.

Causes • malignancy • hyperparathyroidism (primary or tertiary in known renal failure) • granulomatous disorders − TB, sarcoidosis • drugs − vitamin D, thiazide diuretics, lithium, indigestion remedies • other − adrenal failure, hyperthyroidism, immobilization, rhabdomyolysis (muscle breakdown) Management Severe hypercalcaemia with CNS symptoms requires urgent treatment. • Check renal function and electrolytes. Association with hypokalaemia is common and increases the risk of arrhythmias. • Rehydrate the patient with 0.9% NS at an initial rate of 200–300 ml/hour until urine output >200 ml/hour, then 3–6 litres over 24 hours. • Determine the rate according to the degree of initial dehydration, medical history (cardiac or renal failure), as well as regular monitoring of urine output, and hydration status (pulse, lying and standing BP, JVP, peripheral perfusion, and oedema). If equipment is available, a urinary catheter may be useful to monitor urine output and ﬂuid balance. • In a patient with known cardiac or renal impairment, or once the patient is hydrated, use a loop diuretic, e.g. 40 mg furosemide every 4–6 hours with continued IV saline. Electrolytes, especially K and Mg, are likely to fall, and should regularly be checked and supplemented when necessary. • Steroids (e.g. prednisolone 20–40 mg/day) can be effective in certain etiologies (lymphomas, sarcoidosis, TB, metastases, and vitamin D intoxication). • Once the patient is stable, aim to investigate and treat the underlying cause.

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6. Infection prevention and control Table of contents 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 6.10 6.11 6.12 6.13 Principles of hospital infection prevention and control . . . . . . . . . . . . . Health worker role in hospital infection prevention and control . . . . . . . . Standard precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hand hygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appropriate personal p protection equipment (PPE) . . . . . . . . . . . . . . . . . pp p p q p Respiratory hygiene and cough etiquette . . . . . . . . . . . . . . . . . . . . . . Prevention of needle-stick and injuries from sha sharp instruments arp i nstruments . . . . . . . . Environmental cleaning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Linens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Waste disposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Patient care equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Select additional infection control interventions intervent tion ns including PPE, based on the risk assessment, epidemiology, or epidemiolog gy, o r likely pathogen . . . . . . . . Special precautions for acute respiratory diseases yd is seases that are prone to result in epidemics or pa pandemics andemics . . . . . . . . . . . . . . . . . . . . . . . . . infectious patients Special precautions for inf fec cti tiou o s TB patie i nts . . . . . . . . . . . . . . . . . . . Precautions when caring for pat patient conﬁ tie ient with suspected or con nﬁrm rmed ed Filovirus (Ebola, Marburg) haemorrhagic fever haemorr rhagic feve er . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

257 258 258 259 262 265 266 268 269 269 270 271 273 274 275

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6. Infection prevention and control 6.1 Principles of hospital infection prevention and control Infection prevention and control (IPC)1,2 are integral to the provision of safe health care. Hospital IPC aims to prevent transmission of communicable diseases including TB, 3,4 blood-borne and enterically transmitted pathogens, acute respiratory diseases,5 as well as to prevent infection during medical procedures (see Section 7 Procedures) or surgery (covered in other sources). The purpose of IPC includes preventing the transmission of both endemic and epidemic infections. Community-acquired infections can be ampliﬁed by transmission within the health facility in the absence of effective IPC practices, with transmission to other patients, visitors, and health workers. These practices are ongoing requirements that apply every day, as well as when there are novel organisms causing an acute respiratory disease or a hemorrhagic fever. This manual for limited-resource settings assumes middle or high TB burden, requiring consistent attention to TB infection control. Hospital managers should refer to other sources on developing, implementing, and monitoring an IPC programme6, training health workers in IPC, providing adequate infection control commodities, assuring a safe blood supply, managing a sterilization section within the hospital,7 and improving the infrastructure to make the hospital a safer work environment. Hospital infrastructure should be arranged and improved as necessary to facilitate hand hygiene, safe waste management, and patient placement. Triage and waiting areas should be well ventilated (open air shelters with a roof are recommended for patient waiting areas), and narrow, poorly ventilated corridors avoided as patient waiting areas. Improving air ventilation8 in rooms for patient care includes leaving windows and doors open when possible to maximize cross ventilation. Prioritize

1 Core components for infection prevention and control programmes. Report of the Second Meeting of the Informal Network on Infection Prevention and Control in Health Care. WHO, 2008 (WHO/HSE/EPR/2009.1). Available at http://www.who.int/csr/resources/publications/WHO_HSE_EPR_2009_1/en/index.html 2 Operations Manual for Delivery of HIV Prevention, Care and Treatment at Primary Health Centres in HighPrevalence, Resource-Constrained Settings. WHO, 2008 (under revision). Available at http://www.who.int/hiv/ pub/imai/operations_manual/en/index.html 3 WHO policy on TB infection control in health care facilities, congregate settings and households. WHO, 2009. Available at http://whqlibdoc.who.int/publications/2009/9789241598323_eng.pdf 4 Implementing the WHO Policy on TB Infection Control in Health-Care Facilities, Congregate Settings and Households. A framework to plan, implement and scale-up TB infection control activities at country, facility and community level. TBCTA, 2010. Available at http://www.stoptb.org/wg/tb_hiv/assets/documents/ TBICImplementationFramework1288971813.pdf 5 WHO interim guidance: infection prevention and control in health care for conﬁrmed or suspected cases of pandemic (H1N1) 2009 and inﬂuenza-like illnesses. WHO, 16 December 2009 (updated from 29 April 2009 and 25 June 2009 versions). Available at http://www.who.int/csr/resources/publications/swineﬂu/ swineinﬁnfcont/en/index.html 6 Core components for infection prevention and control programmes. WHO, 2008. Available at http://whqlibdoc. who.int/hq/2009/WHO_HSE_EPR_2009.1_eng.pdf 7 Sterilization Manual for Health Centers. AMRO-PAHO and USAID, 2009 http://new.paho.org/hq/index. php?option=com_content&task=view&id=2106&Itemid=229&lang=en 8 Natural Ventilation for Infection Control in Health-Care Settings. WHO, 2009. Available at http://whqlibdoc.who. int/publications/2009/9789241547857_eng.pdf

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IPC recommendations based on assessment of the risk of nosocomial infection in the speciﬁc health-care facility and in speciﬁc patient care areas. This Section is aimed at health workers who should refer to the IPC guidelines and use appropriate precautions in their clinical work.

Health worker role in hospital infection prevention and control • Ensure a safe working environment. A safe hospital environment is a high priority for the well-being of staff, patients and visitors. Each health worker should promote a climate of safety to prevent transmission of pathogens in the hospital. • Standard infection control precautions9 should be used, as a minimum, in the care of all patients, staff, and visitors. Standard precautions are meant to reduce the risks of transmission of pathogens from both recognized and unrecognized sources. • Assess the risk of exposure to body substances or contaminated surfaces BEFORE any health-care activity. Make this a routine! Risk assessment is critical. Assess all health-care activities to determine the level of risk then use appropriate personal protection equipment (PPE) (see Section 6.3). • Implement source control measures for all persons with respiratory symptoms through promotion of respiratory hygiene and cough etiquette (see Section 6.4). • Triage, early detection, or suspicion of particular diseases can lead to appropriate seating, hospitalization, and isolation precautions, which can reduce transmission.

Standard precautions for all patients include:10,11 • hand hygiene (see Section 6.2) • appropriate personal protective equipment (PPE) (see Section 6.3): ° gloves ° facial protection (eyes, nose, and mouth) ° gown • respiratory hygiene and cough etiquette (see Section 6.4) • prevention (and management) of injuries from sharp instruments (see Section 6.5) • environmental cleaning (see Section 6.6) • appropriate handling of contaminated linens (see Section 6.7) • waste disposal (see Section 6.8) • patient care equipment (see Section 6.9).

9 Infection control standard precautions in health care. WHO, 2006. Available at http://www.who.int/csr/ resources/publications/4EPR_AM2.pdf 10 WHO interim guidelines on infection prevention and control of epidemic and pandemic-prone acute respiratory diseases in health care. WHO, 2007. Available at http://www.who.int/csr/resources/publications/swineﬂu/ WHO_CD_EPR_2007_6/en/index.html 11 Infection control standard precautions in health care. WHO, 2006. Available at http://www.who.int/csr/ resources/publications/4EPR_AM2.pdf

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6.2 Hand hygiene12 • Ensure availability of hand-washing facilities with clean running water. • Ensure availability of hand hygiene products (clean water, soap, single-use clean towels, and alcohol-based hand rub). Alcohol-based hand rubs should be made available at every point of care and are the standard of care. • When to wash hands with soap and running water: ° when hands are visibly dirty. • When to use alcohol-based hand rub: ° when hands appear clean (i.e. are not visibly soiled). Indications for hand hygiene • Before and after any direct contact between a health worker and a patient and contact between patients, whether or not gloves are worn. Hands should be washed before gloves are put on. • Immediately after gloves are removed. • Before handling an invasive device. • After touching blood, body ﬂuids, secretions, excretions, non-intact skin, and contaminated items, even if gloves are worn. • During care, e.g. when moving from a contaminated to a clean body site of the same patient. • After contact with inanimate objects in the immediate vicinity of the patient. • Ensure that hands are dry before starting any activity. • Dry hands with single-use towels.

12 WHO Guidelines on Hand Hygiene in Health Care. WHO, 2009. Available at http://whqlibdoc.who.int/ publications/2009/9789241597906_eng.pdf

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Techniques for hand hygiene Hand washing (40–60 seconds) • Wet hands and apply soap; rub all surfaces; rinse hands and dry thoroughly with a single use towel; use towel to turn off faucet and dispose of the used towel.

Figure: How to wash the hands with soap and water13

13 WHO Guidelines on Hand Hygiene in Health Care. WHO, 2009. Available at http://whqlibdoc.who.int/hq/2009/ WHO_IER_PSP_2009.07_eng.pdf

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Techniques for hand hygiene Hand rubbing (20–30 seconds) • Apply enough product to cover all areas of the hands; rub hands until dry.

Figure: How to cleanse the hands with an alcohol-based formulation14

14 Sterilization Manual for Health Centers. AMRO-PAHO and USAID, 2009. Available at http://new.paho.org/hq/ index.php?option=com_content&task=view&id=2106&Itemid=229&lang=en

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6.3 Appropriate personal protective equipment (PPE) Assess the risk of exposure to body substances or contaminated surfaces BEFORE any health-care activity. Make this a routine! • Select PPE based on the assessment of risk: ° clean, non-sterile gloves ° clean, non-sterile ﬂuid-resistant gown ° mask and eye protection or a face shield. • Ensure that there is a continued supply of PPE. • Educate and train hospital staff how to wear, remove, and dispose of PPE. Some PPE is used based on the procedure or type of patient care, no matter what organism (these are part of standard precautions). Additional PPE may need to be added based on the patient's likely diagnosis and suspected pathogen (e.g. if suspect acute respiratory disease of concern, see Section 6.1). Pathogens differ as to whether they are spread by contact, by large droplets (requiring droplet precautions) or by very small droplet nuclei which can travel more than a meter and stay suspended in the air (requiring airborne precautions).

Figure: Personal protective equipment

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PPE to use for any patient according to likely exposure to blood, secretions, non-intact skin Gloves • Wear gloves if there is any chance of touching blood, body ﬂuids, secretions, excretions, mucous membranes, or skin, especially skin that is not intact. • Change between tasks and procedures on the same patient after contact with potentially infectious material, to prevent further contamination. • Remove after use, before touching non-contaminated items and surfaces, and before going to another patient. Perform hand hygiene immediately after removal. Facial protection (eyes, nose, and mouth) • Wear a surgical or procedure mask and eye protection (eye visor, goggles), or a face shield, to protect mucous membranes of the eyes, nose, and mouth during activities that are likely to generate splashes or sprays of blood, body ﬂuids, secretions, or excretions. • Masks should been used only when it is useful and recommended. Gown • Gowns protect the skin and prevent soiling of clothing during activities that are likely to generate splashes or sprays. • Wear a gown whenever there is any risk of splashes of blood or body ﬂuids. • If splashing with blood or other body ﬂuids is anticipated and gowns are not ﬂuid-resistant, wear a waterproof apron over the gown. • Remove soiled gowns as soon as possible, and perform hand hygiene.

Steps to wear PPE 1. Assess risk 2. Select and gather the necessary PPE 3. Put on the gown

4. Put on the mask

5. Put on eye protection

6. Put on gloves (over cuff)

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Steps to remove PPE

1. Peel off gown and gloves and roll inside-out

2. Dispose of safely

3. Perform hand hygiene

4. Remove cap and eye protection (from behind head)

5. Put eye protection in a separate container for reprocessing

6. Remove mask from behind head

7. Perform hand hygiene

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6.4 Respiratory hygiene and cough etiquette • Educate all staff, health workers, patients, and hospital visitors on respiratory hygiene and cough etiquette. ° Covering mouth and nose when coughing or sneezing. ° Hand hygiene after contact with respiratory secretions. ° Spatial separation of persons with acute febrile respiratory symptoms. • Have tissues available in the waiting area or provide a medical mask. • When tissues, cloths, or face masks are not available, all staff, health workers, patients, and visitors need to be instructed to lift their arm up and cover their nose and mouth with the inner surface of the arm or forearm when they cough or sneeze. • Remind all staff, health workers, patients, and visitors to dispose of the tissues and masks in no-touch receptacles and to wash their hands. • Have posters, at least, in patient waiting areas to remind patients and health workers. Persons with respiratory symptoms should apply source control measures • Such persons need to cover their nose and mouth with a tissue or mask when coughing or sneezing, dispose of used tissues and masks appropriately, and perform hand hygiene after coughing or sneezing. Actions for health-care facilities • Place patients with acute febrile respiratory symptoms at least 1 metre (3 feet) away from others in common waiting areas. • Post visual alerts at the entrance to health-care facilities instructing persons with respiratory symptoms to practice respiratory hygiene and cough etiquette. • Make hand hygiene resources, tissues, and masks available in common areas and areas used for the evaluation of patients with respiratory illnesses.

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6.5 Prevention of needle-stick and injuries from other sharp instruments15 Unsafe injection practices can transmit blood-borne pathogens, including hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. Use care when handling, using, cleaning, and disposing of needles, scalpels, and other sharps. • Do not bend, break, or otherwise manipulate used needles, scalpels, or other sharp instruments. • Do not recap needles. • Keep a sharps container nearby when giving injections. Discard single-use needles and syringes immediately after use and directly into the sharps container, without recapping and without passing to another person. • Close, seal, and send sharps containers for incineration before they are completely full (follow your facility protocol carefully). Indications for glove use when giving injections Wear non-sterile, well-ﬁtting, single-use gloves: • When there is a likelihood of coming into direct contact with a patient’s blood or other potentially infectious materials (e.g. body ﬂuids, moist body substances, and saliva), mucous membranes, and non-intact skin; • When performing venepuncture or venous access injections, because of the potential for blood exposure at the puncture site; • If the health worker’s skin is NOT intact or if the patient’s skin is NOT intact (e.g. through eczema, cracked or dry skin). Precautions Do not use gloves: • When undertaking routine intradermal, subcutaneous, and intramuscular injections: ° if the health worker’s skin is intact ° if the patient’s skin is intact. • Gloves do not provide protection against needlestick or other puncture wounds caused by sharp objects. • Needles, scalpels and other sharps should be handled with extreme caution.

15 WHO best practices for injections and related procedures toolkit. WHO, 2010. Available at http://whqlibdoc.who. int/publications/2010/9789241599252_eng.pdf

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Summary of best practices for injections DO • Carry out hand hygiene (use soap and water or alcohol rub), and wash carefully, including wrists and spaces between the ﬁngers, for at least 30 seconds. • Use one pair of non-sterile gloves per procedure or patient. • Use a single-use device for blood sampling and drawing. • Disinfect the skin at the venepuncture site. • Discard the used device (a needle and syringe is a single unit) immediately into a robust sharps container. • If recapping a needle is unavoidable, use the onehand scoop technique. 1. Leave the needle cap on a ﬂat surface, placed against a ﬁrm, upright surface with the cap opening facing towards you. 2. Lift the needle and syringe vertically and guide the tip of the used needle into the cap using only one hand. 3. Once the tip is covered, use the other hand to ﬁx the cap into place. 4. Clean the surface with disinfectant afterwards to avoid leaving any blood. • Seal the sharps container with a tamper-proof lid. • Place laboratory sample tubes in a sturdy rack before injecting into the rubber stopper. • Immediately report any incident or accident linked to a needle or sharps injury, and seek assistance. • Assess for need then start post-exposure prophylaxis (PEP) as soon as possible (see Section 19.6). DO NOT • DO NOT forget to clean your hands. • DO NOT use the same pair of gloves for more than one patient. • DO NOT wash gloves for reuse. • DO NOT use a syringe, needle, or lancet for more than one patient. • DO NOT touch the puncture site after disinfecting it. • DO NOT leave an unprotected needle lying outside the sharps container. • DO NOT recap a needle using both hands. • DO NOT overﬁll or empty sharps from a container. • DO NOT inject into a laboratory tube while holding it with the other hand. • DO NOT delay PEP after exposure to potentially contaminated material. Beyond 72 hours, PEP is NOT effective.

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6.6 Environmental cleaning • Use adequate procedures for the routine cleaning and disinfection of environmental and other frequently touched surfaces. ° Floors and horizontal work surfaces should be cleaned at least once a day. ° Cleaning should always be carried out from “clean” areas to “dirty” areas, in order to avoid contaminant transfer. ° Dry sweeping with a broom should never be done. ° Rags with dust should not be shaken out and surfaces should not be cleaned with dry rags. Cleaning with a moistened cloth helps to avoid contaminating the air with air-born particles. • Clean BEFORE you disinfect. • Change cleaning solutions and equipment frequently, as these items will get contaminated quickly (follow your hospital protocols). Table: Cleaning, disinfecting, or sterilizing16 Manual cleaning with water and detergent Disinfection (sodium hypochlorite 1% in-use dilution, bleaching powder, alcohol (70%) Sterilization (steam under pressure, dry heat sterilization, automated chemical)

Setting Floors, work tops Spillage – of blood, body ﬂuids, secretions, and excretions Commode, toilet seats Mops, wash mops Dressing trolleys Mattress and pillows (always cover with plastic covers) Reusable instruments AMBU bag and mask

9 9 9 9 9 9 9 9 9 9 9 9 9 9

16 Core components for infection prevention and control programmes. WHO, 2008. Available at http://whqlibdoc. who.int/hq/2009/WHO_HSE_EPR_2009.1_eng.pdf

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6.7 Linens17 Handle, transport, and process used linen so as to: • Prevent skin and mucous membrane exposure and contamination of clothing. • Avoid transfer of pathogens to other patients or the environment: ° All used linen and waste should be placed in bags or containers that are able to withstand transportation without being damaged. ° Any solid matter on soiled linen should be removed and ﬂushed down a toilet. ° Used linen should be handled carefully to prevent contamination of surrounding surfaces or people. ° Used linen should be washed according to normal routines.

6.8 Waste disposal • Ensure safe waste management. • Treat waste contaminated with blood, body ﬂuids, secretions, and excretions as clinical waste, in accordance with local regulations. • Human tissue and laboratory waste that is directly associated with specimen processing should be treated as clinical waste. • Segregate at the point of generation the 4 categories of waste: 1. sharps 2. non-sharps infectious waste 3. non-sharp non-infectious waste 4. hazardous waste. • Discard single use items properly.

17 Sterilization Manual for Health Centers. AMRO-PAHO and USAID, 2009. Available at http://new.paho.org/hq/ index.php?option=com_content&task=view&id=2106&Itemid=229&lang=en

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6.9 Patient care equipment • Handle equipment soiled with blood, body ﬂuids, secretions, and excretions in a manner that prevents skin and mucous membrane exposure, contamination of clothing, or transfer of pathogens to other patients or the environment. • Clean, disinfect, sterilize, and reprocess reusable equipment appropriately before use with another patient. Table: How to set up 3 colour-coded waste containers for most rooms in the hospital (plus a hazardous waste container in the pharmacy and laboratory only) Waste category Sharps (needles, scalpels) – infectious or not Segregate using colourcoded waste containers YELLOW • Safe sharps container must be: • puncture-proof • covered • closable • upright and stable during use • leak-proof at sides and bottom • clearly labelled for user YELLOW OR RED • Bags or containers • 15–40 litre capacity, with lids Collect • Close lid or cover, seal with tape, and submit for waste pickup when they are no more than ¾ full. • Never overﬁll or force items into these containers. • Collect regularly for disposal. Dispose • Sharps should be disposed of in a sharps pit (a buried drum in small centres or emergency structures, a concrete-lined sealed pit in other settings). • Off-site disposal may be necessary for safe incineration or other safe treatment at the district level (if available) or a private facility in charge of collection and treatment. • Non-sharps infectious waste should be buried in a pit ﬁtted with a sealed cover and ventilation pipe for on-site treatment in small health centre settings. • Otherwise, treat on-site or off-site with hightemperature incineration or steam sterilization. • Special arrangements may be needed for disposing of placentas, according to local custom. • May be included in the municipal waste stream or buried in a pit or landﬁll site. • Non-food and non-medical items may be recycled. • If space is limited, this waste should be incinerated. Ashes and residues should be buried in a pit.

Non-sharps infectious waste* (anatomical waste, pathological waste, dressings, used syringes, used single-use gloves)

• Containers should be collected, emptied, cleaned, disinfected, and replaced after each intervention (e.g. in an operating or maternity unit) or twice daily. • Bags should not be cleaned and reused but disposed of as sharps infectious waste.

Non-sharp, non-infectious waste (paper, packaging)

BLACK • Containers 20–60 litre capacity

• Should be collected, emptied, cleaned and replaced daily. • Alternatively, plastic bags may be used inside the containers for easy removal and disposal.

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Hazardous waste**

Appropriately labelled containers placed in secure locations.

• These may be stored in a small, labelled container at the pharmacy.

• Follow speciﬁc and appropriate treatment protocol and dispose of at the facility or send to a central health facility. • Manage stock of chemicals and pharmaceuticals well to reduce waste quantities and save on purchase costs.

* Cholera stools, body ﬂuids from other highly infectious diseases. ** Hazardous waste includes some outdated drugs, laboratory reagents, strong disinfectants; radioactive waste, batteries, mercury, etc. Each hazardous waste requires speciﬁc treatment and disposal methods based on national regulations.

6.10 Select additional infection control interventions including PPE, based on the risk assessment, epidemiology, or likely pathogen. Droplet precautions Additional precautions for infections transmitted by large droplets A respiratory aerosol of certain infections produces large particles or droplets (>5 µm in diameter) that typically remain suspended in the air for a limited period of time and settle within 1 m (3 feet) of the source. What to do in addition to standard precautions when such droplet transmission is possible. • All health workers for all patient care within 1 meter of the patient should wear a medical mask or surgical mask (tight ﬁtting). • Use single rooms for infectious patients. Otherwise, cohort patients with same suspected etiology. If not possible, place patient beds at least 1 m apart and arranged to keep a distance between patients.

Airborne precautions Additional precautions for infections transmitted by small droplet nuclei Smaller particles (small droplet nuclei ≤5 µm in diameter) evaporate quickly; the resulting dried residues settle slowly from the air, and remain suspended in the air for variable lengths of time. What to do in addition to standard precautions when airborne transmission is possible. Particulate respirator, e.g. N-95 or similar • Use adequately ventilated single rooms (≥12 ACH). If single rooms are not possible, cohort patients with the same diagnosis. Airborne precaution rooms can be naturally or mechanically ventilated, with adequate air exchange rate of at least 12 ACH and controlled direction of air ﬂow.

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Contact precautions Additional precautions for infections transmitted by contact Contact transmission can be direct (direct body surface to body surface contact and physical transfer of micro-organisms) or indirect (e.g. contaminated hands or equipment that carry and transfer the micro-organisms). What to do in addition to standard precautions • Gloves and gowns for all patient care. • Use disposable equipment or dedicate equipment for patient care. If equipment must be shared among patients, clean and disinfect it between each patient use. • Use single rooms. Otherwise, cohort patients with the same diagnosis. If not possible, place patient beds at least 1 m apart. For pathogens of potential international concern, a single room is more important. Table: Precautions by suspected organisms – examples Precaution Droplet precautions – transmitted by large droplets (in addition to standard precautions) Disease or organisms include Any patient with acute respiratory diseases (ARD) transmitted through large droplets. These include human inﬂuenza (seasonal, pandemic) and ARD with no pathogen identiﬁed (inﬂuenza-like illness); pathogens of potential international concern (avian inﬂuenza A (H5N1)), SARS*). See Section 6.11. • Infectious TB – see Section 6.12 • Measles • Varicella • Adenovirus, para-inﬂuenza, RSV • Pathogens of potential international concern (avian inﬂuenza A (H5N1)), SARS*) • Vibrio cholera, Shigella species There are many known pathogens that do not require additional precautions; however, these still require risk assessment and use of standard precautions. These include common bacterial respiratory infections caused by organisms such as Streptococcus pneumoniae, Haemophilus inﬂuenzae, Chlamydia spp., Mycoplasma pneumoniae. Most blood-borne pathogens including HIV and HBV.

Airborne precautions – transmitted by small droplet nuclei (in addition to standard precautions) Contact precautions (in addition to standard precautions)

Standard precautions only (includes all blood-borne pathogens)

* Note that some organisms require both droplet and contact precautions (in addition to standard precautions).

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6.11 Special precautions for acute respiratory diseases (ARDs) that are prone to result in epidemics or pandemics Separate and fast track patients with or suspected to have ARDs of potential concern • ARDs of potential concern include SARS-CoV, new inﬂuenza viruses causing human infection, and novel ARDs that can cause large-scale outbreaks and outbreaks with high morbidity and mortality. • Place patients who are coughing or have a suspected ARD of concern in an area separate from other patients and "fast-track" for rapid diagnosis and treatment. ° They should move to the front of the queue for all services and be assessed promptly. ° They should wait near an open window or in a comfortable area separate from the general waiting room. • Accommodate ARD patients at least 1 metre away from other patients. • For suspected ARDs of concern, prevent contact with contaminated equipment and the environment. ° Place the patient in a single room or cohort with similarly infected patients. ° Limit patient unprotected movement and have them wear a mask when moving about. Table: Precautions for ARDs according to speciﬁc clinical settings and procedures18 Infection control measures Adequately ventilated single room with >12 ACH Simple surgical mask Respirator N95 Eye protection

Hand hygiene

Setting or procedure Reception (without direct patient contact) ER Quick check Physical exam Patient waiting area General nursing care Blood collection Nebulization Induced sputum

9 9 9 9 9 9

9 9 9 9 9 9 9 9 9

9 9 9

9 9

18 Infection control strategies for speciﬁc procedures in health-care facilities: Quick reference guide. WHO, 2008. Available at http://whqlibdoc.who.int/hq/2008/WHO_HSE_EPR_2008.2_eng.pdf

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Gown

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Table: Precautions for ARDs according to speciﬁc clinical settings and procedures18 Infection control measures Adequately ventilated single room with >12 ACH Simple surgical mask Respirator N95 Eye protection

Hand hygiene

Setting or procedure Aerosol-generating procedures associated with pathogen transmission, e.g. intubation or extubation, and manual ventilation, suctioning, autopsy, or surgery involving the use of high-speed devices

Respiratory etiquette

Gloves

Gown

6.12 Special precautions for infectious TB patients • As for Acute respiratory diseases, place patients who are coughing or have suspected TB in an area separate from other patients and have them "fasttracked" for rapid diagnosis and treatment. ° They should move to the front of the queue for all services and be assessed promptly. ° They should wait near an open window or in a comfortable area separate from the general waiting room. ° "Fast-track" aims to minimize time spent in the hospital for patients suspected of having TB. • Community-based approaches for the management of TB patients (including MDR-TB) should be prioritized over hospitalization ° Complement with education of household members and other close contacts on TB infection control. • Avoid unnecessary admissions of TB patients to health-care facilities. ° Open doors and windows to use the natural air ﬂow in the hospital. • On TB wards, the infectious TB patient should wear a medical mask, especially if correct cough etiquette is not observed. ° The health care workers should wear an N-95 mask when taking care of an infectious TB patient in a close environment. • Patients with known or suspected drug-resistant TB (DR-TB) should be separated from other patients, including other TB patients.

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6.13 Precautions when caring for patients with suspected or conﬁrmed Filovirus (Ebola, Marburg) haemorrhagic fever19 Careful application of standard precautions should prevent Filovirus haemorrhagic fever transmission. Current WHO recommendations for direct patient care for known or suspected Filovirus haemorrhagic fever patients • Restrict all non-essential staff from patient care areas. • Maintain a log of persons entering the patient’s room. • Limit the number of visitors allowed access to the patient to include only those necessary for the patient’s well-being and care, such as a child’s parent. • Ensure that all visitors use PPE according to the facility guidelines. Prior to entering the isolation area, provide all visitors with instructions on using PPE correctly, and instructions for correct hand hygiene practices, • Do not allow other visitors to enter the care area, and ensure that any visitors wishing to observe the patient do so from an adequate distance from the care area (approximately 15 m). • Apply infection control precautions to avoid any possible unprotected direct contact with blood and body ﬂuids when providing care to any Filovirus patient, including suspected cases. ° Perform hand hygiene before and after direct patient care, after any contact with potentially contaminated surfaces, and after removal of PPE. Neglecting to perform hand hygiene after removing PPE will reduce or negate any beneﬁts of the protective equipment. ° Wear gloves when entering the patient care area. ° Wear a disposable, impermeable gown to cover clothing and exposed skin. Wear a waterproof apron over any permeable gown or when undertaking any strenuous activity (e.g. carrying a patient). ° Wear facial protection to prevent splashes to the nose, mouth, and eyes. Facial protection can be achieved by means of (1) medical mask and eye protection (eye visor or goggles), or (2) with a face shield. • Before exiting the isolation area of a patient with suspected Filovirus infection, carefully remove and dispose of protective equipment. • When removing protective equipment, be careful to avoid any contact between the soiled items (e.g. gloves, gowns) and any area of the face (eyes, nose, or mouth). • Ensure that clinical and non-clinical personnel are assigned exclusively to Filovirus patient care areas and that members of staff do not move freely between the isolation areas and other clinical areas during the outbreak. • Limit the use of needles and other sharp objects as much as possible. • Limit the use of phlebotomy and laboratory testing to the minimum necessary for essential diagnostic evaluation and patient care. See Section 19 for TB and HIV prevention and care services for health workers.

19 Interim Infection Control Recommendations for Care of Patients with Suspected or Conﬁrmed Filovirus (Ebola, Marburg) Haemorrhagic Fever. WHO, 2008. Available at http://www.who.int/csr/bioriskreduction/ﬁlovirus_ infection_control/en/

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7. Procedures Table of contents 7.1 7.2 General considerations in performing procedures . . . . . . . . . . 7.1.1 Patient consent. . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.2 Safety considerations, precautions and anaesthesia . . . Diagnostic procedures . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 Skin biopsy – shaving or scraping . . . . . . . . . . . . . . 7.2.2 Skin biopsy – punch . . . . . . . . . . . . . . . . . . . . . . . 7.2.3 Skin snip for the diagnosis of microﬁlariasis . . . . . . . . 7.2.4 Skin biopsy – excision. . . . . . . . . . . . . . . . . . . . . . 7.2.5 Fine needle aspiration (FNA) . . . . . . . . . . . . . . . . . . 7.2.6 Lymph node biopsy (excisional) . . . . . . . . . . . . . . . . 7.2.7 Bone marrow aspiration and biopsy . . . . . . . . . . . . . 7.2.8 Pelvic examination. . . . . . . . . . . . . . . . . . . . . . . . 7.2.9 Cervical cancer screening: Pap smear . . . . . . . . . . . 7.2.10 Cervical cancer screening: visual screening . . . . . . . . 7.2.11 Colposcopy, cervical biopsy and endocervical curettage 7.2.12 Clinical breast examination . . . . . . . . . . . . . . . . . . 7.2.13 Endometrial biopsy . . . . . . . . . . . . . . . . . . . . . . . 7.2.14 Gram stain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.15 Wet mount. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.16 Urinalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.17 Taking stool samples, including Cary-Blair for cholera . . 7.2.18 Crude clotting time. . . . . . . . . . . . . . . . . . . . . . . . 7.2.19 Thin and thick blood ﬁlms for malaria . . . . . . . . . . . . 7.2.20 AFB (Ziehl Neelsen) . . . . . . . . . . . . . . . . . . . . . . . 7.2.21 Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . Therapeutic procedures . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.1 Chest tube (intercostal chest drain) . . . . . . . . . . . . . 7.3.2 Urinary catheter insertion – female . . . . . . . . . . . . . . 7.3.3 Marsupialization for Bartholin’s cyst or abscess . . . . . . 7.3.4 Intrauterine device (IUD) placement . . . . . . . . . . . . . 7.3.5 Reduction of paraphimosis . . . . . . . . . . . . . . . . . . . 7.3.6 Urinary catheter insertion – male . . . . . . . . . . . . . . . 7.3.7 Suprapubic catheter. . . . . . . . . . . . . . . . . . . . . . . 7.3.8 Inserting a nasogastric (NG) tube . . . . . . . . . . . . . . . 7.3.9 Gastric lavage . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.10 Venous cutdown . . . . . . . . . . . . . . . . . . . . . . . . . Diagnostic and therapeutic procedures . . . . . . . . . . . . . . . . 7.4.1 Thoracentesis (chest tap) . . . . . . . . . . . . . . . . . . . 7.4.2 Lumbar puncture . . . . . . . . . . . . . . . . . . . . . . . . . 7.4.3 Paracentesis (abdominal tap) . . . . . . . . . . . . . . . . . 7.4.4 Arthrocentesis (joint aspiration) . . . . . . . . . . . . . . . . 7.4.5 Pericardiocentesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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7. Procedures1,2 7.1 General considerations in performing procedures 7.1.1 Patient consent Before performing a procedure, it is important to receive consent from the patient. If the patient is unable to give consent (e.g. the patient is comatose or similarly incapacitated), a proxy (a family member or legal guardian) may do so on behalf of the patient. In such situations, the proxy should make the decision he or she believes the patient would make if they were able and competent. The decision to obtain consent involuntarily should not be taken lightly, and the patient should have the right to appeal. Explain what will be done before doing the procedure: • Explain why the procedure is necessary: ° What are the beneﬁts? ° What are the risks, including pain associated with the procedure? • Ask if the patient has questions or concerns and address them. • Check that the patient has understood. • Obtain permission to proceed. • Document on the patient chart the discussion and consent. • Be mindful of the comfort and privacy of all patients and their families.

7.1.2 Safety considerations, precautions and anaesthesia For most of the procedures in this Section, it can be helpful to have an assistant who can help prepare, position, and comfort the patient in addition to assisting with the procedure. A female chaperone or assistant should be present during some procedures in women including those described in Sections 7.2.8, 7.2.9, 7.2.10, 7.2.11, 7.2.12, 7.2.13, 7.3.2, 7.3.3, and 7.3.4. Some health facilities prepare a trolley that is kept stocked with instruments and materials used to perform common procedures. The contents will vary depending on the types and frequency of procedures at a given health facility. Standard precautions, safe injection practices, and safe waste management should be used before, during, and after all procedures. See Section 6. • These include hand hygiene and gloves for all procedures, and face protection and a gown when relevant. • Always use care when handling, using, cleaning, and disposing of needles, scalpels and other sharps. • Treat waste contaminated with blood, body ﬂuids, secretions, and human tissue as clinical waste in accordance with local regulations. • Sterile gloves should be used and a sterile ﬁeld maintained for: ° excision skin biopsy 1 Surgical Care at the District Hospital. WHO, 2003. Available at www.who.int/surgery/publications/en/SCDH.pdf 2 Comprehensive cervical cancer control: a guide to essential practice. WHO, 2006. Available at whqlibdoc.who. int/publications/2006/9241547006_eng.pdf

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° lymph node biopsy ° thoracocentesis ° chest tube placement ° lumbar puncture ° paracentesis, arthrocentesis, pericardiocentesis ° bone marrow biopsy ° urinary catheter insertion ° IUD placement ° suprapubic urinary catheter placement. • A sterile ﬁeld requires the careful application of an antiseptic and draping with sterile drapes, such as towels or paper drapes. • Always remember to sterilize or disinfect all reusable equipment after a procedure. Anaesthesia using lidocaine Most of the procedures below can be done with anaesthesia using lidocaine in one of two ways: • Locally ° Lidocaine is injected into the area to be anaesthetized; larger areas can be covered with a ﬁeld block by injecting widely around the area in a diamond pattern. • Digital block ° Lidocaine is injected at the base of the digit or penis at the 2, 6, and 10 o’clock positions, in order to anaesthetize the entire digit (do not use epinephrine (adrenaline) here). Digital block is preferable, where possible, as it requires smaller doses of anaesthetic for a given area. • The dose of lidocaine will vary widely by procedure and size of the area to be anaesthetized. The table below gives maximum doses for lidocaine with and without epinephrine.

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Maximum drug doses for lidocaine Agent Lidocaine Concentration % 0.5 1.0 2.0 Lidocaine-epinephrine 0.5 1.0 2.0 Maximum safe dose mg 300 300 300 500 500 500 Maximum volume ml 60 30 15 100 50 25

* Clinical Procedures in Emergency Medicine, 4th Edition (adapted). James R. Roberts, Jerris R. Hedges (Eds). Saunders, Philadelphia, 2004.

• Avoid using lidocaine with epinephrine on the digits, penis, or other extremities. This can lead to vasoconstriction and gangrene. • Using a small needle (25- to 30- gauge) for injecting lidocaine will reduce pain and bleeding. Also, small needles slow the speed of the injection and reduce tissue distortion. They should be used with a small syringe, usually 10 ml. • When using lidocaine for local anaesthesia, always draw back the plunger before injecting, to make sure the needle is not in a blood vessel. • Try to minimize the number of punctures (and associated pain) by not withdrawing the needle completely after the initial puncture. Instead, redirect it along a separate path. • Lidocaine jelly may be used for certain procedures (e.g. urinary catheter insertion, IUD placement).

7.2 Diagnostic procedures 7.2.1 Skin biopsy – shaving or scraping Indications • Best used for raised lesions or those on convex surfaces. Contraindications • Do not perform shave biopsy of pigmented lesions – melanoma is more difﬁcult to stage if shaved. Equipment • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • scalpel blade and handle • culture media • microscope slides • formalin.

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Procedure 1. Cleanse the area of the biopsy with skin antiseptic. 2. Anaesthetize the area with 1–2% lidocaine. 3. If ﬂat, inject anaesthetic or saline under the lesion to raise it slightly. 4. Hold the scalpel parallel to the skin and begin. Complete the incision in one stroke. The aim is to take only a specimen of superﬁcial tissue.

5. If done for the diagnosis of cutaneous leishmaniasis, the slit-skin technique should be used. Incise several millimetres outward from the active border of a lesion, making sure to go deep enough to penetrate the dermis. This should be followed by a scrape as above. 6. Dress the wound with simple dry gauze dressing. If the subcutaneous tissue is encountered, the technique for an excision biopsy should be used to close the wound.

Diagnosis of cutaneous leishmaniasis (see Section 11.20) • The diagnostic yield for cutaneous leishmaniasis will be increased by: ° using several techniques (needle aspirate, punch biopsy, scraping) ° taking several specimens with each technique ° biopsying multiple areas of the lesion, including edges. Note that scrapings should be taken last to avoid contamination. • Needle aspirates should be sent for culture. • Punch biopsy samples should be divided into three parts and sent for: ° culture ° impression smear (similar to thin smear) ° histopathology (poor for diagnosis, but useful for excluding other causes). • Scrapes should be sent for histopathology.

Investigations • If suspicion is for neoplasm, and enough biopsy material is available, send in formalin. If not much material, perform a thin smear, allow to air dry, and ﬁx with methanol.

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7.2.2 Skin biopsy – punch Indications • any inﬂammatory lesions or suspected Kaposi sarcoma • leishmaniasis. Equipment • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • cylindrical punch biopsy knife • formalin • suture material, needle driver, forceps. Procedure 1. Cleanse the area of the biopsy with skin antiseptic. 2. Anaesthetize the area with 1–2% lidocaine. 3. Stretch the skin perpendicular to the Langer’s lines (natural creases in the skin). 4. Hold the cylindrical knife (trephine) perpendicular to the skin and gently push downward while rotating it clockwise and counter clockwise to cut through the skin. The trephine should be withdrawn after penetrating into the subcutaneous tissue.

5. Use a forceps or needle (the one used to anaesthetize the skin may be reused here) to lift the specimen, and cut it free from the underlying tissue. Be sure to make the cut below the dermis. Avoid squeezing the specimen with a haemostat or forceps to avoid crush artefact.

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6. If the wound is less than 2 or 3 mm, it can be dressed and allowed to heal by secondary intention. Wounds larger than 4 mm should be sutured with one or two simple sutures. Investigations • Send the biopsied tissue in formalin.

7.2.3 Skin snip for the diagnosis of microﬁlariasis Indications • Diagnosis of onchocerciasis or other skin ﬁlariasis. Equipment • antiseptic • 23- to 25-gauge needles • razor blade or scalpel • water or saline • microscope slides and cover slips • inverted microscope. Procedure 1. Select the sites with the highest numbers of microﬁlariae for examination. • In Latin America – over the scapula or iliac crest. • In Africa – the iliac crest or calf. • In Yemen – a skin snip not indicated because the most frequent clinical manifestation is a licheniﬁed dermatitis (sowda) in which microﬁlaria are rarely found. 2. 1–2 snips should be taken from the sites as described above. 3. Clean the skin with antiseptic and allow it to dry. 4. Insert a ﬁne sterile needle almost horizontally into the skin and raise the point of the needle, lifting with it a small piece of skin measuring about 2 mm in diameter and height.

5. Cut off the piece of skin with a sterile razor blade or scalpel.

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6. Be sure to disinfect all instruments used during the procedure. 7. Place the tissue sample on a microscope slide with a few drops of saline or water. Cover with cover slip. Send the specimen to the laboratory immediately, as the movement of the microﬁlaria decreases and eventually ceases with time. Comments • Usually, the species and number of microﬁlariae emerging from the skin snip are reported. The number will be reported as 1–4, 5–14, 15–49, 50–100 or >100 per snip. If more than one snip is taken from one subject, then a mean skin microﬁlariae density is calculated. • Besides the microﬁlariae of Onchocerca volvulus, those of Mansonella streptocerca in Africa and Mansonella ozzardi in Latin America may also inhabit the human skin. • Microﬁlariae in the eye may be examined by using a slit lamp. See Section 10.12.

7.2.4 Skin biopsy – excision Indications • basal cell and squamous cell carcinomas (squamous cell carcinoma is lifethreatening and should be treated with wide local surgical excision.) • melanoma. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • scalpel blade and handle • formalin • suture material, needle driver, forceps Procedure 1. Cleanse the area of the biopsy with skin antiseptic. 2. Anaesthetize the area with 1–2% lidocaine. 3. Incise the skin with a scalpel parallel to the direction of the skin lines (Langer’s lines). These can be found by placing two ﬁngers on opposite sides of the incision and gently squeezing them and the skin together. 4. Use elliptical incisions, making the long axis large enough to close the skin without deformity. A rule of thumb is to make the long axis twice as long as the short axis.

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5. Lift the sample with forceps and separate it from the underlying tissue. 6. Excise subcutaneous lesions after gaining access through the skin incision. Do not remove skin unless the subcutaneous mass is adherent. 7. Close the wound with simple interrupted sutures as needed. Investigations • Send biopsied tissue in formalin.

7.2.5 Fine needle aspiration (FNA) Indications • FNA is a quick and minimally invasive procedure to evaluate a mass or lymphadenopathy (see Section 10.5). Contraindications • Pulsatile or air-ﬁlled mass. Equipment • antiseptic • 10 ml syringe, 22-gauge needle (large bore needles exacerbate bleeding and tumour seeding) • microscope slides • mask for the health worker if TB is suspected. Procedure 1. Clean the skin with antiseptic. 2. Fix the lymph node or mass so that it will not move. A right-handed clinician grasps the mass with the left hand and the syringe in the right hand. 3. Enter the lymph node parallel to the ﬁngers of the left hand, ensuring that the left hand ﬁngers are not in any danger. 4. Apply gentle suction syringe by pulling back the plunger 2–3 ml. 5. The mass is entered and multiple, sequential passes are made without exiting the skin surface. If the skin is exited, air will be pulled into the syringe and the specimen will be sucked from the bore of the needle into the syringe. This will make it difﬁcult to get the specimen onto the slide. 6. Release the syringe completely and exit the skin. 7. Place a small drop of aspirated ﬂuid on a glass slide. It may be necessary to carefully remove the needle (with the specimen cored in the centre) and withdraw the plunger of the syringe, then re-attach the needle and gently depress the plunger, pushing the specimen out.

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8. A smear is made by laying another glass slide on top of the drop of ﬂuid and pulling the slides apart to spread the ﬂuid or, using a needle, to scrape it across the slide. Investigations • If suspected TB lymphadenopathy, send AFB smear. See Section 15. • If there is a fair volume of specimen, consider sending ﬂuid for mycobacterial or bacterial culture. • If suspected malignancy, spray with ﬁxative and send for cytology. • Wet smears can be placed in 95% ethyl alcohol and treated with the Papanicoulau technique and stains. • Specimens should be air dried and prepared for a Wright-Giemsa stain when the differential diagnosis includes salivary, lymphoproliferative or fatty tumours. • If suspected plague, aspirate and look for small gram-negative or bipolarstaining (“safety-pin”) ovoid coccobacilli on a smear. Also send for culture (slow growing). Complications • Pneumothorax – see Quick Check page 46 and Section 4.2 for immediate management. (If signiﬁcant, the patient will require a chest tube.) • Haemorrhage or haematoma Comments • If suspected TB, send sputum samples for AFB smear; consider chest X-ray (see Section15). • Failure to establish an accurate diagnosis should lead to an excisional biopsy of the lymph node (see Section 7.2.6) • If a cyst is encountered in the neck, it should be completely evacuated, and ﬂuid and a portion of the capsule sent for cytology.

7.2.6 Lymph node biopsy (excisional) Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • scalpel blade and handle • suture material, needle driver, forceps • formalin • culture media. Procedure 1. Lymph nodes are located beneath the fascia and, therefore, require deeper dissection than skin or subcutaneous lesion biopsies. A general anaesthetic may be required. 2. Make an incision along the skin lines and dissect through the subcutaneous tissue, while controlling any bleeding that may arise.

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3. Identify the lymph node with a ﬁngertip and incise the overlying superﬁcial fascia. 4. Dissect the node from surrounding tissue without directly grasping it. 5. Instead, grasp the attached adventitial tissue with a small artery forceps, or place a ﬁgure-of-8 suture into the node for traction. 6. Separate all the tissue attached to the node. 7. Control the hilar vessels with forceps and ligate them with absorbable suture after the node has been removed. Investigations • Send biopsied tissue for histology in formalin. • If suspected bacterial infection, send a portion of the node for culture.

7.2.7 Bone marrow aspiration and biopsy Indications • unexplained blood disorders (e.g. anaemia, elevated blood count, high or low platelets, etc.) see Sections 10.18 and 10.19 • suspected haematologic malignancy • diagnosis of suspected leishmaniasis, schistosomiasis, or other mycobacterial, fungal, or parasitic infection • diagnosis of iron metabolism disorders • evaluation of fever of unknown origin • evaluation of splenomegaly. Contraindications • absolute ° haemophilia ° severe disseminated intravascular coagulopathy (DIC) ° other severe bleeding disorder. • relative ° low platelets (<20 x 109/litre) may require a platelet transfusion ° skin infection or osteomyelitis near the chosen site. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- and 21-gauge needles) • scalpel blade and handle • bone marrow aspiration needle with removable stylet and 1–2 ml syringe • bone marrow biopsy (Jamshidi) needle with a device for removal of the

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biopsied tissue • dressing material • microscope slides, culture media, and other collection materials as needed. Procedure 1. Bone marrow aspiration and bone marrow biopsy are specialized procedures, and should be done by a clinician experienced in doing the procedure. 2. Discuss with the pathology laboratory prior to the procedure to determine which tests are available and how sampled tissue should be sent. 3. Patients may beneﬁt from being pre-medicated with paracetamol. Diazepam or midazolam may be given in case of severe anxiety. 4. It is advisable to have an assistant to help with specimen preparation at the end of the procedures; aspirate samples can clot quickly and must be rapidly prepared to avoid this. 5. The posterior and anterior iliac crests, sternum, and various other sites may be used for bone marrow biopsy and aspiration. Biopsy (but not aspiration) is contraindicated at the sternum due to the risk of penetration into the thoracic cavity and resulting haemorrhage. The posterior iliac crest is preferred over the anterior iliac crest. 6. Position the patient lying face down or lying on the side opposite to that where the procedure will be done. 7. Identify the landmarks to be used for the procedures: posterior iliac crest, posterior superior iliac spine, or anterior superior iliac spine. 8. Identify the site, usually three ﬁnger widths from the midline and two ﬁnger widths below the posterior iliac crest, and cleanse with antiseptic. 9. Anaesthetize the skin and subcutaneous tissue at the site using the 23-gauge needle. Switch to the 21-gauge needle, penetrate to the periosteum, and anaesthetize a single 2 cm area, anticipating that two separate (but close) sites will be required for the biopsy and aspiration. 10. While waiting for the anaesthetic to take effect, make sure to have all the materials required to collect the biopsied tissue or aspirated ﬂuid. 11. Make a small 3 mm incision at the site. Bone marrow aspiration 1. Insert the bone marrow aspiration needle (with stylet) into the site, holding it perpendicular to the skin. When the periosteum is encountered, turn the needle in the direction of the anterior superior iliac spine. 2. Gently twist the needle back and forth (not more than 180°) to penetrate into the marrow cavity. Warn the patient that they may experience pain when this occurs. 3. At this point the stylet should be removed, the small syringe attached, and the marrow aspirated. No more than 0.5 ml should be aspirated at a time; larger quantities are prone to clotting. Once the required number of aspirates have been obtained, the needle should be withdrawn with stylet in place.

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Bone marrow biopsy 1. Using the same incision, insert the (larger) bone marrow biopsy needle. It should be aimed in the same direction, but at a slightly different spot on the periosteum. 2. Twist until it is lodged ﬁrmly in the bone, then remove the stylet and advance further, about 15–20 mm. 3. In order to separate the biopsied sample from the underlying tissue, change the direction of the needle and twist once again. Advance again for a few millimetres and remove the needle. This is done to ensure that the sample remains in the needle when it is removed. 4. Remove the needle and cover the site with a dressing, holding pressure for a few minutes. 5. The specimen can be removed by threading the stylet through the cutting end of the needle. 6. Remember to examine the biopsied material before ﬁnishing: if it appears to be white or glistening tissue, it may be bone or cartilage and not bone marrow, and the biopsy should be repeated. Aftercare • Instruct the patient to lie still until bleeding stops, at least 10–15 minutes. If bleeding continues, apply pressure and have the patient wait for at least 1 hour before getting up. • Paracetamol may be continued for 1 day for pain control. Investigations • To be discussed with the pathology laboratory in advance. Standard tests may include aspirate and buffy coat smears, biopsy section, iron stain, clot section, AFB smear, and mycobacterial cultures. Complications • bleeding • needle breakage • tumour seeding • infection.

7.2.8 Pelvic examination After taking a history, perform a pelvic examination. There are 3 components of the female genital examination: 1. an external genital examination 2. a speculum examination 3. a bimanual examination. Issues to consider before the examination • A female chaperone or assistant should be present during the examination. • Have all necessary equipment and supplies ready. Ensure the speculum used is at a comfortable temperature.

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• Ask the woman to empty her bladder (urinate) and remove her underwear. Be particularly sensitive to her sense of modesty about uncovering normally clothed areas, or if the examination is perceived to be invasive. • Position the woman on the examination table.

External genital exam • Using a gloved hand, look for redness, lumps, swelling, unusual discharge, sores, tears, and scars around the genitals and in between the skin folds of the vulva. These can be signs of a sexually transmitted infection.

Speculum exam 1. Hold the speculum blades together sideways and insert them into the vagina. Be careful not to press on the urethra or clitoris because these areas are very sensitive.

2. When the speculum is halfway in, turn it so the handle is down.

3. Gently open the blades and look for the cervix. Move the speculum slowly and gently until the entire cervix is visualized.

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4. Tighten the screw (or otherwise lock the speculum in the open position) so it will stay in place.

5. Check the cervix, which should look pink, round, and smooth; although this may vary with parity. • There may be small, yellowish cysts, areas of redness around the opening (cervical os) or a clear mucoid discharge; these are normal ﬁndings. 6. Look for any abnormalities, which may include the following: • Vaginal discharge and redness of the vaginal walls, which are common signs of vaginitis. If the discharge is white and curd-like, there is probably a yeast infection. See Section 10.15.4. • Ulcers, sores, or blisters. Genital ulcers may be caused by syphilis, chancroid, herpes virus or, in some cases, cancer. Sores and blisters usually are caused by the herpes virus. See Section 11.15. • Easy bleeding when the cervix is touched with a swab, or a mucopurulent discharge, which are signs of a cervical infection. See Section 10.15.4. • An abnormal growth or tumour, which might be cervical cancer. See Section 10.15.8. 7. Gently pull the speculum until the blades are clear of the cervix. Then allow the blades to close being careful not to pinch the vaginal wall, and remove the speculum. Bimanual exam 1. The bimanual examination allows the examiner to palpate the reproductive organs inside the abdomen. 2. Test for cervical motion tenderness. • Put the pointing and the middle ﬁnger of a gloved hand in the woman’s vagina. • Turn the hand palm up. • Palpate the cervix to see if it is ﬁrm and round. • Then put one ﬁnger on either side of the cervix and move the cervix gently while watching the woman’s facial expression. • If this causes pain (the woman may grimace), there is cervical motion tenderness, and she may have an infection of the womb, tubes or ovaries (pelvic inﬂammatory disease (PID) see Section 10.15.5), or an ectopic pregnancy. If her cervix feels soft, she may be pregnant.

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3. Use the ﬁngers that are in the vagina to move the pelvic organs toward the abdomen, allowing the hand that is on the abdomen to palpate them. The womb may be tipped forwards or backwards. It should feel ﬁrm, smooth, and smaller than a lemon. • If the womb feels soft and large, the woman is probably pregnant. • If it feels lumpy and hard, she may have a ﬁbroid or other growth. • If it hurts her when palpated, she may have an infection. • If it does not move freely, she may have scars from an old infection. 4. Palpate the tubes and ovaries. If these are normal, they will be hard to feel: • If there are lumps that are bigger than an almond or that cause severe pain, she may have an infection or other condition needing urgent treatment. • If she has a painful lump, and her period is late, she may have an ectopic pregnancy. This is an emergency – see Section 10.15 and perform Quick Check. 5. Palpate the inside of the vagina. Make sure there are no unusual lumps, tears, or sores. 6. Ask the woman to cough or push down as if she were passing stool • Look to see if something bulges out of the vagina. If it does, she may have a fallen (prolapsed) womb or fallen bladder.

7.2.9 Cervical cancer screening: Pap smear Equipment • speculum • wooden spatula or brush • microscope slides • ﬁxative Procedure 1. Begin by performing a speculum exam (see Section 7.2.8 above). 2. Insert the long tip of the wooden spatula or brush into the os, and rotate it through a full circle (360°).

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3. Smear both sides of the spatula or brush onto a glass slide with one or two careful swipes. 4. Sample any abnormalities outside the cervical os, and smear on another slide. 5. Immediately ﬁx each slide. Either use spray ﬁxative, at a right angle to and a distance of 20 cm from the slide, or immerse the slide in a container of 95% ethanol for at least 5 minutes. 6. Gently close and remove the speculum. 7. Place all used instruments in decontamination solution. Investigations and comments After taking the smear, label each slide carefully and send for pathology. • The pathology report will include the specimen adequacy, as well as the presence or absence of malignancy. ° Comments regarding specimen adequacy can include: ◊ satisfactory for evaluation (note presence or absence of endocervical transformation zone component); ◊ unsatisfactory for evaluation (with the reason speciﬁed). ° Comments regarding malignancy can include (general categorization): ◊ negative for intraepithelial lesion or malignancy; ◊ epithelial cell abnormality with the following descriptors • atypical squamous cells (ASC); • atypical squamous cells of undetermined signiﬁcance (ASC-US); • atypical squamous cells, cannot exclude HSIL (ASC-H); • low-grade squamous intraepithelial lesion, including HPV changes and mild dysplasia, CIN1 (cervical intraepithelial neoplasia (CIN)); • high-grade squamous intraepithelial lesion, including moderate and severe dysplasia, CIN2, CIN3; • squamous cell carcinoma; • atypical glandular cell. ° Other comments, such as: ◊ endometrial cells in a woman ≥40 years of age.

7.2.10 Cervical cancer screening: visual screening In visual screening, the provider applies 3–5% acetic acid (in VIA) or Lugol’s iodine solution (in VILI) to the cervix, and then looks to see if there is any staining. A VIA test is positive if there are raised and thickened white plaques or acetowhite epithelium; a VILI test is positive if there are mustard or saffron-yellow coloured areas, usually near the squamocolumnar junction (SCJ). Either test is suspicious for cancer if a cauliﬂower-like fungating mass or ulcer is noted on the cervix. Visual screening results are negative if the cervical lining is smooth, uniform and featureless; it should be pink with acetic acid and dark brown or black with Lugol’s iodine. • Visual methods are not recommended for use in postmenopausal women, because their transition zone is most often inside the endocervical canal and not visible on speculum exam. Equipment • speculum • cotton swab • 3–5% acetic acid or Lugol’s iodine solution.

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Procedure 1. Begin by performing a speculum exam (see Section 7.2.8 above). 2. Adjust the light source in order to get the best view of the cervix. 3. Use a cotton swab to remove any discharge, blood, or mucus from the cervix. 4. Identify the SCJ, and the area around it. 5. Apply acetic acid or Lugol’s iodine to the cervix; wait a minute or two to allow colour changes to develop. Observe any changes in the appearance of the cervix. Give special attention to abnormalities close to the transformation zone. 6. Inspect the SCJ carefully, and be sure to visualize all of it. Report if the cervix bleeds easily. If acetic acid was used, look for any raised and thickened white plaques or acetowhite epithelium. If Lugol’s iodine was used, look for saffronyellow coloured areas. Remove any blood or debris appearing during the inspection. 7. Use a fresh swab to remove any remaining acetic acid or iodine solution from the cervix and vagina. 8. Gently remove the speculum. 9. Record observations and test result. Draw a map of any abnormal ﬁndings on the record form. 10. Discuss the results of the screening test with the patient. See Section 10.15.8.

7.2.11 Colposcopy, cervical biopsy, and endocervical curettage

Indications Indications for colposcopy and biopsy include the following: • an abnormal screening test • suspicious cervical lesions seen on speculum examination • to map abnormalities before cryotherapy or LEEP. Indications for endocervical curettage include the following. • The patient has abnormal ﬁndings on Pap smear, but no abnormality is seen with colposcopy. • The Pap smear revealed a glandular lesion. These usually arise from the columnar epithelium inside the canal. In this case, endocervical curettage must be performed regardless of the colposcopy ﬁndings. • Colposcopy was unsatisfactory because the entire transformation zone was not seen. Equipment • speculum • cotton swab • colposcope

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• • • • • • •

saline 3–5% acetic acid forceps punch biopsy endocervical curette Monsel’s paste formalin.

Procedure 1. Pain from cervical biopsies can be reduced by having the patient take paracetamol or ibuprofen 1–2 hours prior to the procedure. 2. Inspect the cervix at low-power magniﬁcation (5X to 10X), looking for any obvious areas of abnormality (e.g. leukoplakia, condylomata). Identify the transformation zone and the original and new squamocolumnar junctions (SCJ). If the entire SCJ is not visible, inspect the cervical canal using an endocervical speculum. If the entire SCJ is still not visible, the colposcopic procedure is termed inadequate or unsatisfactory and endocervical curettage should be done (see Step 8 below). 3. Apply saline to the cervix. Inspect the cervix with a green ﬁlter and 15X magniﬁcation, noting any abnormal vascular patterns. 4. After telling the patient that she might feel a mild stinging sensation, apply acetic acid. Wait 1 or 2 minutes to allow colour changes to develop. Observe any changes in the appearance of the cervix. Give special attention to abnormalities close to the SCJ. 5. Integrate the ﬁndings of the saline test and the acetic acid test to make a colposcopic assessment. 6. Tell the woman that a biopsy of her cervix will be taken, and this may cause cramping. 7. Take cervical biopsies of the most abnormal areas. 8. If necessary, perform endocervical curettage. Hold the curette like a pen and scrape the endocervical canal in short, ﬁrm strokes until it is completely sampled. Keep the curette inside the canal during the entire procedure. 9. If active bleeding is noted, apply Monsel’s paste to the bleeding areas. 10. Withdraw the colposcope and gently remove the speculum. After the procedure • Advise the woman how to take care of herself when she goes home. ° She should abstain from sexual intercourse until she has no more discharge or bleeding. If this is not possible, she should use condoms. ° She should not insert anything into the vagina for 3 or 4 days. ° Tell her the signs and symptoms of complications: active bleeding, serious cramping or lower abdominal pain, pus-like discharge, or fever. If she experiences any of these, she needs to return to the hospital. • Provide condoms and teach her how to use them. Investigations • Send the biopsied and curetted tissue in formalin.

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7.2.12 Clinical breast examination The clinical breast examination consists of 2 components, inspection and palpation. The examination should include the neck, chest, and axillae in addition to the breasts. A female chaperone or assistant should be present throughout. Inspection • The patient should be respectfully asked to remove any clothing from the waist up. • During each of the following steps, look for any asymmetry, bulging, or skin changes (including dimpling or swelling) in the breasts. The nipples should be carefully observed for retraction or discharge. • Begin with the patient in the seated position (unclothed from the waist up). • Ask the patient to raise her arms over her head. • Ask the patient to lower her arms and place them on her hips, pressing in order to contract the pectoralis muscles. Palpation • While the patient is seated, the examiner should palpate the regional lymph nodes, paying special attention to the axillary nodes. • The patient should then be positioned supine. While examining a given breast, the arm on that side should be raised above her head. • Breast palpation requires a systematic approach covering the entire chest wall, with each side bounded by the clavicle, sternum, inferior-most rib, and mid-axillary line. The examiner should examine this entire area using a radial approach, concentric circles, or vertical strips. The pads of the ﬁngers and not the ﬁngertips should be used for palpation.

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7.2.13 Endometrial biopsy Indications • infertility (to determine the response of the endometrium to ovarian stimulation) • postmenopausal bleeding (in order to rule out uterine cancer) • suspected pelvic tuberculosis • suspected chronic endometritis. Contraindications • pregnancy. Equipment • speculum • cotton swab • iodine • forceps • tenaculum or vulsellum • uterine sound • long needle and syringe • lidocaine, long needle, syringe • cervical dilators • biopsy curette and syringe • formalin • microscope slides • culture media. Procedure A female chaperone or assistant should be present throughout. 1. Pain from endometrial biopsies can be reduced by having the patient take paracetamol or ibuprofen 1–2 hours prior to the procedure. 2. Carry out the procedure during the patient’s premenstrual phase. 3. After positioning the patient, perform a bimanual exam to determine the size of the uterus and direction of the cervix. 4. Perform a speculum examination (see Section 7.2.8 above). 5. Cleanse the cervical os with iodine. 6. Grasp the cervix with a toothed tenaculum and pass a uterine sound to determine the size of the uterus. If the sound cannot be passed, or the patient experiences signiﬁcant pain, perform a cervical block for anaesthesia using lidocaine. 7. Ensure that the patient has been adequately anaesthetized. If the sound still cannot be passed, attempt to dilate the cervix using narrow metal dilators, and then proceed with sounding the uterus.

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8. Insert an endometrial biopsy curette and obtain at least 4 pieces of the endometrium for histopathological examination. 9. Examine for the secretory changes that identify the cycle as ovulatory.

Investigations • Send the tissue biopsies in formalin and ask for Gram stain or AFB smear, or both, and culture depending on clinical suspicion. Complications • Uterine perforation – suspect in patients with signs of intraperitoneal haemorrhage (abdominal distension, hypotension) or signiﬁcant vaginal bleeding not due to cervical laceration. Perform quick check, manage, and refer for emergency surgery. • Abdominal cramping. • Vasovagal reﬂex (dizziness, fainting). • Bleeding. • Post-procedure infection.

7.2.14 Gram stain Equipment • microscope slide • Bunsen burner or ﬂame • rystal violet • iodine • decolouriser: acetone or ethanol • safranin. Procedure 1. Swab sample onto a slide. 2. Heat ﬁx, this may be done by passing the slide through a ﬂame. 3. Stain with crystal violet (60 seconds) and rinse. 4. Stain with iodine (60 seconds) and rinse. 5. Decolourise with acetone or ethanol for a few seconds (until the liquid runs clear). 6. Stain with safranin (60 seconds) and rinse. 7. Gently blot dry and examine under oil immersion (1000X). Gram-positive organisms will appear purple, Gram-negative organisms will appear red.

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7.2.15 Wet mount Equipment • cotton swab • microscope slide and cover slip • 10% potassium hydroxide (KOH). Procedure 1. Collect specimen: Take a sample of discharge with a swab from the side walls or deep in the vagina where discharge accumulates. 2. Prepare slide: Smear swab across slide and mix with 1 or 2 drops of saline on a glass slide and cover with a cover slip. 3. What to look for: Examine at 100X magniﬁcation and look for typical jerky movement of motile trichomonads. Examine at 400X magniﬁcation to look for yeast cells and trichomonads. 4. To make identiﬁcation of yeast cells easier in wet mount slides, mix the vaginal swab in another drop of saline and add a drop of 10% KOH to dissolve other cells. See Section 10.15.4 for interpretation.

7.2.16 Urinalysis Equipment • sterile container • urinalysis dipstick • test tubes • microscope slide. Procedure 1. For men, a midstream sample of urine collected in a sterile container will sufﬁce. Women should be asked to clean the external genitalia prior to collection. Voided urine should be examined within 1 hour from the time of collection. 2. If a centrifuge is not available, unspun urine may be tested with a urinalysis dipstick. Dipstick testing allows for the determination of urine pH and speciﬁc gravity, with the presence or absence of protein, glucose, WBC, RBC, leukocyte esterase, and nitrite. 3. Centrifuging allows for the examination of urine sediment, enabling better quantiﬁcation of RBCs, WBCs, and bacteria, and the detection of epithelial cells, crystals, and casts. Centrifuge a urine sample at 3000 rpm for at least 3 minutes. After pouring off the supernatant (clear portion on top of the pellet), the sediment should be resuspended with a gentle shake. Place a small amount of this ﬂuid on a microscope slide for examination.

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7.2.17 Taking stool samples, including Cary-Blair for cholera Equipment • cotton swab • sterile plastic bag • Cary-Blair media • ﬁlter paper • saline. Procedure Take stool samples before giving antibiotics to the patient. There are several ways to take samples. • A fresh stool can be taken (cotton-tipped rectal swab soaked in liquid stool, placed in a sterile plastic bag) and transported quickly (within 30 minutes since amoebic trophozoites die and become unrecognizable after that) to the laboratory. • A transport medium such as Cary-Blair or peptone water allows better conservation of samples. See below. • Use strips of blotting paper or ﬁlter paper soaked with liquid stool. Place in a sealed tube or plastic bag, with 2 or 3 drops of normal saline (NaCl 9%) so that the specimen does not dry out. Refrigeration during transport is not necessary. Tubes of Cary-Blair transport medium can be stored at ambient temperature for 1 to 2 years. The medium can be used as long as it does not appear dried out, contaminated, or discoloured. Instructions for the use of Cary-Blair medium • • • • • • Moisten the swab in sterile Cary-Blair transport medium. Insert the swab 2 to 3 cm into the rectum and rotate. Withdraw the swab and examine it to make sure that it carries some visible faecal material. Immediately place the swab in the transport medium, pushing it right to the bottom of the tube. Break off and discard the top of the stick touching the ﬁngers. Dispatch the sample to reach the laboratory within 7 days (it is not necessary to refrigerate the sample).

Stool direct smear3 • With a wax pencil or other marker, write the patient’s name or identiﬁcation number and the date at the left-hand side of the slide. • Place a drop of saline in the centre of the left half of the slide and place a drop of iodine in the centre of the right half of the slide. N.B.: Iodine wet mount preparations are most useful for protozoan organisms, less so for helminths. • With an applicator stick or match, pick up a small portion of faeces (approximately 2 mg which is about the size of a match head) and add it to the drop of saline. Repeat and add it to the drop of iodine. Mix the faeces with the drops to form suspensions. • Cover each drop with a coverslip by holding the coverslip at an angle, touching the edge of the drop, and gently lowering the coverslip onto the slide so that air bubbles are not produced. Note: Ideal preparations containing 3 Bench aids for the diagnosis of intestinal parasites. WHO, 2004. Available at http://www.who.int/wormcontrol/ documents/benchaids/training_manual/en/

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2 mg of faeces are uniform – not so thick that faecal debris can obscure organisms, nor so thin that blank spaces are present. • Examine the preparations with the 10X objective or, if needed for identiﬁcation, higher power objectives of the microscope in a systematic manner (either up and down or laterally) so that the entire coverslip area is observed. When organisms or suspicious objects are seen, one may switch to higher magniﬁcation to see the more detailed morphology of the object in question.

Chemical test for occult blood in stools4 This test is used for screening for parasitic infection, e.g. intestinal schistosomiasis, or for detection of bleeding in the intestine caused by polyps, tumours, or inﬂammation. Note: For 1 day before the examination, the patient should not: • eat any meat • take any drugs containing iron compounds • brush teeth vigorously. Materials and reagents • centrifuge • conical centrifuge tube • applicators • measuring cylinder, 20 ml • test-tubes • test-tube rack • positive control tube (containing a 1% solution of blood in water) • negative control tube (containing distilled water) • acetic acid, 10% solution (reagent No. 2) • hydrogen peroxide (fresh 10% solution) • 95% ethanol • aminopyrine, crystalline. Note: The glassware used for the test must be clean, with no traces of blood. Method 1. Immediately before carrying out the test, prepare a solution of aminopyrine: • put about 0.25 g of aminopyrine in the bottom of a test-tube • add 5 ml of 95% ethanol. 2. Put a portion of stool (approximately 4 ml) in a centrifuge tube. Add 7 ml of distilled water and mix thoroughly. 3. Centrifuge at low speed (1000 g) for about 5 minutes, or until the solids are precipitated (a hand-operated centrifuge can be used). 4. Decant the supernatant ﬂuid into another test-tube and keep it. 4 Manual of basic techniques for a health laboratory, 2nd edition. WHO, 2003. Available at http://whqlibdoc.who. int/publications/2003/9241545305.pdf

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5. Add to the test-tube containing the supernatant ﬂuid, without mixing: • 10 drops of 10% acetic acid solution • 5 ml of the aminopyrine solution. To prevent mixing, hold the tip of the pipette containing the aminopyrine solution against the inside wall of the test-tube and allow the liquid to run down the wall. 6. Add 10 drops of the 10% hydrogen peroxide solution. Do not mix. Let it stand for 1 minute. The results must be read within 5 minutes of adding the hydrogen peroxide solution. Results If the reaction is positive, a red colour appears between the two layers of liquid. Report the results as follows: • pale red = positive reaction (+) • red = strong positive reaction (++) • dark red = very strong positive reaction (+++) • no change in colour = negative reaction (-)

7.2.18 Crude clotting time Indications • diagnose haemophilia • monitor anticoagulant therapy • detect coagulation disorders (as in certain types of snake-bite and see Section 10.19). Equipment • cotton swab • needle and syringe • test tube without anticoagulant • watch or clock. Procedure 1. Collect 4 ml of blood in a clean glass tube without any anticoagulant. 2. The blood tube is tilted every 15 seconds while keeping time. 3. The ﬁrst appearance of a clot is noted and timed. 4. The normal coagulation time in glass tubes is 5–15 minutes.

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7.2.19 Thin and thick blood ﬁlms for malaria5 Indications • diagnosis of malaria (see Section 11.25). Equipment • 2 microscope slides • methanol • Giemsa solution. Procedure 1. Place a small amount of blood near the middle of the slide for the thin ﬁlm. Place two or three smaller drops off to the side for the thick ﬁlm. Place the slide on a ﬂat surface. 2. Hold another slide over the ﬁrst at a 45 degree angle so that it just touches it. Slowly drag the upper (spreader) slide towards the drop of blood.

3. On contact with the spreader slide, the blood should spread along the width of the slide.

4. The spreader should then be drawn smoothly and rapidly in the opposite direction, producing a feathered edge. 5. Join the drops of blood intended for the thick ﬁlm using a corner of the spreader slide. This should not require excessive stirring, only 3 to 6 circular or rectangular movements.

6. Allow the slide to air dry and label with a soft lead pencil. 7. Fix the thin ﬁlm by adding a few drops of methanol and allow to dry. Try to avoid exposing the thick ﬁlm to methanol. 8. Flood the slide with Giemsa solution and allow 30–45 minutes out of sunlight. 9. Rinse with water, drain, and air dry.

5 Bench aids for the diagnosis of malaria infection. WHO, 2002.Available at http://whqlibdoc.who.int/ publications/2000/9241545240.pdf

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10. On the thick ﬁlm, leukocyte nuclei should appear a deep, rich purple. Malaria parasites should have deep red chromatin and pale purplish blue cytoplasm. Non-lysed erythrocytes may appear at the periphery; in P. vivax and P. ovale infections Schuffner’s stippling may be present.

7.2.20 AFB (Ziehl Neelsen)6 Indications • diagnosis of TB. Equipment • microscope slide • Bunsen burner or spirit lamp • 3 mm wire loop • forceps • Ziehl Neelsen carbol fuchsin • decolouriser: 3% HCL-ethanol or 20–25% H2SO4 • methylene blue 0.1%. Procedure 1. Label slide carefully. 2. Using loop, take sputum sample from most dense portion of specimen (sample blood-specked, opaque, greyish, or yellowish cheesy mucus when present). 3. Smear the sample onto a slide over an area 2.0 X 1.0 cm; the broken end of a wooden stick may be used. 4. Air dry for 15 minutes. 5. Heat ﬁx the sample by passing the slide smear side up through a Bunsen burner 3 times. The proper thickness of a heat ﬁxed smear has been achieved when newsprint is just readable through it. 6. Flood the slide with carbol fuchsin. 7. Heat the slide until steam rises from the slide and wait 10 minutes. 8. Rinse with water and drain. 9. Flood the slide with decolouriser and wait 3 minutes. 10. Rinse with water and drain. 11. Flood the slide with methylene blue and wait 1 minute. 12. Rinse with water and drain. 13. Air dry. 14. Heat ﬁx smear. 15. Acid-fast bacilli will appear as red, slender, rod-shaped bacilli against a blue background.

6 AFB smear staining. WHO/Union, 2004. Available at http://www.theunion.org/index.php/en/resources/scientiﬁcpublications/item/185-afb-smear-staining.

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7.2.21 Ultrasound This Section provides a brief introduction to clinician-performed, bedside trauma and obstetrical ultrasound for the trained district clinician. It is a simpliﬁed, stepby-step description of how and when to perform these ultrasound examinations. For more details, please consult an ultrasound-dedicated text.7,8 Additional ﬁgures (1a to 8) referred to below may be found at the end of this Section. Equipment • ultrasound machine (with curved or phased array probe, and transvaginal probe) • ultrasound gel (do not use alcohol; shampoo or water are acceptable gel substitutes) • non-alcohol-based cleaning solution or wipes for probes • condom or probe cover for transvaginal probe.

Trauma ultrasound Trauma ultrasound can be performed quickly at the patient’s bedside, and provides time-sensitive information to determine the presence of intra-abdominal or intrathoracic haemorrhage. While ultrasound provides useful information regarding the presence or absence of bleeding, it cannot usually diagnose speciﬁc organ injury or the source of bleeding. The ultrasound exam should be performed soon after the patient arrives. Indications • torso trauma with suspected haemoperitoneum, haemothorax, or haemopericardium • torso trauma with hypotension, tachycardia, or shock. Procedure 1. Place the patient in the supine position, using cervical spine stabilization if necessary. 2. Place the ultrasound probe on the patient’s body in 4 regions to assess for free ﬂuid, which will appear black on the ultrasound screen. The ﬂuid will accumulate between the solid organs, which appear grey on the ultrasound screen. This ﬁgure shows the 4 regions for trauma ultrasound. a. Pericardial (subxiphoid). Place the probe in the subxiphoid region of the abdomen, with the probe marker facing the patient’s right side. Aim the probe into the left chest, and assess for free ﬂuid between the muscular myocardium (grey in colour on the ultrasound screen) and the pericardium (bright white in colour on the screen) (see ﬁgures 1a–1b).

RUQ Pericardial Pelvic

LUQ

7 Manual of diagnostic ultrasound. Volume 1, Second Edition. WHO, 2011. Available at http://whqlibdoc.who.int/ publications/2011/9789241547451_eng.pdf 8 Manual of ultrasound for low-resource settings. Partners in Health, 2011. Available at http://parthealth.3cdn. net/6e013074d8f4c4c7d8_mlblfxb8q.pdf

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b. Right upper quadrant (RUQ). Place the probe in the right mid axillary line, along ribs 10–12, with the probe marker facing the head. Assess for free ﬂuid between the liver and kidney (haemoperitoneum) or superior to the diaphragm, which appears as a thin bright white line on the screen (haemothorax) (see ﬁgures 2a–2b). c. Left upper quadrant (LUQ). Place the probe in the left posterior axillary line, along ribs 9–11, with the probe marker facing the head. The liver is larger than the spleen, so the splenorenal interface is usually more superior than the RUQ view. Assess for free ﬂuid between the spleen and diaphragm, spleen and kidney, and superior to the diaphragm (see ﬁgures 3a–3b). d. Pelvic. Place the probe in the suprapubic region, with the probe marker facing towards the patient’s right side. This view needs to be performed with a full bladder, or free ﬂuid can be easily missed. Assess for ﬂuid between the urinary bladder (also ﬁlled with black ﬂuid) and the uterus (in a female) or the rectum (in a male) (see ﬁgures 4a–4b). Potential pitfalls • Failure to ﬁnd ﬂuid using ultrasound in the case of haemoperitoneum, haemothorax, or haemopericardium. Repeat the ultrasound exam if needed. If the patient’s hypotension worsens, consider aspiration. • Since both simple ﬂuid and blood appear black on the ultrasound screen, pre-existing ascites and uroperitoneum from a ruptured bladder can cause free ﬂuid in the abdomen, which will appear similar to haemoperitoneum. If unsure of the cause of the free ﬂuid, an aspiration can help distinguish the cause.

Basic 1st trimester obstetric ultrasound Obstetric ultrasound has many uses including assessment for ectopic pregnancy, estimation of gestational age, assessment of placental abnormalities (including previa, fetal demise conﬁrmation, oligo and polyhydramnios), and conﬁrmation of fetal lie. This section focuses on assessment for intra-uterine pregnancy in cases of suspected ectopic pregnancy. Indications • Vaginal bleeding or abdominal pain with a positive pregnancy test or suspected pregnancy. • First trimester pregnancy with hypotension, tachycardia, syncope or shock. • Suspected ectopic pregnancy with or without risk factors (prior ectopic, prior pelvic infection, prior tubal ligation, pregnancy despite IUD). Procedure 1. Place the patient in the supine position, with the bladder full for transabdominal ultrasound or empty for transvaginal ultrasound. 2. Begin with transabdominal ultrasound with the probe position in the suprapubic area, and with the probe marker towards the patient’s right side. 3. View the urinary bladder and, deep to the bladder, the uterus. Scan through the uterus from superior to inferior, and then turn the probe marker toward the head and scan in a sagittal plane, moving the probe to the right and left. This ensures that you will see the entire uterus.

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4. If no pregnancy is seen inside the uterus, assess for free ﬂuid outside the uterus, which could be a sign of ectopic pregnancy. The process is similar to the trauma ultrasound pelvic view. 5. If a pregnancy is seen inside the uterus, it is important to see not only a gestational sac (a sac of ﬂuid that appears black on the screen), but also a yolk sac (a bright white ring that is within the gestational sac) or fetal pole (a small embryo that appears grey on the ultrasound screen). The yolk sac or fetal pole will be seen as early as 1 week after a missed period. If a gestational sac is seen without a yolk sac or fetal pole, an ectopic pregnancy could still exist (see Figure 5). If an intrauterine pregnancy is observed, this essentially rules out ectopic pregnancy. It is rare to have both intrauterine and ectopic pregnancies. 6. If unable to view a pregnancy using transabdominal views, ask the patient to empty her bladder and prepare the transvaginal probe with a cover or condom. Use gel both inside and outside the probe cover and avoid air pockets within the cover. The probe must be disinfected between each use. Note that transvaginal ultrasound allows for earlier and more reliable detection of intrauterine or ectopic pregnancy (except in the case of abdominal pregnancy). 7. Insert the probe 4–5 centimetres into the patient’s vagina and view the uterus in both sagittal (probe marker towards the sky) and coronal (probe marker towards the patient’s right side) views. Scan the entire uterus and assess for intrauterine pregnancy and presence of free ﬂuid as described above. 8. If the uterus is empty or contains only a gestational sac, attempt to view free ﬂuid elsewhere in the abdomen (as described in the Trauma ultrasound section above). An empty uterus or uterus with only ﬂuid inside (no embryo or yolk sac) with haemoperitoneum on ultrasound should raise suspicion for a ruptured ectopic pregnancy (Figure 8). Potential pitfalls • Both simple ﬂuid and blood appear black on the ultrasound screen. If there is concern whether ﬂuid in the abdomen or pericardium may be blood or ascites, and the patient is haemodynamically unstable, a diagnostic peritoneal aspiration or culdocentesis should be performed. See Section 7.4.3. • Failure to suspect ectopic pregnancy in patients with vaginal bleeding, abdominal pain, or hypotension during pregnancy. • Misdiagnosis of ﬂuid inside the uterus as a true intra-uterine pregnancy and missed diagnosis of ectopic pregnancy. • Failure to diagnose free ﬂuid in the abdomen and pelvis as a potential sign of a ruptured ectopic pregnancy in the patient with no visible intrauterine pregnancy. Comments • Ultrasound is considered safe in pregnancy, and there is no risk of ionizing radiation.

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7.3 Therapeutic procedures 7.3.1 Chest tube (intercostal chest drain) Indications • Pneumothorax: ° Tension pneumothoraces require immediate needle decompression followed by chest tube. See Quick Check page 22 for details. ° Small pneumothoraces (rim of air less than 3 cm between lung and chest wall) may resolve spontaneously or require only simple aspiration. ° Any intubated patient with a pneumothorax will require a chest tube. • Haemothorax • Haemopneumothorax • Acute empyaema. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine with epinephrine (5–10 ml syringe, 23- to 25-gauge needle) • scalpel • curved forceps and clamp • chest tube and underwater seal drainage system (or one-way valve device and drainage bag) • suture material (0 or 1–0 sutures required to anchor tube) ° needle driver, large curved artery forceps • dressing material. Procedure 1. Patients may require sedation and large amounts of analgesia for this procedure, as it can be quite painful. Consider ketamine. 2. Position the patient lying face up with arm of the involved side raised over the head. If the patient is unable to lie down due to respiratory distress, he or she may sit up in a bed or chair. Supplemental oxygen may be helpful.

3. Choose the site, usually the 5th or 6th intercostal space at the midaxillary line. In order to avoid damage to vital organs, stay within the “triangle of safety” deﬁned inferiorly by the nipple line in men or the base of the breast in women, anteriorly by the border of the pectoralis major muscle, and posteriorly by the latissumus dorsi muscle. The apex of the triangle should be just below the axilla. 4. Caution should be exercised throughout the procedure as broken ribs can easily pierce gloves. Double-gloving can help prevent this. 5. Prepare the skin with antiseptic.

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6. Using lidocaine, inﬁltrate the skin and muscle. Note the length of needle needed to enter the pleural cavity (this may be useful later when inserting the drain).

7. Aspirate ﬂuid from the chest cavity to conﬁrm position of the needle. 8. Make a 3–4 cm horizontal incision just above the rib to avoid damaging the vessels under the lower part of the rib.

9. Use more lidocaine to anaesthetize the intercostal tissues and pleura at the site of insertion. 10. Use blunt dissection to penetrate the intercostal tissue to the pleura. Insert the closed clamp over the top of the rib and, once past the rib, open and spread to dissect, slowly enlarging the opening while proceeding inward. This will create a tunnel through which the tube may be inserted.

11. Insert a ﬁnger into the tunnel to conﬁrm that it has penetrated through to the pleural space. A ﬁnger should be swept around to ensure the liver or spleen is not nearby.

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12. Use the same forceps to grasp the tube at its tip and introduce it into the chest. Never use a sharp instrument to introduce the tube. For pneumothorax, angle the tube up; for pleural effusion, angle down and towards the back. Be sure to insert the tub far enough that all drainage holes are inside the pleural space.

13. Close the incision with interrupted skin sutures. Use 1 stitch to anchor the tube by leaving the ends of that suture very long and wrapping and tying the ends ﬁrmly around the tube several times. Leave an additional suture untied adjacent to the tube for closing the wound after the tube is removed. Apply a gauze dressing. Further secure the tube with adhesive tape. 14. Connect the tube to the underwater seal drainage system and mark the initial level of ﬂuid in the drainage bottle. Alternatively, a one-way valve device and drainage bag may be used.

Aftercare and tube removal • Routine administration of antibiotics to prevent infection is not necessary; however, there may be some beneﬁt if there are penetrating chest injuries. • Place a pair of large artery forceps by the bedside for clamping the tube when changing the bottle. The drainage system is patent if the ﬂuid level swings freely with changes in the intrapleural pressure. Persistent bubbling over several days suggests a bronchopleural ﬁstula and is an indication for referral. • Change the connecting tube and the bottle at least once every 48 hours, replacing them with sterile equivalents. • If there is no drainage for 12 hours, despite milking the tube, clamp the tube for a further 6 hours and X-ray the chest. If the lung is satisfactorily expanded, the clamped tube may be removed. • To remove the tube, ﬁrst carefully remove the dressing. Paracetamol given beforehand will reduce discomfort during the procedure. Clean the skin with antiseptic. Hold the edges of the wound together with ﬁngers and thumb over the gauze while cutting the skin stitch that is anchoring the tube. Ask the patient to inhale and valsalva, and withdraw the tube rapidly as an assistant ties the previously loose stitch.

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Complications • Re-expansion pulmonary oedema – while the evidence is not clear, it may be prevented by removing less than 1.5 litres of ﬂuid at a time. • Chest tube malposition may be subcutaneous, intraparenchymal, or elsewhere. If the patient is stable, reposition chest tube. If the patient becomes unstable, see Section 2 Quick Check for management. • Recurrent pneumothorax may be due to chest tube malposition; consider repositioning or replacing. If tension pneumothorax develops, see Section 2 Quick Check for management. • Empyaema – if the patient appears severely ill, see Section 2 Quick Check and Section 3.2 for management.

7.3.2 Urinary catheter insertion – female Indications • acute urinary retention • monitoring urinary output. Contraindications • possible fracture of the pubic symphisis (demonstrated by blood at the urethral opening after trauma). Equipment • sterile gloves and sterile towels or drapes • antiseptic • 2% lidocaine jelly or mineral oil • urinary catheter • 10 ml syringe ﬁlled with water or saline • tape and suture material • container for drainage. Procedure A female chaperone or assistant should be present throughout. 1. Position the patient lying face up with knees bent and apart. 2. Put on sterile gloves and, with sterile swabs, apply antiseptic to the labia and urethra. Isolate the area with a perforated sterile towel. 3. Check the integrity of the urinary catheter balloon, and then lubricate the catheter with a generous amount of sterile liquid parafﬁn (mineral oil) or lidocaine jelly. 4. Gently insert the urinary catheter into the urethra, which usually is located just at the top of the vaginal opening, and 2.5 cm below the clitoris. In some women, it can be difﬁcult to see, and must be found by palpation. 5. Insert at least 20 cm of the catheter to ensure that it is in the bladder.

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6. Fixing the catheter. • If a Foley catheter is being used, inﬂate the balloon with 10–15 ml of sterile water or clean urine. Partially withdraw the catheter until its balloon abuts the bladder neck. • If the catheter has no balloon, knot a ligature around the catheter just beyond the urethral opening and carry the ends to one side, securing them with tape to the lower abdomen or thigh. 7. Secure the catheter to the patient’s thigh using tape. 8. Connect the catheter through a closed system to a sterile container. 9. Take care to decompress a chronically distended bladder slowly as rapid release of more than one litre of urine can cause fainting. Aftercare • If the catheterization was traumatic, administer an antibiotic with a Gramnegative spectrum for 3 days. • Change the catheter if it becomes blocked or infected, or as otherwise indicated. • Ensure a generous ﬂuid intake to prevent calculus formation in recumbent patients, who frequently have urinary infections, especially in tropical countries. Complications • Urinary tract infection or sepsis – if the patient appears to be in shock, with fast heart rate and low blood pressure, see pages 19–20 Quick Check for immediate management. • Bladder rupture is a rare complication of chronic indwelling urinary catheters – if the patient is in severe pain or shock or the rupture is determined to be intraperitoneal, see pages 23–24 Quick Check for immediate management and arrange for emergency surgery. • Vaginal placement. • Urethral trauma.

7.3.3 Marsupialization for Bartholin’s cyst or abscess Indications • Asymptomatic Bartholin’s cysts in women under 40 can be left alone. Pain or interference with sexual activity are indications for drainage. • Asymptomatic Bartholin’s cysts in women over 40 should be drained and biopsied due to the risk of carcinoma. • Any Bartholin’s abscess (cyst with clear evidence of infection) should be treated with incision, drainage, and marsupialization to prevent recurrence. Equipment • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • small forceps • scalpel blade and handle • suture material, needle driver, forceps • 5 ml syringe

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• • • •

microscope slides culture media formalin dressing material.

Procedure A female chaperone or assistant should be present throughout. 1. Perform an external genital exam. Clean the area around the cyst or abscess with antiseptic. 2. Anaesthetize the area with lidocaine. 3. Hold the cyst with forceps and make a 1–3 cm vertical incision in the most prominent part, usually immediately outside the hymenal ring. 4. Once the pus or contents of the cyst cavity have been drained, evert the wound edges and suture them to the adjacent mucosal tissue, using absorbable suture. This opening will shrink over time and form a new oriﬁce for the gland, allowing it to drain freely. 5. Dress the area so that any drainage will collect. Investigations • If abscess, send for Gram stain and culture. • In women older than 40 with cyst or abscess, send a tissue sample in formalin to rule out carcinoma.

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7.3.4 Intrauterine device (IUD) placement (copper-bearing IUD) Indications • IUDs are safe and suitable for nearly all women, including women who: ° have or have not had children ° are not married ° are of any age, including adolescents and women over 40 ° have just had an abortion or miscarriage (provided there is no evidence of infection) ° are breastfeeding ° do hard physical work ° have had an ectopic pregnancy ° have had PID ° have certain vaginal infections ° have anaemia ° are infected with HIV, or on antiretroviral therapy and doing well. Contraindications • recent, untreated puerperal sepsis or septic abortion • unusual vaginal bleeding (should be evaluated prior to insertion) • current cervical or endometrial cancer; gestational trophoblast disease • untreated pelvic tuberculosis • symptomatic cervicitis • current pregnancy • clinical judgement should be used in special cases: ° between 48 hours and 4 weeks since giving birth; ° noncancerous (benign) gestational trophoblast disease; ° current ovarian cancer; ° is at very high individual risk for gonorrhoea or Chlamydia; ° has AIDS and is not clinically well on antiretroviral therapy (HIV alone is not a contraindication). Equipment • sterile gloves • speculum • cotton swab • antiseptic • tenaculum • uterine sound • IUD • scissors. Procedure A female chaperone or assistant should be present throughout. 1. Explain the insertion procedure to the patient; show her the instruments to be used and the IUD. Tell her that she will experience some discomfort or cramping during the procedure, and that this is to be expected. 2. Ibuprofen (200–400 mg), paracetamol (325–1000 mg), or other pain relief may be given 30 minutes before insertion to help reduce cramping and pain. Do not give aspirin, which slows blood clotting.

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3. Perform a pelvic examination to assess eligibility, ﬁrst by doing a bimanual examination and then a speculum examination to inspect the cervix. Consider the following questions. • Is there any type of ulcer or discoloration on the vulva, vagina, or cervix (suggesting a STI)? • Does the client feel pain in her lower abdomen when the cervix is moved (suggesting PID)? • Is there tenderness in the uterus, ovaries, or fallopian tubes (adnexal tenderness) (suggesting PID)? • Is there a purulent cervical discharge (suggesting a STI or PID)? • Does the cervix bleed easily when touched (suggesting a STI or cervical cancer)? • Is there an anatomical abnormality of the uterine cavity that will prevent correct IUD insertion (distorts uterine anatomy and prevents proper placement)? • Was the size or position of the uterus not determined (essential to ensuring proper placement)? If the answer to any of the above questions is “yes”, refer the patient for diagnosis and treatment as appropriate, and counsel regarding other methods of contraception. 4. If the patient is eligible, clean the cervix and vagina with appropriate antiseptic. 5. Slowly insert the tenaculum through the speculum and close the tenaculum just enough to gently hold the cervix and uterus steady. 6. Pass the uterine sound through the cervix to measure the depth and position of the uterus. Do not use force when inserting the sound; this increases the risk of uterine perforation. Do not allow the sound to touch any non-sterile surfaces, including the speculum and vaginal walls. 7. Load the IUD into the inserter while both are still in the unopened sterile package. Loading requires the horizontal arms of the IUD to be placed into the tube. The plastic rod should be inserted into the other end of the tube. This will be used to push the IUD free of the inserter once inside the uterus. 8. Insert the IUD and then remove the inserter. Do not allow the IUD or inserter to touch any nonsterile surfaces, including the speculum and vaginal walls. 9. Cut the strings on the IUD, leaving about 3 centimetres hanging out of the cervix. 10. After insertion, allow the patient to rest. She should remain on the examination table until she feels ready to get dressed. 11. Remind the patient about common side-effects, including changes in her bleeding patterns (especially in the ﬁrst few months after insertion). 12. Tell her she should return immediately if: • she is unable to feel the strings

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• the IUD has partially come out • she feels the symptoms of PID • she thinks she might be pregnant. Complications • Uterine perforation – in patients with signs of intraperitoneal haemorrhage (abdominal distension, hypotension) or signiﬁcant vaginal bleeding not due to cervical laceration, see Quick Check page 20 for management and refer for emergency surgery • Ectopic pregnancy – should be suspected in women who present with unusual abdominal pain or tenderness, abnormal vaginal bleeding, or giddiness or fainting. If the patient is in shock, see Quick Check pages 19–20 for immediate management, and refer for diagnosis and care as appropriate. • Intrauterine pregnancy – when coexistent with an IUD, increases the risk of preterm delivery and miscarriage (and septic miscarriage). If the woman does not wish to continue the pregnancy, provide appropriate counselling. If she decides to continue, the IUD should be carefully removed. If she wishes to keep the IUD, her pregnancy should be followed closely. • PID can occur if the woman has Chlamydia or gonorrhoea when an IUD is placed. See Section 10.15 for management. • Changes in bleeding patterns (may result in or contribute to anaemia).

7.3.5 Reduction of paraphimosis Paraphimosis occurs most commonly in children. Diagnose it by recognizing a retracted, swollen and painful foreskin. The glans penis is visible, and is surrounded by an oedematous ring with a proximal constricting ring. Differential diagnoses: • inﬂammation of the foreskin (balanitis) due, for example, to infection • swelling caused by an insect bite • In these cases, the glans is not visible. Equipment • sterile gloves and sterile towels • antiseptic • lidocaine without epinephrine, 5–10 ml syringe, 23- to 25-gauge needle • scalpel • two artery forceps • straight scissors • suture material, needle driver, forceps. Procedure • Treat paraphimosis by reduction of the foreskin or, if this fails, by dorsal slit. Circumcision, performed as a non-emergent procedure is the deﬁnitive treatment.

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Manual reduction of the foreskin 1. Sedate the patient if necessary – consider ketamine. 2. Cleanse the skin of the genitalia with antiseptic. 3. Isolate the penis with a perforated towel and inject lidocaine in a ring around its base. 4. Once local anaesthesia is achieved, take hold of the oedematous part of the penis in the ﬁst of one hand and squeeze ﬁrmly; a gauze swab may be necessary for a ﬁrm grip. Exert continuous pressure, changing hands if necessary, until the oedema ﬂuid passes proximally under the constricting band to the shaft of the penis. 5. Usually then, the foreskin can be pulled over the glans.

Phimotic ring incision 6. If manual reduction fails, a phimotic ring incision may be performed. 7. Once the penis has been cleaned with antiseptic and draped as above, inﬁltrate proximally to distally through the constricting phimotic ring at the 12 o’clock position. Try to follow a line that is perpendicular to the phimotic ring. 8. Incise slowly along that same line, taking care to not penetrate too deeply in order to avoid lacerating the penile shaft. The result should be a diamond shaped defect created when the edges of the incised ring spring apart. 9. Most lacerations resulting from the procedure require only simple suturing.

Dorsal slit 10. Following the placement of a phimotic ring incision, the foreskin is easily reducible. When incised to the distal tip of the foreskin, the phimotic ring incision becomes a dorsal slit. 11. Ensure that adequate anaesthesia has been achieved by touching the forceps to the inside of the foreskin. 12. Clamp the foreskin with 2 artery forceps on either side of the most distal tip of the existing incision and incise between them using a pair of straight scissors. 13. Some patients may have continued bleeding or oozing, or there may be separation of the incised layers of foreskin after unclamping the forceps. In this case, running absorbable sutures can be placed on each side of the incision. These should begin proximally at the apex and continue distally. The result will be a defect that appears to be an upside down “v” when the foreskin is reduced. Aftercare • It is important to reduce the foreskin post-procedure to prevent phimosis. • Circumcision, if desired, may be performed as a non-emergent procedure once swelling and inﬂammation have diminished.

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7.3.6 Urinary catheter insertion – male Indications • acute urinary retention • monitoring urinary output. Equipment • sterile gloves and sterile towels or drapes • antiseptic • 2% lidocaine jelly or mineral oil • urinary catheter • 10 ml syringe ﬁlled with water or saline • tape and suture material • a container for drainage. Procedure 1. Position the patient lying face up. 2. Wash the area with soap and water, retracting the foreskin to clean the furrow between it and the glans. Put on sterile gloves and, with sterile swabs, apply antiseptic to the urethra and glans. Isolate the penis with a perforated sterile towel. 3. Check the integrity of the urinary catheter balloon and then lubricate the catheter with a generous amount of sterile liquid parafﬁn (mineral oil) or lidocaine jelly. If right-handed, stand to the patient’s right, hold the penis vertically and slightly stretched with the left hand, and introduce the urinary catheter gently with the other hand.

At 12–15 cm, the catheter may stick at the junction of the penile and bulbous urethra, in which case angle it down to allow it to enter the posterior urethra. A few centimetres further, there may be resistance caused by the external bladder sphincter. This may be overcome by asking the patient to relax the perineal and rectal region while gently advancing the catheter.

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4. Urine escaping through the catheter conﬁrms entry into the bladder. Advance the catheter 5–10 cm before inﬂating the balloon. This prevents the balloon inﬂating in the prostatic urethra.

5. Remember to pull the foreskin back over the glans once the catheter has been placed. If left retracted (glans exposed), the foreskin can contract, causing a paraphimosis.

6. Fixation of the catheter: • If a Foley catheter is being used, inﬂate the balloon with 10–15 ml of sterile water or clean urine. Partially withdraw the catheter until its balloon abuts on the bladder neck. • If the catheter has no balloon, knot a ligature around the catheter just beyond the urethral opening and carry the ends along the body of the penis, securing them with a spiral of strapping brought forward over the glans and the knot.

7. Strap the penis and catheter laterally to the abdominal wall; this will avoid a bend in the catheter at the penoscrotal angle and help to prevent compression ulceration.

8. Connect the catheter through a closed system to a sterile container. 9. Take care to decompress a chronically distended bladder slowly; rapid release of more than 1 litre of urine can cause fainting.

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Aftercare • If catheterization was traumatic, administer an antibiotic with a Gram-negative spectrum for 3 days. • Change the catheter if it becomes blocked or infected, or as otherwise indicated. Ensure a generous ﬂuid intake to prevent calculus formation in recumbent patients, who frequently have urinary infections, especially in tropical countries. Complications • Urinary tract infection, sepsis. If the patient appears to be in shock, with fast heart rate and low blood pressure, see Quick Check page 20 for immediate management. • Bladder rupture is a rare complication of chronic indwelling urinary catheters. If the patient is in severe pain or shock, or the rupture is determined to be intraperitoneal, see Quick Check pages 19–20 for immediate management and arrange for emergency surgery. • Urethral or prostate trauma.

7.3.7 Suprapubic catheter Indications • Bladder puncture may become necessary if urethral catheterization fails. Contraindications • Caution should be taken in patients with previous abdominal surgeries; they may have developed adhesions that put them at greater risk for bowel injury during placement. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • 16-gauge needle, 50 ml syringe • trochar and cannula • 10 ml syringe ﬁlled with water or saline • tape and suture material • a container for drainage • dressing material. Procedure 1. Assess the extent of bladder distension by inspection and palpation. If available, ultrasound will help to conﬁrm the insertion site. 2. If proceeding to suprapubic puncture immediately after catheterization has failed, remove the perforated sheet that was used to isolate the penis and centre the opening of a new sheet over the midline above the pubis. Do not use the same gloves as for the failed urinary catheterization.

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3. Clean the area with antiseptic. 4. Raise a weal of local anaesthetic in the midline, 2 cm above the symphysis pubis, and then continue with deeper inﬁltration. Make a simple puncture 2 cm above the symphysis pubis in the midline with a 16-gauge needle attached to a 50 ml syringe. This should be done by slowly advancing the needle while aspirating. Urine should be easily aspirated when the needle reaches the bladder. If there is difﬁculty placing the catheter as described below, urine may be aspirated using this syringe to relieve discomfort. 5. Introduce the trochar and cannula and advance them vertically with care. After meeting some resistance, they will pass easily into the cavity of the bladder, as conﬁrmed by the ﬂow of urine when the trochar is withdrawn from the cannula. 6. Introduce the catheter well into the bladder. Once urine ﬂows freely from the catheter, withdraw the cannula. Inﬂate the catheter balloon. 7. Fix the catheter to the skin with the stitch used to close the wound and connect it to a bag or bottle. Take care that the catheter does not become blocked, especially if the bladder is grossly distended. If necessary, clear the catheter by syringing with saline. Complications • Bowel perforation. If the patient develops severe abdominal pain and tenderness, the bowel wall may have been perforated. See Quick Check page 23 for immediate management and arrange for emergency surgery. • Leakage of urine into the abdomen.

7.3.8 Inserting a nasogastric (NG) tube Indications • upper GI bleed • small bowel obstruction • evaluation of gastrointestinal injury • preoperative gastric decompression. Contraindications • facial fractures (use orogastric tube instead) • severe coagulopathy • oesophageal stricture • recent alkali ingestion (may cause oesophageal perforation). Equipment • NG tube • lubricant • a cup of water • a 50–100 ml syringe. 322 Therapeutic procedures Vol. 1 • 7. Procedures: July 2011

Procedure 1. Elevate the head of the bed, or ask the patient to assume an upright, sitting position. 2. In order to determine the appropriate length of tubing to be inserted, measure from the xyphoid (bottom of the sternum or breastbone) to the ear and then to the nose. Add 15 cm to this distance to obtain the insertion distance. The NG tube itself may be used to measure, marking the approximate point on the tube with tape. 3. Lubricate the tube with a liberal quantity of waterbased lubricant prior to insertion. 4. The tube should then be inserted gently in the posterior (not superior) direction. Proceed gently to avoid trauma to the tissue behind the nose. If there is resistance, attempt to use the other nostril. 5. If the patient is having difﬁculty, instruct them to sip some water while simultaneously trying to pass the tube. 6. The patient can help direct the tube into the oesophagus by putting their chin to their chest. Tracheal insertion should be suspected if there is excessive coughing or condensation inside the tube. 7. Make sure to conﬁrm placement of the tube before using it, especially in patients with an altered level of consciousness. Successful placement in the stomach can be conﬁrmed by rapidly pushing air into the tube with a large syringe; there should be gurgling sounds which can be heard through a stethoscope placed on the stomach. A chest X-ray may be done to conﬁrm placement. 8. The tube should be secured carefully to the nose and the patient’s gown (to avoid displacing the tube if there is a sudden tug). A butterﬂy type bandage or tape may be used to secure the tube to the nose. Avoid the tube pressing on the medial or lateral aspects of the inner nostril, as this may result in necrosis or bleeding. Complications • Vomiting and aspiration during placement. If the patient begins to have difﬁculty breathing, see Quick Check page 17 for immediate management. • Pulmonary placement. If the patient develops chest pain and shortness of breath, or has a suggestive chest X-ray, they may have a pneumothorax. See Quick Check page 46 and Section 4.2 for immediate treatment. The patient will likely require a chest tube. • Intracranial placement. If the nasogastric tube is suspected to be in the cranium, call for surgical help. • Gastric erosions and bleeding if the tube is in place long term.

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7.3.9 Gastric lavage Indications • Gastric lavage is VERY RARELY indicated in the management of overdose. It is for patients who have ingested a potentially fatal amount of poison, AND the procedure can be performed within 1 hour of ingestion. See Section 3.8 Poisoning. Absolute contraindications • unconsciousness or depressed sensorium with unprotected airway (possibility of aspiration) • ingestion of corrosive substances because of the danger of perforation • ingestion of hydrocarbons, unless a more toxic substance is combined with the hydrocarbon, such as pesticide (possibility of aspiration) • presence of frank convulsions (possibility of aspiration) • patient at risk of haemorrhage or gastrointestinal perforation • an uncooperative patient (the tube can injure the gastrointestinal tract). Equipment • suction apparatus • orogastric or NG tube • 100 ml syringe • water or saline. Procedure 1. Patients who are comatose or unable to protect the airway must be intubated prior to lavage. If intubation is not possible, lavage should not be attempted. 2. Place the patient on their left side with the head down by 15–30°. This is important to reduce the risk of aspiration. 3. Measure and mark the length of tube needed before insertion. 4. If the patient has ingested a solid poison (e.g. tablets), insert an appropriately sized (French 36–40) and properly lubricated orogastric tube. If the patient vomits, carefully and quickly apply suction to remove the vomitus. Do not use force to pass the tube. 5. If the patient has ingested a liquid poison (e.g. pesticide), insert a properly lubricated nasogastric tube. If the patient vomits, carefully and quickly apply suction to remove the vomitus. Do not use force to pass the tube. 6. Check the proper positioning of the tube in the stomach by air insufﬂation or aspiration with pH testing of aspirate. 7. Instil and lavage with no more than 100–300 ml lukewarm or tepid water or normal saline. Remove the ﬂuid before giving more. Repeat until 1–2 litres have been given and removed. Large volume lavages are unlikely to offer signiﬁcant beneﬁt since the ﬁrst few 100 ml will remove the majority of the poison that remains. Complications • aspiration pneumonia (see Section 3.2 for management) • laryngospasm

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• • • •

cardiac arrhythmias hypoxia and hypercapnia mechanical injury to the throat, oesophagus and stomach ﬂuid and electrolyte imbalance.

7.3.10 Venous cutdown Indications • Used as a means of obtaining venous access in emergencies when no other options are available: ° shock ° pulseless cardiac arrest ° IV drug users with sclerosed veins ° distorted surface anatomy. Contraindications • Should not be performed if less invasive means of obtaining venous access are available. • There is infection over cutdown site. • Relative: ° coagulation disorders ° impaired immunity ° impaired wound healing. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • suture material • scalpel • curved haemostat • scissors • venous dilator • large bore IV catheter • IV tubing • needle driver • forceps • antibiotic ointment • tape • dressing material.

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Procedure 1. The most commonly used vessels for venous cutdown include the greater saphenous, basilic, and cephalic veins. The saphenous vein is easily accessible at its location just anterior to the medial malleolus, and the accompanying nerve is relatively unimportant, making it a good site for cutdown.

2. Clean the area with antiseptic and cover with sterile drapes; be sure to maintain strict aseptic technique. 3. The skin and subcutaneous tissue should be anaesthetized with lidocaine.

4. A tourniquet may be placed proximal to the cutdown site; this will help visualize the vein. 5. Using the scalpel, incise the skin perpendicular to the vein. A longitudinal incision will not allow the required degree of exposure.

6. Carefully isolate and mobilize the vein using blunt dissection.

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7. Using the haemostat, gently lift the vein free from the underlying connective tissue and pass two sutures under it proximal and distal to the site on the vein that will be cannulated.

8. Tie the distal suture. The proximal suture may be left untied, as it will be used to control any bleeding. 9. Incise the vein at a 45° angle between the two sutures. Do not incise more than halfway through as this may cause the vein to tear and retract from the ﬁeld.

10. Use the venous dilator to lift the proximal corner of the incision and carefully cannulate the vein with the IV catheter. This may be the longest part of the procedure. The IV tubing may now be attached.

11. The proximal suture should be tied around the vein and the catheter to hold it in place.

12. The tourniquet may now be removed and the incision closed.

13. Once access has been established, the cutdown site should be dressed and the extremity splinted to prevent kinking or dislodgement of the cannula.

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Complications • haematoma • infection • phlebitis and thromboembolism • injury to surrounding structures.

7.4 Diagnostic and therapeutic procedures 7.4.1 Thoracentesis (chest tap) Indications • Diagnostic: new pleural effusion that is not due to congestive heart failure. • Therapeutic: dyspnoea that is caused by large pleural effusions. • See Sections 10.6 and 15. Contraindications • thrombocytopaenia • bleeding diathesis • pre-existing infection at the site of needle insertion. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle, 20-gauge needle) • 16-gauge needle; obese patients may require longer needle – consider using a spinal needle • 30 ml syringe – may need larger (50–100 ml) for large effusions • drip giving set • haemostat • microscope slides • specimen tubes and culture media. Procedure 1. The patient should be seated with arms and head supported (e.g. sitting backwards on a chair). A nurse or assistant may help with this. 2. Localize the pleural effusion by determining the level where dullness to percussion begins when percussing the posterior chest from top to bottom. 3. Choose a site on the posterior chest in the mid-scapular line (approximately 5–10 cm lateral to the spine). Use an interspace below the point where dullness to percussion begins, but above the 9th rib (to avoid subdiaphragmatic puncture). 4. Clean the area with antiseptic; be sure to maintain strict aseptic technique. 5. The skin and subcutaneous tissue should be anaesthetized with lidocaine using a 25-gauge needle.

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6. Using a longer, 20-gauge needle, anaesthetize the pleura, and gently aspirate until pleural ﬂuid is noted in the syringe. Then remove the needle and note the depth of insertion needed for the thoracentesis needle. • Make sure that the needle is positioned and advanced just above the rib. This assures that the intercostal nerve and blood vessels, which are located just below each rib, will not be injured.

7. In the previous puncture site, insert a 16-gauge needle attached to a large syringe or to a drip giving set with the end either placed into a bucket or attached to a urine bag. Be aware that some drip giving set chambers have one-way valves which need to be cut off to allow ﬂow. 8. Advance the needle slowly, keeping it above the top of the rib. Aspirate gently while advancing the needle. 9. When pleural ﬂuid is noted, place a haemostat on the needle to prevent it from accidentally advancing forward. 10. Remove the necessary amount of pleural ﬂuid (usually 100 ml for diagnostic studies). • Do not remove more than 1500 ml of ﬂuid at once as this can increase the risk of pulmonary oedema or hypotension. In addition, the risk of pneumothorax from needle laceration of the visceral pleura is higher if an effusion is completely drained. • Warn the patient that he or she is likely to want to cough as the lungs expand.

11. The patient may experience signiﬁcant pain if a large volume of ﬂuid is removed. Paracetamol may be used to control it, although a stronger analgesic occasionally may be required. 12. Gently remove the needle. 13. A post procedure chest X-ray is not routinely required but should be done if there is any suspicion of pneumothorax.

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Investigations • Lab studies distinguish an exudate from a transudate (see Sections 10.6 and 15 for interpretation). • Collect 4 separate tubes of ﬂuid: ° tube 1 (plain, red top), protein, LDH, and glucose; ° tube 2 (EDTA, purple top), cell count and differential, cytology; ° tube 3 (sterile), Gram stain and culture (any sterile container may be used for the Gram stain and culture); ° tube 4 (sterile), keep sample in case further studies required, e.g. AFB smear, mycobacterial culture. Complications • pneumothorax (see Quick Check page 46 and Section 4.2 for immediate management) – if signiﬁcant, the patient will require a chest tube • haemothorax (see Quick Check page 46 and Section 4.2 for immediate management) – the patient will likely require a chest tube • spleen or liver puncture – if the needle is suspected to have punctured the spleen or liver, see Quick Check page 20 and Section 4.2 for immediate management and call for surgical help if the patient is unstable • re-expansion pulmonary oedema – while the evidence is not clear, it may be prevented by removing less than 1.5 litres of ﬂuid at a time • air embolism if the patient becomes unstable, with fast breathing, fast heart rate, low blood pressure, or focal neurological deﬁcits – see Quick Check page 19 for immediate management • infection • vasovagal episode.

7.4.2 Lumbar puncture Indications • suspected CNS infection (meningitis, encephalitis) • suspected subarachnoid haemorrhage • diagnosis of meningeal carcinomatosis and meningeal leukaemia • diagnosis of tertiary syphilis • follow-up of therapy for meningitis • evaluation of dementia • treatment of increased intracranial pressure caused by cryptococcal meningitis • treatment of pseudo tumour cerebri • introduction of drugs, anaesthetics or radiographic media in the CNS. Contraindications • Infection at the site. • Increased intracranial pressure evidenced by focal neurological signs, papilloedema, altered mental status, or recent seizure. Lumbar puncture performed on a patient with increased intracranial pressure can lead to fatal cerebral herniation (brain shift) (see Section 10-10b). • Bleeding disorder or low platelets.

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Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • 20- to 22-gauge spinal needle with stylet • CSF pressure manometer or IV tubing and pole • dressing material • microscope slides • specimen tubes and culture media. Procedure 1. Lumbar puncture can be a painful procedure, and some patients may require IV sedation, especially if they are delirious or uncooperative. It is advisable to pre-medicate all patients with paracetamol; however, this should not delay the procedure and the administration of antibiotics. 2. Carefully examine the patient for signs of increased intracranial pressure as described above. If increased intracranial pressure or a CNS space-occupying lesion is suspected, obtain a CT scan of the brain (if available) before performing the lumbar puncture (see Section 10-10b for further details). 3. This manual recommends performing a lumbar puncture prior to the administration of antibiotics if it can be done within 15 minutes. If this is not possible, or if the lumbar puncture is deferred, always give empirical antibiotics if meningitis is suspected. 4. Position the patient lying on one side with the spine ﬂexed (draw shoulders forward and bring thighs towards the abdomen). Patients may also be positioned sitting upright with the spine ﬂexed. However, this position will not allow for accurate measurement of the opening pressure. It may be helpful to have an assistant in front of the patient to help with positioning and reassurance.

5. Lumbar punctures are typically performed at the level of the L4–L5 interspace, well below the end of the spinal cord. The interspace may be found by drawing an imaginary line between the iliac crests. Placing four ﬁngers on the iliac crests with thumbs pointing inwards, towards the spine, may help. 6. Clean area with antiseptic. 7. Anaesthetize the skin and subcutaneous tissues with lidocaine.

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8. Gently introduce the spinal needle with bevel turned upward and angled slightly towards the head. Slowly advance. If the needle hits bone, withdraw to just under the skin and change angles (usually aiming more steeply towards the head) before advancing the needle again.

9. When the subarachnoid space is entered, there may be a slight “give”. At this point, the stylet should be carefully withdrawn to conﬁrm the ﬂow of cerebrospinal ﬂuid (CSF). It should ﬂow freely from the needle and should not ever be aspirated. 10. Measure opening pressure (usually between 10–20 cm H20). • Breath holding or straining can increase opening pressure. Reassure the patient and have them relax. • If elevated, remove only 5 ml of spinal ﬂuid and remove the needle. • If a manometer is unavailable, IV tubing that has been marked using a tape measure and attached to an IV pole can be used to measure opening pressure.

11. Collect 2 ml CSF in each of 4 collection tubes. In patients with cryptococcal meningitis, up to 30 ml may be removed at once (see Section 11.5). 12. Replace stylet and remove the needle. Apply pressure with sterile dressing for a few minutes. Investigations (see Section 10.10b for interpretation) • Collect 4 separate tubes of ﬂuid: ° tube 1, protein, glucose ° tube 2, Gram stain ° tube 3, save ﬂuid for further study ° tube 4, cell count (total and differential). • Additional tests: ° if known or suspected HIV-positive, India ink, cryptococcal latex agglutination (CrAg) ° AFB smear

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° ° ° ° °

VDRL or RPR bacterial culture mycobacterial culture fungal culture cytology.

Complications • Cerebral herniation – if the patient becomes unstable, with slow breathing, slow heart rate, high blood pressure, altered consciousness, or focal neurological deﬁcits, see Quick Check page 18 for immediate management and call for surgical help. • If post-lumbar puncture headache (is worse when standing), treat with paracetamol. Other complications may include: • severe radicular pain • paraparesis • infection • bleeding.

7.4.3 Paracentesis (abdominal tap) Indications • Diagnostic ° sample for investigation of ascites of undetermined etiology ° evaluation for peritonitis ° evaluation of intra-abdominal haemorrhage or bowel perforation in trauma. • Therapeutic ° relief of abdominal pain and discomfort caused by tense ascites ° relief of dyspnoea caused by elevated diaphragm from ascites ° initiation of peritoneal dialysis. Contraindications • a bleeding diathesis (other than DIC) as the risk of bleeding is very low • bowel distention or obstruction • infection or surgical scars at the site of needle entry. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • needle and syringe • drainage bag and tubing or IV drip giving set • dressing material • microscope slides • specimen tubes and culture media.

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Procedure 1. The patient should be instructed to empty their bladder. Occasionally, insertion of a urinary catheter may be required. 2. Patients with signiﬁcant ascites can be positioned lying face up; those with less ascites can be positioned lying down on the left side. 3. The left lower quadrant (2–3 cm lateral to the border of the rectus muscles) has been shown to be a good site for paracentesis. The right lower quadrant and a site 3–4 cm below the umbilicus have also been used. 4. Cleanse the area with antiseptic. 5. Anaesthetize the puncture site with lidocaine. 6. Carefully insert the needle at the site. A small amount of “give” may be felt as the needle enters the peritoneal cavity. Caution is required to avoid sudden penetration of the needle.

7. Remove only the necessary amount of ﬂuid. A drainage bag attached to the needle with tubing may be used when large amounts of ﬂuid must be removed. Note that removal of more than 1 litre of ﬂuid may result in postparacentesis hypotension.

Investigations (see Section 10.9 for interpretation) • Routine investigations include cell count and differential, albumin, total protein, Gram stain, and culture. • If tuberculous peritonitis is suspected, send sample for AFB smear and mycobacterial culture. • If malignancy is suspected, send sample for cytology. • Glucose and amylase may be useful.

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Complications • Post-paracentesis hypotension. Give ﬂuids acutely – usually self-resolving (see Quick Check page 19 for immediate management). • Bowel perforation. If the patient develops severe abdominal pain and tenderness, the bowel wall may have been perforated (see Quick Check page 20 for immediate management and arrange for emergency surgery). • Puncture site infection. • Abdominal wall haematoma. • Continued leakage of ascitic ﬂuid.

7.4.4 Arthrocentesis (joint aspiration) Indications • suspected infectious or crystal-induced arthropathy • unexplained joint effusion or monoarthritis • symptomatic relief from a large effusion • see Section 10.13 Painful joints. Contraindications • signiﬁcant overlying cellulitis or soft tissue infection • bleeding diathesis • joint prosthesis. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine (5–10 ml syringe, 23- to 25-gauge needle) • 21-gauge needle and syringe • dressing material • microscope slides • specimen tubes and culture media. Procedure (knee joint aspiration) 1. Position the patient lying face up on the examination table. Examine the knee to determine the size of the joint effusion, and presence of any overlying skin infection. 2. Palpate the superolateral or superomedial aspect of the patella and mark a spot 1 cm superior and lateral to this point. Cleanse the area with skin antiseptic. 3. The area may be anaesthetized, but merely stretching the skin may also help reduce discomfort. 4. Steady the patella with one hand.

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5. Insert a 21-gauge needle (with an appropriately sized syringe attached) at a 45° angle to the knee, aiming for below the patella.

6. Fluid should be easily aspirated once the needle has penetrated more than a few centimetres. Gently compressing the opposite side of the joint may increase ﬂow. 7. Once sufﬁcient ﬂuid has been withdrawn to ease the patient’s symptoms, the needle may be withdrawn and the ﬂuid in the syringe sent for studies. Investigations (see Section 10.13 Painful joints for interpretation) • cell count and differential, protein • Gram stain and culture • polarized microscopy (if in an area with high prevalence of crystal-induced arthritis). Complications • Latrogenic septic arthritis if the patient appears to be in shock, with fast heart rate and low blood pressure, see Quick Check page 19 for immediate management. • Other complications may include: • joint instability • re-accumulation of joint effusion.

7.4.5 Pericardiocentesis Indications • diagnostic sample to determine etiology of effusion • cardiac tamponade (semi-elective or emergent). Contraindications • small pericardial effusion • traumatic haemopericardium, haemopericardium due to aortic dissection, and purulent pericarditis (surgical approach preferred) • bleeding diathesis. Equipment • sterile gloves and sterile towels or drapes • antiseptic • lidocaine, 5–10 ml syringe, 23- to 25-gauge needle

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• long 18-gauge needle • dressing material • microscope slides and culture media. Procedure 1. If possible, this procedure should be done by an experienced operator with guidance from ﬂuoroscopy or echocardiography or ultrasound, and in a cardiac catheterization laboratory or operating room. 2. After the area has been sterilized and anaesthetized, the needle should be inserted 1 cm to the left of the xiphoid process, and directed towards the left shoulder. One should maintain a 30° angle to the skin to avoid the pleura and nearby arteries.

3. While the needle is being inserted, aspiration should be gently and intermittently attempted until ﬂuid is withdrawn. A “pop” or sudden change in the density of the tissue being penetrated may occur, indicating that the pericardium has been accessed. Sanguineous pericardial ﬂuid may be distinguished from blood by dropping a small amount onto a clean, dry sponge. If it is pericardial ﬂuid, the resulting spot should appear much lighter than blood. 4. In the emergency or tamponade situation, the removal of even 50 ml may at least temporarily improve haemodynamics. 5. No more than 1 litre of ﬂuid at a time should be aspirated in order to avoid acute right ventricular dilatation. Investigations • Gram stain, chemistry and culture • cytology • if tuberculous pericarditis is suspected, perform adenosine deaminase and send for mycobacterial culture. Complications • Myocardial or coronary vessel laceration may present in a delayed fashion as hemopericardium or cardiac tamponade – (see Quick Check page 20 for immediate management and call for surgical help). • Acute left or right ventricular failure with pulmonary oedema (see Quick Check page 20 and Section 3.2.5). • Arrhythmia – obtain ECG and treat according to national guidelines. If the

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patient appears to be in shock, with fast heart rate and low blood pressure, see Quick Check page 20 for immediate management. • Pneumothorax (see Quick Check page 46 and Section 4.2 Trauma for immediate management). If signiﬁcant, the patient will require a chest tube. • Air embolism – if the patient becomes unstable, with fast breathing, fast heart rate, low blood pressure, or focal neurological deﬁcits, see Quick Check page 20 for immediate management. • Puncture of peritoneal cavity or abdominal organs. If the patient develops severe abdominal pain and tenderness, an abdominal organ may have been punctured. See Quick Check page 24 for immediate management and call for surgical help.

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Fig 1a Normal Pericardium

1b Free ﬂuid in Pericardium

Fig 2a Normal RUQ

2b Free ﬂuid in RUQ

Fig 3a Normal LUQ

3b Free ﬂuid in LUQ

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Fig 4a Normal Pelvis

4b Free ﬂuid in Pelvis

Fig 5 Gestational sac with yolk sac in early pregnancy

Fig 6 Early pregnancy with fetus

Fig 7 Fetal Heart Rate with M-mode

Fig 8 Ruptured ectopic with empty uterus and free ﬂuid

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8. Medicines/therapies Table of contents 8.1 8.2 8.3 8.4 A guide to the use of different analgesics . . . . . . . . . . . . . . . . . Information on equivalence for interchangeability- corticosteroids . Iron content of different salts. . . . . . . . . . . . . . . . . . . . . . . . . Summary of medicines/therapies in adolescents and adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347 347 347 348 349 350 350 351 352 353 353 354 354 355 355 355 356 356 357 357 357 358 358 358 359 359 360 360 361 361 361 362 362 363 363 364 364 365 365 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

345 346 349 346 366 366 367 367 368 368 369 369 370 372 373 374 374 375 375 376 377 378 379 379 380 380 380 381 381 382 384 384 385 386 386 387 387 387 388 389 391 391 392 392 393

Acamprosate . . . . . . . . . . . . . . . Acetazolamide. . . . . . . . . . . . . . Acetylcysteine . . . . . . . . . . . . . . Acetylsalicyclic acid (aspirin) . . . . . . Aciclovir . . . . . . . . . . . . . . . . . Albendazole . . . . . . . . . . . . . . . Amiloride . . . . . . . . . . . . . . . . . Amitriptyline . . . . . . . . . . . . . . . Amoxicillin . . . . . . . . . . . . . . . . Amoxicillin with clavulanic acid . . . . . Amphotericin B (conventional) . . . . . . Amphotericin B (liposomal) . . . . . . . . Ampicillin . . . . . . . . . . . . . . . . Antiretrovirals Abacavir (ABC) . . . . . . . . . . . Atazanavir + ritonavir (ATV/r) . . . . Didanosine (ddI) . . . . . . . . . . . Efavirenz (EFV) . . . . . . . . . . . . Emtricitabine (FTC) . . . . . . . . . . Lamivudine (3TC). . . . . . . . . . . Nevirapine (NVP) . . . . . . . . . . Lopinavir + ritonavir (LPV/r) . . . . . Saquinavir (SQV) . . . . . . . . . . . Tenofovir (TDF) . . . . . . . . . . . . Zidovudine (ZDV, AZT) . . . . . . . . Artemether . . . . . . . . . . . . . . . . Artemether + lumefantrine . . . . . . . . Artesunate . . . . . . . . . . . . . . . . Artesunate + amodiaquine . . . . . . . . Artesunate + sulfadoxine–pyrimethamine Artesunate + meﬂoquine . . . . . . . . . Artesunate + clindamycin . . . . . . . . Aspirin (see acetylsalicylic acid Atropine) Atropine . . . . . . . . . . . . . . . . . Atropine eye drops . . . . . . . . . . . . Azithromycin . . . . . . . . . . . . . . . Beclometasone inhaler . . . . . . . . . . Benzathine benzylpenicillin. . . . . . . . Benznidazole . . . . . . . . . . . . . . . Benzyl benzoate . . . . . . . . . . . . . Benzoyl peroxide . . . . . . . . . . . . .

Benzylpenicillin (penicillin G) . . . . . Betametasone . . . . . . . . . . . . Biperiden. . . . . . . . . . . . . . . Buprenorphine . . . . . . . . . . . . Calamine lotion . . . . . . . . . . . . Calcium gluconate . . . . . . . . . . Carbamazepine. . . . . . . . . . . . Ceﬁxime . . . . . . . . . . . . . . . Ceftriaxone . . . . . . . . . . . . . . Charcoal, activated. . . . . . . . . . Chloramphenicol . . . . . . . . . . . Chloramphenicol eye drops/ointment . Chlorhexidine . . . . . . . . . . . . Chloroquine . . . . . . . . . . . . . Chlorphenamine . . . . . . . . . . . Chlorpromazine . . . . . . . . . . . Ciproﬂoxacin . . . . . . . . . . . . . Clarithromycin . . . . . . . . . . . . Clindamycin . . . . . . . . . . . . . Clindamycin topical . . . . . . . . . Clofazimine . . . . . . . . . . . . . . Clomipramine . . . . . . . . . . . . Cloxacillin . . . . . . . . . . . . . . Coal tar. . . . . . . . . . . . . . . . Codeine . . . . . . . . . . . . . . . Cotrimoxazole (TMP-SMZ) . . . . . . Dapsone . . . . . . . . . . . . . . . Deferoxamine . . . . . . . . . . . . Dexamethasone . . . . . . . . . . . Diazepam . . . . . . . . . . . . . . Diethylcarbamazine . . . . . . . . . Dihydro-artemisinin + piperaquine . . Diloxanide . . . . . . . . . . . . . . Dithranol . . . . . . . . . . . . . . . Dopamine . . . . . . . . . . . . . . Doxycycline . . . . . . . . . . . . . Eﬂornithine . . . . . . . . . . . . . . Enalapril . . . . . . . . . . . . . . . Epinephrine (adrenaline) . . . . . . . Ergometrine . . . . . . . . . . . . . Erythromycin . . . . . . . . . . . . .

Erythromycin topical . . . . . . . . . . . . Ethambutol . . . . . . . . . . . . . . . . . Ethanol . . . . . . . . . . . . . . . . . . . Ferrous sulphate . . . . . . . . . . . . . . Fluconazole . . . . . . . . . . . . . . . . Flucytosine (5-FC) . . . . . . . . . . . . . Fluoxetine . . . . . . . . . . . . . . . . . Fluphenazine . . . . . . . . . . . . . . . . Folic acid . . . . . . . . . . . . . . . . . . Folinic acid . . . . . . . . . . . . . . . . . Furosemide. . . . . . . . . . . . . . . . . Gabapentin . . . . . . . . . . . . . . . . . Ganciclovir . . . . . . . . . . . . . . . . . Gentamicin . . . . . . . . . . . . . . . . . Gentamicin eye drops . . . . . . . . . . . Griseofulvin . . . . . . . . . . . . . . . . Haloperidol . . . . . . . . . . . . . . . . . Hydralazine IV . . . . . . . . . . . . . . . Hydrochlorthiazide . . . . . . . . . . . . . Hydrocortisone . . . . . . . . . . . . . . . Hydrocortisone cream . . . . . . . . . . . Hydroxypropyl methylcellulose eye drops . Ibuprofen. . . . . . . . . . . . . . . . . . Insulin (soluble) . . . . . . . . . . . . . . Ipratropium bromide . . . . . . . . . . . . Isoniazid . . . . . . . . . . . . . . . . . . Isosorbide dinitrate. . . . . . . . . . . . . Itraconazole . . . . . . . . . . . . . . . . Ivermectin . . . . . . . . . . . . . . . . . Ketamine . . . . . . . . . . . . . . . . . . Lactulose. . . . . . . . . . . . . . . . . . Levonorgestrel . . . . . . . . . . . . . . . Lidocaine. . . . . . . . . . . . . . . . . . Magnesium sulfate . . . . . . . . . . . . . Malathion . . . . . . . . . . . . . . . . . Mebendazole. . . . . . . . . . . . . . . . Meglumine antimoniate . . . . . . . . . . Melarsoprol . . . . . . . . . . . . . . . . Methadone . . . . . . . . . . . . . . . . . Methylthioninium chloride (methylene blue) Metoclopramide . . . . . . . . . . . . . . Metronidazole . . . . . . . . . . . . . . . Miconazole. . . . . . . . . . . . . . . . . Midazolam . . . . . . . . . . . . . . . . . Miltefosine . . . . . . . . . . . . . . . . . Misoprostol . . . . . . . . . . . . . . . . Morphine. . . . . . . . . . . . . . . . . . Mupirocin . . . . . . . . . . . . . . . . . Naloxone . . . . . . . . . . . . . . . . . . Naltrexone . . . . . . . . . . . . . . . . . Neostigmine . . . . . . . . . . . . . . . . Nifurtimox . . . . . . . . . . . . . . . . . Nitrofurantoin . . . . . . . . . . . . . . . Omeprazole . . . . . . . . . . . . . . . . Ondansetron . . . . . . . . . . . . . . . . Oseltamivir . . . . . . . . . . . . . . . . . Oxytocin . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

395 395 396 396 397 398 398 399 399 400 400 401 401 402 403 403 404 405 406 406 407 407 407 408 408 408 409 409 410 411 411 412 412 413 414 414 415 416 416 417 417 418 420 420 421 421 422 422 423 423 423 424 424 425 425 426 426

Paracetamol . . . . . . . . . . . . . . . . . . 427 Paromomycin . . . . . . . . . . . . . . . . . 427 Pentamidine . . . . . . . . . . . . . . . . . . 428 Permethrin . . . . . . . . . . . . . . . . . . . 429 Phenobarbital . . . . . . . . . . . . . . . . . 430 Phenoxymethyl-penicillin (penicillin V) . . . . . 431 Phenytoin . . . . . . . . . . . . . . . . . . . 432 Pilocarpine eye drops . . . . . . . . . . . . . 433 Podophyllum resin . . . . . . . . . . . . . . . 433 Polyvidone iodine (povidone–iodine) . . . . . . 434 Polyethylene glycol electrolyte solution . . . . 434 Potassium permanganate . . . . . . . . . . . 434 Potassium chloride . . . . . . . . . . . . . . . 435 Praziquantel . . . . . . . . . . . . . . . . . . 435 Prednisolone . . . . . . . . . . . . . . . . . . 436 Primaquine . . . . . . . . . . . . . . . . . . . 438 Procaine benzylpenicillin G . . . . . . . . . . . 438 Propranolol. . . . . . . . . . . . . . . . . . . 439 Pyridoxine (vitamin B6) . . . . . . . . . . . . . 440 Pyrimethamine . . . . . . . . . . . . . . . . . 440 Quinine . . . . . . . . . . . . . . . . . . . . . 441 Quinine + clindamycin . . . . . . . . . . . . . 441 Rifampicin . . . . . . . . . . . . . . . . . . . 442 Rifampicin + isoniazid + pyrazinamide + ethambutol hydrochloride . . . . . . . . . 443 Salbutamol . . . . . . . . . . . . . . . . . . . 444 Salicylic acid . . . . . . . . . . . . . . . . . . 444 Selenium sulﬁde . . . . . . . . . . . . . . . . 445 Senna . . . . . . . . . . . . . . . . . . . . . 445 Sodium bicarbonate . . . . . . . . . . . . . . 446 Sodium cromoglycate . . . . . . . . . . . . . 446 Sodium nitrite . . . . . . . . . . . . . . . . . 446 Sodium nitroprusside . . . . . . . . . . . . . . 447 Sodium stibogluconate . . . . . . . . . . . . . 447 Sodium thiosulfate . . . . . . . . . . . . . . . 448 Spectinomycin . . . . . . . . . . . . . . . . . 448 Spironolactone . . . . . . . . . . . . . . . . . 448 Streptomycin . . . . . . . . . . . . . . . . . . 449 Sulfadiazine . . . . . . . . . . . . . . . . . . 449 Sulfadoxine with pyrimethamine (SP) . . . . . . 450 Sulfamethoxazole with trimethoprim (TMP-SMX) (see cotrimoxazole) Suramin . . . . . . . . . . . . . . . . . . . . 450 Terbinaﬁne . . . . . . . . . . . . . . . . . . . 451 Tetracaine (amethocaine) eye drops . . . . . . 451 Tetracycline . . . . . . . . . . . . . . . . . . 451 Tetracycline eye ointment . . . . . . . . . . . 452 Thiamine . . . . . . . . . . . . . . . . . . . . 452 Tranexamic acid (TXA) . . . . . . . . . . . . . 453 Tretinoin . . . . . . . . . . . . . . . . . . . . 453 Triclabendazole . . . . . . . . . . . . . . . . 454 Trimethoprim-sulfamethoxazole (see cotrimoxazole) Urea . . . . . . . . . . . . . . . . . . . . . . 454 Valproic acid (sodium valproate) . . . . . . . . 455 Vitamin B6 (see pyridoxine) Vitamin B12 (hydroxocobalamin) . . . . . . . . 456 Vitamin K (phytomenadion) . . . . . . . . . . . 456

8. Medicines/therapies Section 8 covers only the treatment recommendations for conditions covered in this manual and does not serve as a comprehensive list of indications for each medicine. Also, it does not include routine contraception, vaccines, or immunoglobulin therapy. Information on medicines in this section is drawn from the WHO Model Formulary,1 Pharmacological treatments of mental disorders in primary health care 2, manufacturers’ product literature, UpToDate3, and evidence-based formularies such the British National Formulary4 and Australian Medicines handbook.5 Other sources include the Sanford Guide to Antimicrobial Therapy.6 These summaries do not cover all adverse reactions and interactions. The information given should be interpreted in the light of professional knowledge and by reference to the approved product information for the individual drugs and should be supplemented as necessary by specialist advice. Where deemed important, the principles of prescribing and medicine administration are dealt with in the relevant Sections of the manual. For example, principles of prescribing in mental health disorders are in Section 10.11. Where possible, adverse reactions are classiﬁed according to their probable incidence: common = incidence of 1% or more; infrequent or rare = incidence of less than 1%. Section 8 is subdivided into: 8.1 Analgesics for pain relief 8.2 Information on equivalence for interchangeability- corticosteroids 8.3 Iron content of different salts 8.4 Information on individual medicines in adolescents and adults Section 8 should be adapted in each country to match national guidelines and essential medicines lists. Please also refer to the updated WHO essential medicines list and the 2008 WHO Model Formulary.1 The medicines list in 8.4 is not comprehensive. For a more complete list and for speciﬁc medicine interaction information, see the 2008 WHO Model Formulary.1

WHO Model Formulary. WHO, 2008. Available at www.who.int/selection_medicines/list/WMF2008.pdf Pharmacological treatment of mental disorders in primary health care. WHO, 2009. UpToDate, available at http://www.uptodate.com/store. Joint Formulary Committee (2010). British National Formulary. 60th ed. London, British Medical Association and Royal Pharmaceutical Society of Great Britain. Available through HINARI (http://extranet.who.int/hinari/en/ journals.php). 5 Rossi, S. ed, Australian Medicines Handbook 2008. Adelaide, Medicines Handbook Pty Ltd, 2008. 6 Gilbert DN, Ellopoulos GM, Moellering RC, Saag MS, Chambers HF, eds. The Sanford Guide to Antimicrobial Therapy. 40th ed. Sperryville, Antimicrobial Therapy, 2010.

1 2 3 4

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343

For renal and hepatic impairment drug dosage adjustments, please refer to appendices 4 and 5 in 2008 WHO Model Formulary1 and Section 11.31 in this manual. Some of the other common or important indications for the medicines that are not addressed in this manual are listed in the left column under “Other indications”. Special advice for prescribing medications for the elderly • Drugs that commonly cause problems in the elderly include hypnotics, diuretics, nonsteroidal anti-inﬂammatory drugs, antihypertensives, psychotropics, and digoxin. • For some medications, start low, go slow, expect unusual side-effects and drug interactions. • See Section 18 Geriatric care.

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8.1 A guide to the use of different analgesics (see Section 20 Palliative care) Starting dose in adolescents and adults

Analgesics Non-opioid Paracetamol (also lowers fever)

Range

Side-effects/ cautions

1 gram every 4–6 hours but no more than 4 grams in 24 hours

Only 1 tablet (500 mg) may be required in the elderly or the very ill or when combined with an opioid. Mild pain might be controlled with every 6 hour dosing.

Do not exceed 4 grams in 24 hours (more can cause serious liver toxicity).

STEP 1

Aspirin (acetylsalicylic acid) (also anti-inﬂammatory and lowers fever)

600 mg (2 tablets of 300 mg) every 4 hours

Avoid use if gastric problems. Stop if epigastric pain, indigestion, black stools, petechiae, or bleeding. Avoid in presence of any bleeding. Do not give to children under 16 years.

Ibuprofen (also anti-inﬂammatory and lowers fever)

1.0 200–400 mg 3–4 times daily. Maximum 2.4 g daily.

Maximum daily dose of 2.4 g

With or after food

Opioid for mild to moderate pain (give in addition to aspirin or paracetamol) STEP 2 Codeine (if not available, consider alternating aspirin and paracetamol) Codeine phosphate 30 mg every 4 hours Codeine phosphate 30–60 mg every 4 hours. Maximum daily dose for pain 180–240 mg – switch to morphine if pain management inadequate. Give laxative to avoid constipation unless diarrhoea.

Opioid for moderate to severe pain Oral morphine: 5 mg/5 ml or 50 mg/5 ml or tablets Give by mouth but, if necessary, can be given rectally. IV or IM or subcutaneously Initially, morphine sulfate 2.5–10 mg every 4 hours, increased by 30–50% if pain persists According to pain There is NO ceiling dose See Section 20. Give laxative to avoid constipation unless diarrhoea. Excessive dosage can reduce respiratory rate.

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345

8.2 Information on equivalence for interchangeability – corticosteroids Table: Corticosteroid equivalents Steroid Hydrocortisone Prednisone/prednisolone Methylprednisolone Dexamethasone Equivalent dose 100 mg 25 mg 20 mg 4 mg Half-life 8–12 hours 12–36 hours 12–36 hours 36–54 hours

Table: Classiﬁcation of potencies of topical corticosteroids and interchangeability Mild hydrocortisone hydrocortisone acetate 0.5%, 1% 0.5%, 1% Potent betamethasone dipropionate betamethasone valerate hydrocortisone butyrate mometasone furoate triamcinolone acetonide Very potent clobetasol propionate 0.05% 0.1% 0.1% 0.1% 0.1%

Moderate betamethasone valerate clobetasone butyrate triamcinolone acetonide

0.02%, 0.05% 0.05% 0.02%

0.05%

8.3 Iron content of different iron salts Iron salt Ferrous fumarate Ferrous gluconate Ferrous sulfate Ferrous sulfate, dried Amount 200 mg 300 mg 300 mg 200 mg Content of ferrous iron 65 mg 35 mg 60 mg 65 mg

8.4 Summary of medicines/therapies in adolescents and adults Note: These summaries do not include dosing or administration to children less than 10 years of age. References to Sections in this manual are in parentheses. Medicines not included in the WHO Model Formulary are in italics.

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Drug Indication Common: Pruritus, maculo-papular rash; diarrhoea; changes in libido Infrequent or rare: Nausea, vomiting, abdominal pain; bullous skin reactions, angioedema, anaphylactic reactions Pregnancy/breastfeeding: Not recommended during pregnancy or breastfeeding.

Formulations Dosage

Adverse effects

Special groups/comments

Acamprosate

Tablet: 333 mg enteric coated

Maintenance of abstinence in alcohol dependence (16.5)

>55 kg: 2 tablets 3 times daily. <55 kg: 2 tablets twice daily

Use with caution: Renal or hepatic impairment (give lower doses) Does not alter CNS effects of drinking alcohol or withdrawal symptoms Pregnancy/breastfeeding:Avoid in ﬁrst trimester of pregnancy. Contraindications: Hypokalaemia, hyponatraemia, acidosis, severe renal impairment, severe hepatic impairment, chronic angle-closure glaucoma (may mask deterioration) Use with caution: In the elderly, diabetes mellitus, gout, history of renal stones, sulfonamide allergy Counselling: Take tablets with meals to reduce the risk of stomach upset. Pregnancy/breast feeding: Clinical experience indicates that use of acetylcysteine for treatment of paracetamol overdose is effective and beneﬁts outweigh risks. Use with caution: In patients with asthma or history of bronchospasm, but do not delay acetylcysteine treatment Administration: IV: Dilute requisite dose in glucose intravenous infusion 5% as follows: initially 200 ml given over 15 minutes, then 500 ml over 4 hours, then 1 litre over 16 hours. Oral: Dilute to a 5% solution in soda pop, juice, or water prior to oral or nasogastric administration. Storage:A change in the colour of the solution to light purple has sometimes been noted; this colour change is not thought to indicate signiﬁcant impairment of safety or efﬁcacy. Store below 25°C.

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Paresthesia (of hands, face, feet, or mucocutaneous junctions), fatigue, drowsiness, depression, decreased libido, bitter or metallic taste; nausea, vomiting, abdominal cramps, diarrhoea, black faeces; polyuria, renal stones; metabolic acidosis, hypokalaemia, hyponatraemia Infrequent or rare: Transient myopia; Stevens-Johnson syndrome; aplastic anaemia (especially in the ﬁrst 6 months), thrombocytopenia, agranulocytosis, neutropenia Common: Flushing, urticaria, itch Infrequent or rare: Anaphylactoid or hypersensitivity-like” reactions including angioedema, bronchospasm/ respiratory distress, hypotension, and, rarely, tachycardia or hypertension. Usually occur 15–60 minutes after start of infusion. (Manage by reducing infusion rate or suspending infusion until reaction has settled; stop infusion if severe anaphylaxis occurs; rash – use an antihistamine; acute asthma – use short-acting beta2 agonist such as salbutamol.) Once an anaphylactoid reaction is under control, infusion can normally be restarted at the lowest infusion rate (100 mg/kg in 1 litre over 16 hours).

Acetazolamide

Tablet: 250 mg

Pre-operative treatment of acute angle-closure glaucoma (10.12.2)

Oral: Initially 250 mg then 500-750 mg per day in divided doses until patient reaches referral care.

(Other indications: Adjunctive treatment of chronic open-angle glaucoma)

Acetylcysteine

Injection: 200 mg/ml (intended for antidotal, not mucolytic, use) Oral: 100 mg/ml

Summary tables

Paracetamol overdosage (3.8.1)

IV: Initially 150 mg/kg over 15 minutes; then 50 mg/kg over 4 hours; then 100 mg/kg over 16 hours

Oral: Loading dose of 140 mg/kg; THEN 4 hours after loading dose, initiate maintenance dose of 70 mg/kg administered at 4-hour intervals for 17 doses. Continue until 72 hours post-ingestion (longer if LFTs abnormal).

347

348 Adverse effects Common: Gastrointestinal irritation with slight blood loss, tinnitus; deafness (large doses), nausea, dyspepsia, vomiting, increased bleeding time, headache, dizziness Infrequent or rare: Steven Johnson syndrome, iron deﬁciency anaemia, renal impairment, oesophageal ulceration, major GI bleeding, blood dyscrasias, Reyes syndrome. Allergy, bronchospasm angioedema, urticaria or rhinitis in hypersensitive patients (particularly in people with asthma) * If overdose, see Section 3.8. Special groups/comments Pregnancy/breastfeeding: Precautions in the ﬁrst and second trimesters – low doses probably not harmful. Consider alternative for analgesia. Use not recommended in third trimester due to impaired platelet function and risk of haemorrhage. Delayed onset and increased duration of labour with increased blood loss; avoid analgesic doses if possible in last few weeks (low doses probably not harmful); with high doses, closure of fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of newborn; kernicterus in jaundiced neonates. Breastfeeding: Short course safe in breastfeeding at usual dosage (monitor infant, regular use of high doses could produce hypoprothrombinaemia in infant if neonatal vitamin K stores low; possible risk of Reye syndrome; avoid breastfeeding 1–2 hours after dose to minimise infant exposure. Contraindications: In hypersensitivity (including asthma, angioedema, urticaria or rhinitis) to acetylsalicylic acid or any other NSAID, active peptic ulceration, bleeding disorders, and in children and adolescents under 16 years (Reye syndrome) Not for treatment of gout Use with caution: in asthma, heart failure, uncontrolled hypertension, allergic disease, previous peptic ulceration, renal impairment, hepatic impairment, G6PD deﬁciency, dehydration, and in the elderly Administration: Give with food, large quantities (~240 ml) of water (unless ﬂuid restricted) or milk to minimize gastric irritation. Counselling: If you develop swollen ankles, difﬁculty in breathing, black stools or vomit that looks like coffee grounds stop taking the medicine.

Drug Indication

Formulations Dosage

Acetylsalicylic acid (aspirin)

Tablet: 100 mg, 300 mg

Acute coronary syndrome/ myocardial infarction (Quick Check page 20)

Oral: 300 mg (preferably chewed or dispersed in water) given immediately as a single dose

Summary tables

Mild to moderate pain (20.2, 2.4); fever (10.1.2)

300 mg–600 mg every 4 hours as needed; higher doses (900mg ) may be useful for analgesia in some patients; maximum 4 grams in 24 hours

(Other indications: acute ischaemic stroke; prophylaxis of cerebrovascular disease or myocardial infarction; acute migraine attack; inﬂammatory arthritis)

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Drug Indication Common: Nausea, vomiting, diarrhoea, hallucinations (with high dose), headaches, lethargy, confusion, seizures Pregnancy: Precautions in the ﬁrst trimester Breastfeeding: Considered safe

Formulations Dosage

Adverse effects

Special groups/comments

Aciclovir

Tablet: 200 mg, 400 mg, 800 mg Oral suspension: 200 mg/5 ml Infusion: 250 mg vial Eye ointment: 3% W/W Infrequent or rare: Hypersensitivity reactions; agitation, vertigo, dizziness, weakness; oedema, renal impairment; arthralgia; sore throat; abdominal pain, constipation; hepatitis, jaundice; blood disorders (anaemia, thrombocytopenia, leukopenia), StevensJohnson syndrome, toxic epidermal necrolysis, anaphylaxis Severe local inﬂammation on intravenous infusion

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Herpes simplex virus (HSV); genital herpes, initial or recurrent episode (11.15)

Oral: 400 mg 3 times daily OR 200 mg 5 times daily for 7–10 days (longer if new lesions appear or incomplete healing)

Use with caution: In renal impairment, with concurrent administration of other nephrotoxic drugs, use of IV form in patients with underlying neurological abnormalities, in elderly patients

Prophylaxis for recurrent herpes simplex (chronic suppression)(11.15)

Oral: 200 mg 3–5 times daily OR 400 mg twice daily Interrupt every 6–12 months for reassessment.

HSV encephalitis or hepatitis (11.15)

IV: 10 mg/kg 3 times daily for 14–21 days

Administration: Maintain adequate hydration with IV use (balance with risk of cerebral oedema in patients with encephalitis). Infuse IV dose over 1 hour to prevent renal damage. Ensure adequate ﬂuid intake (1.5–2 litres/day), which should also be maintained with oral administration to prevent crystallization in the renal tubules. Changes in renal function during treatment usually respond to rehydration and/or dosage reduction.

HSV oesophagitis (11.15, 10.7b.3):

Oral: 200 mg 5 times daily OR 400 mg 3 times daily for 7–10 days

• If NOT immunocompromised

Oral: 400 mg orally 5 times daily for 14–21 days

Counselling: Drink plenty of ﬂuids (at least 1.5–2 litres/daily). Tablet can be dissolved in water if desired. If taking 5 times daily, take every 4 hours during waking hours.

• If immuno-compromised

Oral: 400 mg twice daily AND ART

Summary tables

• HSV oesophagitis suppression

See dosing in 11.45.1

Varicella (chickenpox) (11.45.1)

Herpes zoster (shingles) (11.45.2)

Oral: 800 mg 5 times daily for 7 days (begin within 72 hours of appearance of rash to be effective) AND 3% eye ointment every 4 hours if ophthalmic involvement

Herpes keratitis (10.12.2)

Apply 1 cm ointment 3% directly to eye 5 times daily; continue for at least 3 days after healing is complete. OR oral aciclovir 400 mg 5 times daily until healing is complete

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350 Adverse effects Common: During treatment of neurocysticercosis, neurological symptoms (fever, headache, worsening of disease, probably due to CNS reaction to dying parasites) Special groups/comments Pregnancy/breastfeeding: Recommended for use only during the second and third trimesters of pregnancy and only when there are no alternatives and beneﬁt outweighs risk. Administration: Check liver function tests and blood counts before longer-term treatment and twice during each cycle (every 2 weeks). Cease therapy if enzymes greater than twice normal limit. Counselling: Chew and take on an empty stomach. Infrequent or rare: GI intolerance, increase in liver enzymes, reversible alopecia, rash, reversible leukopenia, bone marrow suppression (pancytopenia, aplastic anaemia, agranulocytosis), Stevens-Johnson syndrome Contraindications: Do not co-administer ivermectin if onchocerciasis or loaisis are co-endemic with ﬁlariasis. Pregnancy/breastfeeding: Not recommended in pregnancy or breastfeeding; consider alternatives. Contraindications: Hyperkalaemia, renal failure Common: Hyperkalaemia, hyponatraemia, hypochloraemia (especially when combined with thiazide diuretics), weakness, headache, nausea/vomiting, constipation, impotence, dizziness, muscle cramps Infrequent or rare: Diarrhoea, anorexia, dry mouth, abdominal pain, ﬂatulence, polyuria, rash, pruritus, visual disturbances, mild psychiatric disturbances, palpitations Use with caution: In the elderly, debilitated patients with cardiopulmonary disease or uncontrolled type 1 diabetes; in patients with cirrhosis, may precipitate renal failure, hyperchloraemic metabolic acidosis, hepatic encephalopathy; with medicines that can increase potassium concentration (ACE inhibitors) Counselling: Take in the morning. Dizziness with standing may occur.

Drug Indication

Formulations Dosage

Albendazole

Tablet: 400 mg (chewable)

Strongyloidiasis (if ivermectin not available) (11.36)

Oral: 400 mg twice daily for 3 days (consider longer course in immunocompro-mised patients). THEN maintenance at 400 mg monthly.

Summary tables

Cysticercosis, as alternative to praziquantel in uncomplicated cases (11.7)

Oral: 15 mg/kg daily for 8 days

Filariasis (11.12)

Oral: 400 mg as a single dose + diethyl-carbamazine OR albendazole 400 mg/twice daily for 2 weeks + ivermectin as a single dose

Ascaris (10.7), hookworm (10.18) • Treatment • Prophylaxis

Oral: 400 mg as a single dose

Oral: 400 mg as a single dose every 6 months

Amiloride

Tablet: 5 mg

Oedema (10.4.4)

Oral: 10 mg daily in 1–2 divided doses; give in combination with furosemide

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(Other indications: Liver cirrhosis)

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Manufacturer advises against use unless essential, particularly during ﬁrst and third trimesters. Breastfeeding: Use with caution if indicated and if the drug of choice; reversible withdrawal symptoms and adverse effects possible (monitor infant for drowsiness). Preferably, give as a single nightly dose after breastfeeding. Contraindications: Patient has taken an MAO-I within 2 weeks, recent myocardial infarction, arrhythmias (especially heart block), bipolar disorder, severe liver disease. Do not use in adolescents.

Amitriptyline Common: Orthostatic hypotension (fall risk), dizziness, sedation, dry mouth, constipation, nausea, difﬁculty urinating, blurred vision, headache, confusion, disorientation, increased liver enzymes, worsening depression, anxiety, insomnia, ejaculatory problems, impotence, appetite and weight changes Serious side-effects: Cardiac arrhythmias, heart attack, stroke, seizures, hyperthermia, heat stroke, mania/hypomania If overdose, see Section 3.8.

Tablet: 25 mg, 50 mg

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Depression (10.11.6); neuropathic pain (10.10a); herpetic neuralgia (11.45)

Oral: Start 50 mg at bedtime AND Increase gradually as necessary by 25–50 mg every 1–2 weeks to 100–150 mg daily. Maximum dose of 200 mg daily for depression; up to 300 mg for neuropathic pain (single dose, preferably at bedtime or in divided doses). Note: delay in onset of effect

For elderly and medically ill: Start at 25 mg at night, can be increased gradually to maximum tolerated dose of 100 mg per day

Use with caution: In elderly, patients with cardiac history; epilepsy, hepatic impairment, thyroid disease, pheochromocytoma, history of mania, psychoses, angleclosure glaucoma, history of urinary retention, concurrent electroconvulsive therapy, anaesthesia. May increase the risk of suicidal thinking and behaviour. Prone to multiple signiﬁcant drug interactions.

Summary tables

Counselling: Blurred vision and dry mouth may be troublesome but may lessen or disappear after about 7 days. Try to take it at night to reduce daytime drowsiness. You may feel dizzy on standing when taking this medicine; get up gradually from sitting or lying to minimize this effect. Avoid driving and operating machinery until you know how you react to this medicine. Do not stop taking the medicine suddenly. If you suddenly stop taking amitriptyline, you may experience withdrawal symptoms such as nausea, headache, and lack of energy. Your clinician will probably decrease your dose gradually. May increase the effects of alcohol.

351

352 Adverse effects Pregnancy: Not known to be harmful Breastfeeding: Considered safe Contraindications: Known hypersensitivity/ anaphylaxis to penicillins or other beta-lactams Use with caution: If history of allergy or renal impairment. Maintain adequate hydration with high doses (risk of crystalluria). Reduce dose if severe renal failure. Counselling: Swallow the capsule whole with a glass of water at the start of a meal or slightly before. Common: Nausea, vomiting, diarrhoea; hypersensitivity reaction (discontinue if severe rash, urticaria, wheezing); superinfection including candidiasis Special groups/comments Infrequent or rare: Fever, erythema, exfoliative dermatitis, angioedema, C. difﬁcile colitis, anaphylaxis, bronchospasm, interstitial nephritis, serum sickness-like syndrome, haemolytic anaemia, toxic epidermal necrolysis, erythematous rashes (common in glandular fever, lymphocytic leukaemia, cytomegalovirus infection, Epstein-Barr virus infection, possibly HIV)

Drug Indication

Formulations Dosage

Amoxicillin

Tablet/capsule: 250 mg, 500 mg Powder for oral liquid: 125 mg/5 ml

Non-severe pneumonia (10.6.3)

Oral: 500–1000 mg 3 times daily for 5–7 days

Summary tables

Sinusitis (11.35)

Oral: 1 gram 3 times daily for 7 days

Non-severe cutaneous anthrax (10.2.10)

Oral: 500 mg every 8 hours for 7–10 days

Refractory gastritis/ PUD–eradication regimen for documented H. pylori infection (10.7a.2)

Oral: 1 g twice daily AND clarithromycin AND omeprazole for 1 week

Dental abscess (10.17.5) and peritonsillar abscess (10.17.9)

Oral: 500 mg to 1 g 3 times daily for 5–7 days AND metronidazole

(Other indications: Bronchitis; otitis media; osteomyelitis; endocarditis prophylaxis; postsplenectomy prophylaxis)

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Drug Indication Common: Transient increase in liver enzymes and bilirubin Breastfeeding: Considered safe. See amoxicillin. Contraindications: Known severe hypersensitivity to penicillins or other beta-lactams Pregnancy/breastfeeding: Not known to be harmful.

Formulations Dosage

Adverse effects

Special groups/comments

Amoxicillin with clavulanic acid (co–amoxiclav) Doses are based on amoxicillin component.

Tablet/capsule: amoxicillin 500 mg + clavulanic acid 125 mg; amoxicillin 875 mg + 125 mg clavulanic acid

Septic abortion (10.15.6)

Oral: 500 mg 3 times daily for 5 days (double in severe infections)

Use with caution: In history of mild hypersensitivity to betalactams, renal impairment, hepatic impairment Administration: Renal dose adjustment required (do not use high doses with CrCl ≤30 ml/hour). 875 mg orally every 12 hours can be substituted for 500 mg orally every 8 hours. Counselling: To minimize stomach upset, take at the start of a meal.

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Acute generalised exanthematous pustulosis; very rarely hepatic events have been reported, predominantly in males and elderly patients; these may be associated with prolonged treatment. In some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Common: Acute infusion reactions (fever, chills, headache, hypotension) – these become less frequent over time; thrombophlebitis, anaemia, nephrotoxicity (major dose-limiting toxicity); hypokalaemia, hypomagnesaemia Use with caution: In renal impairment use liposomal amphotericin if possible (see Section 11.5). Infrequent or rare: Anaphylaxis occurs rarely with any IV amphotericin product. Headache, anorexia, weight loss, nausea, vomiting, diarrhoea; muscle and joint pain; cardiovascular toxicity (arrhythmias and cardiac arrest, due to rapid infusion and electrolyte disturbances); neurological disorders, abnormal liver function (discontinue treatment)

Lower urinary tract infection (11.44)

Oral: 500 mg 3 times daily for 3–7 days

Dental abscess (10.17.5); peritonsillar abscess (10.17.9)

Oral: 500 mg 3 times daily or 875 mg every 12 hours for 14 days.

Cholecystitis (10.7a)

Sinusitis (11.35) (Other indications: Otitis media; cellulitis)

Oral: 1 g 3 times daily or, if severe, 4 times daily 875 mg twice daily for 7 days Pregnancy/breastfeeding: Use with caution in pregnancy or breastfeeding, if clinically indicated. Available safety data are limited.

Amphotericin B (conventional)

Infusion, intravenous: 50 mg vial (dissolve 50 mg in 10 ml sterile water and make up to 500 ml with 5% glucose to give 100 mcg/ml)

Summary tables

Cryptococcosis (11.5)

See Section 11.5 for dosing and administration.

Histoplasmosis (moderate– severe) (11.16); penicilliosis (moderate–severe) (11.29)

IV: 0.7 mg/kg until clinical improvement (usually 14 days) THEN itraconazole maintenance therapy

Visceral and cutaneous leishmaniasis (11.20)

See Section 11.20

Administration: Follow instructions in Section 11.5. Give via D5W IV infusion (incompatible with NS, 1/2 NS, other saline-containing solutions, or preservatives) over 2 to 6 hours. Infusion time may be reduced to approximately 1 hour in patients who tolerate treatment well. If the patient experiences discomfort during infusion, the duration of infusion may be increased. Existing IV line should be ﬂushed with D5W prior to infusion (if not feasible, administer through a separate line).

(Other indications: disseminated deep fungal infections)

353

354 Adverse effects See conventional amphotericin B. Incidence of decreased renal function and infusion-related events are lower than with conventional amphotericin B. Special groups/comments If available, liposomal amphotericin B should be used instead of conventional amphotericin B in patients with renal failure; or switch from amphotericin B if renal impairment develops. Available at decreased cost through WHO-Gilead partnership for leishmaniasis (see http://www.gilead.com/visceral_ leishmaniasis). Pregnancy/breastfeeding: Use with caution in pregnancy or breastfeeding, if clinically indicated. Available safety data are limited. Use with caution: In renal impairment; continue to monitor electrolytes and renal function tests despite lower incidence of adverse renal effects than with conventional amphotericin. Administration: See conventional amphotericin B. Common: Nausea, vomiting, diarrhoea Infrequent or rare: Haemolytic anaemia, interstitial nephritis, blood disorders, C. difﬁcile colitis Hypersensitivity reaction (discontinue if severe), anaphylaxis Pregnancy: Not known to be harmful. Breastfeeding: Considered safe Contraindications: Severe hypersensitivity to penicillins and other beta-lactams Use with caution: In mild hypersensitivity to beta-lactams with renal impairment. Erythematous rashes common in glandular fever, lymphocytic leukaemia, Epstein-Barr virus, cytomegalovirus infection. Administration: Injection contains 2.7 mmol (62 mg) sodium/ gram. Reduce dose in severe renal failure. For a patient who experiences chills, fever, hypotension, nausea, or other nonanaphylactic infusion-related reactions, premedicate with the following drugs 30–60 minutes prior to drug administration: paracetamol OR hydrocortisone 50–100 mg.

Drug Indication

Formulations Dosage

Amphotericin B (liposomal)

Injection, powder for reconstitution: 50 mg (contains soy, sucrose 900 mg)

Visceral and cutaneous leishmaniasis (11.20)

See Section 11.20 for dosing.

Cryptococcal meningitis in patients with renal impairment (11.5)

See Section 11.5 for dosing.

Summary tables

Ampicillin

Injection: 500 mg vial, 1 g vial

Severe infections (septic abortion (10.15.6); septic shock (3.1.5); upper urinary tract infection (pyelonephritis) (11.44)

IM/IV: 250 mg/kg daily, divided every 4 hours (range 6–12 g/ day) AND gentamicin for 10–14 days AND, for septic abortion, clindamycin

Empirical therapy for meningitis, if ceftriaxone not available (10.10b.3)

IM/IV: 250 mg/kg daily divided every 4 hours (range 6–12 g/day) AND gentamicin + cotrimoxazole for 10–14 days

Initial empirical antibiotics for emergency management (QC p. 19)

IM/IV: 2 g in a single dose AND gentamicin 240 mg

Cholangitis (10.7a.2), peritonitis (10.7a.2)

IV: 2 g every 4 hours AND gentamicin + metronidazole for 10–14 days

Listerial meningitis (10.10b.3)

IV: 2 g IV every 4 hours for at least 21 days PLUS gentamicin

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Leptospirosis (11.22)

(Other indications: Mastoiditis; osteomyelitis)

IV: 500 mg to 1 g every 6 hours for 7 days

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments

ANTIRETROVIRALS for HIV infection Note: antiretroviral therapy must include at least 3 ARVs. See Sections 13 and 14. Common: Nausea, vomiting, diarrhoea Infrequent or rare: Life-threatening hypersensitivity reactions, blood disorders, lipodystrophy, lactic acidosis Pregnancy/breastfeeding: Limited safety data available, but continuation of antiretroviral therapy throughout pregnancy is recommended. Potential alternate if AZT and TDF are not tolerated during pregnancy. Use with caution: In hepatic disease. Can lead to potential life-threatening lactic acidosis. Safe to use after lactic acidosis. Do not use after ABC hypersensitivity reactions. Pregnancy/breastfeeding: Generally safe Use with caution: In haemophilia: possible increased bleeding episodes Administration: Take both at same time with food Common: Nausea, vomiting, diarrhoea, Infrequent or rare: Acute pancreatitis, lactic acidosis, peripheral neuropathy, lipodistrophy, hyperuricaemia

Abacavir (ABC)

Tablet: 300 mg Oral liquid: 100 mg/ml

Antiretroviral (13, 14)

Oral: 300 mg twice daily or 600 mg once daily

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Diarrhoea; indirect hyperbilirubinaemia, clinical jaundice, hyperglycaemia, fat maldistribution; nephrolithiasis; prolonged PR interval – ﬁrstdegree symptomatic AV block in some patients Contraindications: Do not use with stavudine (d4T).

If hepatic impairment (mild), 200 mg twice daily (maximum)

Atazanavir + ritonavir (ATV/r)

Capsule 300 mg atazanavir; capsule ritonavir 100 mg

Oral: 300 mg ATV and 100 mg ritonavir once daily

Antiretroviral (13, 14)

Didanosine (ddI)

Capsule: 400 mg

Antiretroviral (13, 14)

Oral: 250 mg once daily if <60 kg; 400 mg once daily if >60 kg Ensure sufﬁcient antacid from buffered tablets at least 1 hour before food or on empty stomach

Pregnancy/breastfeeding: Lactic acidosis with hepatic steatosis may be more frequent in pregnant women. Should be used during pregnancy only if there is NO alternative.

Summary tables

Use with caution: In renal or hepatic impairment; see dose adjustment in Section 11.31.

355

356 Adverse effects Common: Hypersensitivity reaction; Rash – generally mild, often resolves within 3–5 days without need to change ART (but discontinue if severe) Often self-limiting CNS toxicities: Insomnia, abnormal dreams; less commonly, persistent and severe CNS toxicity (depression, confusion) Hepatic toxicity: Elevated liver enzymes (if seropositive for hepatitis B or C) Hyperlipidaemia; male gynaecomastia; potential teratogenicity (ﬁrst trimester of pregnancy) Infrequent or rare: Stevens-Johnsons syndrome Special groups/comments Pregnancy/breastfeeding: Potential risk of teratogenicity in ﬁrst trimester. Safe after ﬁrst trimester. Provide effective contraceptives after delivery. Discuss risk and beneﬁt of using EFV with women who are planning to become pregnant or who may become pregnant. If a woman is diagnosed as pregnant before 28 days of gestation or plans to become pregnant, EFV should be stopped and NVP or a PI substituted. There is no indication for termination of pregnancy in women exposed to EFV in the ﬁrst trimester. Provide effective contraceptive for women of reproductive age who are taking EFV and choose to avoid conception. Use with caution: In hepatic impairment (avoid if severe), severe renal impairment, elderly, history of mental illness or substance abuse. Rash usually resolves within 3-5 days, but discontinue ART and monitor AST or ALT if rash severe or if accompanied by blisters, desquamation, involvement of mucous membranes, or fever; seek urgent medical care. See Section 13. Seek urgent medical care also in severe CNS toxicities or if depression, confusion occurs. Contraindications: History of severe psychiatric illness Administration: Take at bedtime on an empty stomach. Suggested substitution if not tolerated: NVP, or bPI if neither NNRTI is tolerated; or triple NRTI if no other options Common: Nausea/vomiting, abdominal pain, diarrhoea, headache, peripheral neuropathy Pregnancy/breastfeeding: There is limited experience with use during pregnancy. Use with caution: In renal impairment, hepatic disease Active against HBV (see Section 11.14)

Drug Indication

Formulations Dosage

Efavirenz (EFV)

Capsule: 100 mg, 200 mg Tablet: 600 mg Oral solution: 150 mg/5 ml

Oral: 600 mg once daily

Antiretroviral (13, 14)

Summary tables

See Section 14 for use of EFV as ARV prophylaxis against MTCT of HIV.

Emtricitabine (FTC)

Capsule: 200 mg Oral liquid: 10 mg/ml

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Antiretroviral (13)

Oral: 200 mg once daily

Drug Indication Common: Well tolerated; occasional nausea and diarrhoea, pancreatitis Active against HBV (see Section 11.14) Pregnancy/breastfeeding: Favourable safety proﬁle

Formulations Dosage

Adverse effects

Special groups/comments

Lamivudine (3TC)

Tablet: 150 mg Oral solution: 50 mg/5 ml

Antiretroviral (13, 14)

Oral: 150 mg twice daily OR 300 mg once daily

See Section 14 for use as ARV prophylaxis against MTCT of HIV. Common: Nausea and vomiting, rash (including Stevens-Johnson syndrome) Infrequent or rare: Toxic epidermal necrolysis, hepatotoxicity jaundice, abdominal pain, diarrhoea, hypersensitivity reactions

Nevirapine (NVP)

Tablet: 200 mg

Vol. 1 • 8. Medicines/therapies: July 2011 Common: GI intolerance, nausea, vomiting, diarrhoea, headache Infrequent or rare: Hyperlipidaemia (especially hypertriglyceridaemia), elevated transaminases, hyperglycaemia, fat maldistribution, PR interval prolongation, QT interval prolongation, torsade de pointes, lipodystrophy Use with caution: Close clinical and hepatic enzyme monitoring needed in patients taking ritonavir superboosting. Suggested substitute: ATV/r

Antiretroviral (13, 14)

Oral: 200 mg once daily for ﬁrst 14 days; THEN (if no rash present) 200 mg twice daily

Pregnancy/breastfeeding: Avoid using in pregnant women with CD4 count >350. In women with CD4 count of 250–350 increased risks of maternal hepatotoxicity; use, with close monitoring, as beneﬁt exceeds risk in those who require ART. Contraindications: Severe hepatic failure, pregnancy with CD4 >350 Use with caution: In hepatic impairment or history of chronic hepatitis; monitor liver function. Counselling: Advise patients about the signs or symptoms of hypersensitivity reactions. Seek immediate medical attention if such symptoms develop. Pregnancy/breastfeeding: Continuation of antiretroviral therapy throughout pregnancy is recommended; close monitoring of blood glucose recommended, as risk of pregnancy-related hyperglycaemia may be increased.

See Section 14 for use as ARV prophylaxis against MTCT of HIV.

Lopinavir + ritonavir (LPV/r)

Tablet: Fixed dose combination of (LPV 200 mg + RTV 50 mg) and (LPV 100 mg + RTV 25 mg)

Summary tables

Antiretroviral (13, 14)

Oral: LPV 200 mg + RTV 50 mg (2 tablets) twice daily

In patients taking rifampicin, use ritonavir super-boosting (LPV 400 mg + RTV 400 mg OR LPV 800 mg + RTV 200 mg) twice daily.

Administration: Possible increased bleeding episodes in patients with haemophilia

357

358 Adverse effects Special groups/comments Common: Diarrhoea, headache, increased transaminases, dyslipidaemia, hyperglycaemia, buccal and mucosal ulceration, unconjugated hyperbilirubinaemia Use with caution: In severe hepatic impairment Administration: Take with a fatty meal or up to 2 hours after meal. Avoid garlic capsules, which reduce plasma saquinavir concentration) Common: Nausea, vomiting, diarrhoea, abdominal pain, headache, dizziness Pregnancy/breastfeeding: Continuation of antiretroviral therapy throughout pregnancy is recommended; close monitoring of blood glucose recommended, as risk of pregnancy-related hyperglycaemia may be increased. Pregnancy/breastfeeding: Concern of HBV ﬂare if HBV–HIV co-infected mother stops the medication postpartum. Limited data available on potential maternal and infant bone toxicity. Contraindication: Renal impairment Use with caution: In underlying renal disease, age >40 years, BMI <18.5 (or body weight <50 kg), diabetes mellitus, hypertension, concomitant use of a bPI or nephrotoxic drug Administration: Do not use with ddI (levels increased). Active against HBV (see Section 11.14) Common: Nausea, vomiting, diarrhoea, headache, fatigue, myalgia Infrequent or rare: Bone marrow suppression (macrocytic anaemia, neutropenia); pancreatitis, lactic acidosis with hepatic steatosis, CNS problems, insomnia, pigmentation of nails, skin, oral mucosa Pregnancy/breastfeeding: Well tolerated, risk of anaemia Contraindications: Abnormally low neutrophil counts or severe anaemia (Hb <7.0 g/dl and/or ANC <750 cells/mm3); high risk for anaemia and neutropaenia if CD4 count <200, BMI <18.5 (or body weight <50 kg), anaemia at baseline. Use with caution: In vitamin B12 deﬁciency, renal or hepatic impairment, elderly patients Infrequent or rare: Renal insufﬁciency, Fanconi syndrome, hypertriglyceridaemia, osteomalacia. Severe acute exacerbation of hepatitis may occur in HBV co-infected patients who discontinue TDF.

Drug Indication

Formulations Dosage

Saquinavir (SQV)

Capsule: 200 mg

Antiretroviral (13, 14)

Oral: 1 g twice daily (with 100 mg ritonavir booster)

Summary tables

Tenofovir (TDF)

Tablet: 300 mg

Antiretroviral (13, 14)

Oral: 300 mg tablet once daily

Zidovudine (ZDV, AZT)

Capsule: 250 mg

Antiretroviral (13, 14)

Oral: 250–300 mg twice daily

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See Section 14 for use as ARV prophylaxis against MTCT of HIV.

Drug Indication Common: Refer to artesunate. Neurotoxicity has been reported in animal studies, particularly with very high doses of intramuscular artemether, but has not been substantiated in humans.

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Both artesunate and quinine may be considered as options for the treatment of severe malaria during pregnancy. See note under artesunate Use with caution: In all patients, artemether IM should only be used if parenteral formulations of artesunate or quinine are not available, as its absorption may be erratic.

Artemether

Injection: 80 mg/ml in 1 ml ampoule

Severe malaria (note: IV artesunate is preferred) (QC, p.20 and 11.25)

Loading dose: IM (in anterior thigh): 3.2 mg/kg then 1.6 mg/kg daily until patient can take oral.

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Abdominal pain, anorexia, diarrhoea, nausea/vomiting, palpitation, cough, headache, dizziness, sleep disturbances, asthenia, arthralgia, myalgia, pruritus, rash, QT prolongation Infrequent or rare: Paraesthesia, ataxia, hypoaesthesia, increased liver transaminases

Start appropriate oral treatment as soon as tolerated and give full course (see Section 11.25). Pregnancy/breastfeeding: Not recommended in ﬁrsttrimester pregnancy unless no other treatment immediately available. Contraindications: History of arrhythmias, clinically relevant bradycardia, or CHF with reduced LV ejection fraction; family history of sudden death or prolonged QT interval. Administration: Lumefantrine absorption is enhanced by co-administration with fat. Counselling: Take this ACT immediately after a meal or drink containing at least 1.2 g fat. Dizziness may impair ability to perform skilled tasks such as operating machinery and driving.

Artemether + lumefantrine

Co-formulated tablets of 20 mg artemether + 120 mg lumefantrine

Uncomplicated P. falciparum malaria, ﬁrstline (11.25)

Oral: 80 mg artemether and 480 mg lumefantrine twice daily for 3 days

Summary tables

359

360 Adverse effects Generally well tolerated Special groups/comments Pregnancy/breastfeeding: Both artesunate and quinine may be considered as options for the treatment of severe malaria during pregnancy. Treatment must not be delayed; so, if only one of the drugs artesunate, artemether, or quinine is available, then that should be started immediately. Give quinine if possible during ﬁrst trimester; for second and third trimesters, artesunate is preferred, as it is for all adolescents and adults. Use with caution: In patients who must perform skilled tasks, such as operating machinery or driving, that would be impaired by dizziness. Administration: The solution should be used immediately after the powder is dissolved. It should not be used for intravenous infusion if the solution appears cloudy or if sediment is present. Common: Anorexia, abdominal pain, nausea; somnolence, insomnia; cough. Infrequent or rare: Weakness, anaemia, vertigo. Amodiaquine (at higher doses and/or during prolonged treatment) may lead to leukopenia and neutropaenia, agranulocytosis; nervous system disorders. Rare: Neuromyopathy, transient accommodation disorders, corneal opaciﬁcation (regresses once treatment stops) but, very rarely, irreversible retinopathy; hepato-biliary disorders: severe, sometimes fatal hepatitis; slate-gray pigmentation of the skin, notably affecting the ﬁngers and mucous membranes. Pregnancy: Not recommended in ﬁrst-trimester pregnancy unless no other treatment immediately available Breastfeeding: No data available on the excretion of artesunate/amodiaquine ﬁxed-dose combination in breast milk. Continuation can be considered while taking into account safety proﬁle of artesunate/amodiaquine ﬁxed-dose combination tablets. Contraindications: Previous hypersensitivity to amodiaquine or artesunate, history of liver toxicity or neutropenia during treatment with amodiaquine, retinopathy (in cases of frequent treatment) Use with caution: Avoid if possible in PLHIV on zidovudine or efavirenz. Counselling: Somnolence, dizziness, or weakness may occur. May impair ability to perform skilled tasks such as operating machinery and driving. Infrequent or rare: Mild gastrointestinal disturbances, dizziness, tinnitus, reticulocytopenia, neutropenia, elevated liver enzyme values, ECG abnormalities (bradycardia, prolongation of the QT interval), Type 1 hypersensitivity reactions in approximately 1 in every 3000 patients. Post-treatment hemolysis has been observed with high cumulative doses. (Patients should be monitored for signs of hemolysis after parasitologic cure.)

Drug Indication

Formulations Dosage

Artesunate

Injection: 60 mg ampoule with separate ampoule of 5% sodium bicarbonate

Severe malaria (QC p. 20, 11.25.5)

IM/IV: 2.4 mg/kg on admission AND repeat at 12 hours, 24 hours; then once daily. Start appropriate oral treatment as soon as tolerated, and give full course. See Section 11.25.5.

Summary tables

Artesunate + amodiaquine

Co-formulated tablets of artesunate + amodiaquine, 25/67.5 mg, 50/135 mg, or 100/270 mg. Blister packs of separate scored tablets also exist.

Uncomplicated P. falciparum malaria, ﬁrst-line (11.25)

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Oral: 200 mg artesunate and 540 mg amodiaquine ﬁxed-dose combination once daily for 3 days

Drug Indication Common: Nausea/vomiting, anorexia, diarrhoea Infrequent or rare: See cotrimoxazole. Breastfeeding: Safe to use

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Not recommended in the ﬁrst trimester unless no other treatment immediately available.

Artesunate + sulfadoxine– pyrimethamine

Co-blistered, scored tablets of 50 mg artesunate and tablets of 500 mg sulfadoxine + 25 mg pyrimethamine

Uncomplicated P. falciparum malaria, ﬁrstline (11.25) See cotrimoxazole. Common: Nausea/ vomiting, diarrhoea, abdominal pain, anorexia, headache, dizziness, loss of balance, sleep disorders (abnormal dreams) Infrequent or rare: Neurological and psychiatric disturbances (convulsions, depression, hallucinations, panic attacks, emotional instability, aggression, suicidal ideation), cardiac conduction problems, muscle weakness/rash, disturbances in liver function tests

Oral: 200 mg artesunate once daily for 3 days AND 1500 mg/75 mg sulfadoxine- pyrimethamine as a single dose on day 1

Use with caution: Do not choose this option if patient is taking cotrimoxazole prophylaxis.

Vol. 1 • 8. Medicines/therapies: July 2011 Breastfeeding: Safe to use Use with caution: Avoid in severe hepatic impairment, cardiac conduction disorders. See artesunate and clindamycin. Breastfeeding: See clindamycin.

Artesunate + meﬂoquine

Co-blistered, scored tablets of 50 mg artesunate and 250 mg base of meﬂoquine

Pregnancy: Not recommended during the ﬁrst trimester unless no other treatment immediately available.

Uncomplicated P. falciparum malaria, ﬁrstline (11.25)

Oral: 200 mg artesunate once daily for 3 days AND 1500 mg meﬂoquine, usually split on days 2 and 3 (e.g. 4 tablets on day 2 and 2 on day 3)

Contraindications: Do not give meﬂoquine within 60 days of prior administration. History of neuropsychiatric disorders, epilepsy, hypersensitivity to quinine

Counselling: May impair ability to perform skilled tasks such as operating machinery and driving. These effects may continue up to 3 weeks after the last dose. Pregnancy: Not recommended during the ﬁrst trimester unless no other treatment available.

Summary tables

Artesunate + clindamycin

See clindamycin and artesunate

Uncomplicated P. falciparum malaria, ﬁrstline (11.25)

Oral: Artesunate 2 mg/kg once daily AND clindamycin 10 mg/kg twice daily for 7 days

361

362 Adverse effects Common: Dry mouth, tachycardia, blurred vision, photophobia, constipation, urinary retention, ﬂushing, delirium, fever Infrequent or rare: Vomiting, headache, paralytic ileus, rash, acute angle-closure glaucoma, seizures Special groups/comments Pregnancy: May be used at recommended doses. Can affect fetal heart rate. Breastfeeding: Use with caution in breastfeeding; monitor infant (e.g. drying of secretions, temperature rise). May suppress milk production. Contraindications: Angle-closure glaucoma. Use with caution: In Down syndrome, myasthenia gravis, pyloric stenosis, ileus, prostatic enlargement, cardiac disorders, hypoxia, and in the elderly. Patients with pyrexia and in warm environments: Monitor temperature and keep patients cool. Use may precipitate acute attack of angle-closure glaucoma, particularly in the elderly or long-sighted. Common: Transient stinging, raised intraocular pressure, local irritation, hyperaemia, oedema, contact dermatitis, systemic toxicity (in very young and elderly) Precautions: May cause sensitivity to light and blurred vision. Contraindications: Angle-closure glaucoma Counselling:Avoid skilled tasks, such as operating machinery or driving, until your vision is clear.

Drug Indication

Formulations Dosage

Atropine

Injection: 1 mg (sulfate) in 1 ml ampoule

Organophosphate poisoning (3.8.1)

IM/IV: Give bolus 1–3 mg (aim for clear lungs, stable blood pressure and dry mucous membranes) THEN double initial dose if no improvement at 5 minutes. See Section 3.8.1 for further treatment and monitoring.

Summary tables

Beta-blocker overdose with hypotension (3.8.1)

IV: 0.5–1 mg. Repeat every 3–5 minutes to a total dose of 0.04 mg/kg

Beta-blocker overdose: prophylaxis before inserting NG tube (3.8.1)

IV: 0.6 mg

Block muscarinic effects of neostigmine (3.9.2)

IV: 25–30 mcg/kg given 30–60 seconds before neostigmine administration

(Other indications: Bradycardia; heart block with hypotension)

Atropine eye drops

Solution (eye drops): 0.5%, 1% (sulfate)

Iritis, uveitis; prereferral treatment for bacterial corneal infection (10.12.2)

1 drop (0.5% or 1% solution) up to 4 times daily

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(Other indications: Cycloplegic refraction procedures)

Drug Indication Common: Nausea/ vomiting, diarrhoea, abdominal pain and cramps, headache, dizziness, drowsiness, candida infections, taste disturbances

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Use, with caution, in pregnancy or breastfeeding, if clinically indicated. Available data on safety are lmited. Contraindications: Hypersensitivity to macrolides Use with caution: In renal impairment, hepatic impairment; in combination with other medications that can prolong QT interval; myasthenia gravis Administration: Capsule should be taken on an empty stomach. Oral suspension can be taken with food. Counselling: Swallow whole at least 1 hour before or 2 hours after food. Do not take with aluminium or indigestion remedies containing magnesium.

Azithromycin

Capsule: 250 mg, 500 mg, 600 mg

Uncomplicated genital chlamydial infections (10.15.4)

Oral: 1 g as a single dose (>45 kg) OR 20 mg/kg as a single dose (<45 kg)

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Constipation, hepatitis, hepatic failure, syncope, insomnia, agitation, anxiety, asthenia, paraesthesia, hyperactivity, thrombocytopenia, haemolytic anaemia, interstitial nephritis, acute renal failure, photosensitivity, tooth and tongue discoloration, C. difﬁcile colitis; hypersensitivity reactions including anaphylaxis Common: Oropharyngeal candidiasis; cough, dysphonia; bruising, facial skin irritation following nebulisation Breastfeeding: Considered safe Infrequent or rare: Adrenal suppression, growth retardation in adolescents, impaired bone metabolism, cataract, glaucoma with high doses or when combined with oral steroids, paradoxical bronchospasm, urticaria, rash, angioedema, sleep disorders, anxiety, behavioural changes Use with caution: If active or quiescent TB possible.

Trachoma (10.12.5)

Oral: 20 mg/kg up to 1 g once annually AND tetracycline ointment

Early syphilis (11.37)

Oral: 2 g once (do not use in PLHIV)

Mycobacterium avium complex (MAC) (11.27)

Oral: 600 mg daily AND ethambutol for 6 months

Yaws (10.2.5)

Oral: 30 mg/kg (maximum 2000 mg) single dose Pregnancy: Beneﬁt of treatment greater than risk. Not known to be harmful.

Beclometasone inhaler

Inhalation: aerosol 50 mg per dose (dipropionate); 250 mg (dipropionate) per dose

Chronic asthma, COPD (10.6.4, 10.6.5)

See Section 10.6 for dosing.

Summary tables

363

364 Adverse effects Common: Pain/inﬂammation at injection site Pregnancy: Not known to be harmful. Breastfeeding: Considered safe (monitor infant) Contraindications: Severe hypersensitivity to penicillins or other beta-lactams Use with caution: With history of allergy, renal failure, heart failure. Administration: Given by deep IM injection only. Give doses of more than 900 mg as two injections at separate sites. Do not give IV. Avoid intrathecal injection. Special groups/comments Infrequent or rare: Hypersensitivity reactions, including anaphylaxis, haemolytic anaemia, interstitial nephritis, blood disorders, CNS toxicity, Jarisch-Herxheimer reaction Common: Dermatitis with cutaneous eruptions (rash and rash erythematous); generalized oedema; fever, myalgias, arthralgias; gastrointestinal disorders; depression of bone marrow; polyneuropathy, paresthaesia, peripheral neuropathy, among others Pregnancy/breastfeeding: Not recommended in ﬁrst trimester; use, with caution, in second and third trimester or breastfeeding if clinically indicated. Available data on safety are limited. Contraindications: Renal impairment; hepatic impairment Administration: Preferably after meals

Drug Indication

Formulations Dosage

Benzathine benzylpenicillin

Injection: benzathine benzylpenicillin 1.8 g (equal to 2.4 million IU) in 5 ml vial

Streptococcal pharyngitis (10.17.9)

IM: 900 mg (1.2 million IU) as a single dose

Secondary prophylaxis of rheumatic fever (11.32)

IM: 900 mg (1.2 million IU) every 3–4 weeks

Summary tables

Early syphilis (11.37)

IM: 1.8 g (2.4 million IU), divided between 2 sites, as a single dose

Late syphilis (11.37)

IM: 1.8 g (2.4 million IU), divided between 2 sites, once weekly for 3 consecutive weeks

Yaws (10.2.5)

IM: 900 mg (1.2 million IU) as a single dose

Benznidazole

Tablet: 100 mg

Chagas disease (11.42)

Oral: 5 mg/kg daily, divided in 2 or 3 daily doses, over 60 consecutive days (maximum 300 mg/day)

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Drug Indication Infrequent or rare: Local irritation, burning sensation, itch dermatitis, CNS stimulation (e.g. seizures with excessive use)

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: May be used in pregnancy at the recommended dose, but permethrin is the preferred treatment during pregnancy.

Benzyl benzoate

Lotion: 25%

Scabies (10.2.3); empirical treatment of itching papular lesions (10.2.3)

Topical: Follow instructions in 10.2.3.

Pediculosis (10.2.8)

Vol. 1 • 8. Medicines/therapies: July 2011 Pregnancy/breastfeeding: Safe to use Use with caution: Avoid contact with eyes, mouth, and mucous membranes; avoid use of occlusive dressings. Common: Initial irritation: skin dryness or peeling, feeling of warmth, mild stinging, erythema, but subsiding with continued use (in some cases may need to reduce frequency of application or temporarily suspend use) Infrequent or rare: Contact sensitivity (occasionally, even one application can cause severe irritation).

Apply to affected area THEN wash off 24 hours later (further applications may be needed after 7 and 14 days).

Breastfeeding: May be used at the recommended dose if it is the treatment of choice; systemic absorption likely to be minimal with topical use, but excess lotion should be wiped from nipple areas, and infant skin contact, minimized. Use with caution: Do not use on inﬂamed or broken skin. Avoid contact with eyes and mucous membranes. Administration: See Section 10.2.3. Do not bathe before application. Application to the face and genitals can cause irritation; an alternative agent such as permethrin is preferable. Counselling: Remember to apply also between ﬁngers and toes, under nails, in skin folds, navel, between the buttocks, and on groin area. If you wash your hands or any other parts of the body during the treatment period, you should reapply the lotion to the washed areas.

Benzoyl peroxide

Cream or lotion: 2.5%, 5%

Summary tables

Acne (10.2.3)

Initially apply directly to clean skin on alternate days, increasing frequency to 1–2 times daily as tolerance to irritant effect develops. Continue until 2 weeks after lesions disappear.

Counselling: Before applying, wash affected area with mild soap or soap substitute and warm water. Gently pat dry. Then apply a thin layer to the affected area and rub in gently. May bleach fabrics, hair, and skin. Avoid excessive exposure to sunlight.

365

366 Adverse effects See benzathine benzylpenicillin. See benzathine benzylpenicillin. Special groups/comments Pregnancy/breastfeeding: May be used in pregnancy and breastfeeding; systemic absorption likely to be minimal with topical use. Contraindications: Untreated skin infections, broken skin, rosacea, acne, perioral dermatitis Common: Folliculitis, steroid rosacea, perioral dermatitis, atropy-thinning of the skin, striae, depigmenatation, dilated vessels, acne at site of application, exacerbation of local infection or worsening of the condition; local trophic changes (particularly on the face and in skin folds) Infrequent or rare: Contact dermatitis, hyperaesthesia, subcutaneous tissue atrophy, hypertrichosis Use with caution: In psoriasis (may precipitate severe pustular psoriasis on withdrawal; avoid in widespread plaque psoriasis). If used on a large area of the body or for a long time, risk for adrenal suppression (particularly with an occlusive dressing). Avoid use on the face for more than 7 days. Secondary infection requires treatment with an appropriate antimicrobial. Counselling: Apply a thin layer by smoothing gently into skin, preferably after bathing.

Drug Indication

Formulations Dosage

Benzylpenicillin (penicillin G)

Intravenous: 600 mg (1 million IU); 3 g (5 million IU) (sodium or potassium salt) in vial

Streptococcal endocarditis (11.10)

IV: 7.2–10.8 g (12–18 million IU) daily in 4 or 6 equally divided doses for 4 weeks

Summary tables

Neurosyphilis (11.37)

IV: 1.8–2.4 g (3–4 million IU) every 4 hours for 2 weeks

Severe anthrax (10.2.10, 10.6.2)

IV: 2.4–3.6 g (4–6 million IU) every 6 hours for 7–10 days

Leptospirosis (11.22)

(Other indications: Otitis media; gas gangrene; actinomycosis; osteomyelitis; brain abscess)

IV: 900 mg (1.5 million IU) every 6 hours for 7 days

Betametasone (topical)

Cream, ointment: 0.1%

Severe inﬂammatory skin conditions including papular lesions; eosinophilic folliculitis; pityrosporum folliculitis; papular urticaria; eczema; contact, atopic dermatitis; numular eczema; seborrhoeic dermatitis; psoriasis; itchy papular lesions (10.2)

Apply sparingly 1 or 2 times daily.

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(Other indications: Lichen planus)

Drug Indication Pregnancy/breastfeeding: Appears to be safe

Formulations Dosage

Adverse effects

Special groups/comments

Biperiden Common: Nausea, vomiting, dry mouth, constipation, dyspepsia; blurred vision, mydriasis, dry eyes; urinary retention, tachycardia; sedation, confusion, memory disturbance especially in elderly Infrequent or rare: arrhythmia, dizziness, drowsiness, headache, hallucinations, fever, anaphylaxis, acute angle-closure glaucoma, myasthenia gravis, gastrointestinal obstruction

Injection: 5 mg IM/IV Tablet: 2 mg

Acute dystonic reaction (QC p. 29)

IM: 5 mg (give IV if condition life-threatening); maximum 20 mg in 24 hours

Vol. 1 • 8. Medicines/therapies: July 2011 Opioid agonist effects Pregnancy: Previously commenced therapy can be maintained. Common: Euphoria; constipation, anorexia, nausea, vomiting, sweating, headache, dizziness, vasodilatation; dry mouth, fatigue, sedation, anxiety. postural hypotension, miosis, decreased libido Infrequent or rare: Hallucinations, confusion, spasm of urinary or biliary tract, hypotension, vertigo, bradycardia, tachycardia, palpitations, hypothermia, rash, facial ﬂushing, urticaria Opioid antagonist effects (which can occur if used soon after a full opioid agonist such as methadone) mimic those of naltrexone in opioid dependence. Common: Vomiting, nausea, diarrhoea, anxiety, agitation, restlessness, insomnia, muscle aches, sweating, dilated pupils, tachycardia, hypertension. Infrequent or rare: Delirium, involuntary ejaculation

Antipsychotics causing extrapyramidal side-effects such as parkinsonism or dystonia (10.11.4)

Oral/IV: Start with 1 mg twice daily. Increase to 2 mg 3 times daily to a target dose of 3–12 mg daily.

Buprenorphine

Tablet given sublingually: 2 mg, 8 mg

Opioid withdrawal (3.6.2)

SL: 2–16 mg/day for 3–14 days

Breastfeeding: Caution in breastfeeding; poor oral bioavailability, but monitor infant for opiate side-effects. Use with caution: Must not be given while the person has any signs of opioid toxicity due to risk of precipitating withdrawal syndrome. Buprenorphine has both opioid agonist and antagonist properties and may precipitate withdrawal symptoms in people with high degree of tolerance to opioids, including those prescribed opioids for pain. When injected, buprenorphine has a similar abuse potential to injected heroin and may lead to dependence. Unlike most opioid analgesics, the effects of buprenorphine are only partially reversed by naloxone. Counselling: Place the tablet under the tongue and keep in place until dissolved. Do not chew or swallow the tablet.

Opioid substitution treatment (17.4)

SL: Start at 2–8 mg and increase by up to 8 mg daily as needed up to a maximum of 32 mg. Average dose is usually 12–16 mg daily.

Summary tables

367

368 Adverse effects Special groups/comments Common: Nausea, vomiting, constipation; injection site reactions; fall in blood pressure Infrequent or rare: Bradycardia/arrhythmia, peripheral vasodilation, renal calculi, severe tissue damage with extravasation Pregnancy: Use only when indicated (no controlled trials or animal studies). Breastfeeding: Calcium in breastmilk is normal nutritional component. Contraindications: Conditions associated with hypercalcaemia and hypercalciuria (for example, some forms of malignant disease) Use with caution: In renal impairment, sarcoidosis, history of nephrolithiasis Administration: Monitor ECG (and plasma calcium if feasible) with IV administration. Do not give by subcutaneous or IM route, as it will cause tissue necrosis. For infusion, dilute 100 ml of calcium gluconate 10% in 1 litre of glucose 5% or sodium chloride 0.9%, and give at an initial rate of 50 ml/hour, adjusted according to response.

Drug Indication

Formulations Dosage

Calamine lotion

Mild pruritus; mild drug reactions (10.2)

Lotion: calamine 15%, zinc oxide 5%, bentonite 3%, sodium citrate 0.5%, liquid phenol 0.5%, glycerine 5% + water to 100 ml

Calcium gluconate

IV: 100 mg/ml in 10 ml ampoule (10%)

Summary tables

Hypotension with calcium channel blocker overdose (3.8.1)

IV: 0.6 ml/kg (600 mg/kg) to a maximum of 30 ml over 5 minutes; can be repeated every 10–20 minutes, up to 4 doses

Antidote for magnesium sulfate toxicity (QC p. 28)

IV: 1 g (10 ml of 10% solution) over 10 minutes

Hyperkalemia with ECG changes or K >6.5 mmol/l (5.2.2)

(Other indication: Hypocalcaemic tetany)

IV: 10 ml of calcium gluconate 10% slowly, given over 2–5 minutes; may repeat after 5 minutes titrated and adjusted to ECG improvement

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Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Avoid in pregnancy. May be used in breastfeeding (monitor infant for drowsiness).

Carbamazepine

Oral liquid: 100 mg/5 ml Tablet (chewable): 100 mg, 200 mg Tablet (scored): 100 mg, 200 mg Common: Drowsiness, dizziness, ataxia, headache, diplopia (may be associated with high plasma levels); dry mouth; mild transient generalized erythematous rash (withdraw if worsens or other symptoms); diarrhoea or constipation; leukopenia, thrombocytopenia; increased liver enzymes (usually not clinically signiﬁcant)

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Antibody deﬁciency, exfoliative dermatitis, Stevens-Johnson syndrome, systemic lupus erythematosus, agranulocytosis; aplastic anaemia, multiorgan hypersensitivity syndrome (including fever, severe skin disease, lymphadenopathy, haematologic abnormalities, hepatitis); psychiatric disorders, or facial dyskinesia, jaundice/hepatitis, acute renal failure, cardiovascular problems (arrhythmias, heart block heart failure), neuropsychiatric problems, impotence/male infertility, photosensitivity, pulmonary hypersensitivity, confusion/agitation (elderly), SIADH Common: Nausea, vomiting, diarrhoea, abdominal discomfort; headache Pregnancy/breastfeeding: Safe to use Contraindications: Cephalosporin hypersensitivity Infrequent or rare: Allergic reactions (including anaphylaxis), erythema multiforme; transient hepatitis, jaundice; leukopenia, thrombocytopenia, agranulocytosis, aplastic anaemia, haemolytic anaemia; interstitial nephritis

Generalized tonic-clonic seizures, partial seizures (3.5, 10.10c)

Oral: initially 100–200 mg 1–2 times daily (tablets) OR 50–100 mg every 6 hours as oral suspension THEN Increase gradually by ~200 mg every week as needed (usual maintenance dose is 400–1400 mg daily in divided doses)

Contraindications: Atrioventricular conduction abnormalities, history of bone marrow depression, porphyria; history of sensitivity to tricyclic antidepressants, oxcarbazepine, or other structurally related drugs; use of MAO-Is within past 2 weeks; on antiretrovirals for HIV (lowers levels)

Bipolar disorders (10.11.5)

Oral: initially 200 mg daily at bedtime THEN gradually increase to 400–600 mg daily (divided doses); in severe cases may need 1000 mg

Use with caution: In hepatic impairment, renal impairment, cardiac disease, skin reactions, history of blood disorders, glaucoma, elderly. Monitor blood counts before and during treatment. Avoid sudden withdrawal. Prone to multiple drug interactions. Monitor for drug interactions when starting any new medication.

(In elderly or medically ill: see Section 10.11.5)

Peripheral neuropathy (10.10a.6); neuropathic pain (20.3)

100 mg once or twice daily, THE increase to 200 mg 3 or 4 times daily (up to 1.6 g daily in some patients)

Counselling: Take with food to help prevent stomach upset. This medicine may cause drowsiness, dizziness, or blurred vision, especially at the start of treatment or when the dose is increased. If affected, do not drive or operate machinery. May increase the effects of alcohol. Tell your health care provider that you are taking carbamazepine before starting any new medicine including herbal and OTC products.

Summary tables

Ceﬁxime

Capsule: 400 mg

Gonorrhoea, uncomplicated (10.15.4)

Oral: 400 mg as a single dose

Gonococcal dermatitisarthritis syndrome (10.13.2)

Oral: 400 mg twice daily to complete total 7–10 days, after ceftriaxone for 3 days.

Use with caution: In sensitivities to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction); renal impairment Note: Can cause false positive urinary glucose (if tested for reducing substances) and false positive Coombs’ test.

Gonococcal septic arthritis (10.13.2)

Oral: 400 mg twice daily to complete 14–21 days, after ceftriaxone for 3 days.

369

370 Adverse effects Common: Diarrhoea, nausea; rash, electrolyte disturbances, pain and inﬂammation at injection site Special groups/comments Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for side-effects) Contraindications: Cephalosporin hypersensitivity (anaphylaxis, hives), porphyria, hypoalbuminaemia or impaired bilirubin binding Use with caution: In history of allergy to beta-lactams (minor rash), pre-existing gallbladder disease Administration: Incompatible with calcium; do not give via calcium-containing solutions. Divide IM dose over 1 g between 2 sites. Infrequent or rare: Antibiotic-associated colitis (particularly with higher doses), hypersensitivity reactions (including anaphylaxis), erythema multiforme, transient hepatitis/jaundice, blood disorders (leukopenia, thrombocytopenia, agranulocytosis, aplastic anaemia, haemolytic anaemia), interstitial nephritis, pancreatitis, cholecystitis, pseudolithiasis (dose-dependent, asymptomatic, and reversible biliary sludge formation due to calcium–ceftriaxone complex, which usually resolves after treatment stopped), nephrolithiasis (formation of calcium– ceftriaxone renal stones, sometimes requiring treatment, usually reversible) pain, tenderness at IM injection site (can reconstitute with 1% lidocaine for patient comfort)

Drug Indication

Formulations Dosage

Ceftriaxone

Injection: 250 mg, 1 g (as sodium salt) in vial

First-line empirical antibiotic coverage for emergency management (QC p. 19); septic shock (3.1.5); severe pneumonia (3.2.3); acute pyelonephritis (11.44); septic abortion (10.15.6)

IV: 1 g daily for 7–14 days for severe infection

Summary tables

Endocarditis - viridans streptococci (11.10)

IV: 2 g daily for 4 weeks

Meningitis (10.10b.3)

IV: 2 g twice daily for 5–14 days

Cholangitis (10.7a.2)

IV: 1 g daily AND metronidazole for 10–14 days

Spontaneous bacterial peritonitis (10.9.2)

IV: 2 g daily for 5–10 days

Gonorrhoea, uncomplicated (10.15.4, 11.13)

IM: 250 mg as a single dose

Prophylaxis of contacts of meningococcal meningitis (10.10b.2)

IM: 250 mg as a single dose

Gonorrhoea, arthritis (10.13.5)

IV: 1 g daily, continuing 1–2 days after improvement; THEN ceﬁxime to complete 14–21 days treatment

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Gonorrhoea, conjunctivitis (10.12.2)

IM: 1 g as single dose prereferral

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments

PID (10.15.5)

Severe cellulitis (10.2.2)

IM: 250 mg as a single dose AND doxycycline + metronidazole

Leptospirosis- moderate to severe disease (11.22)

IV: 1 g daily for 7–10 days

IV: 1 g daily for 7 days

Typhoid fever (11.43)

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IV/IM: 1–2 g daily for 10–14 days

Summary tables

371

372 Adverse effects Common: Nausea/vomiting, constipation, black stools, colicky abdominal pain Infrequent or rare: Diarrhoea, aspiration pneumonitis, dehydration and electrolyte imbalances, gastrointestinal obstruction/faecal impaction in dehydrated patients Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding Contraindications: Poisoning by hydrocarbons, with high potential for harm if aspirated; poisoning by corrosive substances – may prevent visualization of lesions caused by poison Use with caution: In drowsy or unconscious patients – risk of aspiration (intubate via nasogastric or gastric tube before administration) Not effective for poisoning with alkalis, acids, heavy metals, iron, lithium, toxic alcohols, glycols, or hydrocarbons such as kerosene Administration: Improve palatability by chilling. It may be easier for some patients to take it in a covered container with a large straw or with eyes shut. Special groups/comments

Drug Indication

Formulations Dosage

Charcoal, activated

Powder

Antidote for some poisons (3.8)

Oral (adults and adolescents >13 years of age): 50–100 g

Summary tables

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Drug Indication Common: Nausea/vomiting, headache, reversible bone marrow suppression

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use with caution in pregnancy; risk of neonatal “grey syndrome” with high doses close to term. Breastfeeding: Not recommended with systemic use

Chloramphenicol

Capsule: 250 mg Injection: 1 g (sodium succinate) vial Oily injection: 500 mg/ml, 2 ml ampoule (for IM use only) Infrequent or rare: Diarrhoea, stomatitis/ glossitis, depression, hypersensitivity reactions (including anaphylaxis), aplastic anaemia, peripheral/optic neuritis, minor disulﬁram-like reactions, grey baby syndrome (premature and newborn infants), C. difﬁcile colitis

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Severe infections such as sensitive H. inﬂuenzae meningitis (10.10b.3); H. inﬂuenzae epiglottitis (3.2.2)

IV: 1 gram every 6 hours

Empirical treatment of bacterial meningitis if anaphylaxis to penicillin (10.10b.3)

IV: 1 gram every 6 hours AND cotrimoxazole

Use with caution: In porphyria reduce high doses as soon as clinically indicated; avoid repeated courses and prolonged use. Reduce dose in hepatic and severe renal impairment. Blood counts required before and during treatment. Plasma concentration monitoring required in the elderly and in hepatic or renal impairment; renal and hepatic dose adjustment required. Counselling: Tell your doctor if you get pale skin, sore throat, fever, tiredness or weakness, or unusual bleeding or bruising in the months after you stop taking the medicine.

Epidemics of meningococcal meningitis (10.10b)

IM (oily): 100 mg/kg (maximum 3 g) as a single dose; repeat after 24–48 hours if necessary

Typhoid fever if known antibiotic sensitivity (11.43)

Oral: 2 to 3 g in 4 divided doses for 14 days

Rickettsial diseases in pregnant women (11.33)

Oral: 500 mg 4 times daily for 5–7 days

Tetanus (11.39)

Summary tables

IV: 1 gram every 6 hours

(Other indications: Cerebral abscess; mastoiditis; relapsing fever; plague; psittacosis; tularemia; Whipple disease)

373

374 Adverse effects Common: Transient stinging Pregnancy/breastfeeding: Safe to use Contraindications: Chloramphenicol hypersensitivity Maximum duration of use: 7 days; prolonged use may lead to overgrowth of non-susceptible organisms Infrequent or rare: Unpleasant taste, hypersensitivity reactions (local allergy, angioedema, anaphylaxis), dermatitis. (Large, population-based studies have found no association between use of chloramphenicol eye drops and aplastic anaemia.) Special groups/comments Infrequent or rare: Skin irritation/local contact dermatitis Pregnancy/breastfeeding: May be used in pregnancy and breastfeeding. Systemic absorption likely to be minimal with topical use. Use with caution: Not for use in body cavities. Avoid contact with middle ear, eyes, brain and meninges.

Drug Indication

Formulations Dosage

Chloramphenicol – eye drops and ointment

Drops: 0.5% Ointment: 1%

Superﬁcial bacterial infections of the eye; prophylaxis against bacterial infection following minor ocular trauma (10.12.2)

Eye drops: 1 or 2 drops, every 2 hours for the ﬁrst 24 hours; THEN decrease to every 6 hours until 48 hours after resolution

Summary tables

(Other indications: blepharitis)

Ointment: May be used at bedtime (if eye drops used during day) or 3–4 times daily (if eye ointment used alone).

Chlorhexidine

Solution: concentrate for solution, 5%

Multiple skin infections, itching (10.2.8)

0.05% aqueous solution applied to affected areas

(Other indications: Disinfection of clean instruments; pre-operative skin disinfection and hand washing)

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Drug Indication Pregnancy: Beneﬁt exceeds risk when indicated for treatment of acute malaria. Breastfeeding: Use with caution.

Formulations Dosage

Adverse effects

Special groups/comments

Chloroquine

Tablet: chloroquine base (as phosphate or sulfate) 100 mg, 150 mg

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Nausea, vomiting, diarrhoea, abdominal pain or cramps; headache; rash, pruritus Infrequent or rare (with prolonged treatment): Psychotic episodes, anxiety, personality changes, visual disturbances (doserelated retinopathy), hair loss, blue-black pigmentation of mucous membranes and skin, photosensitivity, tinnitus, hearing loss, bone marrow suppression, hypersensitivity reactions, atrioventricular block, porphyria, exacerbation of psoriasis, neuromyopathy Common: Drowsiness, headache, psychomotor impairment, antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastro-intestinal disturbances Infrequent or rare: Hypotension, palpitations, arrhythmias, extrapyramidal effects, dizziness, confusion, depression, sleep disturbances, tremor, convulsions, hypersensitivity reactions (including bronchospasm, angioedema, and anaphylaxis, rashes, and photosensitivity reactions), blood disorders, liver dysfunction, angle-closure glaucoma.

Malaria caused by P. malariae, P. vivax, or P. ovale (11.25.3)

(Other indications: Malaria prophylaxis; rheumatoid arthritis)

Oral: Initially 10 mg/kg (600 mg) as a single dose THEN 5 mg/kg (300 mg) 6–8 hours later THEN 5 mg/kg (300 mg) daily on next 2 days (24 and 48 hours after initial dose) THEN full antirelapse treatment of 14 days of primaquine in P. vivax and P. ovale infections, except during pregnancy and breastfeeding

Use with caution: In hepatic and renal impairment, neurological disorders (avoid for prophylaxis if epilepsy history), severe gastrointestinal disorders, G6PD deﬁciency, pre-existing auditory damage, elderly. May exacerbate psoriasis or myasthenia gravis. If patient continues to deteriorate after chloroquine, administer quinine intravenously (suspect resistance). Counselling: Take with food to minimize nausea and vomiting. If part or all of a dose is vomited, the same amount should be taken again immediately. Pregnancy/breastfeeding: May be used at recommended doses in pregnancy and breastfeeding (monitor infant for drowsiness). Use with caution: In the elderly; may cause a paradoxical stimulation. Also, use with caution in prostate enlargement, urinary retention, ileus or pyloroduodenal obstruction, glaucoma, renal impairment, hepatic impairment, epilepsy. Counselling: Drowsiness may impair ability to perform skilled tasks such as operating machinery or driving. Drowsiness may diminish after a few days of treatment.

Chlorphenamine (chlorpheniramine)

Tablet: 4 mg Injection: 10 mg/ml, 1 ml ampoule; (if necessary, injection solution can be diluted with sodium chloride 0.9% injection)

Itching (10.2.8)

Oral: 4 mg every 4–6 hours (maximum 24 mg daily)

Summary tables

Allergic reactions, anaphylaxis (adjunct) (3.1.3)

SC/IM/IV: 10–20 mg (maximum 40 mg in 24 hours); give IV over 1 minute

375

376 Adverse effects Special groups/comments Pregnancy: Use, with caution, in pregnancy, if beneﬁt is greater than risk. Breastfeeding: Use caution (monitor infant for drowsiness). Contraindications: CNS depression/impaired consciousness; bone marrow depression; phaeochromocytoma, porphyria, basal ganglia disease, parkinsonism Common: Extrapyramidal side-effects: Acute dystonic reaction or severe muscle spasm, stiffness, tremor, motor restlessness, agitation, Parkinson’s syndrome; with prolonged administration, potentially irreversible involuntary movements (tardive dyskinesia) Autonomic side-effects: Drowsiness; orthostatic hypotension, dizziness; tachycardia; dry mouth; blurred vision; constipation; urinary retention Other: Nausea, anorexia, dyspepsia; headache; apathy, confusion, depression, nightmares, insomnia; weight gain; photosensitivity; rash; galactorrhoea, gynaecomastia, sexual dysfunction, impotence, menstrual irregularities; jaundice, altered liver enzymes Use with caution: In cardiovascular and cerebrovascular disorders, dementia, respiratory disease, epilepsy, acute infections, renal and hepatic impairment (avoid if severe), history of jaundice, leukopenia (blood count required if unexplained fever or Infection), hypothyroidism, myasthenia gravis, prostatic hypertrophy, angle-closure glaucoma, organophosphate poisoning; subarachnoid haemorrhage, metabolic disturbances (hypokalaemia, hypocalcaemia, hypomagnesaemia), seizure disorders; in patients on other QT-prolonging medications Elderly/debilitated (including HIV stage 3 or 4): Haloperidol preferred; alternative is chlorpromazine at one-third to half adult dose. Avoid abrupt withdrawal. Check blood counts if unexplained fever or infection. Administration: Avoid skin contact with injection solution or oral liquid, as there is a risk of contact dermatitis. Oral hygiene is very important with regular use of oral liquid. Counselling: Warn patients that this medication may impair ability to perform skilled tasks such as operating machinery or driving. If taking liquid form, daily oral hygiene is very important. Infrequent or rare, serious:Neuroleptic malignant syndrome; hyperthermia, hyperpyrexia, heat stroke; blood disorders, including leukopenia, thrombocytopenia, aplastic anaemia; lupus erythematosus-like syndrome; exfoliative dermatitis; seizures; cholestatic jaundice; arrhythmias; respiratory depression at high doses Other infrequent or rare: ECG changes; hypothermia; corneal and lens opacities; purplish pigmentation of the skin, cornea and retina (with prolonged high doses)

Drug Indication

Formulations Dosage

Chlorpromazine

Tablet: 100 mg Oral liquid: 25 mg/5 ml Injection: 25 mg/ml, 2 ml ampoule

Psychosis (including schizophrenia) (10.11.4)

Oral: Initially 75 mg at night

Summary tables

Typical effective dose is 75–300 mg daily, but up to 1000 mg may be necessary in severe cases.

Vomiting (10.7c.3, 14.1.11)

Oral/IM/IV: 25–50 mg 4 times daily until vomiting stops

Tetanus spasms (11.39)

IM: 50–150 mg every 4–8 hours

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Drug Indication Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Contraindicated in pregnancy and breastfeeding due to theoretical risk of injury to developing cartilage; consider alternatives where possible; use only if no available alternatives and beneﬁt is greater than risk. Contraindications: History of quinolone-associated tendon disorder

Ciproﬂoxacin

Tablet: 250 mg Solution for IV infusion: 2 mg/ml

Severe infections: acute pyelonephritis (11.44); typhoid fever (11.43)

Oral: 500 mg twice daily OR IV: 400 mg twice daily for 10–14 days

Cholecystitis (10.7a.2)

Oral: 500 mg twice daily for 5–7 days AND metronidazole

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Hepatitis, jaundice, pancreatitis; dizziness, sleep disorders; convulsions, paraesthesia, movement disorders (discontinue use); hypersensitivity reactions (if severe rash, discontinue), petechiae, haemorrhagic bullae, erythema nodosum; photosensitivity reaction; psychiatric symptoms (depression, confusion, hallucinations – discontinue if occurs); haemolytic anaemia; C. difﬁcile colitis. Tendon damage (including rupture) has been reported rarely in patients receiving quinolones. Tendon rupture may occur within 48 hours of starting treatment; cases have also been reported several months after stopping a quinolone. If tendinitis is suspected, the quinolone should be discontinued immediately.

Cholangitis (10.7a.2)

IV: 400 mg twice daily AND metronidazole for 10-14 days

Oral: 500 mg twice daily for 7 days

Use with caution: In elderly patients and those on corticosteroids (higher risk of tendonitis/rupture); in history of epilepsy or seizure, renal impairment, G6PD deﬁciency, myasthenia gravis (risk of exacerbation). Prone to multiple drug interactions. If TB infection is suspected, limit use if there are alternate antibiotics available. Administration: Give IV infusion over at least 60 minutes.

Isosporiasis with intolerance to cotrimoxazole or resistance to ampicillin and cotrimoxazole) (11.18)

Prophylaxis: Oral: 500 mg 3 times a week

PID (10.15.5)

See table in Section 10.15.5.

Uncomplicated gonorrhoea if susceptible (10.15.4); gonococcal conjunctivitis (10.12.2)

Oral: 500 mg as a single dose

Summary tables

Anthrax, cutaneous (10.2.10)

Oral: 500 mg twice daily for 7-10 days

Counselling: Oral: Take 1 hour before or 2 hours after meals. Drink plenty of ﬂuids while taking it. Dairy products; antacids; and iron, zinc, or calcium supplements may reduce absorption; do not take within 2 hours of a ciproﬂoxacin dose. This medication may impair ability to perform skilled tasks such as operating machinery or driving. Avoid extended exposure to sunlight (discontinue if photosensitivity occurs; report to clinician).

Anthrax, severe (10.2.10)

IV: 400 mg twice daily for 7-10 days

Prophylaxis, meningococcal meningitis in non-epidemic situations (10.10b.3)

Oral: 500 mg as a single dose

Cholera (10.7d.2)

Oral: 1 g as a single dose

377

378 Adverse effects Common: Dyspepsia. Special groups/comments Pregnancy: Use alternative macrolides in pregnancy where possible. Breastfeeding: Caution in breastfeeding (monitor infant for side-effects) Contraindications: Sensitivity to macrolide antibiotics. Known interactions with many drugs. Use with caution: In renal impairment Counselling: Before starting or stopping any other medicines, tell your doctor that you are taking this medication. Infrequent or rare: Tooth and tongue discoloration; smell and taste disturbances, stomatitis, glossitis; headache, arthralgia, myalgia, hepatitis, pancreatitis; tinnitus, dizziness, insomnia, nightmares, anxiety, confusion, psychosis, paraesthesia; convulsions; hypoglycaemia; interstitial nephritis, renal failure; leukopenia, thrombocytopenia; pulmonary inﬁltration with eosinophilia; prolonged QT interval, torsade de pointes; on IV infusion, local tenderness, phlebitis. See also erythromycin adverse effects.

Drug Indication

Formulations Dosage

Clarithromycin

Tablet: 250 mg, 500 mg Oral suspension: 125 mg/5 ml, 250 mg/5 ml

MAC treatment in PLHIV (11.27)

Oral: 500 mg twice daily AND ethambutol 15 mg/kg daily for 6 months

Summary tables

Helicobacter pylori infection eradication (10.7a.2)

Oral: 500 mg twice daily AND amoxicillin + omeprazole for 7 days

Buruli ulcer (10.2.10)

Oral: 7.5 mg/kg twice daily (not to exceed 500 mg twice daily) AND rifampicin for 8 weeks

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Drug Indication Common: Nausea, vomiting, diarrhoea, abdominal pain or cramps; rash, contact dermatitis Pregnancy: Not known to be harmful

Formulations Dosage

Adverse effects

Special groups/comments

Clindamycin

Capsule: 150 mg Injection: 150 mg/ml, 2 ml ampoule

Cellulitis (10.2.2)

Oral: 300-450 mg every 8 hours (maximum 450 mg every 6 hours)

Breastfeeding: Unknown safety; amount in milk probably too small to be harmful. Discontinue immediately if diarrhoea or colitis develops. Contraindications: Diarrhoeal states, porphyria Use with caution: In hepatic impairment. Monitor liver function during prolonged therapy.

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Unpleasant taste in the mouth; oesophagitis; altered liver enzymes, jaundice; blood disorders (leukopenia, granulocytosis, eosinophilia, thrombocytopenia); pain/induration/abscess after intramuscular injection, thrombophlebitis after intravenous injection, erythema multiforme, polyarthritis; C. difﬁcile colitis (see Section 10.7d) Common: Dry, scaly, or peeling skin Infrequent or rare: Contact dermatitis, irritation, burning sensation, itch Pregnancy/breastfeeding: Safe to use

Complicated soft tissue infection including necrotizing fasciitis (10.2.2)

IM/IV: 900 mg every 8 hours AND ampicillin or cloxacillin

Septic abortion (10.15.6)

IV: 900 mg every 8 hours AND ampicillin/penicillin + gentamicin for 14 days

Administration: Dilute in glucose 5% or normal saline to concentration not more than 12 mg/ml and infuse slowly (not more than 30 mg/minute) to reduce risk of adverse cardiac effects. Single doses over 600 mg by intravenous infusion only and should not exceed 1.2 g over 1 hour. Counselling: Take with a full glass of water. Stop taking this medication and tell your doctor immediately if you develop diarrhoea.

PID (10.15.5)

See table in Sectoin 10.15.5.

Uncomplicated P. falciparum malaria in ﬁrst trimester pregnant woman (11.25)

Oral: 600 mg twice daily AND quinine (600 mg every 8 hours) for 7 days

(Other indications: Staphylococcal bone and joint infections; endocarditis prophylaxis)

Summary tables

Clindamycin, topical

Gel/lotion: clindamycin 1% (as phosphate)

Moderate acne (10.2.3)

Gel: Apply to lesions once daily.

Lotion: Apply to the lesions twice daily. Continue until 2 weeks after lesions disappear.

Counselling: Noticeable improvement usually seen in 6 weeks; however, 8–12 weeks of treatment may be required before maximum beneﬁt is seen. Before applying, wash affected area with a mild soap and warm water, rinse thoroughly, and pat dry. Avoid contact with eyes, lips, and inside of your nose or mouth.

379

380 Adverse effects Pregnancy: No information Breastfeeding: May cause reversible skin discoloration in nursing infants Use with caution: In liver and renal impairment and pre existing GI symptoms Counselling: This medication is absorbed best if taken with food. Your skin may become pink to brownish-black while you are taking this medicine, but this is reversible. Avoid exposure to sunlight. Tears and urine may turn reddish-brown. Special groups/comments Common: Nausea/ vomiting (hospitalize if persistent), abdominal pain, headache, tiredness, brownish-black discoloration of lesions, pink to brownish-black discoloration of skin including areas exposed to light; reversible hair discoloration; dry skin; red discoloration of faeces, urine, and other body ﬂuids; rash, pruritus. Infrequent or rare: Photosensitivity, acne-like eruptions, anorexia, eosinophilic enteropathy, bowel obstruction, dry eyes, dimmed vision, macular and subepithelial corneal pigmentation; elevation of blood sugar, weight loss, splenic infarction, lymphadenopathy, GI bleeding, constipation, taste disorder, dizziness, drowsiness See amitriptyline. Pregnancy: Use, with caution, in pregnancy if clinically indicated and drug of choice. Breastfeeding: Caution in breastfeeding (monitor infant for drowsiness) Contraindications: See amitriptyline. See benzylpenicillin. Common: Nausea/vomiting, transient increases in liver enzymes and bilirubin Infrequent or rare: Cholestatic hepatitis Use with caution: In patients with history of mild hypersensitivity to beta-lactams, renal/hepatic impairment Counselling: This medicine is absorbed best if taken on an empty stomach at least half an hour before food or 2 hours after food. Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for side-effects) Contraindications: Known severe hypersensitivity to penicillins or other beta-lactams

Drug Indication

Formulations Dosage

Clofazimine

Capsule: 50 mg, 100 mg

Leprosy (multibacillary) (11.21)

See Section 11.21 for dosing of clofazimine as part of multidrug treatment for multibacillary leprosy

Summary tables

Type 2 lepra reaction if inadequate response to prednisolone or if steroids contraindicated (11.21)

200-300 mg daily in 2-3 divided doses for maximum 3 months

Clomipramine

Capsule: 10 mg, 25 mg

Obsessive-compulsive disorders; phobic states, panic attacks (10.11.7)

Oral: see instructions in Section 10.11.7.

Cloxacillin

Capsule: 500 mg, 1 g Powder for injection: 500 mg in vial

Cellulitis (10.2.2)

Oral: 500 mg every 6 hours IV: 1-2 g every 6 hours

S. aureus endocarditis (11.10)

IV: 2 g every 4 hours or 3 g every 6 hours for 6 weeks

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Septic arthritis due to S. aureus (10.13.2)

IV: 2 g every 6 hours for 2-4 weeks

Drug Indication Common: irritation, photosensitivity reactions; skin, hair, and fabrics discoloured. May be used with salicylic acid in psoriasis Infrequent or rare: hypersensitivity Contraindications: inﬂamed, broken or infected skin.

Formulations Dosage

Adverse effects

Special groups/comments

Coal tar

Solution: 5%.

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Nausea, vomiting, constipation; dizziness, headache, miosis, difﬁculty with micturition, urinary retention, dry mouth, dyspepsia Infrequent or rare: Dependence, biliary spasm, palpitations, bradycardia, tachycardia, hypothermia, hallucinations/mood changes, rash; in large doses, convulsions, respiratory depression, hypotension

Chronic psoriasis, either alone or in combination with exposure to ultraviolet light (10.2.7)

Topical: apply directly to the affected area 1–3 times daily, preferably starting with lower strength preparation or add 100 ml to bath of tepid water and soak affected area for 10–20 minutes, once daily to once every 3 days for at least 10 baths.

Administration: Skin protection possibly required to reduce photosensitivity reactions. Bathing can be alternated with exposure to ultraviolet (UVB) rays, allowing at least 24 hours between exposure and treatment with coal tar.

Codeine

Tablet: 30 mg (phosphate)

Pregnancy/breastfeeding: Considered safe at recommended doses in both pregnancy and breastfeeding Contraindications: Conditions where inhibition of peristalsis should be avoided; abdominal distension; acute diarrhoeal conditions such as ulcerative colitis or antibiotic-associated colitis; acute respiratory depression Use with caution: With prolonged use, tolerance or dependence may occur in elderly and debilitated patients and patients with hepatic or renal impairment. 6–10% of Caucasians and 1-2% of Asians lack the enzyme CYP2D6 (necessary to metabolise codeine to morphine) and are, therefore, unlikely to obtain analgesia with codeine.

Acute or chronic pain (20.2, 20.4)

Oral: 30 mg every 4 hours; maximum dose for pain 240 mg; consider switch to morphine when a dose of 180 mg is reached.

Summary tables

381

382 Adverse effects Common: Nausea, vomiting, diarrhoea; headache; hyperkalaemia; rash; anorexia, sore mouth, fever Special groups/comments Pregnancy: Avoid in ﬁrst trimester. However, if a pregnant woman with HIV requires cotrimoxazole prophylaxis, it should be started regardless of the stage of pregnancy. Pregnant women in malarial areas who are taking cotrimoxazole should not be given sulfadoxinepyrimethamine-based intermittent preventive therapy for malaria. See Sections 13 and 14 for PMTCT and management of cotrimoxazole side-effects. Breastfeeding women living with HIV should continue to receive cotrimoxazole prophylaxis. Contraindications: Severe renal or hepatic impairment; previous severe reactions to sulfa-containing drugs. Use with caution: In predisposition to folate deﬁciency, patients with a sulfa allergy, elderly, and G6PD deﬁciency. See Section 13.3 for response to rash. Discontinue immediately if anaemia or new jaundice appears. Renal dose adjustment required. Avoid in blood disorders except with specialist supervision. Administration: IV: Dilute each 5 ml in 100–125 ml ﬂuid, preferably glucose 5%, and infuse over 60–90 minutes. Maintain adequate ﬂuid intake. Counselling: Take this medicine with food to reduce stomach upset. Tell your doctor if you get a sore throat, fever, troublesome rash, cough, difﬁculty breathing, joint pain, dark urine, or pale stools. If taking prolonged high dose treatment: Drink a lot of ﬂuid – at least 2–3 litres daily. Infrequent or rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity – discontinue immediately; drowsiness; liver damage (including jaundice and hepatic necrosis), pancreatitis, C. difﬁcile colitis, myocarditis, cough and shortness of breath, pulmonary inﬁltrates, aseptic meningitis, depression, convulsions, peripheral neuropathy, ataxia, tinnitus, vertigo, hallucinations, hypoglycaemia, blood disorders (including leukopenia, thrombocytopenia, megaloblastic anaemia, eosinophilia), hyponatraemia, renal disorders (including interstitial nephritis), arthralgia, myalgia, vasculitis, systemic lupus erythematosus; rhabdomyolysis reported in HIVinfected patients; crystalluria

Drug Indication

Formulations Dosage

Cotrimoxazoletrimethoprim with sulfamethoxazole (TMP-SMX)

(doses based on the trimethoprim component)

Tablet: sulfamethoxa-zole 100 mg + trimethoprim 20 mg; sulfamethox-azole 400 mg + trimethoprim 80 mg (singlestrength=SS); sulfamethoxazole 800 mg + trimethoprim 160 mg (double-strength=DS); Injection: sulfamethoxa-zole 80 mg + trimethoprim 16 mg/ml, 5 ml and 10 ml ampoules

Summary tables

P. jirovecii (P. carinii) pneumonia (PCP) (10.6.3)

IV: 5 mg/kg (based on the trimethoprim component) 4 times daily for 21 days

Primary prophylaxis for PLHIV (see 13.3 for indications for primary prophylaxis); secondary prophylaxis after PCP pneumonia (10.6.3), isosporiasis (11.18), toxoplasmosis (11.40)

1 DS tablet or 2 SS tablets once daily. Total daily dose is 960 mg (800 mg SMX + 160 mg TMP)

Acute bacterial meningitisempirical treatment in absence of ceftriaxone (10.10b.3)

IV: 10–20 mg/kg (based on the trimethoprim component) daily divided into 2–4 doses AND ampicillin

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Acute bacterial meningitis with anaphylaxis to penicillin (empirical or for conﬁrmed N. meningitidis, H. inﬂuenzae, S. pneumoniae) (10.10b.3)

IV: 10–20 mg/kg (based on the trimethoprim component) daily divided into 2–4 doses AND chloramphenicol

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments

Listeria meningitis with anaphylaxis to penicillin (10.10b.3)

IV: 10–20 mg/kg (based on the trimethoprim component) daily divided into 2–4 doses

Severe pneumonia, suspect community- associated MRSA where cotrimoxazole has activity (3.2.3)

Add IV cotrimoxazole to regimen

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Septic arthritis where MRSA suspected

IV: 15–20 mg/kg (based on the trimethoprim component) daily divided into 2–4 doses for 2–4 weeks

Epididymitis with suspected coliforms (10.16.4); donovoniasis (granuloma inguinale) (10.14.3)

Oral: 2 SS or 1 DS twice daily for 14 days.

Empirical treatment for prostatitis (10.16.5)

Oral: 2 SS or 1 DS twice daily for 21 days

Persistent diarrhoea in immunocompromised patients (10.17d.2), isosporiasis (11.18)

Oral: 2 DS tablets twice daily for 14 days THEN 1 DS tablet twice daily for 3 weeks

Toxoplasmosis (11.40)

Oral: 2 DS tables 3 times daily for 6 weeks

Summary tables

Uncomplicated cellulitis, furuncle, carbuncle, abscess (10.2.2), sinusitis (11.35)

Oral: 1 to 2 DS tablets twice daily for 7–10 days

Oral: 1 DS tablet twice daily for 7 days

383

384 Adverse effects Common: Nausea/vomiting, diarrhoea, abdominal pain or cramps, hepatitis, rash, fever, jaundice, headache, nervousness, blurred vision Special groups/comments Pregnancy: Third trimester use can result in neonatal haemolysis and methaemoglobinaemia; folic acid 5 mg daily should be given to mother. Breastfeeding: Continue breastfeeding, monitor infant for jaundice. Use with caution: In anaemia, susceptibility to haemolysis Administration: Obtain full blood count before starting treatment; then again each week for the ﬁrst month, and then each month during treatment. Counselling: Take dapsone with food to reduce stomach upsets. Stop medication and inform your doctor if troublesome rash occurs. Pregnancy: Use only if beneﬁt greater than risk (risk of teratogenicity). Breastfeeding: Caution in breastfeeding; not recommended, but low oral bioavailability so unlikely to cause adverse effects Use with caution: In renal impairment, aluminium encephalopathy (may exacerbate neurological dysfunction) Administration: Perform eye and ear examinations before treatment and at 3-month intervals during treatment. Infrequent or rare (dose-related and uncommon at doses used for leprosy): haemolysis, methaemoglobinaemia, allergic dermatitis including Stevens-Johnson syndrome Common: Nausea, vomiting, diarrhoea, abdominal cramps or pain; injection-site reactions (including redness, pain, swelling rashes and itch); hypotension (especially when given too rapidly by intravenous injection); asthma; fever, headache, arthralgia and myalgia; growth retardation; bone deformities Infrequent or rare: Disturbances of hearing and vision (including lens opacity and retinopathy); acute respiratory distress syndrome, neurological disturbances (including dizziness, neuropathy and paraesthesia), Yersinia and mucormycosis infections, rash, renal impairment, blood dyscrasias, anaphylaxis

Drug Indication

Formulations Dosage

Dapsone

Tablet: 25 mg, 50 mg, 100 mg

Leprosy, paucibacillary (11.21)

Oral: 100 mg daily for 6 months AND rifampicin on day 1 of each month

Leprosy, multibacillary (11.21)

Oral: 100 mg daily for 12 months AND rifampicin + clofazimine (see Section 11.21)

Summary tables

Alternative to cotrimoxazole prophylaxis for PLHIV allergic to sulfa-based medicines (13.3)

Oral: 100 mg daily

Deferoxamine (desferrioxamine mesilate)

Powder for injection: 500 mg (mesilate) in vial

Acute iron poisoning (3.8.1)

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(Other indications: Chronic iron overload including hemoglobinopathies; aluminium overload in end-stage renal disease; diagnosis of iron or aluminium overload)

IV (slow): Initially 15 mg/kg per hour THEN reduce after 4–6 hours so that total dose does not exceed 80 mg/kg in 24 hours.

Drug Indication See prednisolone. In addition: Burning and tingling in perineal area (high dose IV treatment)

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Use in pregnancy only if drug of choice and beneﬁt greater than risk (risk of intrauterine growth retardation); unlikely to be harmful at low doses (<40 mg daily prednisolone equivalent) Breastfeeding: Caution in breastfeeding; prednisolone preferred Contraindications: Systemic infection (unless life-threatening or speciﬁc antimicrobial therapy given); avoid live virus vaccines in those receiving immunosuppressive doses.

Dexamethasone Also, see steroid equivalents table in Section 8.2. Dexamethasone has a long duration of action and very high glucocorticoid activity in conjunction with insigniﬁcant mineralocorticoid activity. This makes it particularly suitable for high-dose therapy in conditions where ﬂuid retention would be a disadvantage.

Tablet: 500 mg, 4 mg Injection: 4 mg/ml, 1 ml ampoule

Addison’s disease (adrenal insufﬁciency) (3.4.3)

IV: 8 mg; then repeat every 8 hours

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Cerebral oedema associated with malignancy (20.3)

IV/IM: Initially 24 mg daily; THEN reduce by 2 mg/day to lowest effective maintenance dose.

Bacterial meningitis (consider before antibiotics but do not delay antibiotics) (10.10b.3)

IV: 10 mg every 6 hours for 4 days

(Other indications: Some malignant neoplasms, to help prevent chemotherapyinduced emesis)

Use with caution: In patients with infections (symptoms may be masked until advanced stage; clinical presentation may be atypical); can activate or exacerbate TB, amoebiasis, strongyloidiasis; in the elderly and adolescents, hypertension, recent myocardial infarction, congestive heart failure, liver failure, renal impairment, diabetes mellitus (including family history), osteoporosis, glaucoma (including family history), severe affective disorder (particularly if history of steroid-induced psychosis), epilepsy, psoriasis, peptic ulcer, hypothyroidism, history of steroid myopathy. Adrenal suppression can occur during prolonged treatment and persist for years after stopping treatment. Administration: Monitor weight, blood pressure, ﬂuid and electrolyte balance, and blood glucose throughout prolonged treatment.

Summary tables

385

386 Adverse effects Common: Sedation and other side-effects that appear similar to alcohol intoxication Special groups/comments Pregnancy: Avoid regular use (use only if necessary, e.g. seizure control). Use minimum effective dose for shortest duration; associated with increased risk of cleft palate; withdrawal symptoms in newborns have been reported Breastfeeding: Use with caution; short-acting benzodiazepines preferred if needed. Adverse effects possible (monitor infant for drowsiness and poor feeding) Contraindications: Respiratory disease, acute pulmonary insufﬁciency, sleep apnoea, severe hepatic impairment, myasthenia gravis, acute angle closure glaucoma Infrequent or rare: Nausea/vomiting, diarrhoea, abdominal pain or cramps, respiratory depression (usually due to an excessive dose), withdrawal syndrome, hypotension, bradycardia, dependence and abuse, drowsiness and light-headedness the next day, confusion and ataxia (especially in elderly), amnesia, dependence, muscle weakness, paradoxical increase in aggression, visual disturbances, changes in libido, incontinence or urinary retention, blood disorders, raised liver enzymes/jaundice, hypotension with rapid IV administration Use with caution: In muscle weakness, history of alcohol or drug abuse, marked personality disorder, elderly or debilitated, porphyria, hepatic impairment (avoid if severe), renal impairment. Repeated use even in therapeutic doses can lead to a dependence syndrome. This is unlikely when it is prescribed in standard doses for up to 4 weeks, but beyond this the risk increases in proportion to the duration of treatment and daily dose. Avoid abrupt withdrawal. Counselling: This medication may impair ability to perform skilled tasks such as operating machinery or driving. Common: Nausea, vomiting; headache, dizziness Infrequent or rare: Immunological reaction Pregnancy/breastfeeding: Not for use in pregnancy Contraindications: DEC should not be used in areas where onchocerciasis or loiasis is co-endemic, due to possible severe adverse reactions. Patients should be examined for co-infection before using DEC. Use with caution: In renal impairment, cardiac disorders

Drug Indication

Formulations Dosage

Diazepam

Tablet: 2 mg, 5 mg Injection: 5 mg/ml rectal solution: 10 mg/2 ml

Anxiety (10.11.7); adjuvant analgesia for muscle spasms and anxiety-related pain (20.3)

Oral: see Section 10.11.7

Summary tables

Convulsions (QC pages 6 and 19, 3.5); organophosphate or chloroquine poisoning (3.8)

10 mg IV slowly, or rectally if no IV access; can be repeated after 10 minutes if convulsion does not stop. DO NOT give IM.

Acute alcohol withdrawal (3.7.1)

Up to 20 mg, according to the severity of alcohol withdrawal, every 1-2 hours until patient is calm and mildly sedated (See Section 3.7.1 for how to titrate diazepam dose.)

Amphetamine or cocaine acute intoxication with severe agitation or anxiety (3.6)

See Section 3.6.3.

Insomnia

See Section 20.7.

Diethylcarbamazine (DEC)

Tablet: 50 mg, 100 mg

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Filariasis (11.12)

Oral: 6 mg/kg in 3 divided doses for 12 days OR 6 mg/kg as a single dose AND albendazole 400 mg in a single dose. Repeat every 6 months if microﬁlaraemic or symptomatic.

Drug Indication Common: Headache, eosinophilia, cough, potential for QTc prolongation Pregnancy: Not recommended in the ﬁrst trimester of pregnancy

Formulations Dosage

Adverse effects

Special groups/comments

Dihydro-artemisinin + piperaquine

Co-formulated tablet of 40 mg dihydroartemisinin and 320 mg piperaquine

A ﬁrst-line antimalarial regimen for symptomatic, uncomplicated P. falciparum malaria (11.25.3) Common: Flatulence Infrequent or rare: Vomiting, pruritus, urticaria Common: Local irritation; excessive erythema or spread of lesions (discontinue use); conjunctivitis following contact with eyes; staining of skin, hair, and fabrics.

See dosing in table in 11.25.3.

Administration: Take with water on an empty stomach. If a patient vomits within 30 minutes of taking drug, the whole dose should be re-administered; if a patient vomits within 30-60 minutes, half the dose should be re-administered. Pregnancy: Defer treatment until after the ﬁrst trimester. Breastfeeding: Manufacturer advises to avoid. Precautions: irritant (avoid contact with eyes, mucous membranes and healthy skin). Contraindications: hypersensitivity; avoid use on face, groin, acute eruptions, excessively inﬂamed areas. Administration: Localize application to plaques by application in Lassar's paste (zinc paste 96%, salicylic acid 2%, liquid parafﬁn 2) or white soft parafﬁn to surrounding skin. Dithranol must be protected from light and should be supplied in appropriate light-occlusive containers. Counselling: Wash hands thoroughly after use

Diloxanide

Tablet: 500 mg (furoate)

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Luminal amoebicide (11.1.1)

Oral: 500 mg 3 times daily for 5 days

Dithranol

Ointment: 0.1-2%

Moderate to severe psoriasis (10.2.7)

Note: Stability is a problem with dithranol preparations, especially those of low strength. Addition of salicylic acid, ascorbic acid or oxalic acid as an antioxidant stabilises dithranol products and prevents discolouration and inactivation. Stability appears to be best in soft parafﬁn and least in cream bases.

Topical: start with 0.1%, carefully apply directly to lesions only, leave in contact for 30 minutes, then wash off thoroughly; repeat application daily, gradually increasing strength to 2% and contact time to 60 minutes at weekly intervals; some 0.1–0.5% strength preparations are suitable for overnight use

Summary tables

387

388 Adverse effects Common: Nausea/vomiting, tachycardia, ectopic beats, palpitations, anginal pain; hypotension with dizziness, hypertension (in overdosage), headache, dyspnoea Infrequent or rare: Allergic reaction including anaphylaxis (due to sodium metabisulphite in products), abnormal ventricular conduction, bradycardia, piloerction, uraemia, mydriasis, peripheral vasoconstriction, asthma exacerbation, necrosis/gangrene at injection site Special groups/comments Pregnancy: Use only if beneﬁt is greater than risk and no alternatives are available. Breastfeeding: May be used at recommended doses if beneﬁt is greater than risk; short half-life and rapidly destroyed in the GI tract. Contraindications: Tachyarrhythmia, ventricular ﬁbrillation, ischaemic heart disease, phaeochromocytoma, hyperthyroidism. Correct hypovolaemia before administration; maintain blood volume during treatment. Correct hypoxia before or at same time as starting treatment. See Section 3.1. Use with caution: If history of peripheral vascular disease Administration: Dilute before use in glucose 5% or normal saline and infuse into a large vein. Do not add to sodium bicarbonate or other strongly alkaline solutions.

Drug Indication

Formulations Dosage

Dopamine

Infusion, intravenous: 200 mg in 5 ml ampoule

Shock not responding to ﬂuid boluses (3.1)

IV: See vasopressor dosing table and instructions in Section 3.1.

Summary tables

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Drug Indication Common: Nausea/vomiting, diarrhoea, anorexia, epigastric burning, staining of growing teeth and occasional dental hypoplasia, photosensitivity Infrequent or rare: Tinnitus, hypersensitivity reactions, visual disturbances, hepatotoxicity, blood disorders, C. difﬁcile colitis, oesophagitis and oesophageal ulceration

Formulations Dosage

Adverse effects

Special groups/comments

Doxycycline

Capsule: 100 mg

Non-severe pneumonia (10.6.3)

Oral: 100 mg twice daily for 5- 7 days

See Section 11.25.

Pregnancy/breastfeeding: Not indicated after week 8 due to effects on fetal bone growth and dental discolouration; short courses can be used if alternative not appropriate; implicated in causing maternal hepatotoxicity, especially in third trimester (dose-related). May be used for a single short course of 7-10 days (monitor infant for side-effects). Use with caution: In hepatic impairment, porphyria, systemic lupus erythematosus Counselling: Advise patients to take capsules whole, with plenty of ﬂuid, while sitting or standing to prevent oesophageal irritation; may give with milk/food to counter gastric irritation. Avoid exposure to sunlight or sunlamps.

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In combination with quinine or artesunate to complete course of treatment for severe malaria; as second-line P. falciparum antimalarial treatment; or for travellers (11.25)

Syphilis, early latent- only for non-pregnant and pencillian allergic (11.37)

Oral: 100 mg twice daily for 14 days

Syphilis, late latent or undetermined duration (11.37)

Oral: 100 mg twice daily for 30 days

Uncomplicated genital chlamydia (10.15.4); nongonococcal urethritis; rickettsial diseases (11.33); leptospirosis (11.22)

Oral: 100 mg twice daily for 7 days

Summary tables

Lympogranuloma venereum (10.14.3)

Oral: 100 mg twice daily for 14 days

Granuloma inguinale (donovaniasis) (10.14.3)

Oral: 100 mg twice daily until healed

PID (10.15.5)

Oral/IV: See table in Section 10.15.5.

Trench fever (11.2.3)

Oral: 100 mg twice daily for 4-6 weeks

389

390 Adverse effects Special groups/comments

Drug Indication

Formulations Dosage

Bacillary angiomatosis (11.2.4)

Oral: 100 mg twice daily for 3 weeks

Cat scratch fever (11.2.2)

Oral: 100 mg twice daily for 1014 days AND rifampicin

Cholera (10.7d.2)

Oral: 300 mg as a single dose

Severe acne (10.2.3)

Oral: 50 mg daily for 3-6 months

Summary tables

Anthrax, cutaneous (10.2.10); uncomplicated cellulitis, furuncle, carbuncle, abscess (10.2.2)

Oral: 100 mg twice daily for 7-10 days

Leptospirosis (11.22)

Oral: 100 mg twice daily for 7 days

Eosinophilic folliculitis (10.2.3)

Oral: 100 mg twice daily for 8-12 weeks

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Drug Indication Common: Anaemia, leukopenia, thrombocytopenia, convulsions, impaired hearing, vomiting, abdominal pain, headache, facial oedema

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Contraindicated in pregnancy and breastfeeding Use with caution: In renal impairment hospitalize and supervise closely during treatment. Administration: Monitor blood count for bone marrow suppression. Pregnancy: Avoid in pregnancy. Breastfeeding: Amount excreted probably too small to be harmful. Contraindications: Hypersensitivity to ACE inhibitors (including angioedema) Use with caution: In renal impairment, peripheral vascular disease, aortic stenosis, hepatic impairment Administration: When starting, stop diuretics for 24 hours and start with a low dose at bedtime. Check renal function and electrolytes before starting. Counselling: While taking this medicine, you may feel dizzy on standing. Get up gradually from sitting or lying to minimize this; sit or lie down if you feel dizzy. Do not take potassium supplements while you are taking this medicine unless prescribed by your clinician.

Eﬂornithine

Injection: 200 mg/ml in 100 ml bottle

Human African trypanosomiasis T.b. gambiense meningoencephalitic stage (11.41)

IV (slow infusion over 2 hours): 200 mg/kg every 12 hours for 7 days AND oral nifurtimox (If nifurtimox is not available, give eﬂornithine 100 mg/kg IV every 6 hours for 14 days.)

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Hypotension if diuretics coprescribed, cough, hyperkalaemia, headache, dizziness, fatigue, nausea, renal impairment, stomatitis, glossitis Infrequent or rare: See current formulary such as BNF

Enalapril

Tablet: 2.5 mg

HIV-associated nephropathy (11.31.5)

Oral: 2.5 to 40 mg daily. See Section 11.31.5 for dose adjustment.

(Other indications: Hypertension; heart failure)

Summary tables

391

392 Adverse effects Common: anxiety, headache, fear, palpitations, tachycardia, tremor, dizziness, sweating, pallor, nausea, vomiting, hyperglycaemia. Infrequent or rare: hypertension, arrhythmias, angina, pulmonary oedema (a sign of excessive dosage or extreme sensitivity), tissue necrosis (if injected IM or SC) Pregnancy: May be used at the recommended doses Breastfeeding: Caution in breastfeeding. Monitor infant for side-effects such as irritability, restlessness, tremor. Use with caution: In hyperthyroidism, hypertension, diabetes mellitus, heart disease, arrhythmias, cerebrovascular disease, second stage of labour, and the elderly Administration: Intravenous epinephrine should be given only by those experienced in its use and in a setting where patients can be carefully monitored. Special groups/comments Common: Nausea, vomiting Pregnancy: Contraindicated at induction of labour or ﬁrst and second stages of labour as can cause premature uterine contractions and decrease uterine blood ﬂow (possible fetal hypoxia and death) Breastfeeding: Single dose post-partum compatible with breastfeeding; avoid prolonged or multiple dosing Contraindications: Vascular disease, severe cardiac disease (angina pectoris), severe hypertension, severe renal or hepatic impairment, sepsis, pre-eclampsia or eclampsia Use with caution: In cardiac disease, hypertension, renal impairment, multiple pregnancy, porphyria Infrequent or rare: Headache, dizziness, tinnitus, abdominal pain, chest pain/palpitations, dyspnoea, bradycardia, transient hypertension, stroke, myocardial infarction, pulmonary oedema

Drug Indication

Formulations Dosage

Epinephrine (adrenaline)

Injection: 1 mg in 1 ml ampoule (1:1000)

Anaphylaxis (QC p. 11, 3.1.3)

IM (1:1000): 0.5 ml in a single dose if 50 kg (0.3 ml if 30 kg, 0.4 ml if 40 kg) THEN may repeat at 5-minute intervals

Summary tables

Septic shock not responding to ﬂuid boluses (3.1.5); cardiogenic shock (3.1.4)

IV infusion: See vasopressor dosing table and instructions in Section 3.1

IM: 0.5 mg (0.5 ml of 1:1000)

Severe bronchospasm if no inhaled salbutamol available (3.2.4)

Ergometrine

Injection: 200 mcg (0.2 mg) (hydrogen maleate) in 1 ml ampoule

Haemorrhage in early pregnancy (QC p. 24)

IM: 0.2 mg in a single dose AND repeat IM or IV if bleeding continues

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Postpartum haemorrhage: heavy bleeding continues with soft uterus after oxytocin given and placenta delivered or after manual removal of placenta (QC p. 25, 27)

IV (slow) or IM: 0.2 mg

Drug Indication Common: Nausea/vomiting, diarrhoea, abdominal pain or cramps

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Not known to be harmful in pregnancy or breastfeeding

Erythromycin

Tablet: 250 mg Capsule: 250 mg Infusion: 500 mg vial

Early syphilis (11.37)

Oral: 500 mg 4 times daily for 14 days

Contraindications: Hypersensitivity to erythromycin or other macrolides, porphyria

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Allergic reactions, reversible hearing loss, jaundice, cardiac effects, myasthenia-like syndrome, erythema multiforme (Stevens-Johnson syndrome)/ toxic epidermal necrolysis, QT prolongation, C. difﬁcile colitis

Late latent syphilis (11.37)

Oral: 500 mg 4 times daily for 30 days

Use with caution: In hepatic impairment, predisposition to QT interval prolongation (including electrolyte disturbances and concomitant use of drugs that prolong the QT interval). Prone to multiple drug interactions.

Uncomplicated genital Chlamydia; non-gonococcal urethritis (10.15.4)

Oral: 500 mg twice daily for 7 days

Lympogranuloma venereum (10.14.3)

Oral: 500 mg 4 times daily for 14 days

Administration: Reconstitute injection with water for injection only. Dilute further for administration. Parenteral erythromycin is an irritant and may cause thrombophlebitis. Infuse at a rate of 1-5 mg/ml over 60 minutes or slower, via a central vein where possible. Avoid extravasation.

Granuloma inguinale (donovaniasis) (10.14.3)

Oral: 500 mg 4 times daily until healed

Chancroid (10.1.3)

Oral: 500 mg 4 times daily for 7 days

Severe pneumonia (3.2.3) or non-severe pneumonia not responding to oral therapy after 3 days (10.6.3)

IV/oral: 500 mg 4 times daily AND ceftriaxone OR ampicillin + gentamicin for 10-14 days

Summary tables

Non-severe pneumonia (10.6)

Oral: 500 mg 4 times daily for 5-7 days

Rheumatic fever, primary treatment if allergic to penicillin (11.32)

Oral: 250 mg 4 times daily for 10 days

393

394 Adverse effects Special groups/comments

Drug Indication

Formulations Dosage

Rheumatic fever, secondary prophylaxis (11.32)

Oral: 250 mg twice daily

Streptococcal pharyngitis (10.17.9)

Oral: 250 mg 4 times daily for 10 days

Severe acne (10.2.3)

Oral: 500 mg twice daily

Summary tables

Cholera in areas with tetracycline resistance (10.7d.2)

Oral: 500 mg 4 times daily for 3 days

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Drug Indication Common: Dry skin, itch, stinging, burning feeling Pregnancy/breastfeeding: Safe to use Infrequent or rare: Desquamation, erythema If irritation occurs, apply less frequently; if it persists, stop treatment.

Formulations Dosage

Adverse effects

Special groups/comments

Erythromycin, topical

Gel/lotion: erythromycin 2%

Mild to moderate acne (10.2.3)

Gel: Apply once a day in a thin ﬁlm to affected area. Lotion: Apply twice daily in a thin ﬁlm to affected area. See Section 10.2.3 Common: Optic neuritis Infrequent or rare: peripheral neuritis (especially in legs), rash, pruritus, urticaria, thrombocytopenia, gout, jaundice

Counselling: Before applying, wash affected area with a mild soap and warm water, rinse thoroughly, and pat dry. Avoid contact with eyes, lips, and inside of your nose or mouth. Noticeable improvement may be seen in 3–4 weeks. However, 6–12 weeks of treatment may be required before maximum beneﬁt is seen. Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for side-effects, including jaundice) Contraindications: History of optic neuritis and severe renal impairment Use with caution: In elderly with ocular defects, renal impairment Administration: Ocular examination recommended before and during treatment; patients should report visual disturbances immediately and discontinue treatment. Renal dose adjustment required. Counselling: If you see less clearly or colour vision is affected, stop the medication and tell your clinician.

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Ethambutol

Tablets: 100 mg, 400 mg

Tuberculosis, initial phase of combination therapy (15.3)

Oral: 15 mg/kg daily or 30 mg/kg 3 times a week

MAC (in HIV-infected patients) (11.27)

15 mg/kg/day AND clarithromycin or azithromycin for 6 months

Summary tables

395

396 Adverse effects Common: Signs of intoxication, confusion, drowsiness, coma, respiratory depression, hypoglycaemia Special groups/comments Pregnancy/breastfeeding: Judgement needed; however, fetus is more likely to be at risk from metabolic derangements from ethylene glycol/methanol poisoning than from ethanol as antidote. Avoid breastfeeding during ethanol treatment since ethanol passes into breast milk. Contraindications: Hypersensitivity to ethanol. Use with caution: Causes CNS depression, and effects are additive with other CNS depressants, e.g. benzodiazepines. Increased risk of hypoglycaemia in those with alcohol dependence. In patients taking drugs that inhibit aldehyde dehydrogenase, e.g. disulﬁram, metronidazole, griseofulvin, use can result in acetaldehyde syndrome (nausea, ﬂushing, autonomic instability). Common: Constipation (particularly in older patients; occasionally leads to faecal impaction), diarrhoea, dark stools, nausea, epigastric pain, gastrointestinal irritation Infrequent or rare: Haemosiderosis Pregnancy/breastfeeding: Safe to use Contraindications: Haemosiderosis, haemochromatosis; any form of anaemia not caused by iron deﬁciency; patients receiving repeated blood transfusions; parenteral iron therapy Administration: If side-effects occur, the dose may be reduced; alternatively, another iron salt may be used, but an improvement in tolerance may simply be a result of a lower content of elemental iron. See Section 10.18.3 for monitoring, duration of treatment. Counselling: Although iron preparations are best absorbed on an empty stomach, they may be taken after food to reduce gastrointestinal adverse effects. Keep out of children's reach.

Drug Indication

Formulations Dosage

Ethanol

Oral liquid: 40–43% alcohol (vodka or whisky)

Ethylene glycol or methanol poisoning (3.8.1)

Oral (or by NG): Loading: 1.8 ml/kg over 15–30 minutes (diluted). Maintenance dose: 0.2 ml/kg/ hour (non-drinker) or 0.46 ml/kg/ hour (heavy alcohol user)

Summary tables

Ferrous sulfate See elemental iron equivalents in Section 8.3.

Tablet: equivalent to 60 mg iron

Iron-deﬁciency anaemia (10.18.3)

Elemental iron, 60 mg for mild anaemia, 120 mg (plus 400 mcg folic acid) for moderate to severe anaemia daily

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Preventive iron supplementation in pregnant women without anaemia (14.1.1)

Elemental iron 100 mg AND 400 mcg folic acid daily

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Single dose unlikely to pose a risk to fetus, but avoid high dose or prolonged treatment. Breastfeeding: Safe in usual dosage for short-term treatment (monitor infant for side-effects)

Fluconazole

Capsule: 50 mg Infusion, intravenous: 2 mg/ml Oral liquid: 50 mg/5 ml Infrequent or rare: Nausea/vomiting, abdominal pain, diarrhoea, headache, hepatic disorders, dizziness, seizures, alopecia, rash (withdraw treatment), hypersensitivity reactions, blood disorders, hypokalaemia

Vaginal candidiasis (10.15.4, 11.4)

Oral: 150 mg as a single dose

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Recurrent oral candidiasis (10.17.3, 11.4)

Oral: 100-200 mg daily for 7-14 days

Oesophageal candidiasis (10.7b.3, 11.4)

IV/oral: 100-200 mg daily for 14-21 days

Use with caution: In renal impairment, sensitivity to other azoles. Monitor liver function (discontinue if signs or symptoms of hepatic disease). Prone to multiple drug interactions. Renal dose adjustment required. Counselling: Tell your doctor if you feel unusually tired, nauseous, or are not eating, or if you notice dark urine, pale faeces, or yellowing of the white of your eyes or skin.

Invasive candida disease and candidemia (11.4)

IV/oral: 400 mg daily, continued for 14 days after last fever

Cryptococcal meningitis, with or without amphotericin B (11.5)

See options in Section 11.5

Cryptococcal meningitis (secondary prophylaxis) (11.5)

Oral: 200 mg daily until the patient is on successful ART and CD4 count is maintained above 200 for 6 months

Pityriasis versicolor (10.2.8)

Oral: 400 mg as a single dose

Summary tables

Dermatophytosis (10.2.7)

Oral: 150-300 mg weekly until cure (6–12 months)

Leishmaniasis, cutaneous (11.20.1)

Oral: 200 mg daily for 6 weeks

397

398 Adverse effects Common: Nausea/vomiting, rash, diarrhoea Infrequent or rare: Cardiotoxicity, confusion, hallucinations, convulsions, headache, sedation, vertigo, alterations in liver function tests (hepatitis and hepatic necrosis reported), toxic epidermal necrolysis; blood disorders including thrombocytopenia, leukopenia, aplastic anaemia Pregnancy: Avoid in pregnancy (teratogenic in animal studies); consider alternatives; use only if beneﬁt greater than risk. Breastfeeding: Not recommended until more information available; use only if beneﬁt greater than risk; consider alternatives. Use with caution: In elderly, renal impairment, pre-existing bone marrow suppression Administration: Monitor liver function, kidney function, and blood counts when use with amphotericin B (check weekly in renal impairment or in blood disorders). Renal dose adjustment required. Storage: Keep at 15–25 0C (forms ﬂuorouracil above 25 0C and can precipitate below 15 0C). Counselling: Take the capsule with food. Common: Restlessness, nervousness, insomnia, anorexia and other gastrointestinal disturbances, headache, sweating, decreased libido Infrequent or rare: Marked akathisia (inner restlessness), bleeding abnormalities in patients taking aspirin or non-steroidal anti-inﬂammatory drugs Pregnancy: Use with caution; self-limiting withdrawal symptoms have been reported in newborns (e.g. distress, poor feeding, sleep disturbances). Breastfeeding: Not recommended; long half-life, may accumulate in breast milk; if required, use lowest effective dose. Contraindications: In combination with MAO-Is Use with caution: Renal or hepatic failure (consider dose reduction), diabetes mellitus. Prone to multiple drug interactions. Special groups/comments Administration: Although symptomatic relief may be apparent within the ﬁrst 1–3 weeks, optimum antidepressant effect usually requires at least 4 weeks or more of therapy. Watch for agitation and suicidal ideation and behaviour (see Section 10.11). If history of mania or bipolar disorder, use a mood stabilizer ﬁrst (see Section 10.11.5 on bipolar disorder for details).

Drug Indication

Formulations Dosage

Flucytosine (5-FC)

Capsule: 250 mg Infusion: 2.5 g in 250 ml

Cryptococcal meningitis (as an adjunct to amphotericin) (11.5)

IV/oral: 100 mg/kg daily in 4 divided doses for 14 days

Summary tables

Fluoxetine

Capsule/tablet: 20 mg

Moderate or severe depression (10.11.6); chronic anxiety disorders (10.11.7)

Oral: Initiate treatment with 20 mg daily (to reduce risk of side-effects that undermine adherence, may start at 10 mg (e.g. half a tablet) once daily and increase to 20 mg if the medication is tolerated); THEN if no response in 4–6 weeks or partial response in 6 weeks, increase dose by 20 mg (maximum dose 60 mg) according to tolerability and symptom response.

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For elderly and medically ill, see Section 10.11.6

Drug Indication See chlorpromazine. Additionally for ﬂuphenazine: pain at injection site

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use with caution; monitor infant for reversible extrapyramidal side-effects. Breastfeeding: Use, with caution, if drug of choice (monitor infant for side-effects such as sedation). Contraindications: See chlorpromazine. Use with caution: See chlorpromazine. Elderly/debilitated (including HIV stage 3 or 4): See chlorpromazine. Counselling: See chlorpromazine. Warn patients that this medication may impair ability to perform skilled tasks such as operating machinery or driving.

Fluphenazine

Injection: 25 mg, 1 ml ampoule

Vol. 1 • 8. Medicines/therapies: July 2011 With the exception of tardive dyskinesia, ﬂuphenazine has more prominent extrapyramidal side effects but fewer autonomic side-effects, than chlorpromazine. Infrequent or rare: Nausea/vomiting, diarrhoea, abdominal pain or cramping

Antipsychotic: maintenance treatment of schizophrenia and other psychosis (10.11.4)

Deep IM injection: Initially 12.5 mg in gluteal region THEN repeat every 2–4 weeks. Typical effective dose is 12.5-100 mg IM every 2-5 weeks.

In elderly or medically ill patients: IM: Initially 6.25 mg deep injection in gluteal region AND repeat IM injections every 2-5 weeks using lowest effective dose.

Folic acid

Tablet: 1 mg, 5 mg

Pregnancy/breastfeeding: May be used at recommended dose in pregnancy and breastfeeding Contraindications: Folate-dependent malignant disease Women receiving antiepileptic therapy need counselling before starting folic acid. Should never be given without vitamin B12 in undiagnosed megaloblastic anaemia or other vitamin B12 deﬁciency states due to risk of precipitating subacute combined degeneration of the spinal cord.

Folate-deﬁciency megaloblastic anaemia (10.18.3)

Oral: 5 mg daily for 4 months (in pregnancy, continue to term); up to 15 mg daily for malabsorption states if needed AND vitamin B12

Summary tables

Sickle-cell disease prophylaxis (10.18.3)

Oral: 1 mg daily

(Other indications: Prevention of neural tube defect in pregnancy; prevention of recurrence of neural tube defect)

399

400 Adverse effects Common: Hypersensitivity reactions Infrequent or rare: Pyrexia after parenteral use Special groups/comments Pregnancy/breastfeeding: Not recommended during pregnancy or breastfeeding. Manufacturer advises use only if potential beneﬁt outweighs risk. Use with caution and at lower doses if renal or hepatic impairment. Does not alter the CNS effects of drinking alcohol or withdrawal symptoms Common: Electrolyte imbalance (hypokalaemia, hyponatraemia, hypomagnesaemia), hyperuricaemia and gout, orthostatic hypotension, hypovolaemia, syncope, dizziness Pregnancy: Consider alternatives; loop diuretics not recommended unless absolutely necessary (e.g. cardiac failure). Neonatal ototoxicity has been reported. Breastfeeding: Limited data. Not recommended; theoretically, may suppress lactation due to diuresis Contraindications: Anuria due to renal failure, precomatose states associated with liver cirrhosis, electrolyte depletion Use with caution: In elderly (reduce dose), hypotensive patients, renal impairment, hepatic impairment, prostatic enlargement Administration: Dose to be diluted in suitable amount of infusion ﬂuid (saline or LR; glucose solutions are unsuitable), depending on hydration of patient, at rate not to exceed 4 mg/minute. Monitor electrolytes, particularly potassium and sodium. Correct hypovolaemia before using in oliguria. IV to PO conversion is 1:2 (e.g. 20 mg IV is equal to 40 mg PO) Infrequent or rare: Hypochloraemic alkalosis, hypocalcaemia, hyperglycaemia (less than with thiazide diuretics), paraesthesia, blood disorders (including thrombocytopenia, leukopenia, agranulocytosis, aplastic anaemia, haemolytic anaemia), bone marrow depression (withdraw treatment); deafness (with rapid administration of large parenteral doses and in renal impairment), hypotension, hypersensitivity reaction (including anaphylaxis), temporary increase in plasma cholesterol and triglyceride concentration

Drug Indication

Formulations Dosage

Folinic acid (calcium folinate, calcium leucovorin)

Injection, powder for reconstitution, folinic acid (as calcium salt) 3 mg/ml in 10 ml ampoule Tablet: 15 mg

Methanol poisoning (3.8.1)

IV: 50 mg every 4 hours for 6 doses

Summary tables

Toxoplasmosis (11.40)

Oral: 10-25 mg with each dose of pyrimethamine

(Other indications: Given with methotrexate and 5 FU chemotherapy)

Furosemide

Tablet: 40 mg Injection: 10 mg/ml

Oedema (not lymphoedema) (10.4.3)

Oral: Initially 20–80 mg daily in morning (higher starting doses recommended when patient not naive to drug or renal impairment)

Maintenance dose: 20–40 mg daily (may be increased to 80 mg daily or more in resistant oedema)

Acute pulmonary oedema (3.2.5)

IV (slow): 20–50 mg (if necessary, increase by 20 mg steps every 2 hours) (see ﬂowchart in Section 3.2.5)

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Oliguria in acute kidney injury (11.31.3)

IV: Initially give 20 mg; monitor urinary response. (see dosing in Section 11.31.3)

Drug Indication Common: Nausea, vomiting, diarrhoea, dry mouth, dyspepsia, constipation, abdominal pain, ﬂatulence; appetite changes, gingivitis, weight gain; hypertension, vasodilation, oedema; dyspnoea, cough, rhinitis

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use with extreme caution; has been associated with fetal abnormalities such as hypospadias, unilateral renal agenesis. Breastfeeding: Use, with caution, in breastfeeding; monitor infant for sedation and lethargy. Caution: Monitor for depression, suicidal ideation, unusual mood, behaviour change; mixed seizure disorder (including absence seizure); renal impairment; encephalopathy Administration: Renal dose adjustment required. Avoid stopping abruptly, which may cause anxiety, insomnia, nausea, pain and sweating. Gradually reduce dose over at least 1 week. Counselling: This medicine may cause drowsiness or dizziness. If affected, do not drive or operate heavy machinery. Pregnancy/breastfeeding: Avoid during pregnancy or breastfeeding unless need justiﬁes the risk. To avoid pregnancy, advise use of an effective contraceptive. Contraindications: Neutropenia (ANC <500) or thrombocytopenia (platelets <25 000); concurrent use with zidovudine Use with caution: Ganciclovir is toxic. Personnel should be adequately protected during handling and administration. If solution comes into contact with skin or mucosa, wash off immediately with soap and water. In patients with renal impairment, renal dose adjustment required. Affects spermatogenesis and fertility. Administration: To avoid phlebitis at the injection site (related to high pH of solution), administer in veins with good ﬂow. Maintain adequate hydration. Monitor blood counts 2–3 times per week.

Gabapentin

Tablet: 300 mg

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Confusion, depression, hostility, sleep disturbances, headache, dizziness, anxiety, amnesia, ataxia, dysarthria, nystagmus, tremor, asthenia, paraesthesia, hyperkinesia; inﬂuenza-like symptoms; impotence, urinary incontinence; leukopenia; myalgia, arthralgia; diplopia, amblyopia; rash, purpura, pruritus, acne; rarely, pancreatitis, hepatitis, jaundice, palpitation, hallucinations, movement disorders, thrombocytopenia, bloodglucose ﬂuctuations in patients with diabetes, tinnitus, acute renal failure, Stevens-Johnson syndrome, alopecia Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, constipation, ﬂatulence, dysphagia; hepatic dysfunction; dyspnoea, chest pain, cough; headache, insomnia, convulsions, dizziness, neuropathy, depression, anxiety, confusion, abnormal thinking, fatigue; weight loss, anorexia; infection, fever, night sweats; anaemia, leukopenia, thrombocytopenia, pancytopenia, renal impairment; myalgia, arthralgia; macular oedema, retinal detachment, vitreous ﬂoaters, eye pain; ear pain, taste disturbance; dermatitis, pruritus; injection-site reactions Infrequent or rare: Chest pain, chills, mouth ulceration, cough, dry mouth, drowsiness, arthralgia, pancreatitis, arrhythmias, hypotension, anaphylactic reactions, psychosis, tremor, male infertility, haematuria, disturbances in hearing and vision, alopecia

Neuropathic pain (if poor response to amitryptiline in HIV patient on ART) (10.10a.6)

Oral: Initial dose of 300 mg daily; THEN increase to 300 mg twice daily; THEN 300 mg 3 times daily as needed THEN titrate with 100 mg increments every 3 days to a maximum of 3.6 g daily (given as 1200 mg 3 times daily or 900 mg 4 times daily

Ganciclovir

Injection: 500 mg vial

Cytomegalovirus (CMV) retinochoroiditis in HIVinfected patients (11.8)

Induction dose: IV: 5 mg/kg twice daily for 3-4 weeks

Summary tables

CMV oesophagitis, gastritis, neurologic, in HIV-infected patients (11.8)

IV: 5 mg/kg twice daily for 3- 6 weeks

See Section 11.8 for maintenance with valganciclovir, if available.

401

402 Adverse effects Common: Nephrotoxicity, ototoxicity Infrequent or rare: Neuromuscular blockade, renal electrolyte wasting (Mg, K, Ca), antibiotic-associated colitis, nausea/vomiting, hypersensitivity reactions Special groups/comments Pregnancy: Avoid unless essential for serious infections; monitor levels to minimize potential for ototoxicity and nephrotoxicity. Breastfeeding: May be used at recommended doses (monitor infant for thrush, diarrhoea) Contraindications: Hypersensitivity to aminoglycoside group of antibiotics Use with caution: In renal impairment, pre-existing tinnitus/ hearing loss, conditions with muscular weakness, obesity, the elderly (dosage adjustment required). Monitor renal, auditory, vestibular function, serumgentamicin concentration. Avoid prolonged use. One-hour (peak) concentration not to exceed 5–10 mg/l (3–5 mg/l for endocarditis) and pre-dose (trough) concentration less than 2 mg/l (less than 1 mg/l for endocarditis). Avoid use with neuromuscular blocking agents (additive toxicity) and other renal/ototoxic agents. Avoid monotherapy with gentamicin especially for severe infections of unclear etiology. Administration: Renal dose adjustment required. Can be dosed daily (4.5 mg/kg every 24 hours) or 1.5 mg/kg every 8 hours. The empirical antibiotic dose for emergency management of 240 mg (QC p. 19) represents the full daily dose for a 60 kg person.

Drug Indication

Formulations Dosage

Gentamicin

Injection: 10 mg, 40 mg (as sulfate)/ml in 2 ml vial

General dosing for infections, due to susceptible organisms, such as upper UTI (11.44); septic shock (3.1.5); severe pneumonia (3.2.3)

IM/IV (slow): 4–6 mg/kg daily in divided doses every 8 hours for 2 weeks AND ampicillin

Summary tables

Initial empirical antibiotics for emergency management (QC p. 19)

IV: 240 mg in a single dose AND ampicillin 2 g IV/IM

Endocarditis from viridans streptococci- noncomplicated cases (as part of combination therapy) (11.10)

IV/IM: 3 mg/kg per 24 hours in 1 dose or in 2 or 3 equally divided doses for 2 weeks AND benzylpenicillin or ceftriaxone or vancomycin

PID (10.15.5)

IV: 1.5 mg/kg every 8 hours AND clindamycin AND metronidazole

Cholangitis and peritonitis (10.7a.2)

IV: 1.5 mg/kg every 8 hours AND ampicillin AND metronidazole

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Brucellosis (11.3)

IV: 5 mg/kg daily in divided doses every 8 hours AND doxycycline for 15 days

Drug Indication Common: Burning, stinging, itching, dermatitis

Formulations Dosage

Adverse effects

Special groups/comments Use with caution: Prolonged use may lead to sensitization and emergence of resistant organisms including fungi; discontinue if there is purulent discharge, inﬂammation, exacerbation of pain.

Gentamicin eye drops

Solution (eye drops): 0.3%

Bacterial conjunctivitis (10.12.2); corneal ulcer or infective keratitis (10.12.2) Common: Nausea, vomiting, diarrhoea, anorexia, headache Infrequent or rare: Leukopenia; hepatotoxicity; sleep disturbances; photosensitivity; systemic lupus erythematosus; rash, toxic epidermal necrolysis, erythema multiforme; peripheral neuropathy; confusion, impaired coordination

1 drop every 2 hours, reducing frequency as infection is controlled THEN continue for 48 hours after healing is complete.

Griseofulvin

Tablets: 125 mg, 250 mg Capsules: 250 mg

Pregnancy: Avoid pregnancy during and for 1 month after treatment; men should not father children within 6 months of treatment. Consider alternative treatments. Breastfeeding: Not recommended; use only if beneﬁt is greater than risk; consider alternatives. Contraindications: Severe liver disease, porphyria, systemic lupus erythematosus Use with caution: In pre-existing hepatic insufﬁciency (closely monitor hepatic function throughout treatment), blood disorders (monitor blood count weekly during ﬁrst month of treatment), penicillin allergy (cross-sensitivity may occur) Counselling: Take with milk or food. May impair ability to perform skilled tasks such as operating machinery or driving. Avoid sun exposure. During treatment and for 4 weeks after, drinking alcohol may cause increased heart rate and skin ﬂushing.

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Scalp, skin, groin infections (10.2.7); foot and nail infections (10.2.7)

Oral: 500 mg to 1 g daily but not less than 10 mg/kg

Duration of treatment depends on the infection and thickness of keratin at site of infection: at least 4 weeks for skin and hair, at least 6 weeks for scalp ringworm and, in severe infection, up to 3 months; 6 months for ﬁngernails, 12 months or more for toe nails.

Summary tables

403

404 Adverse effects See chlorpromazine. Special groups/comments Pregnancy: Use with caution and at lowest effective dose; reversible respiratory depression, extrapyramidal effects, difﬁculty feeding have been reported in newborn. Breastfeeding: Caution in breastfeeding (monitor infant for drowsiness) Contraindications: See chlorpromazine. Use with caution: See chlorpromazine. Elderly/debilitated (including HIV stage 3 or 4): See chlorpromazine. Administration: Monitor blood pressure and maintain supine position for 30 minutes after intramuscular injection. Counselling: This medication may impair your ability to perform skilled tasks such as operating machinery or driving. With the exception of tardive dyskinesia, haloperidol has more prominent extrapyramidal side-effects but fewer autonomic side-effects than chlorpromazine.

Drug Indication

Formulations Dosage

Haloperidol

Tablet: 2 mg; 5 mg Injection: 5 mg in 1 ml ampoule

Psychoses (including schizophrenia) (10.11)

Oral: Initially 1.5-3 mg once daily (typical effective dose is 3-20 mg daily)

Summary tables

In elderly or medically ill patients: Oral: Initially 0.5–1 mg once daily (use the lowest effective dose)

Short-term adjunctive management of agitation, violent behaviour, severe anxiety (QC p. 29) or severe symptoms of acute mania with agitation (10.11.5)

IM/oral: 2 mg every hour up to 5 doses (maximum dose 10 mg).

In elderly and patients with complicating medical illness: IM/oral: 0.5-1 mg every hour up to 3 doses maximum dose 3 mg)

Alcohol withdrawal delirium that persists after the stage of tremor and sweating has subsided (3.7)

See dosing in Section 3.7.

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Antiemetic when other agents not available (10.7c)

Drug Indication Common: Flushing, headache, dizziness, tachycardia, palpitation, oedema

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use only in acute treatment of hypertensive emergencies; avoid large boluses, as fetal distress and arrhythmias have been reported. Breastfeeding: Use, with caution, if beneﬁts are greater than risks; monitor infant for effects such as hypotension, bradycardia, fatigue. Contraindications: Idiopathic systemic lupus erythematosus, severe tachycardia, high output heart failure, myocardial insufﬁciency due to mechanical obstruction, corpulmonale, dissecting aortic aneurysm, porphyria Use with caution: In hepatic impairment, renal impairment, coronary artery disease, cerebrovascular disease. May provoke angina (avoid after myocardial infarction until stabilized). Administration: Renal dose adjustment required. Counselling: This medicine may cause dizziness, especially at the start of treatment. If affected, do not drive or operate heavy machinery.

Hydralazine IV

Powder for injection: 20 mg (hydrochloride) in ampoule Infrequent or rare: Nausea/vomiting, ischaemia, postural hypotension, abnormal liver function, systemic lupus erythematosus-like syndrome, blood disorders (haemolytic anaemia, leukopenia, thrombocytopenia)

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Acute pulmonary oedema with severe hypertension if isosorbide dinitrate not available (3.2.5); severe hypertension in preeclampsia and eclampsia (3.2.5)- see IMPAC MCPC

IV (slow): 5 mg diluted with 10 ml sodium chloride 0.9%; may repeat after 30 minutes

(Other indications: Heart failure; hypertension (oral); hypertensive crisis)

Summary tables

405

406 Adverse effects Special groups/comments Pregnancy: Avoid use; may cause electrolyte disturbances or neonatal thrombocytopenia. Reduction in maternal blood volume may diminish uteroplacental perfusion. Breastfeeding: Use with caution but unlikely to suppress lactation. Contraindications: Severe renal or severe hepatic impairment; hyponatraemia, hypercalcaemia, refractory hypokalaemia, symptomatic hyperuricaemia; Addison’s disease Use with caution: In elderly; electrolytes may need to be monitored with high doses; may aggravate diabetes mellitus and gout; may exacerbate systemic lupus erythematosus; porphyria Counselling: Take the medicine once daily in the morning. While taking this medicine, you may feel dizzy on standing. Get up gradually from sitting or lying to minimize this effect. Sit or lie down if you become dizzy. Associated with long-term treatment, which is not recommended with IV hydrocortisone. See prednisolone. Pregnancy: May be used at the recommended doses; caution in ﬁrst trimester due to possibility of oral cleft; limited fetal exposure due to inactivation by placenta Breastfeeding: May be used at recommended doses; caution with high parenteral/oral doses Contraindications: Not relevant to emergency use. For contraindications related to long-term use, see prednisolone. Common: Dizziness, dry mouth, weakness, muscle cramps, polyuria, orthostatic hypotension, hypokalaemia, hyponatraemia, hypochloraemic alkalosis, hypomagnesaemia hyperuricaemia Infrequent or rare: Nausea/vomiting, weakness, lethargy, drowsiness, seizures, headache, oliguria, arrhythmias, hypercalcaemia, hyperglycaemia, rash, photosensitivity, altered plasma lipid concentration; rarely, impotence (reversible); blood disorders (including neutropenia, thrombocytopenia); pancreatitis, intrahepatic cholestasis, acute renal failure, hypersensitivity reactions (including pneumonitis, severe skin reactions

Drug Indication

Formulations Dosage

Hydrochlorothiazide

Tablet: 25 mg

Oedema (10.4.3); mild hyperkalaemia (5.2.2)

25 mg once daily (12.5 mg in elderly). Increase to 50 mg as needed.

Summary tables

HIV-associated nephropathy (11.31.5)

See Section 11.31.5 for addition hydro-chlorthiazide to enalapril

(Other indications: Hypertension; heart failure)

Hydrocortisone Also see Section 8.2 steroid equivalents table.

Injection: 100 mg (as sodium succinate) in vial

Anaphylaxis (3.1.3); moderate or severe bronchospasm, if suspect asthma or COPD or unable to take oral medication (3.2.4)

IV (slow): 100 mg in a single dose

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Addison’s syndrome (acute adrenal insufﬁciency) (3.4.3); urticaria (10.2.9)

IV: 100 mg initially AND repeat every 8 hours. Convert to oral dose once patient stable.

Drug Indication Infrequent or rare: Exacerbation of local infection, contact dermatitis, perioral dermatitis

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Topical preparations unlikely to cause any adverse effects in pregnancy or breastfeeding, as systemic absorption is expected to be minimal. Breastfeeding: Wipe excess cream from nipple area before feeding. Contraindications: Untreated skin infections, broken skin, rosacea, acne, perioral dermatitis. Occlusive dressings increase penetration into keratinized lesions. Treat secondary infection with an appropriate antimicrobial.

Hydrocortisone cream

Cream: 1%

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Eye irritation Common: Dyspepsia, nausea, diarrhoea; GI ulceration and haemorrhage, raised liver enzymes, headache, dizziness, salt and ﬂuid retention, hypertension Infrequent or rare: Heart failure; hypersensitivity reactions; bronchospasm; renal failure; rarely, hepatic failure; erythaema multiforme, toxic dermal necrolysis; oesophageal ulceration, hyperkalaemia Counselling: Take with or after food.

Topical: Apply a small quantity to the affected area 1–2 times daily until improvement occurs.

Hydroxypropyl methylcellulose (tears naturale)

Drops: 0.5%

Chronic soreness of the eyes associated with reduced or abnormal tear secretion; acute viral conjunctivitis (10.12)

Instill frequently (e.g. hourly) for adequate relief.

Ibuprofen

Tablet: 200 mg, 400 mg

Mild to moderate pain (20.2, 20.4); musculoskeletal disorders; arthritis (10.13); dysmenorrhoea (10.15); fever (10.1); erythema nodosum (10.2)

200–400 mg 3–4 times daily. Maximum 2.4 g daily

Pregnancy/breastfeeding: Avoid unless potential beneﬁt greater than risk; consider alternatives such as paracetamol or opioids; regular use in third trimester may cause closure of fetal ductus arteriosus in utero, possibly persistent pulmonary hypertension of the newborn, delayed onset and increased duration of labour. Use with caution: /;In renal and hepatic disorders, hypersensitivity, and in the elderly. Ibuprofen can reduce the antiplatelet activity of low-dose aspirin and potentially reduce or negate the cardioprotective effect.

Summary tables

407

408 Adverse effects Special groups/comments Pregnancy: Generally accepted as safe (insulin requirements should be assessed in each trimester) Breastfeeding: May be used at recommended doses Use with caution: In renal impairment, hepatic impairment, hypokalaemia Common: Hypoglycaemia, weight gain; hypersensitivity reactions; hypokalaemia, transient oedema; local reactions including erythema, itching, lipodystrophy, lipoatrophy Common: Dry mouth, throat irritation Infrequent or rare: Constipation, tachycardia, atrial ﬁbrillation, urinary retention, acute angleclosure glaucoma Pregnancy/breastfeeding: Safe in pregnancy. Use with caution: In prostatic hypertrophy. Medical supervision with ﬁrst dose due to risk of paradoxical bronchospasm. Counselling: Do not use for immediate relief of symptoms. Administration: Desirable to give also pyridoxine 10 mg daily to prevent peripheral neuropathy in PLHIV. Defer IPT in the presence of active hepatitis (acute or chronic), regular and heavy alcohol consumption, and symptoms of peripheral neuropathy. Stop INH if jaundice or skin rash with or without itching. Stop IPT, and start treatment regimen if active TB develops. Common: Burning, numbness or tingling sensation in hands and feet; drowsiness; anorexia, nausea, abdominal pain; jaundice (other causes excluded), hepatitis; skin rash with or without itching (rarely, but can be serious, e.g. Stevens-Johnson syndrome)

Drug Indication

Formulations Dosage

Insulin (soluble)

Injection: 40 IU/ml in 10 ml vial; 100 IU/ml in 10 ml vial

Diabetic ketoacidosis (3.4.1)

See Section 3.4.1

Hyperkalaemia (5.2.2)

IV: 10–15 units in 50 ml D50 (50% dextrose water) infused over 2 hours THEN dextrose infusion + regular blood glucose monitoring

Summary tables

Overdose of calciumchannel blockers and beta- blockers, given in combination with dextrose (3.8.1)

See Table in 3.8.1

(Other indications: Diabetes mellitus type I; type II after failing oral therapy)

Ipratropium bromide

Inhalation (aerosol): 20 mcg / metered dose

Acute wheezing (QC p. 17); COPD, moderate (10.6)

20 to 40 mcg 4 times daily (2 puffs) AND inhaled salbutamol

Isoniazid (INH) (H)

Tablet: 300 mg

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TB prevention for PLHIV (13.3)

Oral: INH 300 mg daily for at least 6 months is recommended, and up to 36 months in HIVprevalent settings with a high prevalence and transmission of TB AND pyridoxine

Drug Indication Common: Throbbing headache, ﬂushing, dizziness, fainting, postural hypotension, tachycardia Infrequent or rare: Paradoxical bradycardia

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use with caution. Consider alternatives where possible; use minimum effective dose if required in acute situation. Breastfeeding: Use, with caution, if beneﬁt is greater than risk; monitor infant for side-effects. Contraindications: Hypersensitivity to nitrates, hypotension, hypovolaemia, hypertrophic obstructive cardiomyopathy, aortic stenosis, cardiac tamponade, constrictive pericarditis, mitral stenosis; marked anaemia, head trauma, cerebral haemorrhage, angle-closure glaucoma Use with caution: In severe hepatic or renal impairment, hypothyroidism, malnutrition, hypothermia, elderly, or recent MI. Prone to multiple signiﬁcant drug interaction through CYP3A4 enzyme.

Isosorbide dinitrate

Tablet (sublingual): 5 mg

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Dyspepsia, anorexia, fatigue, itch Infrequent or rare: Nausea, vomiting, abdominal pain, diarrhoea, constipation, jaundice, hepatitis; heart failure, pulmonary oedema, headache, dizziness, peripheral neuropathy (discontinue treatment); menstrual disorders; hypokalaemia, rash, pruritus, Stevens-Johnson syndrome, alopecia Potentially life-threatening hepatotoxicity reported very rarely; discontinue if signs of hepatitis develop.

Pulmonary oedema with severe hypertension (3.2.5)

SL: 5 mg sublingual, repeat in 10–15 minutes, not to exceed 10 mg every 2–3 hours

Itraconazole

Capsule: 100 mg; Oral solution 10 mg/ml

Pregnancy: Contraindicated in ﬁrst trimester; use in second or third trimesters only if drug of choice and no alternatives. Breastfeeding: Not recommended – effects unknown. Use ﬂuconazole if available and indicated.

Candidal oesophagitis when ﬂuconazole not available (11.4)

Oral: 100–200 mg twice daily for 10–14 days (may be increased to a maximum of 400 mg daily)

Summary tables

Histoplasmosis (11.16)

200 mg 3 times daily for 3 days. THEN 200 mg twice daily for 6–12 months

Use with caution: In patients with heart failure or risk factors for heart failure, pre-existing hearing loss, hypersensitivity to other azoles. Monitor liver enzymes in patients with liver disease. Administration: Prone to multiple signiﬁcant drug interactions (many leading to severe cardiovascular compromise). (An alternative for candida oesophagitis is the itraconazole solution). Counselling: Take capsule with food for best absorption (oral solution should be taken on empty stomach). Do not take antacids within 2 hours of taking this medicine. Tell your doctor if you feel unusually tired or have loss of appetite, nausea, vomiting, abdominal pain, or dark urine.

Penicilliosis, mild disease (11.29)

200 mg twice daily for 8weeks THEN, in PLHIV, 200 mg daily until 6 months after CD4> 100

Severe disseminated penicilliosis (11.29)

Amphotericin B for 14 days THEN itraconazole 200 mg daily for 10 weeks, continuing in PLHIV until 6 months after CD4>100

Pityriasis versicolor, recurrence (10.2.7)

Pulsed monthly treatment for 3 months

409

410 Adverse effects Common: Strongyloidiasis: Diarrhoea, dizziness, nausea; mild ocular irritation; somnolence Onchocerciasis: Mild Mazzotti reaction within 3 days of treatment (fever, headache, cough, pruritus, conjunctivitis, arthralgia, lymphadenopathy, diarrhoea) Infrequent or rare: Cutaneous or systemic reactions Special groups/comments Pregnancy/breastfeeding: Delay treatment until after delivery and infant is 1 week old. Administration/counselling: Avoid food or alcohol for at least 2 hours before and after a dose. Contraindications: Do not give ivermectin for onchocerciasis in loaiasis co-endemic areas.

Drug Indication

Formulations Dosage

Ivermectin

Tablet: 3 mg, 6 mg

Strongyloidiasis (11.36)

200 mcg/kg as a single dose OR 200 mcg/kg daily for 2 days and then maintenance therapy 6 mg monthly

Summary tables

Filariasis (11.12)

200–400 mcg/kg as a single dose AND albendazole 400 mg twice daily for 2 weeks

Onchocerciasis (in non Loa Loa endemic areas) (11.28)

150 mcg/kg as a single dose every 6 or 12 months

Scabies (10.2.4)

200 mcg/kg as a single dose and repeat in 2 weeks.

Norwegian (crusted) scabies (10.2.4)

Combine ivermectin with topical scabicide (benzyl benzoate or permethrin)

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Drug Indication Pregnancy: Safe to use Breastfeeding: Limited data; avoid use.

Formulations Dosage

Adverse effects

Special groups/comments

Ketamine

Injection: 50 mg, 100 mg (as hydrochloride) /ml in 10 ml vial

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Raised BP and pulse rate, increased muscle tone (sometimes tonic-clonic and resembling seizures), lacrimation, nausea, vomiting, nystagmus, raised intracranial pressure, diplopia; emergence reactions (may occur after recovery and up to 24 hours), which vary in severity between pleasant dreamlike states to vivid imagery, hallucinations, nightmares and emergence delirium (often consisting of dissociative or ﬂoating sensations), confusion, excitement, irrational behaviour Infrequent or rare: Raised intraocular pressure, arrhythmias, hypotension, bradycardia, laryngospasm; anxiety, insomnia; increased salivation, apnoea, rashes, injection-site reactions, anaphylaxis Common: Flatulence, abdominal discomfort, cramps Infrequent or rare: Diarrhoea, dehydration, hyponatraemia, hypokalaemia Pregnancy: No evidence of harm Breastfeeding: Use caution.

Sedation during short procedures; induction for intubation (QC p. 28 and 31)

IV: 1–2 mg/kg IV over 2 minutes May repeat 0.5 mg/kg IV every 10 minutes as needed OR IM: 4 mg/kg

Contraindications: Where elevation of blood pressure would constitute a serious hazard, including eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma Use with caution: In increased cerebrospinal ﬂuid pressure, predisposition to hallucinations or nightmares. Ketamine has abuse potential and can itself cause dependence. Administration: For intravenous injection, dilute 100 mg/ml strength to a concentration of not more than 50 mg/ml with dextrose 5% or sodium chloride 0.9% or water. Give IV slowly; rapid administration may result in respiratory depression and enhanced hypertensive response. Emergence reactions can be eliminated by co-administrating benzodiazepine such as diazepam or midazolam and by minimizing stimulation during the recovery period.

Lactulose

Lactulose solution: 3.1–3.7 g/5 ml

Summary tables

Hepatic encephalopathy in cirrhosis (10.9.2)

20–30 g (30–45 ml) 3–4 times daily; adjust dose every 1–2 days to produce 2–3 soft stools daily

Use with caution: In patients with electrolyte imbalance, diabetes mellitus; solution contains galactose and lactose. Administration: May mix with fruit juice, water, or milk. Onset of action is 1–3 days.

411

412 Adverse effects Common: Nausea/vomiting, breast tenderness, headache, dizziness, abdominal pain Irregular vaginal bleeding for 1–2 days; next menstrual bleeding starts earlier or later than expected Special groups/comments Pregnancy: No harm to fetus if pregnancy should occur Breastfeeding: Unknown safety in breastfeeding but duration of use of ECPs is brief. Administration: The duration of use of ECP is brief; thus less clinical impact is expected in severe cardiovascular complications, angina, migraine, severe liver disease. Counselling: If vomiting occurs within 2 hours after taking levonorgestrel, a replacement dose should be taken. An antiemetic can be taken one-half to one hour before the replacement dose. No protection against STI/HIV Pregnancy: Avoid in third trimester Breastfeeding: Amount too small to be harmful Contraindications: Adjacent skin infection, inﬂamed skin, severe anaemia, heart disease Use with caution: In CHF (lower dosage) and following cardiac surgery, bradycardia, hepatic impairment, severe respiratory depression, and in the elderly Common: Dizziness, paraesthesia, drowsiness, confusion; apnoea, respiratory depression; coma, seizures; hypotension, arrhythmias, heart, block, bradycardia (may lead to cardiac arrest); nystagmus (early sign of overdose)

Drug Indication

Formulations Dosage

Levonorgestrel

Tablet: .75 mg; 1.5 mg

For emergency contraception (ECP) (14.5.2)

1.5 mg taken as a single dose within 120 hours of unprotected sex, sexual assault OR 0.75 mg followed by another dose of 0.75 mg 12 hours later

Summary tables

Lidocaine (with or without epinephrine)

Injection: 1%, 2% in vial Topical: 2–4%

Local anaesthesia (7.1.2); nerve block (20.3)

Local inﬁltration and nerve block, using 0.5% solution, up to 250 mg (50 ml) in adults

Local inﬁltration and nerve block, using 1% solution, up to 250 mg (25 ml) in adults

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(Other indications: Arrhythmias; spinal and other anaesthesia)

With epinephrine: 0.5% solution up to 400 mg (80 ml) or 1% solution up to 400 mg (40 ml) in adults

Drug Indication Common: Nausea, vomiting, thirst, ﬂushing of skin, hypotension, arrhythmias, coma, respiratory depression, drowsiness, confusion, loss of tendon reﬂexes, muscle weakness Pregnancy: Safe for short-term use in third trimester (neonatal respiratory depression if excessive dose)

Formulations Dosage

Adverse effects

Special groups/comments

Magnesium sulfate

Injection: 500 mg/ml in 2 ml ampoule; 500 mg/ml in 10 ml ampoule (50%)

See instructions in QC p. 28.

Breastfeeding: Mother treated with parenteral magnesium for pre-eclampsia can breastfeed. Contraindications: Bradycardia or AV block, pre-existing hypermagnesaemia, renal insufﬁciency/failure Use with caution: In myasthenia gravis, liver or renal impairment

Prevention of seizures in severe pre-eclampsia; eclampsia convulsions and prevention of recurrence (QC p. 28)

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Severe bronchospasm not responding to salbutamol (3.2.4); torsade de pointes/ VF/ pulseless VT from toxicity due to quinine (3.8.1)

IV: 2 g over 20 minutes

Aluminium/zinc phosphide toxicity (3.8.1)

IV: 1 g every 6 hours

Tetanus (11.39)

IM: 5 g OR IV: 75 mg/kg loading dose THEN 2–3 g hourly as needed until spasms controlled (with or without diazepam)

Administration: For intravenous injection, dilute 1 part of magnesium sulfate injection 50% with at least 1.5 parts of water for injection. For intramuscular injection, mix magnesium sulfate injection 50% with 1 ml lidocaine injection 2%. Monitor urine output. Before giving next dose, ensure that: • knee jerk is present • urine output >100 ml/4 hours • respiratory rate >16/minute. Otherwise, do not give magnesium and consider calcium gluconate for toxicity. Note: Magnesium sulfate 1 g is approximately equivalent to Mg 4 mmol.

Summary tables

413

414 Adverse effects Infrequent or rare: Skin irritation, contact dermatitis, allergy Breastfeeding: Safe to use Counselling: Avoid contact with eyes. Do not use on broken or secondarily infected skin. Use lotion no more than once a week for 3 consecutive weeks. Pregnancy: Avoid use; permethrin preferred. Special groups/comments Pregnancy: Contraindicated in ﬁrst trimester; consider alternatives before using in second or third trimester. Breastfeeding: May be used; 2–10% of oral dose absorbed, and some excretion into breast milk expected. Counselling: Take dose between meals. Infrequent or rare: Nausea, vomiting, diarrhoea, abdominal pain or cramps; headache, dizziness; hypersensitivity reaction; with high doses; increased liver enzymes; alopecia; bone marrow depression

Drug Indication

Formulations Dosage

Malathion

0.5% in an aqueous basis

Head lice (pediculosis capitis) (10.2.8)

Rub 0.5% preparation into dry hair and scalp, allow to dry naturally; THEN remove by washing after 12 hours. THENRepeat application after 7 days.

Summary tables

Crab lice (pediculosis pubis) (10.2.8)

Apply 0.5% aqueous preparation over whole body, allow to dry naturally, THEN wash off after 12 hours or overnight. THEN repeat application after 7 days

Mebendazole

Tablet: 500 mg, 100 mg

Hookworm (10.18); ascaris (10.7)

500 mg orally in a single dose OR 100 mg twice daily for 3 days (Repeat after 3–4 weeks if eggs persist in stool)

500 mg as a single dose every 6 months as prophylaxis

Ascaris, hookworm prophylaxis every 6 months in adolescent girls and women of childbearing age (19.1)

500 mg twice daily for 5 days

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Persistent diarrhoea in immunocompromised patients (10.7d.2) (Other indications: Echinocococcus infections prior to surgery or not amenable to surgery, nematode infections including enterobiasis, trichuriasis, capillariasis)

Drug Indication Pregnancy: Uncertain safety Breastfeeding: Contraindicated

Formulations Dosage

Adverse effects

Special groups/comments

Meglumine antimoniate

Injection: 30%, equivalent to approximately 8.1% antimony in 5 ml ampoule Common: Nausea, vomiting, abdominal pain, anorexia; ECG changes (possibly requiring dose reduction or withdrawal); cough; arthralgia, myalgia; elevated liver enzymes,jaundice, renal function impairment; lethargy

Visceral leishmaniasis (11.20.2)

See table in Section 11.20.2.

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Secondary prophylaxis of leishmaniasis in HIVinfected patient (11.20.3)

IM/IV: 20 mg/kg every 3 or 4 weeks

Contraindications: Severe cardiac, liver and kidney disorders. Use local therapy if lesion is close to the eyes, multiple (≥3), large (>3 cm diameter), sporotrichoid forms, on the joint, super-infected, or produced by L. brazilensis, L. guyanensis, or L. tropica. Use with caution: The risk of serious, even fatal, toxicity is increased in patients who concomitantly present with: cardiac disease (particularly arrhythmia), renal failure, liver disease, severe malnutrition, severely impaired general condition, advanced HIV infection; pregnancy.

Cutaneous leishmaniasis, local treatment (11.20.1)

Intralesional injection: 1 to 5 intralesional injections, every few days or weekly, with or without cryotherapy

Cutaneous leishmaniasis, systemic treatment (11.20.1)

IV/IM: 20 mg/kg for 21 days

Mucocutaneous leishmaniasis (L. braziliensis) (11.20.1)

IM: 20 mg/kg daily until slit-skin smears are negative and for at least 4 weeks thereafter THEN, if inadequate response, 10–15 mg/kg every 12 hours for same period if inadequate response.

Administration: If any of the above cautions is present, provide protein-rich diet throughout treatment and correct iron and other nutritional deﬁciencies. Monitor cardiac, renal and hepatic function. Successful treatment of mucocutaneous leishmaniasis may induce severe inﬂammation around lesions (may be life-threatening if pharyngeal or tracheal involvement); may require corticosteroids.

Summary tables

Repeat for at least twice as long if relapse. (If unresponsive to this treatment, treat with pentamidine or amphotericin B.)

415

416 Adverse effects Common: Jarisch-Herxheimer-like reaction (chills; fever; general feeling of illness or discomfort); headache; rigidity; sweating, peripheral neuropathy, reactive encephalopathy in 5-10% patients. Infrequent or rare: myocardial damage, hypertension, hypersensitivity, blood dyscrasias such as agranulocytosis; hepatic and renal dysfunction. Pregnancy/breastfeeding: Contraindicated in pregnancy Special groups/comments Use with caution: Hospitalization and close medical supervision (intensive care) required during treatment. Suspend treatment if reactive encephalopathy. Treat intercurrent infections such as pneumonia and malaria before treatment with melarsoprol. Use with caution in malnutrition (if possible, correct with a protein-rich diet); G6PD deﬁciency; leprosy (may precipitate erythema nodosum). Administration: Avoid extravasation–injection is very irritating. Patients should be supine and fast for at least 5 hours after injection. Common: Drowsiness, dizziness, respiratory depression, QT interval prolongation, dysmenorrhoea, hyperprolactinaemia, dry eyes, dry mouth Rare: torsade de pointes, hypothermia, restlessness, raised intracranial pressure, agitation/confusion (especially in the elderly), urinary retention with high doses (especially in the elderly) Pregnancy: May be used; not associated with birth defects; caution in third trimester as chronic use is associated with neonatal opioid withdrawal symptoms. Breastfeeding: Monitor adverse effects such as sedation (no adverse effects reported with 20 mg/day or less); infant withdrawal reported with sudden cessation. Contraindications: Acute bronchial asthma or hypercarbia, respiratory depression in absence of appropriate airway equipment, paralytic ileus Do not give to patients showing signs of intoxication from alcohol or depressant drugs (such as diazepam). Use with caution: In patients with renal or hepatic impairment, hypothyroidism, convulsive disorders, decreased respiratory reserve as in asthma, hypotension, elderly, prostatic hyperplasia, adrenal insufﬁciency, head trauma. Prone to multiple drug interactions. Dose adjustment recommended if severe renal and/or hepatic impairment. Counselling: This medication may impair your ability to perform skilled tasks such as operating machinery and driving.

Drug Indication

Formulations Dosage

Melarsoprol

Injection: 3.6% solution, 5 ml ampoule (180 mg active compound)

Trypanosomiasis, meningoencephalitic stage (11.41)

2.2 mg/kg slow IV injection per day for 7–10 days

Summary tables

Methadone

Concentrate for oral liquid: 5 mg/ml, 10 mg/ml (hydrochloride) Oral liquid: 5 mg/5ml, 10 mg/5ml

Acute opioid withdrawal (3.6.2)

Oral: Initially 15–20 mg. Gradually increase to 40 mg/day. Taper off over 3–28 days. (See Section 3.6.2.)

Opioid substitution therapy (OST) (17.4)

Oral: Initially 20 mg, with an additional 10 mg after 4 hours. If tolerance is low or uncertain, start with a dose of 10 mg (see Section 17.4).

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(Optimal dosing range is 60–120 mg.)

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Uncertain safety in pregnancy and breastfeeding. Use with caution. Contraindications: Severe renal impairment, methaemoglobinaemia due to chlorate or induced by sodium nitrite in treatment of cyanide poisoning, G6PD deﬁciency (may cause haemolytic anaemia) Use with caution: Monitor blood methaemoglobin throughout treatment

Methylthioninium chloride (methylene blue) Common: Nausea/vomiting, abdominal pain, chest pain, headache, dizziness, confusion, profuse sweating, hypertension, hypotension, haemolytic anaemia (in G6PD deﬁciency); methaemoglobinaemia with high dosage; bluish skin discoloration; blue saliva, urine, and faeces

Injection: 10 mg/ml in 10 ml ampoule

Acute methaemoglobinaemia (propanil poisoning) (3.8.1)

IV (loading dose): 2 mg/kg over 5 minutes THEN further dose of 1 mg/kg if no improvement. See Section 3.8.1 for for monitoring and further dosing.

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Drowsiness, headache restlessness, dizziness Infrequent or rare: Extrapyramidal symptoms (especially children/young adults), hyperprolactinaemia, depression, diarrhoea, hypotension, hypertension, neuroleptic malignant syndrome (rare), rash, cardiac conduction abnormalities following IV administration (rare)

Metoclopramide

Tablet: 10 mg Injection: 5 mg (hydrochloride)/ ml in 2 ml ampoule

Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for side-effects)

Nausea, vomiting (10.7.3, 14.1.11)

Oral/IV: 10 mg every 8 hours

15–19 years (<60 kg): 5 mg 3 times daily

Contraindications: Gastrointestinal obstruction (often used to empty the stomach of blood prior to EGD); within 3–4 days after gastrointestinal surgery, convulsive disorders, phaeochromocytoma Use with caution: In elderly, children, and young adults; hepatic or renal impairment; Parkinson´s disease, epilepsy, depression, porphyria. May mask underlying disorders such as cerebral irritation. Renal dosage adjustment required.

Summary tables

417

418 Adverse effects Common: Nausea/vomiting, diarrhoea, unpleasant metallic taste, dizziness, headache Special groups/comments Pregnancy: May be used if drug of choice. Use has not been associated with increased risk of adverse outcomes. Breastfeeding: May be used at usual doses, but avoid high single-dose therapy or else withhold feeds for 12–24 hours; monitor infant for side-effects; may cause temporary changes to milk taste. Contraindications: Chronic alcohol dependence – disulﬁramlike reaction with alcohol occurs. Precautions: Hepatic disease. Prone to multiple drug interactions through CYP enzyme system. Check for interactions with current and new medications. Administration: Tablets should be swallowed whole with water, with or after food. IV: Give over 15–30 minutes. Infrequent or rare: Furred tongue, glossitis stomatitis paraesthesia, increased liver enzymes, blood disorders, myalgia/arthralgia, peripheral neuropathy, epileptiform seizures, disulﬁram-like reaction, bone marrow depression, alopecia Counselling:Take tablets with food to reduce stomach upset. This medicine may make you feel dizzy or confused. Avoid driving if you are affected. Avoid alcohol during treatment, and for 24 hours after stopping the drug, to prevent nausea, vomiting, ﬂushing, headache, and palpitation. Stop the medicine and inform your doctor if you have any numbness, tingling, pain, or weakness in hands or feet

Drug Indication

Formulations Dosage

Metronidazole

Tablet: 200 mg, 500 mg Suppositories: 0.5 g, 1 g Gel Injection: 500 mg in 100 ml vial

Bacterial vaginosis (10.15.4)

500 mg twice daily for 5 –7 days

Summary tables

Pelvic inﬂammatory disease (10.15.5)

Oral: 400–500 mg twice daily for 14 days AND ceftriaxone + doxycycline or tetracycline

Persistent or chronic diarrhoea in immunocompromised patients (empirical) (10.7d.3)

Oral: 500 mg 3 times daily for 7 days AND cotrimoxazole

Leg ulcers/pressure sores (10.2.10)

Oral: 400 mg every 8 hours for 7 days

Acute necrotizing ulcerative gingivitis or periodontitis (10.17.6)

Oral: 200 mg 3 times daily for 7–10 days

Dental abscess (10.17.5)

Oral: 500 mg 3 times daily AND phenoxymethyl penicillin or amoxicillin

Peritonsillar abscess (10.17.9)

Oral: 500 mg 3 times daily AND amoxicillin

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Antibiotic-associated colitis; Clostridium difﬁcile colitis (10.7d.2)

Oral: 500 mg 3 times daily for 10–14 days; IV form effective if patient cannot take oral pills (same dose)

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments

Urogenital trichomoniasis (10.15.4)

Oral: 2 g as a single dose OR 400–500 mg twice daily for 7 days (also treat sexual partners)

Helicobacter pylori eradication (if allergic to amoxicillin) (10.7a.2)

Oral: 400 mg twice daily AND clarithromycin + omeprazole

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Tetanus (11.39)

Oral/IV: 500 mg 4 times daily for 10 days

Intestinal amoebiasis (11.1.1) or empirical treatment in dysentery after no clinical improvement from 2 courses antiobiotics locally effective for Shigella (10.7d.2)

Oral: 750 mg 3 times daily for 5–10 days THEN diloxanide or iodoquinol or paramomycin

Amoebic liver abscess (11.1.2)

Oral/IV: 750 mg 3 times daily for 5–10 days

Severe anaerobic infections- peritonitis or cholangitis (10.7a.2); septic abortion (10.15.6)

Oral/IV: 500 mg 3 times daily AND ceftriaxone or ampicillin + gentamicin

Summary tables

(Other indications: Dracunculiasis; brain abscess; surgical prophylaxis; animal bites; giardiasis)

419

420 Adverse effects Infrequent or rare: Local irritation, contact dermatitis (discontinue if sensitization occurs) Special groups/comments Pregnancy/breastfeeding: May be used at recommended doses in pregnancy and breastfeeding. Breastfeeding: Remove excess cream from nipple areas before feeding. Use with caution: Contact with eyes and mucous membranes should be avoided. Counselling: Gum patch: Place rounded side of tablet on upper gum above an incisor tooth and hold upper lip ﬁrmly over the gum for 30 seconds using a ﬁnger. If tablet detaches within 6 hours, replace with a new tablet. With each dose, alternate sides of the gum. Common: hypotension, hiccup, cough Pregnancy: Avoid use if possible. High doses during late pregnancy or labour may cause neonatal hypothermia, hypotonia, respiratory depression. Breastfeeding: Present in milk; manufacturer advises avoiding breastfeeding for 24 hours after administration. Contraindications: Marked neuromuscular respiratory weakness including unstable myasthenia gravis; severe respiratory depression; acute pulmonary insufﬁciency Use with caution: In cardiac disease; respiratory disease; myasthenia gravis. Midazolam is associated with profound sedation when high doses are given IV or when used with certain other drugs. Infrequent or rare: GI disturbances, heart rate changes, laryngospasm, bronchospasm, respiratory depression and respiratory arrest (particularly with high doses or on rapid injection); drowsiness, confusion, ataxia, amnesia, headache, euphoria, hallucinations, paradoxical excitement and aggression (in elderly); skin reactions, injection-site reactions, anaphylaxis

Drug Indication

Formulations Dosage

Miconazole

Cream: 2% (nitrate) Suppository: 200 mg Oral gel Gum patch

Candida skin infection (11.4)

Topical: Apply cream twice daily to clean, dry lesions for 5–7 days; continue at least 10 days after the condition clears.

Summary tables

Vulvovaginal candidiasis (10.15.4, 11.4)

Vaginal suppository: 200 mg inserted daily for 3 days

Oral candidiasis (11.4)

Oral: gel 60 mg 4 times daily for 7 days OR gum patch once daily for 7 days

Midazolam

Injection: (as hydrochloride) 1 mg/ml

Pretreatment to prevent emergence reaction with ketamine (QC p. 28)

IV: 0.05 mg/kg over 2 minutes just prior to giving ketamine

Sedation for intubation if not comatose (QC p. 31)

IV: 0.2 mg/kg

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Sedation after intubation (QC p. 34)

Infusion: 0.02–0.1 mg/kg/hour)

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments

Miltefosine Common: Nausea, vomiting, anorexia, diarrhoea – usually brief and resolve as treatment continues. Occasionally severe, requiring treatment interruption. Infrequent or rare: Skin allergy, elevated hepatis transaminases, renal insufﬁciency

Capsule: 10 mg, 50 mg

Visceral leishmaniasis (11.20.2)

See table on treatment options in Section 11.20.2.

Pregnancy/breastfeeding: Do not use in pregnancy or during breastfeeding and assure adequate contraception for women of childbearing age during treatment and for 3 months afterwards.

Secondary prophylaxis in HIV-infected patients with leishmaniasis (11.20.3)

Repeat 28-day courses

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Diarrhoea (may occasionally be severe and require withdrawal; reduced by giving single doses not exceeding 200 mcg and by avoiding magnesium-containing antacids); abdominal pain, dyspepsia, ﬂatulence, nausea, vomiting; abnormal vaginal bleeding (including intermenstrual bleeding, menorrhagia, postmenopausal bleeding); rash; shivering and fever. Infrequent or rare: Uterine rupture

Misoprostol

Oral tablet: 200 mcg

Incomplete abortion (10.15.2)

Oral: Single dose of 400 mcg sublingually or 600 mcg by mouth

Use with caution: In conditions where hypotension might precipitate severe complications (cardiovascular or cerebral disease).

Postpartum haemorrhage not responding to oxytocin plus ergometrine (QC p. 26)

SL: 800 mcg

See other sources for contraindications to use for induction of labour (such as placenta praevia, cephalopelvic distortion, history caesarean section or major uterine surgery, etc.)

Summary tables

421

422 Adverse effects Common: Nausea/vomiting (particularly in initial stages), constipation, dry mouth, drowsiness, anorexia, spasm of urinary and biliary tract, bradycardia, tachycardia, palpitation, euphoria, hallucinations, confusion, hypersensitivity reaction, postural hypotension, dependence, miosis. Larger doses produce respiratory depression, hypotension, muscle rigidity. Special groups/comments Pregnancy: May be used if drug of choice. Not associated with birth defects; high doses or prolonged use near term can cause neonatal respiratory depression and withdrawal symptoms. Breastfeeding: Use caution; monitor adverse effects such as sedation; therapeutic concentrations in breastfeeding infant may be reached with repeated dosing or long-term use. Contraindications: Acute respiratory depression, acute alcoholism, risk of paralytic ileus, raised intracranial pressure or head injury (affects pupillary responses vital for neurological assessment), injection in phaeochromocytoma Use with caution: In renal and hepatic impairment, dependence (severe withdrawal symptoms if withdrawn abruptly), hypothyroidism, convulsive disorders, decreased respiratory reserve and acute asthma, hypotension, prostatic hypertrophy. Reduce dose or avoid in elderly and debilitated. Prone to multiple drug interactions through CPY enzymes; check for interactions with new or current medications. Administration: SC dosing not suitable for oedematous patients. Sustained-release tablets should be taken at regular intervals and not on an as-needed basis for episodic or breakthrough pain. Tablets can be crushed Infrequent or rare: Local reactions including urticaria, pruritus, burning sensation, rash Pregnancy/breastfeeding: Safe in pregnancy and breastfeeding Use with caution: Avoid contact with eyes and mouth.

Drug Indication

Formulations Dosage

Morphine

Injection: 10 mg (morphine hydrochloride or morphine sulfate) in 1 ml ampoule Oral liquid: 10 mg (morphine hydrochloride or morphine sulfate) in 5 ml Tablet: 10 mg (morphine sulfate) Tablet (prolonged-release): 10 mg, 30 mg, 60 mg (morphine sulfate)

Summary tables

Severe acute pain (20.4)

See dosing and precautions in Section 20.4.

Chronic pain (20.2)

See dosing in Section 20.2.

Myocardial infarction (QC p. 8)

IV (slow, 2 mg/min): 10 mg THEN 5–10 mg if necessary

Difﬁcult breathing in terminal illness (20.5)

2.5 mg every 4–6 hours if not on morphine for pain. If on morphine for pain, increase dose by 25%.

Mupirocin

Cream (as mupirocin calcium): 2% Ointment: 2%

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Impetigo (10.2.2); papular urticaria with secondary bacterial infection (10.2.3)

Apply up to 3 times daily for up to 10 days

Drug Indication Common: Hypotension, hypertension, ventricular tachycardia and ﬁbrillation, cardiac arrest; hyperventilation, dyspnoea, pulmonary oedema Infrequent or rare: Agitation, excitement, paraesthesia

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use only if potential beneﬁt is greater than risk; may precipitate withdrawal in fetus of an opioid dependant mother Breastfeeding: Unknown safety; currently not recommended. Use with caution: In physical dependence on opioids, other situations where acute withdrawal syndrome may be precipitated; cardiovascular disease Administration: Naloxone effects last only 40 minutes. Pregnancy/breastfeeding: Not recommended during pregnancy or breastfeeding Use with caution: In individuals with hepatic and renal impairment. If feasible, liver function tests should be routinely carried out. No ingestion of other opioid drugs for previous 5 days. Will block effects of other opioid drugs (if analgesia required)

Naloxone

Injection: 400 mcg/ml (hydrochloride) in 1 ml ampoule

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Nausea/vomiting, abdominal pain, diarrhoea, constipation, reduced appetite, increased thirst; chest pain; anxiety, sleep disorders, headache, reduced or increased energy, irritability, emotional lability, dizziness; chills; urinary retention; delayed ejaculation, decreased potency; arthralgia, myalgia; increased lacrimation; rash, increased sweating Infrequent or rare: Hepatic dysfunction; suicidal ideation, speech disorders, hallucinations, tremor; idiopathic thrombocytopenia Common: Nausea, vomiting, increased salivation, diarrhoea, abdominal cramps. Signs of overdosage: Bronchoconstriction, increased bronchial secretions, lacrimation, excessive sweating, involuntary defaecation and micturition, miosis, nystagmus, bradycardia, heart block, arrhythmias, hypotension, agitation, excessive dreaming, weakness eventually leading to fasciculation and paralysis

Opioid overdose (QC p 18)

IV: 100 mcg in a single dose OR IM: 400 mcg in a single dose OR SC: 800 mcg in a single dose. May repeat every 5 minutes up to 3 times (maximum 10 mg)

If response (i.e. respiratory rate >10/minute), start IV infusion: 0.4 mg/hour for 12 hours

Naltrexone

Tablet: 50 mg

Alcohol dependence (16.5)

Start with 50 mg daily after withdrawal from alcohol or whilst still drinking some alcohol. Maintenance dose: 50–100 mg daily. Important that the patient has not taken any opioid drugs for previous 5 days

Summary tables

Neostigmine

Injection: 500 mcg in 1 ml ampoule Tablet: 15 mg

Pregnancy: Use with caution; no reports of malformation, but neonatal myasthenia gravis and bradycardia are possible in newborns exposed during pregnancy. Breastfeeding: May be used in breastfeeding (monitor infant for adverse effects) Use with caution: In asthma, urinary and intestinal surgery, infection

Snake bite neurotoxicity (3.9)

See Section 3.9

(Other indications: Myasthenia gravis, to reverse non-depolarizing muscle relaxants; postoperative non-obstructive urinary retention)

423

424 Adverse effects Special groups/comments Pregnancy: Uncertain safety in pregnancy, no human data; animal studies have not shown evidence of birth defects. Breastfeeding: Unknown safety in breastfeeding; not currently recommended; use only if potential beneﬁt is greater than risk. Contraindications: Psychiatric or neurological disorders Counselling: Take after meals. Common: Nausea, vomiting, anorexia, diarrhoea, abdominal pain; allergic skin reactions; headache Infrequent or rare: Hepatitis, jaundice; erythema multiforme; pancreatitis; blood disorders; with long-term use, pulmonary ﬁbrosis; possible association with lupus erythematosus-like syndrome; peripheral neuropathy Pregnancy: May be used at recommended doses. Due to risk of fetal haemolysis, avoid use at or near term in patients with G6PD deﬁciency. Breastfeeding: May be used at recommended dose except with neonates and infants who are G6PD-deﬁcient; monitor infants for adverse effects. Contraindications: Impaired renal function, G6PD deﬁciency, porphyria Use with caution: In pulmonary disorders or hepatic impairment, neurological or allergic disorders, anaemia, diabetes mellitus, elderly and debilitated, vitamin B and folate deﬁciency Counselling: Take with food or milk to reduce nausea and improve absorption. This drug can make your urine a brownish colour. Common: Nausea/vomiting, diarrhoea, abdominal pain, anorexia, central nervous system alterations (sleep disturbances, excitatory states, seizures, psychotic behaviour), tremors, muscle weakness, paraesthesia and polyneuritis

Drug Indication

Formulations Dosage

Nifurtimox

Tablet: 30 mg,120 mg, 250 mg

Chagas disease (American trypanosomiasis) (11.42)

Oral: 8–10 mg/kg daily divided in 2 or 3 doses, for 60 consecutive days

Summary tables

Nitrofurantoin

Tablet: 100 mg

Acute lower urinary tract infection (11.44)

Oral: 100 mg twice daily for 5 days

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Drug Indication Common: Nausea, vomiting, abdominal pain, ﬂatulence, diarrhoea, constipation; headache.

Formulations Dosage

Adverse effects

Special groups/comments

Omeprazole

Tablet: 20 mg

Gastritis/peptic ulcer disease (PUD) (10.7a.2)

Oral: 20 mg daily for 4–8 weeks

Pregnancy/breastfeeding: Caution in pregnancy and breastfeeding. Use only when treatments with antacids and H2 antagonists have failed. Use with caution: In renal impairment, hepatic impairment, and the elderly. Prone to multiple drug interactions. Do not administer in combination with clopidogrel. Counselling: Swallow the tablet whole. Do not crush or chew it.

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Dry mouth, peripheral oedema, dizziness, sleep disturbances, fatigue, paraesthesia, arthralgia, myalgia, rash, pruritus, taste disturbance, stomatitis, hepatitis, jaundice, agitation, impotence, fever, depression, hallucinations, confusion, gynaecomastia, interstitial nephritis, hyponatraemia, blood disorders (including leukopenia, leucocytosis, pancytopenia, thrombocytopenia), visual disturbances, sweating, photosensitivity, alopecia, Stevens- Johnson syndrome, toxic epidermal necrolysis. By decreasing gastric acidity, proton pump inhibitors may increase the risk of gastrointestinal infections (including C. difﬁcile infection). Common: Constipation, headache, ﬂushing; injection-site reactions; transient rise in hepatic enzymes Infrequent or rare: Hiccups, hypotension, bradycardia, chest pain, arrhythmias, movement disorders, seizures; on IV administration, rarely, dizziness, transient visual disturbances (very rarely, transient blindness) Pregnancy/breastfeeding: No increased risks found in pregnancy or breastfeeding

Helicobacter pylori gastritis (10.7a.2)

Oral: 20 mg twice daily AND clarithromycin + amoxicillin

Ondansetron

Tablet: 4 mg, 8 mg Injection: 2 mg/ml in 2ml ampoule Liquid: 4 mg in 5 ml

Summary tables

Hyperemesis gravidarum (14.1.11); moderate nausea or vomiting or after chemotherapy for 1–2 days (10.7c.3, 20.2)

Oral: 4 mg every 12 hoursincrease to 8 mg if this dose not effective. IV: 8 mg over 15 minutes every 12 hours OR 1 mg/hour infused continuously for up to 24 hours.

Administration: Give IV doses ≤8 mg over at least 5 minutes and doses >8 mg over at least 15 minutes. No dose adjustment in the elderly or if renal impairment. In severe liver impairment, do not exceed maximum dose of 8 mg.

Severe vomiting

Oral: Up to 24 mg daily oral or IV

(Other indications: Prior to chemotherapy causing severe vomiting)

425

426 Adverse effects Common: Nausea, vomiting, abdominal pain, diarrhoea; headache; conjunctivitis Pregnancy: Unknown safety in pregnancy Breastfeeding: Not recommended until more known; use only if potential beneﬁt is greater than risk. Infrequent or rare: Rash, hepatitis, arrhythmias, neuropsychiatric disorders (in children and adolescents), visual disturbances, StevensJohnson syndrome, toxic epidermal necrolysis Common: Nausea/vomiting, arrhythmia, headache Special groups/comments Pregnancy/breastfeeding: Not known to be harmful in breastfeeding, as rapidly inactivated in GI tract Infrequent or rare: Disseminated intravascular coagulation, rash; anaphylactoid reactions (with dyspnoea, hypotension, or shock); uterine spasm (may occur at low doses), uterine hyperstimulation (usually with excessive doses; may cause fetal distress, asphyxia, and death, or may lead to hypertonicity, tetanic contractions, soft-tissue damage or uterine rupture); water intoxication and hyponatraemia associated with high doses with large infusion volumes of electrolyte-free ﬂuid; in overdose, placental abruption, amniotic ﬂuid embolism Contraindications: Hypertonic uterine contractions, mechanical obstruction to delivery, fetal distress, any condition where spontaneous labour or vaginal delivery inadvisable. Avoid prolonged administration in oxytocin-resistant uterine inertia, severe pre-eclamptic toxaemia, severe cardiovascular disease. Use with caution: Monitor fetal heart rate and uterine motility (discontinue immediately if uterine hyperactivity/fetal distress). To avoid water intoxication with hyponatraemia: (1) use electrolyte-containing diluent (not glucose); (2) increase oxytocin concentration to reduce ﬂuid; (3) restrict ﬂuid intake by mouth; (4) monitor ﬂuid and electrolytes.

Drug Indication

Formulations Dosage

Oseltamivir

Capsule: 30 mg, 45 mg, 75 mg Suspension: 12 mg/ml

Pandemic H1N1; patients with severe inﬂuenza-like illness or at risk for severe ILI (QC p 20, 11.17)

>40 kg: 75 mg twice daily for 10 days

(Note: In severe illness may use 150 mg twice daily)

Summary tables

Oxytocin

Injection: 10 IU in 1 ml ampoule

Treatment of postpartum and post-abortion haemorrhage (QC pp. 25–26)

IM: 10 IU AND Start IV ﬂuids with 20 IU oxytocin at 60 drops/minute See QC p. 25.

(Other indictions: prevention of postpartum haemorrhage- when the anterior shoulder is delivered or immediately after delivery)

Continue oxytocin at 20 IU at 20 drops/minute for at least 1 hour after bleeding stops.

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Drug Indication Common: Increased transaminases Infrequent or rare: Urticarial or erythematous rash, blood disorders, liver damage following overdosage

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for side-effects) Use with caution: In hepatic impairment, renal impairment, alcohol dependence Counselling: Do not exceed 4 grams in 24 hours.

Paracetamol (acetaminophen)

Tablet: 250 mg, 500 mg Dispersible tablets: 500 mg Suppositories: 250 mg, 500 mg

Mild to moderate pain (20.2, 20.4); fever (10.1)

(Other indications: Acute migraine attacks; tension headache) Common: Injection site reactions, elevated liver enzymes

Oral: 0.5–1 g every 4–6 hours (max 4 g daily; max 2 g daily if hepatic impairment, cirrhosis) Rectally: 0.5–1 g every 4–6 hours

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Ototoxicity (reversible at recommended dosage), nephrotoxicity, neurotoxicity (numbness, skin tingling, muscle twitching, convulsions; neuromuscular blockage, respiratory paralysis reported following high doses)

Paromomycin

Injection: 750 mg base (11 mg base = 15 mg paramomycin sulfate) Ointment: 15% paramomycin + 12% methyl benzethonium chloride

Pregnancy: Unknown safety in pregnancy; no human data. Use only if potential beneﬁt is greater than risk. Breastfeeding: Unknown safety in breastfeeding, but poorly absorbed from GI tract so excretion into breast milk likely to be minimal.

Local treatment of cutaneous leishmaniasis (11.20.1)

Ointment twice daily for up to 20 days

See table in Section 11.20.2

Contraindications: Hypersensitivity to aminoglycosides, course of paromomycin treatment in preceding 3 months, concurrent administration of nephrotoxic or ototoxic drugs including aminoglycosides, renal impairment

Visceral leishmaniasis caused by certain species

Summary tables

427

428 Adverse effects Special groups/comments Pregnancy: Potentially fatal visceral leishmaniasis and PCP pneumonia (cotrimoxazole is preferred) should be treated in pregnancy. Breastfeeding: Manufacturer advises avoiding unless essential; not known to be harmful, as rapidly inactivated in GI tract. Contraindications: In severe renal impairment Common: Nausea, vomiting, diarrhoea, taste disturbances; severe reactions, sometimes fatal (hypotension, hypoglycaemia, pancreatitis, arrhythmias); leukopenia, thrombocytopenia; acute renal failure, hypocalcaemia Infrequent or rare: Azotaemia, abnormal liver-function tests, anaemia, hyperkalaemia, dizziness, syncope, ﬂushing, hyperglycaemia, rash, Stevens-Johnson syndrome; on inhalation, bronchoconstriction (may be prevented by prior use of bronchodilators), cough, shortness of breath; discomfort, pain, induration, abscess formation, muscle necrosis at injection site Administration: Risk of severe hypotension following administration. Establish baseline blood pressure and administer with patient lying down; monitor blood pressure closely during administration and at regular intervals until treatment concluded. Avoid direct intravenous injection whenever possible and never give rapidly. Reconstitute with 3–5 ml of water for injection; dilute further to 50–250 ml with glucose 5% or normal saline; give over at least 60 minutes. IM injections should be deep and preferably given into the buttock. Pentamidine is toxic – protect health workers during handling and administration.

Drug Indication

Formulations Dosage

Pentamidine

Powder for injection: 200 mg, 300 mg (isetionate) in vial

Cutaneous leishmaniasis (due to severe side-effects, recommended only if no other treatment available) (11.20.1)

IM/IV: 2–3 mg/kg once daily or every second day for 4–7 doses

Summary tables

Leishmaniasis, secondary prophylaxis in HIV-infected patients (11.20.3)

4 mg/kg (300 mg) every 3–4 weeks

Severe Pneumocystis jirovecii (PCP) pneumonia, treatment if not able to tolerate or unresponsive to cotrimoxazole (10.6.3)

Slow IV/deep IM: 4 mg/kg daily for 5 days; then reduce dose to 2 mg/kg daily to complete 21 days

Human African trypanosomiasis (T. b. gambiense)- haemolymphatic stage (11.41)

IM (deep): 4 mg/kg daily for 7 consecutive days

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Drug Indication Common: Temporary increase in itch, redness, swelling that usually accompany lice or mite infestation Infrequent or rare: Local irritation, rash, oedema

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: May be used; systemic absorption expected to be minimal. Breastfeeding: May be used; systemic absorption expected to be minimal, but avoid application to nipple areas (or withhold breastfeeding during treatment). Contraindications: Do not use on inﬂamed or broken skin. Counselling: Avoid contact with eyes, mouth, and inside the nose. Itch may persist for 2–3 weeks after scabies treatment or 7–10 days after lice treatment. This may not indicate ongoing infection. Scabies: Remember to apply also between ﬁngers and toes, under nails, in skin folds, navel, between the buttocks, and in groin area. If you wash your hands or any other treated parts of the body during the treatment period, you should reapply the lotion to the washed areas.

Permethrin

Cream: 5%

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Scabies (10.2.3); pediculosis (body lice) (10.2.8)

Topical: Apply cream over whole body AND Wash off after 8–12 hours (if hands washed with soap within 8 hours after application, treat again) THEN Repeat after 7 days as necessary.

Pediculosis capitis (head lice) (10.2.8)

Apply to damp hair and leave for 10 minutes before washing off.

Summary tables

429

430 Adverse effects Pregnancy: Not recommended; adverse effects on neurobehavioural development have been reported. Special groups/comments Common: Drowsiness, incoordination, restlessness and confusion (in elderly), impaired memory and cognition, hyperactivity (particularly in the elderly), allergic skin reactions, paradoxical excitement, sleep disorders. With IV: hypotension, respiratory depression, laryngospasm Contraindications: Porphyria, absence seizures Use with caution: In the elderly, impaired renal or hepatic function, respiratory depression Avoid sudden withdrawal. Prone to multiple drug interactions through CYP enzymes; check for interactions with all new and current medications. Counselling: Take once daily at bedtime. May cause drowsiness and affect your ability to drive or operate machinery. Avoid these activities at least until you know how this medicine affects you. Do not stop taking this medicine suddenly without your clinician’s advice. Avoid drinking alcohol, as the medicine may increase the effects of alcohol. Infrequent or rare: Hepatitis, cholestasis; behavioural disturbances, nystagmus, irritability, lethargy, depression, ataxia, hallucinations; osteomalacia; megaloblastic anaemia (may be treated with folic acid), agranulocytosis, thrombocytopenia; allergic skin reactions; very rarely Stevens-Johnson syndrome and toxic epidermal necrolysis; status epilepticus (on treatment withdrawal); Dupuytren’s contracture; lymphadenopathy Breastfeeding: Use with caution in breastfeeding; avoid large doses and monitor for adverse effects; may accumulate in breast milk.

Drug Indication

Formulations Dosage

Phenobarbital

Injection: 200 mg/ml (phenobarbital sodium) Tablet: 15–100 mg (phenobarbital)

Status epilepticus (3.5)

Loading dose: IV: 5–15 mg/kg bolus over 1 hour

Summary tables

Epilepsy (10.10c.2)

Oral: Initiate at 60 mg daily; then maintain at 60–180 mg daily.

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Drug Indication See benzylpenicillin.

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for side-effects) Contraindications: Hypersensitivity to penicillins Use with caution: In renal impairment. Oral penicillin should not be used for the treatment of severe infections. Counselling: Take 1 hour before meals or on an empty stomach.

Phenoxymethyl-penicillin (penicillin V)

Tablet: 500 mg

Streptococcal pharyngitis (10.17.9, 11.32)

Oral: 500 mg twice daily for 10 days

Cutaneous anthrax, nonsevere, if known antibiotic sensitivity (10.2.10)

Oral: 500 mg every 6 hours for 7–10 days

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Dental abscess (10.17.5)

Oral: 250 mg every 6 hours for 5 days

Prevention of recurrent rheumatic fever (11.32)

Oral: 500 mg twice daily

Erysipelas (10.2.2)

Oral: 500 mg every 6 hours for 5–10 days

(Other indications: Otitis media; post-splenectomy prophylaxis)

Summary tables

431

432 Adverse effects Common: Nausea, vomiting, constipation; insomnia, transient nervousness, tremor, paraesthesia, dizziness, headache, anorexia; gingival hypertrophy and tenderness; rash (discontinue; if mild, re-introduce cautiously but discontinue immediately if recurrence), acne, hirsutism, coarse facies Special groups/comments Pregnancy: Risk of teratogenicity; use only if beneﬁt is greater than risk (provide adequate folic acid supplementation to mother); monitor for neonatal bleeding if vitamin K not given at birth. Breastfeeding: May be used in breastfeeding; monitor for sedation and decreased sucking; consider infant serum level monitoring. Contraindications: Porphyria. Avoid parenteral use in sinus bradycardia, sinoatrial block, second- and third-degree heart block, Adams-Stokes syndrome. Use with caution: In hepatic impairment, diabetes mellitus, hypotension, heart failure. Resuscitation facilities must be available for intravenous administration. Administration: Administer phenytoin IV in normal saline and not in same line as diazepam. IV line should be running well, as the drug is caustic and will cause local damage if it extravasates. Monitor blood counts. When decision is made to withdraw treatment, do so preferably over 6 months at a rate not greater than 25 mg each week or 100 mg each month. Counselling: Seek immediate medical attention if you have symptoms such as sore throat, rash, mouth ulcers, bruising, or bleeding. This medication may impair ability to perform skilled tasks such as operating machinery or driving; avoid these activities at least until you know how this medicine affects you. Take with or after food. Good dental hygiene can help to prevent gum enlargement. Do not stop this medicine suddenly without your clinician’s advice. Infrequent or rare: Hepatotoxicity, peripheral neuropathy, dyskinesia, lymphadenopathy, osteomalacia; blood disorders (including megaloblastic anaemia (may be treated with folic acid)), leukopenia (if severe, progressive, or clinically apparent leukopenia develops, withdraw drug, replacing with suitable alternative), thrombocytopenia, aplastic anaemia; polyarteritis nodosa, lupus erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis; pneumonitis, interstitial nephritis; with excessive dosage, nystagmus, diplopia, slurred speech, ataxia, confusion, hyperglycaemia

Drug Indication

Formulations Dosage

Phenytoin

Capsule: 25 mg, 50 mg, 100 mg Injection: 50 mg/ml in, 5 ml vial Tablet: 25 mg, 50 mg, 100 mg Tablet (chewable): 50 mg

Generalized tonic-clonic seizures; partial seizures (10.10c.2)

Oral: Start at 150–200 mg daily, increase by increments of 25–30 mg to reach maintenance at 200–400 mg daily

Summary tables

Status epilepticus (3.5)

Loading dose: IV (slowly over 60 ): 15 mg/kg in normal saline, at a rate of not more than 50 mg/ minute (monitor BP and ECG).

Then oral maintenance dose as above.

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Drug Indication Common: Eye pain, blurred vision, ciliary spasm; ciliary spasm leads to headache and brow ache, which may be most severe in the initial 2–4 weeks of treatment. Infrequent or rare: Lacrimation, myopia, conjunctival vascular congestion, superﬁcial keratitis, vitreous haemorrhage, increased pupillary block; lens opacities (following prolonged use); rarely, systemic effects including hypertension, tachycardia, bronchial spasm, pulmonary oedema, salivation, sweating, nausea, vomiting, diarrhoea

Formulations Dosage

Adverse effects

Special groups/comments Contraindications: Acute iritis, acute uveitis, anterior uveitis, some forms of secondary glaucoma; acute inﬂammation of anterior segment. Use not advisable after angle-closure surgery (risk of posterior synechiae). Use with caution: In retinal disease, conjunctival or corneal damage (monitor intraocular pressure in chronic open-angle glaucoma and in long-term treatment); cardiac disease, hypertension, asthma, peptic ulceration, urinary tract obstruction, Parkinson’s disease. Withdraw treatment if symptoms of systemic toxicity develop. Administration: A darkly pigmented iris may require higher concentration of the miotic or more frequent administration; care should be taken to avoid overdosage. Counselling: If you are using more than one type of eye drop, put in pilocarpine drops last. Causes difﬁculty with adapting to the dark and may cause accommodation spasm. Avoid skilled tasks, for example, operating machinery or driving, until vision is clear.

Pilocarpine eye drops

Drops: 2%, 4% (hydrochloride or nitrate)

Chronic open-angle glaucoma (10.12.4)

1 drop (2% or 4% solution) up to 4 times daily

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Irritation, staining of the skin Infrequent or rare: Systemic effects resulting from cutaneous absorption include nausea, vomiting, abdominal pain, diarrhoea; also, transient leukopenia and thrombocytopenia; renal failure; delayed neurotoxicity including visual and auditory hallucinations, delusions, disorientation, confusion, delirium following excessive application

Emergency treatment of acute angle-closure glaucoma (before surgery) (10.12.2)

1 drop (2% solution) every 10 minutes for 30–60 minutes; then 1 drop every 1–3 hours until intraocular pressure subsides

(Other indications: Ocular hypertension; to antagonize effects of mydriasis and cycloplegia following surgery or ophthalmoscopic examination)

Podophyllum resin

Solution: 10–25%

Pregnancy/breastfeeding: Contraindicated in pregnancy and breastfeeding Use with caution: Avoid use on large areas; very irritant to eyes (keep away from face); avoid contact with normal skin, mucus membranes, open wounds. Administration: Must be applied by a trained health worker Counselling: Avoid contact with face and other sensitive areas.

Summary tables

External anogenital warts; plantar warts (10.2.3)

Apply carefully, avoiding contact with normal tissue; rinse off after 1–6 hours. May be repeated at weekly intervals but no more than 4 times in all. Only a few warts should be treated at any one time.

433

434 Adverse effects Infrequent or rare: Irritation of skin and mucous membranes; may interfere with thyroid function tests Special groups/comments Contraindications: Avoid regular or prolonged use in patients with thyroid disorders or those taking lithium. Administration: Do not use on large open wounds: may produce systemic adverse effects such as metabolic acidosis, hypernatraemia, impairment of renal function. Common: Nausea, vomiting, abdominal cramps, bloating Infrequent or rare: Aspiration pneumonia Note: Risk of ﬂuid and electrolyte imbalance if solution is not correctly formulated Pregnancy: Unknown safety in pregnancy. Breastfeeding: Not recommended until more known; use only if potential beneﬁt is greater than risk. Contraindications: Ileus, GI haemorrhage, haemodynamic instability, uncontrollable vomiting, bowel obstruction or perforation, decreased consciousness with unprotected airway. Use with caution: Avoid occlusive dressings. Administration: In exudative eczematous areas, treatment should be stopped when the skin becomes dry. Note: Potassium permanganate is sometimes supplied as an aqueous stock solution of 1:1000 (0.1%) for dilution before use. To be diluted 1 in 10 to provide a 0.01% (1 in 10 000) solution. Common: Irritant to mucous membranes; skin and fabrics can be stained brown.

Drug Indication

Formulations Dosage

Polyvidone iodine (povidone–iodine)

Solution: 10%

Skin disinfection (10.2)

Apply undiluted solution to the skin area.

Antiseptic for minor wounds and burns (4)

Apply undiluted solution to the affected area twice daily.

Summary tables

Polyethylene glycol electrolyte solution (osmotically balanced mixture)

Solution

Acute iron poisoning and overdose with highly toxic sustained-release preparations, e.g. calcium channel blockers (3.8.1)

Bowel irrigation: 2 litres per hour for adults if tablets are present beyond the stomach

Potassium permanganate

Aqueous solution: 1:10 000 (0.01%)

Wet dressings to assist healing of suppurating superﬁcial wounds, tropical ulcers; pemphigus; tinea pedis; infected eczema (10.2)

Apply dressings soaked in a 1:10 000 solution to affected area until superﬁcial crusts can be gently separated. Change dressings 2 or 3 times daily. Bathe severe weeping lesions in a 1:10 000 solution every 8 hours.

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Drug Indication Common: Nausea/vomiting (severe symptoms may indicate obstruction of oesophagus or small bowel), hyperkalaemia (especially in renal insufﬁciency), rapid infusion toxic to heart

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: May be used for supplementation in pregnancy and breastfeeding; monitor electrolytes to keep maternal serum levels within normal range. Contraindications: Severe renal impairment and plasma potassium concentration above 5 mmol/l Use with caution: In elderly, mild/moderate renal impairment, history of peptic ulcer Administration: Monitor potassium levels. Potassium salts cause nausea and vomiting; therefore, poor compliance is a major limitation to their effectiveness; where appropriate, potassium-sparing diuretics are preferable. Counselling: If you have severe nausea and vomiting, stop the medicine and inform your clinician.

Potassium chloride (KCl)

Solution: 11.2% in 20 ml ampoule (equiv to K+ 1.5 mmol/ ml, Cl− 1.5 mmol/ml); Oral preparations

Hypokalaemia, mild to moderate (5.2.2)

Oral: 20–50 mmol daily after meals

Vol. 1 • 8. Medicines/therapies: July 2011 Usually mild and transient with short course. Many adverse effects result from death of the parasite and are more severe with high parasite burden. Common: Dizziness (dose dependent), headache, malaise, drowsiness; nausea, vomiting, abdominal pain, diarrhoea, anorexia, colic; reversible rises in hepatic transaminases; rectal bleeding Infrequent or rare: arrhythmia Contraindications: Ocular cysticercosis

Hypokalaemia, severe (5.2.2)

Slow IV infusion: 20–40 mmol/l in normal saline (not to exceed 10-20 mmol/hour)

Praziquantel

Tablet: 600 mg

Schistosomiasis (11.34)

Oral: 40 mg/kg as a single dose

Pregnancy: Use not recommended in ﬁrst trimester; consider alternatives. Caution in second and third trimesters; use only if treatment of choice. Breastfeeding: May be used for single-day treatment during breastfeeding

Summary tables

Counselling: Take with food. Swallow with plenty of water to prevent vomiting due to bitter taste. Tablet may be cut into halves or quarters, but do not chew. The medicine may make you feel drowsy or dizzy; if you are affected, do not drive or operate machinery until 24 hours after ﬁnishing your course.

435

436 Adverse effects Special groups/comments Pregnancy: May be used at the recommended doses; caution in ﬁrst trimester due to possibility of oral cleft; limited transplacental transfer. Monitor blood glucose, especially in diabetics. Breastfeeding: May be used at recommended doses; amount in milk low at doses up to 80 mg (monitor infant’s adrenal function if dose is higher) Contraindications: Systemic infection (unless lifethreatening or speciﬁc antimicrobial therapy given). Avoid live virus vaccines in those receiving immunosuppressive doses. Overdosage or prolonged use can exaggerate some of the normal physiological actions of corticosteroids, leading to mineralocorticoid and glucocorticoid side-effects. Mineralocorticoid side-effects: Hypertension, sodium and water retention, potassium and calcium loss Common: Dyspepsia, increased susceptibility to infection (oral, vaginal, intertriginous candidiasis), masking of signs of infected acne, oedema, hypertension, hypokalaemia, hyperglycaemia, weight gain, osteoporosis, spontaneous fractures, increased appetite, delayed wound healing, skin atrophy, growth retardation in children, myopathy, muscle weakness, wasting (particularly symptomatic on drug withdrawal), fat redistribution (producing cushingoid appearance), amenorrhoea, psychosis. euphoria, depression, adrenal suppression, bruising Use with caution: In infections, hypertension, recent myocardial infarction, congestive heart failure, renal impairment, hepatic impairment, diabetes mellitus including family history, osteoporosis, glaucoma including family history, corneal perforation, severe affective disorder, epilepsy, psoriasis, peptic ulcer, hypothyroidism, history of steroid myopathy, and in the elderly; can activate or exacerbate TB, amoebiasis, strongyloidiasis. Prolonged treatment leads to adrenal suppression, which persists for years after stopping treatment. Cushingoid features are increasingly likely with doses above 7.5 mg daily. Risk of chickenpox, measles, and activation of tuberculosis increased.

Drug Indication

Formulations Dosage

Prednisolone Also see Section 8.2 steroid equivalents table.

Tablet; 5 mg, 25 mg

Moderate to life-threatening wheezing (3.2.4)

Oral: 40–60 mg

Summary tables

Pneumocystis jirovecii pneumonia (PCP pneumonia) (10.6.3)

Oral: 40 mg twice daily for 5 days THEN 40 mg daily for 5 days THEN 20 mg daily for 11 days to complete 21 days of treatment

Management of severe persistent asthma (10.6.4)

Oral: 0.5 mg/kg daily (reassess weekly; taper when patient stable for 1 week)

Type 2 lepra reaction (11.21)

See Section 11.21 for dosing.

Vol. 1 • 8. Medicines/therapies: July 2011

Drug Indication Administration: Monitor weight, blood pressure, ﬂuid and electrolyte balance, and blood glucose levels throughout prolonged treatment. The suppressive action of a corticosteroid on cortisol secretion is least when it is given as a single dose in the morning. During corticosteroid withdrawal the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur. Counselling: Take with food to reduce stomach upset. Tell your doctor immediately if you have any signs of infection. If you have been on this medicine for more than 3 weeks, don’t stop the treatment suddenly. Tell your doctor, dentist, or pharmacist that you are on steroids before undergoing any new treatment. Infrequent or rare: Acute pancreatitis, peptic and oesophageal ulceration, vertebral compression fracture, aseptic necrosis of the talus or femoral and humoral heads; facial erythema, suppression of skin test reactions, hyperhidrosis, skin bruising, telangiectasia, myocardial rupture following recent myocardial infarction, congestive heart failure, leucocytosis, hypersensitivity reactions (including anaphylaxis), thromboembolism, malaise, hiccups, headache, vertigo. Glucocorticoid side-effects: Diabetes and osteoporosis can result in osteoporotic fractures, particularly in the elderly. CNS side-effects: Psychological dependence, insomnia, aggravation of schizophrenia, aggravation of epilepsy. Ophthalmologic side-effects: Glaucoma, papilloedema, posterior subcapsular cataracts, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal disease, increased intra-ocular pressure, exophthalmos

Formulations Dosage

Adverse effects

Special groups/comments

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Other indications: With antineoplastic drugs for acute and chronic leukaemias; lymphoma; suppression of inﬂammatory and allergic reactions; inﬂammation of the eye; myasthenia gravis)

Note on steroid dosing: Patients on long term steroid therapy are at risk for a blunted stress response in conditions causing physiologic stress (e.g., severe infection, trauma, during surgery). As a result, standard steroid doses may need to be supplemented. Patients on steroid replacement for primary dysfunction of the hypothalamus-pituitaryadrenal axis HPA axis (for example, Addison disease, hypopituitarism) SHOULD receive higher dose of steroids in conditions causing physiologic stress. A common IV regimen is hydrocortisone 50-100 mg every 8 hours for 2 days. Consult a specialist for assistance on how to provide this supplemental steroid treatment.

Summary tables

437

438 Adverse effects Common: Nausea, vomiting, anorexia, abdominal cramps; dizziness, headache Infrequent or rare: Haemolytic anaemia (frequently in G6PD deﬁciency; withdraw treatment); methaemoglobinaemia (withdraw treatment); haemoglobinuria; agranulocytosis, granulocytopaenia, leukopenia Pregnancy: Uncertain safety in pregnancy; use not recommended. Breastfeeding: Use with caution; limited data. Monitor infants for adverse effects (e.g. haemolysis, jaundice). Avoid in neonates and infants who are G6PD-deﬁcient. Contraindications: Conditions that predispose to granulocytopenia. Monitor blood count. Exclude G6PD deﬁciency before radical treatment for P. vivax and P. ovale but not before single-dose gametocytocidal treatment. Counselling: Give with food if severe nausea/vomiting or abdominal cramps occur. See benzylpencillin. Pregnancy/breastfeeding: Considered safe in both pregnancy and breastfeeding (monitor infant for sideeffects). Contraindications: Hypersensitivity to penicillins or if IV administration needed Use with caution: In renal failure. Observe patient with syphilis or borreliosis for several hours after treatment. Administration: Give by deep IM injection. (Do not give IV.) Can be used for daily outpatient treatment. Probenecid is added to increase serum penicillin levels in neurosyphilis. Special groups/comments Pain and inﬂammation at injection site; Jarisch-Herxheimer reaction (rigors, fever, and hypotension) usually within several hours after treatment of syphilis or borreliosis; probably due to release of endotoxin. Accidental intravascular administration may result in anxiety, agitation, fear of death, hallucinations. These usually resolve in 15–30 minutes and rarely last beyond 24 hours.

Drug Indication

Formulations Dosage

Primaquine

Tablet: 7.5 mg, 15 mg

Radical treatment of P. vivax and P. ovale malaria (after standard chloroquine therapy) (11.25.3)

Oral: 250 mcg/kg daily for 14 days OR 30 mg daily for 14 days

Summary tables

Procaine benzylpenicillin G

Powder for Injection: 1 g vial (1 million IU); 3 g vial (3 million IU)

Neurosyphilis (11.37)

IM: 2.4 g (2.4 million IU) daily AND oral probenecid 500 mg 4 times daily) for 10–14 days

Tropical ulcer (10.2.10)

0.6 g (600 000 IU) daily for 2–4 weeks

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Borreliosis (louse-borne relapsing fever) if not able to take orally (10.1) (Other indications: Diphtheria; animal bites)

IM: 0.6 to 0.8 g (600 000 to 800 000 IU) as a single dose

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use with caution. May cause intrauterine growth restriction, neonatal hypoglycaemia, and bradycardia; risk greater in severe hypertension. Breastfeeding: Present in milk; safe in usual dosage; monitor infant.

Propranolol

Tablet: 20 mg; 40 mg (hydrochloride) Common: Nausea/vomiting, diarrhoea, bradycardia, bronchospasm, cold extremities, fatigue, sleep disturbances including nightmares; heart failure, hypotension, conduction disorders, peripheral vasoconstriction, exacerbation of intermittent claudication, Raynaud's phenomenon; alteration of glucose and lipid metabolism Infrequent or rare: Rash, dry eyes (reversible), sexual dysfunction, exacerbation of psoriasis. purpura, thrombocytopenia

Vol. 1 • 8. Medicines/therapies: July 2011 Counselling: Do not stop taking this medicine suddenly without your clinician’s advice.

Primary prevention of variceal bleeding in patients with documented varices (10.9)

Titrate to achieve a 25% reduction in the heart rate

(Other indications: migraine prophylaxis, essential tremor, stable angina, hypertension, some arrhythmias)

Contraindications: Asthma or history of obstructive airway disease, uncontrolled heart failure, Prinzmetal’s angina, marked bradycardia, hypotension, sick sinus syndrome, second- or third-degree atrioventricular block, cardiogenic shock, metabolic acidosis, severe peripheral arterial disease; phaeochromocytoma Use with caution: In ﬁrst-degree atrioventricular block; renal impairment; liver disease; portal hypertension; diabetes mellitus; myasthenia gravis; history of hypersensitivity Administration: When stopping treatment, reduce dosage gradually over at least 2 weeks.

Summary tables

439

440 Adverse effects Infrequent or rare: Sensory neuropathy reported with high doses given for extended periods Special groups/comments Pregnancy/breastfeeding: May be used in pregnancy and breastfeeding; doses >200 mg/day may suppress lactation. Pregnancy: May be used during pregnancy if it is the drug of choice; avoid in ﬁrst trimester when possible. Breastfeeding: Use, with caution, if it is the drug of choice. Contraindications: Megaloblastic anaemia Use with caution: In hepatic and renal impairment For treatment of toxoplasmosis, pyrimethamine must always be taken with sulfadiazine and should be administered with folinic acid when available. Administration: Give with food if GI disturbances occur. Monitor blood counts in prolonged treatment and give folate supplements throughout treatment. Common: Nausea/vomiting, diarrhoea, depression of haematopoiesis with high doses, megaloblastic anaemia, rashes, insomnia, CNS toxicity (at high doses)

Drug Indication

Formulations Dosage

Pyridoxine (vitamin B6)

Tablet: 25 mg

Ethylene glycol poisoning (3.8.1)

Oral: 50 mg every 6 hours for 6 doses

Peripheral neuropathy (10.10a.6); neuropathic signs on INH (13.3, 15.4.2)

Oral: 50–75 mg daily

Summary tables

Prevention of peripheral neuropathy with INH for prophylaxis or treatment for TB (15.4.2)

Oral: 10 mg daily

Antiemetic in pregnancy (14.1.11)

Oral: 25 mg, up to 3–4 times daily

Pyrimethamine

Tablet: 25 mg, 50 mg

Toxoplasmosis in immunodeﬁciency (11.40)

Oral: 100–200 mg as a single dose THEN 50 mg daily for at least 6 weeks AND sulfadiazine + folinic acid for 6 weeks

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Chorioretinitis (10.12.6)

Oral: 75 mg daily for 3 days THEN 25 mg daily for 4 weeks AND sulfadiazine + folinic acid for same duration (In unresponsive patients, 50 mg daily for a further 4 weeks)

Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Use only if beneﬁt is greater than risk; avoid in ﬁrst trimester when possible, as high doses (>1 g total) may cause fetal deafness. Breastfeeding: Caution; monitor for adverse effects. Avoid in G6PD-deﬁcient infants. Contraindications: Haemoglobinuria, optic neuritis, tinnitus

Quinine Common: Nausea, vomiting, diarrhoea, CNS disturbances, reversible hearing loss, cinchonism, tinnitus, headache, hot and ﬂushed skin, nausea, abdominal pain, rashes, visual disturbances (including temporary blindness), confusion, fever, rash, hypoglycaemia (after parenteral administration), thrombocytopenia, ECG changes Infrequent or rare: Angioedema, intravascular haemolysis, acute renal failure, prolonged QT interval

Tablet: 300 mg Infusion: 300 mg/ ml in 2 ml ampoule

Severe P. falciparum malaria if parenteral artesunate not available (QC p. 20, 11.25.5)

IV/IM (in anterior thigh): 20 mg/ kg over 4 hours; THEN 10 mg/ kg every 8 hours until oral medication is possible

Vol. 1 • 8. Medicines/therapies: July 2011 As for quinine and clindamycin See doxycycline and quinine. Additionally:

Oral: 600 mg quinine sulfate 3 times daily for 7 days AND clindamycin or doxycycline

Use with caution: In atrial ﬁbrillation, conduction defects, heart block, renal impairment, G6PD deﬁciency, myasthenia gravis. With IV use, monitor signs of cardiac toxicity and blood glucose levels. Administration: Oral: If part of all of a dose is vomited within 1 hour, the same amount must be re-administered immediately. IV: Do not give as intravenous bolus injection. Infuse IV quinine over 4 hours, preferably in glucose 5% to reduce risk of hypoglycaemia.

Quinine + clindamycin

Separate blisters with tablets of 150 or 300 mg quinine and tablets of 100 mg doxycycline

Summary tables

Non-severe P. falciparum malaria in ﬁrst-trimester pregnancy (11.25.7); P. falciparum malaria in travellers (11.25.3); secondline treatment for malaria (11.25.4)

Oral: 600 mg of quinine salt given 3 times a day (every 8 hours) for 7 days and 600 mg of clindamycin base twice daily for 7 days

Use with caution: Rifampicin reduces the plasma concentration of quinine, leading to increased treatment failures. Avoid antiarrhythmics, such as ﬂecainide and amiodarone. Antihistamines, such as terfenadine, and antipsychotic drugs, such as pimozide and thioridazine, can increase risk of arrhythmias. Cimetidine can increase quinine levels.

441

442 Adverse effects Pregnancy: Considered safe Breastfeeding: May be used, with caution, at recommended doses Counselling: Urine, tears, saliva, and sputum may become coloured orange-red- do not worry about it as the colour change is harmless. Special groups/comments Common: Nausea, vomiting, diarrhoea, anorexia; headache, drowsiness; arthralgia, myalgia (in the ﬁrst weeks of treatment). Those occurring mainly on intermittent therapy include inﬂuenza-like symptoms (chills, fever, dizziness, bone pain); urine, saliva, other body secretions coloured orange-red. Infrequent or rare: Respiratory symptoms (including shortness of breath); collapse and shock; haemolytic anaemia, thrombocytopenic purpura, disseminated intravascular coagulation, leukopenia, eosinophilia; acute renal failure; alterations of liver function, jaundice; ﬂushing, urticaria, rashes, exfoliative dermatitis, toxic epidermal necrolysis, StevensJohnson syndrome, pemphigoid reactions; oedema; psychoses; adrenal insufﬁciency; muscular weakness, myopathy; menstrual disturbances

Drug Indication

Formulations Dosage

Rifampicin

Capsule or tablet: 150 mg, 300 mg

Buruli ulcer (in combination therapy with streptomycin) (10.2.10)

See Section 10.2 for dosing.

Summary tables

Leprosy- paucibacillary (11.21)

Oral: 600 mg rifampicin once monthly for 6 months AND daily dapsone

Leprosy- multibacillary (11.21)

600 mg rifampicin once monthly for 12 months AND dapsone + clofazimine.

See Section 11.21 for details of dosing.

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Drug Indication See rifampicin, isoniazid, ethambutol, pyrazinamide. Common: Hyperuricaemia, polyarthritis, nausea Infrequent or rare: Hepatotoxicity (including fever, anorexia, hepatomegaly, splenomegaly, jaundice, liver failure); ﬂushing, dysuria, sideroblastic anaemia, photosensitivity

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy/breastfeeding: Considered safe in pregnancy; Beneﬁts of treating TB in pregnant and breastfeeding women outweigh risks of drug side-effects to either mother or infant. Monitor infant for signs of pyridoxine deﬁciency or jaundice; consider maternal or fetal supplementation. Contraindications: Hypersensitivity to rifampicin, hepatic disease, porphyria, optic neuritis, severe renal impairment Use with caution: In hepatic or renal impairment, diabetes mellitus, gout, chronic alcohol dependence, elderly, epilepsy, history of psychosis. Prophylactic pyridoxine 10 mg daily indicated, particularly in HIV-positive patients. Administration: Ocular examination recommended before and during treatment. Three times per week is acceptable alternative provided that patient is receiving directly observed therapy, and is not living with HIV or living in an HIV-prevalent setting. See Section 15.

Rifampicin + isoniazid + pyrazinamide + ethambutol hydrochloride (R + H+ Z+ E)

Tablet: ﬁxed dose combination rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, ethambutol 275 mg

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Tuberculosis (13.10 HIV/TB comanagement, 15 TB)

2HRZE/4HR Oral: Rifampicin 10 mg/kg daily (max 300 mg) AND isoniazid 5 mg/kg (max 600 mg) AND pyrazinamide 25 mg/kg AND ethambutol 15 mg/kg once daily OR rifampicin 10 mg/kg daily (maximum 600 mg) AND isoniazid 5 mg/kg (maximum 900 mg) AND pyrazinamide 25 mg/kg AND ethambutol 15 mg/kg 3 times weekly (given as DOT; 3 times weekly regimen NOT recommended for HIVpositive patients and those from high HIV prevalent settings)

Summary tables

Counselling: Discontinue treatment and seek immediate medical attention if you develop persistent nausea, vomiting, malaise, yellow discoloration of the white of your eye or urine. Tell your health care provider immediately about any changes in your vision. If you are using a combined oral contraceptive (the Pill), patch, vaginal ring, or progestin-only pills, use additional contraception, such as condoms.

443

444 Adverse effects Common: Palpitations, ﬁne tremor (usually hands), headache. Special groups/comments Pregnancy: May be used at recommended doses; asthma management for pregnant and non-pregnant women should be the same. Breastfeeding: May be used at recommended doses (monitor infant) Infrequent or rare: With inhaled dosage forms, hyperglycaemia and hypokalaemia after high doses; muscle cramps; arrhythmias, tachycardia, insomnia, paradoxical bronchospasm, urticaria/angioedema Use with caution: In hyperthyroidism, myocardial insufﬁciency, arrhythmias, susceptibility to QT interval prolongation, hypertension, diabetes mellitus Infrequent or rare: Local irritation, dermatitis, toxicity with excessive application or treatment of large areas Contraindications: Broken or inﬂamed skin. Use with caution: In signiﬁcant peripheral neuropathy; in diabetics at risk of neuropathic ulcers Administration: Avoid application to large areas. Counselling: Avoid contact with eyes, lips, and inside of your nose. Protect surrounding skin; rub warts gently with ﬁle or pumice stone once weekly.

Drug Indication

Formulations Dosage

Salbutamol

Inhalation respirator solution for use in nebulizers: 5 mg (as sulfate)/ml Aerosol: 100 mcg (as sulfate) per dose

Acute bronchospasm (QC p. 17, 3.2.4)

See QC p 17 and 3.2.4 for dosing.

See Sections 10.6.4, 10.6.5.

Summary tables

Asthma and COPD (10.6)

Hyperkalemia (5.2.2)

By nebulizer: 10–20 mg OR IV: 0.5 mg (500 mcg). Administration should be slow, over 15–20 minutes. If neither of these are available, give salbutamol 1200 mcg by metered-dose inhaler with spacer (12 puffs).

Salicylic acid

Solution: 5%

Hyperkeratotic conditions, including warts; adjunct in treatment of psoriasis, ringworm, seborrhoeic dermatitis, ichthyosis (10.2)

Apply directly to affected area once daily, starting with lower strength preparations; gradually increase strength until satisfactory response obtained.

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Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: May be used on the scalp; it should not be used on the body to treat skin infections, as it may be absorbed through the skin. Breastfeeding: Uncertain safety in breastfeeding; use with caution. Use with caution: Do not apply to damaged skin (risk of systemic toxicity); avoid contact with eyes; do not use within 48 hours of applying preparations for hair colouring, straightening, or permanent wave. Administration: To minimize absorption, rinse hair thoroughly after use and remove all traces from skin (including nails). Note: Selenium sulﬁde is widely used in proprietary shampoos.

Selenium sulﬁde Common: Local irritation, hair discolouration or loss. Absorption may result in systemic toxicity including tremors, weakness, lethargy, pain in lower abdomen, occasional vomiting (symptoms usually resolve within 10 days)

Detergent-based suspension 2%, lotion

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Abdominal discomfort, cramps Infrequent or rare: Hypokalaemia (with prolonged use or overdosage) Breastfeeding: Not known to be harmful

Pityriasis versicolor (10.2.7)

Apply lotion with small amount of water to entire affected area; rinse off after 10 minutes. Repeat daily for 7–14 days. OR Apply to affected area at bedtime; rinse off in morning; repeat 1–6 times over 2 weeks; repeat course if necessary.

Seborrhoeic dermatitis (10.2.7)

Detergent-based suspension/ shampoo: Massage 5–10 ml into wet hair and leave for 2–3 minutes before rinsing thoroughly; repeat twice weekly for 2 weeks; then once weekly for 2 weeks; thereafter only when needed.

Senna

Tablet: 7.5 mg (sennosides)

Constipation (10.7d.4, 20.2)

Oral: 2–4 tablets, usually at night. Initial dose should be low; then gradually increased to 30 mg.

Pregnancy: If dietary and lifestyle changes fail to control constipation in pregnancy, moderate doses of poorly absorbed laxatives may be used. A bulk-forming laxative should be tried ﬁrst. An osmotic laxative, such as lactulose, can also be used. Bisacodyl or senna may be suitable, if a stimulant effect is necessary.

Summary tables

Use with caution: Avoid prolonged use unless indicated to prevent faecal impaction.

445

446 Adverse effects No common side-effects. Infrequent or rare: severe allergic reactions (rash; hives; difﬁculty breathing; tightness in chest; swelling of mouth, face, lips, or tongue); irritability; muscle spasms or twitching; pain, redness, or swelling at the injection site Overly aggressive therapy with sodium bicarbonate injection can result in metabolic alkalosis (associated with muscle twitching, irritability, tetany) and hypernatraemia. Therefore, blood pH and electrolytes should be monitored. Common: Burning, stinging Administration: Start treatment with cromoglicate 1 month before the onset of the hay fever season. Counselling: It can take 3–4 weeks to reach full effect. Pregnancy/breastfeeding: Unknown safety in pregnancy and breastfeeding; use with caution; cyanide poisoning likely to be the more signiﬁcant risk. Use with caution: In severe cardiovascular or cerebrovascular disease. Monitor plasma methaemoglobin levels. Special groups/comments Pregnancy/breastfeeding: Unknown safety in pregnancy and breastfeeding; use with caution, if beneﬁt is greater than risk. Common: Nausea/vomiting, abdominal pain, vasodilatation (resulting in syncope, hypotension, tachycardia, ﬂushing), headache, methaemo-globinaemia, cyanosis, dyspnoea/ tachypnea

Drug Indication

Formulations Dosage

Sodium bicarbonate

Injection: IV: 4.2%, 8.4% (intravenous concentrations 1 ampoule = 50 meq = 4.2 grams = 100 mmol)

Summary tables

Treatment of cardiotoxicity from drug overdose (e.g. tricyclic antidepressant, carbamazepine); alkalinization of urine to enhance excretion of salicylate and chlorphenoxy pesticides; correction of metabolic acidosis (3.8.1)

IV: Emergency dosing: Initially, 1–2 mmol/kg over 1–2 minutes. Additional dose: 0.5 mmol/kg every 10 minutes. Maintenance: 100–150 mmol sodium bicarbonate in 1 litre 5% dextrose at 250 ml/hour.

Sodium cromoglycate

Ophthalmic drops: 2%

Allergic conjunctivitis; seasonal keratoconjunctivitis (10.12)

Apply 4 times daily.

Sodium nitrite

Injection: 30 mg/ml in 10 ml ampoule (3% solution)

Cyanide poisoning (3.8.2)

Slow IV infusion: 10 ml of 3% solution over 2–4 minutes THEN sodium thiosulfate

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Drug Indication

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Not recommended in hypertensive crisis in pregnancy. Breastfeeding: Use, with caution, if beneﬁts are greater than risks; monitor infant for effects such as hypotension, bradycardia, fatigue. Contraindications: Severe hepatic impairment, compensatory hypertension, severe vitamin B12 deﬁciency

Sodium nitroprusside Common: Severe hypotension, headache, dizziness, retching, abdominal pain, perspiration, palpitation, arrythmias, apprehension, retrosternal discomfort

Powder for infusion: 50 mg in ampoule

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Nausea/vomiting, anorexia, abdominal pain, diarrhoea; ECG changes; coughing (see Cautions); headache, lethargy; arthralgia, myalgia Infrequent or rare: Jaundice, ﬂushing, bleeding from nose or gum, substernal pain, vertigo, fever, sweating, rash; also reported, pancreatitis and anaphylaxis; pain and thrombosis on intravenous administration; intramuscular injection also painful Contraindications: Cardiac, liver and kidney disorders.

MAO-I toxicity (3.8.1)

(Other indications: Hypertensive crisis)

IV: Initially 0.3–0.5 mcg/kg/ minute increase gradually to 0.5–6 mcg/kg/minute for the desired hemodynamic effect or the appearance of headache or nausea (maximum 8 mcg/ kg/minute). Stop infusion if response satisfactory after 10 minutes.

Sodium stibogluconate (pentavalent antimony compound)

Injection: 100 mg/ml vial

Pregnancy: Uncertain safety in pregnancy; use, with caution, if beneﬁt is greater than risk.

Cutaneous leishmaniasis (11.20.1)

IV/IM: 20 mg/kg daily for 21 days

Secondary prophylaxis of visceral leishmaniasis (11.20.3)

IV/IM: 20 mg/kg per month

Breastfeeding: Limited information suggests that doses up to 1.4 g daily produce low levels in milk, not expected to cause any adverse effects, especially if the infant is older than 2 months; if withholding nursing during therapy is preferred, breastfeeding can be resumed 24–48 hours after last dose.

Post kala-azar dermal leishmaniasis, alternative treatment (11.20.2)

See table in Section 11.20.2

Use with caution: Successful treatment of mucocutaneous leishmaniasis may induce severe inﬂammation around the lesions (may be life-threatening if pharyngeal or tracheal involvement); may require corticosteroid. Administration: IV injections must be given slowly over 5 minutes (to reduce risk of local thrombosis) and stopped if coughing or substernal pain.

Summary tables

447

448 Adverse effects Sodium thiosulfate has low toxicity. Osmotic disturbances may occur but at the recommended doses are usually mild. Special groups/comments Pregnancy/breastfeeding: Unknown safety in pregnancy and breastfeeding; use with caution. Cyanide poisoning likely to be the more signiﬁcant risk. Infrequent or rare: When used in cyanide poisoning, symptoms of thiocyanate toxicity may occur: pain in the joints, blurred vision, hyperreﬂexia, muscle cramps, nausea and vomiting, agitation, delusions, hallucinations, tinnitus Infrequent or rare: Dizziness; nausea; urticaria; chills; fever; headache, insomnia, mild to moderate pain after injection, anaphylaxis Pregnancy/breastfeeding: Use only if indicated. No controlled studies or reports teratogenicity. Use with caution: In renal impairment Pregnancy: Not recommended; consider alternatives where possible. Breastfeeding: Use, with caution, if beneﬁt is greater than risk; amount to infant appears very small, unlikely to cause adverse effects; theoretically may suppress lactation due to diuresis Contraindications: Hyperkalaemia, hyponatraemia, severe renal impairment, Addison’s disease. Monitor blood urea nitrogen and plasma electrolytes; discontinue if hyperkalaemia. Use with caution: In elderly; in patients with diabetes mellitus, renal impairment, hepatic impairment, porphyria Avoid concurrent administration of potassium supplements. Common: Hyperkalaemia, hyponatraemia, hyperchloraemic acidosis, weakness, headache, nausea, vomiting, diarrhoea, breast tenderness Infrequent or rare: GI cramps, drowsiness, menstrual irregularities, transient increase in blood urea nitrogen, gynaecomastia, impotence, rash, ataxia, hepatotoxicity

Drug Indication

Formulations Dosage

Sodium thiosulfate

Injection: 250 mg/ml in 50 ml ampoule (25% solution) Topical solution: 15%

Cyanide poisoning (together with sodium nitrite) (3.8.1)

IV: 50 ml of 25% solution (12.5 g) over 10 minutes

Pityriasis versicolor (10.2.7)

Topical: Apply twice daily for 4 weeks.

Summary tables

Spectinomycin

Powder for injection: 2 g (as hydrochloride) in vial

Alternative treatment for gonorrhoea without dissemination (11.13); gonococcal conjunctivitis (10.12.2)

IM: 2 g as a single dose

Disseminated gonococcal infection (11.13)

IM: 2 g twice daily for 7 days (some data suggest that 3 days is adequate)

Spironolactone

Tablet: 25 mg

Oedema (10.4.3); ascites (10.9)

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(Other indications: Nephritic syndrome; primary hyperaldosteronism; moderate to severe heart failure in patients taking an ACE inhibitor and a beta-blocker)

Oral: 100–200 mg daily. Increase if necessary to 400 mg daily in resistant oedema (usual maintenance dose 25–200 mg daily) AND furosemide

Drug Indication See gentamicin. Also, hypersensitivity reactions, paraesthesia of mouth

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Avoid streptomycin during pregnancy; auditory or vestibular nerve damage possible Breastfeeding: May be used at recommended doses (monitor infant for thrush or diarrhoea) Contraindications: Hearing disorders, myasthenia gravis Use with caution: In patients with renal impairment; elderly patients. Patients over 60 years or those weighing <50 kg may not tolerate doses above 500–750 mg daily. Administration: Monitor auditory, and vestibular function. If poor renal function, adjust dose.

Streptomycin

Injection: 1 g vial

Tuberculosis (initial phase of combination therapy in TB patients returning after defaulting or relapsing from their ﬁrst treatment course) (15)

IM: 15 mg/kg daily. Indicated in combination as 2HRZES/1HRZE/ 5HRE.

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Nausea/vomiting, diarrhoea Infrequent or rare: Hypersensitivity reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis; discontinue if rash develops); systemic lupus erythematosus, myocarditis, serum sickness, crystalluria resulting in haematuria, blood disorders (discontinue if develops), liver damage, cough/ shortness of breath, pancreatitis, CNS problems (convulsions, ataxia, hallucinations), electrolyte disturbances Contraindications: Hypersensitivity to sulphonamides, porphyria Administration: For the treatment of toxoplasmosis, pyrimethamine must always be taken with sulfadiazine.

Buruli ulcer (10.2.10)

IM: 15 mg/kg daily for 8 weeks (in combination therapy with rifampicin 10 mg/kg daily)

Sulfadiazine

Tablet: 500 mg

Toxoplasmosis in immunodeﬁciency (11.40); chorioretinitis (10.12)

Oral: 4–6 g daily in 4 divided doses for at least 6 weeks AND folinic acid + pyrimethamine for 6 weeks

Pregnancy: Uncertain safety in pregnancy. Use, with caution, only if potential beneﬁt is greater than risk; avoid in ﬁrst trimester due to bone marrow toxicity; avoid in third trimester due to risk of neonatal jaundice. Breastfeeding: Limited data; use with caution. Avoid in G6PD-deﬁcient neonates and infants; monitor infants for adverse effects (e.g. haemolysis, jaundice).

Toxoplasmosis (in second and third trimesters of pregnancy if fetal infection has been documented)

Oral: 4 g daily in 4 divided doses AND folinic acid + pyrimethamine

Summary tables

Rheumatic fever, secondary prophylaxis (11.32)

Oral: 1 g daily

Use with caution: In hepatic or renal impairment. Maintain adequate ﬂuid intake to avoid crystalluria. Avoid in blood disorders (except with specialist supervision); monitor blood counts; predisposition to folate deﬁciency, elderly, asthma, G6PD deﬁciency

449

450 Adverse effects Common: Nausea, vomiting, diarrhoea, feeling of fullness; rash, itch Infrequent or rare: Hypersensitivity reaction (Stevens-Johnson syndrome and toxic epidermal necrolysis); hepatitis; cough, dyspnoea; blood disorders (leukopenia, thrombocytopenia, megaloblastic anaemia, purpura) Special groups/comments Pregnancy: Use during pregnancy if treatment of choice; consider folic acid supplementation 5 mg/day. Breastfeeding: Unknown safety; not recommended Contraindications: Already taking cotrimoxazole, hypersensitive to sulfonamides or pyrimethamine, severe hepatic or renal impairment. Avoid in blood disorders (except with specialist supervision). Withdraw treatment if blood disorder, rash, sore throat, mouth ulcers, shortness of breath, or cough occurs. Use with caution: In G6PD deﬁciency, predisposition to folate deﬁciency Infrequent or rare: Immediate and potentially fatal shock and unconsciousness; abdominal pain, diarrhoea, stomal ulceration, dermatitis, abscess, painful joints Pregnancy: Uncertain safety in pregnancy; use, with caution, only if potential beneﬁt is greater than risk (e.g. in trypanosomiasis). Breastfeeding: Unknown safety in breastfeeding; avoid if possible. Contraindications: Hypersensitivity; totally blind patients with onchocerciasis (unless they require relief from the intensely itchy lesions not relieved by safer alternative) Use with caution: In anaphylaxis, renal/hepatic impairment, total blindness, elderly

Drug Indication

Formulations Dosage

Sulfadoxine with pyrimethamine (SP)

Tablet: sulfadoxine 500 mg + pyrimethamine 25 mg

Intermittent preventive therapy in pregnancy (IPTp) where stable transmission of P. falciparum malaria (11.25.8)

Oral: sulfadoxine 1.5 g with pyrimethamine 75 mg (3 tablets) as a single dose under direct observation- give twice during pregnancy, in second and third trimester, 4 weeks apart; if HIV-positive, give 3 doses (see Section 11.25.8.).

Summary tables

Suramin

Powder for injection: 1 g in vial

Trypanosomiasis (ﬁrst stage, T.b. rhodesiense infection) (11.41)

Slow IV injection: 3.3 mg/kg as single dose (after test dose) followed by weekly increments of 6.7 mg/kg, then 10 mg/kg, 13.3 mg/kg,16.7 mg/kg, 16.7 mg/kg in weeks 2 through 6, respectively

Vol. 1 • 8. Medicines/therapies: July 2011

Drug Indication Infrequent: Occasional local irritation and hypersensitivity reactions include mild burning sensation, erythema, itching. If severe, treatment should be discontinued.

Formulations Dosage

Adverse effects

Special groups/comments Use with caution: Avoid contact with eyes and mucous membranes.

Terbinaﬁne

Cream: 1% Ointment: 1% (hydrochloride)

Dermatophytosis (ringworm) (10.2.7)

Apply thinly 1–2 times daily for up to 1 week (tinea pedis), 1–2 weeks (tinea corporis and tinea cruris)

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Burning, stinging, redness Infrequent or rare; allergic reactions Contraindications: Hypersensitivity to ester-type local anaesthetics; eye inﬂammation or infection. Common: Nausea/vomiting, diarrhoea, increased BUN, phototoxicity, rash, increased intracranial pressure, discoloration of teeth/ enamel hypoplasia (young children), antibioticassociated colitis, hypersensitivity reaction Infrequent or rare: Hepatotoxicity, burning or stinging Breastfeeding: Uncertain safety; avoid if possible. Contraindications: Tetracycline hypersensitivity. Use with caution: In renal or hepatic impairment

Cutaneous candidiasis (10.2.9, 11.4); pityriasis versicolor (10.2.7)

Apply thinly 1–2 times daily for up to 2 weeks

Tetracaine (amethocaine) eye drops

Drops: 0.5% (hydrochloride)

Short-acting local anaesthesia of the cornea and conjunctiva

Instill 1 drop

Use with caution: Avoid prolonged use (risk of severe keratitis, permanent corneal opaciﬁcation, scarring, delayed corneal healing). Protect eye from dust and bacterial contamination until sensation is fully restored. Never give patients anaesthetic drops to take home.

Tetracycline

Tablet: 500 mg

Cholera (10.7d.2)

Oral: 500 mg 4 times daily for 3 days

Pregnancy: Contraindicated after week 8 due to effects on fetal bone growth and dental discolouration; short courses can be used if alternative not appropriate; implicated in causing maternal hepatotoxicity, especially in third trimester (dose-related)

Acne (10.2.3)

Oral: 250–500 mg twice daily

Summary tables

Oral: 500 mg 4 times daily for 30 days

Late latent syphilis, syphilis of undetermined duration, and late syphilis (11.37) Syphilis with penicillin allergy in non-pregnant patient (11.37)

Oral: 500 mg 4 times daily for 15 days

451

452 Adverse effects Infrequent or rare: Rash; stinging, burning. No reports of tooth discoloration at usual topical doses Special groups/comments Contraindications: Hypersensitivity to tetracycline group of antibiotics Use with caution: Prolonged use may lead to overgrowth of non-susceptible organisms. Toxic effects are unlikely since any excess thiamine is excreted. Infrequent or rare: Anaphylaxis Pregnancy/breastfeeding: Severely thiamine-deﬁcient mothers should avoid breastfeeding. Administration: If IV, infuse over 30 minutes.

Drug Indication

Formulations Dosage

Tetracycline eye ointment

Ointment: 1% (hydrochloride)

Cobra spit (3.9); bacterial conjunctivitis; corneal erosion (10.12.2)

Apply directly to the eye, 1 application 3–4 times daily

Trachoma, continuous intensive treatment (10.12.5)

Apply directly to the eye, 1 application of ointment in each eye twice daily for at least 6 weeks.

Summary tables

Thiamine

Tablet: 50 mg Injection (vitamin B1) (hydrochloride)

Chronic thiamine deﬁciency (as may occur in alcohol abuse and dependence) (3.5)

IM/IV: 100 mg daily for 5 days THEN switch to oral 100 mg daily

Ethylene glycol poisoning (3.8.1)

IM/IV: 100 mg every 8 hours for 6 doses

Persistent vomiting in pregnancy >2 weeks (14.1.11)

Oral: 100 mg daily- until persistent vomiting stops

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Drug Indication Common: Nausea/vomiting, diarrhoea, allergic skin reactions. Rapid intravenous injection may cause dizziness and/or hypotension. To avoid this response, the solution should not be injected more rapidly than 1 ml per minute. Infrequent or rare: Thromboembolic events, disturbances in colour vision (discontinue)

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: TXA has been used in pregnancy and no harmful effects have been reported. In the CRASH-2 trial, pregnancy was not an exclusion criteria. Weigh the potential risks and beneﬁts for each woman. Breastfeeding: Very small amounts pass into breast milk; an antiﬁbrinolytic effect in the infant is unlikely. Contraindications: History of thromboembolic disease Administration: As early as possible, within 3–4 hours of injury. Reduce injection dose in patients with renal insufﬁciency. TXA solution for injection should not be mixed with blood for transfusion or with infusion solutions containing penicillin or mannitol.

Tranexamic acid (TXA)

Injection, solution: 100 mg/ml (10 ml)

Vol. 1 • 8. Medicines/therapies: July 2011 Common: Local reactions include burning, erythema, stinging, pruritus, dry or peeling skin (discontinue if severe). Increased sensitivity to UVB light or sunlight; temporary changes of skin pigmentation reported Infrequent or rare: Eye irritation and oedema, blistering or crusting of skin

Trauma patients with ongoing signiﬁcant haemorrhage or at risk of signiﬁcant haemorrhage, within 3-4 hours (4.2)

IV: loading dose of 1 g over 10 minutes THEN infusion of 1 g over 8 hours.

Tretinoin

Gel: tretinoin 0.01% (tretinoin is the acid form of vitamin A)

Severe acne (10.2.3)

Apply thinly 1–2 times daily.

Pregnancy: Topical retinoids contraindicated in pregnancy; women of child-bearing age must use effective contraception (oral progestogen-only contraceptives not considered sufﬁciently effective).

Several months of treatment may be needed to achieve optimal response. Treatment should continue until no new lesions develop in 2 weeks.

Summary tables

Use with caution: Topical retinoids should be avoided in severe acne involving large areas. Avoid contact with eyes, nostrils, mouth, mucous membranes; eczematous, broken, or sunburned skin. Avoid exposure to UV light (including sunlight, solariums). If sun exposure is unavoidable, an appropriate sunscreen or protective clothing should be used. Avoid use of retinoids with abrasive cleaners, comedogenic or astringent cosmetics. Allow peeling (e.g. resulting from use of benzoyl peroxide) to subside before using a topical retinoid. Counselling: Some redness and skin peeling may occur initially but settles with time.

453

454 Adverse effects Special groups/comments Use with caution: In severe fascioliasis, biliary colic can occur due to obstruction by dying worms. Common: Nausea, vomiting, diarrhoea, headache, biliary colic due to obstructing worms Common: Transient stinging and local irritation Use with caution: Avoid application to face or broken skin; avoid contact with eyes.

Drug Indication

Formulations Dosage

Triclabendazole

Tablet: 250 mg

Fascioliasis (11.11)

Oral: 10 mg/kg in a single dose

In treatment failure readminister 10 mg/kg, THEN follow by another dose 12–24 hours later (giving a total dose of 20 mg/kg)

Summary tables

Urea

Cream or ointment: 5%, 10%

Hydrating agent and keratolytic for dry, scaling, and itching skin conditions, including mild psoriasis, xeroderma (10.2)

Apply directly to affected area twice daily, preferably to damp skin.

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Drug Indication Common: Nausea, gastric irritation, diarrhoea, increased appetite; weight gain; ataxia, tremor; paraesthesia, drowsiness: elevated liver transaminases, hyperammonaemia

Formulations Dosage

Adverse effects

Special groups/comments Pregnancy: Risk of teratogenicity; use only if beneﬁt is greater than risk; consider folic acid supplementation 5 mg/ day and vitamin K supplementation. Breastfeeding: May be used in breastfeeding. Small amounts excreted in breast milk; use minimum effective dose and monitor infant for adverse effects (e.g. jaundice). Use with caution: Monitor coagulation studies and liver function tests regularly during therapy. Prone to multiple drug interactions through CYP enzymes; check for interactions with all new and current medications. Elderly: See cautions in Section 10.11.5. Administration: Do not use for alcohol withdrawal. Counselling: Take with food to reduce stomach upset. Your appetite may increase when taking this medicines; pay attention to your diet to avoid weight gain. This medication may impair your ability to perform hazardous activities requiring mental alertness. Tell your clinician immediately if fever, rash, abdominal pain, vomiting, yellow eyes or urine, bruising, or bleeding develops. Do not stop taking this medicine suddenly unless advised by your doctor.

Valproic acid (sodium valproate)

Tablet: 200 mg, 500 mg Liquid: 200 mg/ml

Epilepsy (10.10c)

Oral: Initiate at 400 mg daily; increase by 200 mg daily to maximum of 2 g daily in divided doses.

Vol. 1 • 8. Medicines/therapies: July 2011 Infrequent or rare: Hepatotoxicity (can be fatal), pancreatitis, hyponatraemia from drinking excess ﬂuid; blood dyscrasias (anaemia, leukopenia, pancytopenia, thrombocytopenia); severe allergic reaction (including toxic epidermal necrolysis, Stevens-Johnson syndrome). Transient hair loss (regrowth may be curly); increased alertness, aggression, hyperactivity, behavioural disturbances, vasculitis; lethargy, drowsiness, confusion, stupor, hallucinations, menstrual disturbances, hearing loss, rash; peripheral oedema, increase in bleeding time, extrapyramidal symptoms, dementia, encephalopathy, coma, gynaecomastia, Fanconi’s syndrome, hirsutism, acne, enuresis, hyponatraemia. Withdraw treatment immediately if persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness, loss of seizure control.

Mood stabilization in bipolar disorder, acute mania (10.11.5)

Oral: Initiate at 500 mg at night; gradually increase by 200 mg every 7 days until response; typical dose: 1–2 g daily

In elderly or medically ill patients incuding HIV stage 3 or 4: initiate at 200 mg in morning and at night. Increase dose 200 mg every 7 days until clinical response. See 10.11.5

Summary tables

455

456 Adverse effects Infrequent or rare: Nausea, headache, dizziness; fever, hypersensitivity reactions including rash and pruritus, anaphylaxis; injection-site pain; hypokalaemia during initial treatment Special groups/comments Pregnancy: Safe, but megaloblastic anaemia of pregnancy is usually due to folate deﬁciency and should be treated with folate plus vitamin B12. Breastfeeding: Safe to use Contraindications: Sensitivity to B12 (hydroxocobalamin). Use with caution: Establish which deﬁciency is present – vitamin B12 or folate – with a marrow examination and treat the underlying cause. Always give B12 with folic acid in pernicious anaemia; folic acid given alone can precipitate neuropathy if there is underlying unrecognized vitamin B12 deﬁciency. Cardiac arrhythmias secondary to hypokalaemia have been reported during initial therapy; therefore, potassium should be monitored during this period. Administration: Do not give by IV injection. Store below 25 °C; protect from light. Common: Pain, tenderness, erythema at IM site Infrequent or rare: Hypersensitivity reactions Pregnancy: Use only if beneﬁt is greater than risk. Breastfeeding: May be used short-term; caution if chronic dosing required Use with caution: In elderly and hepatic impairment Administration: IV vitamin K should be given slowly over 20 minutes. Note: Vitamin K is not an antidote to heparin.

Drug Indication

Formulations Dosage

Vitamin B12 (hydroxocobalamin)

Intramuscular anhydrous hydroxo-cobalamin 1 mg/ml

Pernicious anaemia and other macrocytic anaemia without neurological involvement

IM: 1 mg 2–4 times weekly for 2 weeks; then 1 mg every 3 months.

Summary tables

Pernicious anaemia and other macrocytic anaemias with neurological involvement

IM: 1 mg on alternate days until no further improvement; then 1 mg every 2 months

Prophylaxis and treatment of other macrocytic anaemias due to vitamin B12 deﬁciency

IM: 1 mg IM every 2–3 months

Vitamin K (phytomenadion)

Injection: 10 mg/ml in 5 ml ampoule Tablet: 10 mg

Rodenticide poisoning (3.8.1) with no bleeding but prolonged INR

Oral: 10–20 mg; may need to continue for weeks if longacting anticoagulant rodenticide

Warfarin therapy (3.8.1) with INR > 9.0 but no bleeding

Oral: 2.5–5 mg

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Rodenticide poisoning or warfarin therapy (3.8.1) with severe haemorrhage

IV: 10 mg

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457

458

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459

460

Vol. 1 • Index, Volumes 1 and 2: July 2011

461

462

Vol. 1 • Index, Volumes 1 and 2: July 2011

463

464

Vol. 1 • Index, Volumes 1 and 2: July 2011

465

466

Vol. 1 • Index, Volumes 1 and 2: July 2011

467

468

Vol. 1 • Index, Volumes 1 and 2: July 2011

. . . . . . . .

QC5, QC24-25-26 . . 10.15.4, 11.4 . . . . . 10.15.4 . . . . . . 11.45 . . . . . 11.45.1 . . . . . 11.45.2 . . . . . 10.16.3 . . . . . 7.3.10

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469

CHF CIN

470

Vol. 1 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

ELISA EPTB ESR ETAT Eto FAST

HIV HIVAN HONK HPV HR HSV HTC HZ IC IDU IDV IgA IgG IgM IM IMAI IMCI IMEESC

FBC FDC FEV1 FFP FNA

IMPAC INH INR IPC IPT IPTp IRIS ITP IU IUD IV

Vol. 1 • Abbreviations and acronyms, Volumes 1 and 2: July 2011

471

JVP K Kcal KCL KJ KOH LAM LDH LDL LEEP LFT LGV LMN LMP LP LPV/r LR MAC MCH MCPC MDI MDR TB MDT mEq Mg MNCH MRI MRSA MSM MTCT MUAC

jugular venous pressure potassium kilocalorie potassium chloride kilojoule potassium hydroxide lactational amenorrhea lactate dehydrogenase low density lipoprotein loop electrosurgical excision procedure liver function tests lymphogranuloma venereum lower motor neuron last menstrual period lumbar puncture lopinavir boosted with ritonavir lactated ringers solution Mycobacterium avium complex maternal and child health Managing Complications in Pregnancy and Childbirth metered-dose inhaler multi-drug resistant tuberculosis multiple drug therapy milliequivalents magnesium maternal, newborn, and child health magnetic resonance imaging methicillin-resistant Staphylococcus aureus men who have sex with men mother-to-child transmission mid upper arm circumference

Na NaCI NFV NG NNRTI NPO NRTI NS NSAID NTD NtRTI NVP OI ORS OST PAS PBS PCP PCPNC PCR PEFR PEP PI PID PITC PLHIV PML PMN

sodium sodium chloride nelﬁnavir nasogastric non-nucleoside reverse transcriptase inhibitor Nil per os (nothing through the mouth or nil by mouth) nucleoside reverse transcriptase inhibitor normal saline nonsteroidal anti-inﬂammatory drug neglected tropical diseases nucleotide reverse transcriptase inhibitor nevirapine opportunistic infection oral rehydration salts opioid substitution treatment para-aminosalycilic acid (4-aminosalycilic acid) peripheral blood smear Pneumocystis jirovecii pneumonia Pregnancy, childbirth, postpartum, and newborn care polymerase chain reaction peak expiratory ﬂow rate post exposure prophylaxis protease inhibitor pelvic inﬂammatory disease provider-initiated testing and counselling people living with HIV progressive multifocal leukoencephalopathy polymorphonuclear neutrophils

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PMTCT PO PPE PPH PR PRBC PT PTB PTSD PTT PUD PV QC R RAPD RBC RDT RPR RR RTV Rx S SAAG SARS SBP SC SCJ sd-NVP SIADH SJS SLE

SMX SP SpO2 spp SQV SS SSRI STB STI T TB TBSA TCA Td TDF TEN TIG TMP TMPSMX TPHA TSH TST TT TTP UMN UO UTI VDRL VIA VL

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VLDL VT VZV WBC WHO

very low density lipoproteins ventricular tachycardia varicella zoster virus white blood cell count World Health Organization

W/W XDR TB Z ZDV

weight of solute/weight of solution extensively drug resistant tuberculosis pyrazinamide zidovudine (also azidothymidine - AZT)

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Writers and reviewers, Volume 1, and process of development, Volumes 1 and 2 Overall clinical editing and writing of Volume 1 of the IMAI District Clinician Manual Sandy Gove (WHO HIV/AIDS – IMAI team leader), Kirsty McHarry (U KwaZuluNatal Centre for Rural Health, South Africa), Hillary Cohen (Maimonides Medical Center, NY, USA), Neeri Moodley (U KwaZulu-Natal Centre for Rural Health, South Africa), Ed Zuroweste (Migrant Clinicians Network, USA), Janet Diaz (WHO GIP consultant and UCSF/SFGH, USA), Matthew Chersich (Centre for Health Policy, U Witwatersrand, South Africa), and Shevin Jacob (U Washington). Editors: Sarah Johnson, Emily Tuthill, John Liddy, Sandra Woods, Ward Rinehart, Cynthia Bloomquist Overall development of the manual was coordinated at WHO on the IMAI team by Fareed Ramzi Asfour (2005–2006), Kirsty McHarry (2006–2009), Sandy Gove (2009–publication), and Neeri Moodley (2009–2011). Other writers contributing to speciﬁc sections are indicated in bold in the lists at the end of this section.

Process for development of the IMAI District Clinician Manual, Volumes 1 & 2 The implementation of many clinical interventions for public health at the The implementation of many clinical interventions for public health at the primary care level requires district hospital clinicians who are able to manage uncomplicated and complicated cases, patients who fail initial empirical treatment interventions, and patients with severe illness requiring urgent treatment and inpatient care. Therefore, a manual outlining the key steps for this clinical management can make an important contribution to improving the quality of care in a district network and thus strengthening the health system. The WHO IMAI District Clinician Manual is a how-to manual addressed to the district clinician, who may be a doctor, clinical ofﬁcer, senior nurse, or other senior health worker at a district hospital in a limited-resource setting. The manual covers adolescents from 10 years of age and adults through to old age and death. It consists of simpliﬁed, operationalized prevention and treatment recommendations for the primary care of patients on initial presentation to a district-level facility. The manual assumes that district hospitals in resource-limited settings have general multipurpose practitioners such as a medical or clinical ofﬁcer but do not have specialist clinicians such as an internist, paediatrician, or psychiatrist (although it may be possible to consult with one). This manual is divided into two volumes, each comprising a number of sections. This, the ﬁrst Volume, covers emergency triage assessment and treatment, and acute care for a severely ill or acutely injured patient within approximately the ﬁrst 24 hours of care. This Volume also describes the clinical procedures commonly applied in this care and gives a summary of drugs used and the steps necessary for infection control. The companion Volume 2 provides a symptom-based approach

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to clinical care for acute and subacute conditions (including mental health) and to the chronic or long-term care of HIV, TB, and alcohol and substance use disorders. Within the manual operationalized guidelines are provided for second-level outpatient and inpatient care of severely ill or complicated patients as well as for primary care of uncomplicated patients. The primary care guidelines for the outpatient care of uncomplicated patients are consistent with the IMAI ﬁrst-level facility guideline modules for chronic HIV care with ART and prevention, acute care, palliative care (symptom management and end-of-life care), MDR and TBHIV co-management, as well as the IMPAC PCPNC and mhGAP guidelines. In addition to clinical guidelines, the manual emphasizes the district clinician’s role in the district as clinical mentor and supervisor to nurse-led clinical teams at the health centre level.

Development of the manual The development of each Section has been overseen by WHO, with input from expert subgroups. The work for each Section was a collaborative effort between the IMAI team and each applicable WHO department, as part of joint and ongoing activities between IMAI and these departments. Many recommendations in the manual are based on WHO normative guidelines developed by various WHO departments and disease control programmes, and they support their diseasecontrol strategies. These include HIV/AIDS, Stop TB, Global Malaria Programme, Neglected Tropical Diseases, Mental Health Gap (mhGAP), RHR STI and cervical cancer guidelines, IMEESC, IMPAC, Global Inﬂuenza Programme (GIP), Global Alert Response (GAR), and others. Where WHO guidelines do not yet exist or are outdated, a review of evidence was conducted. Experts in the subgroups (each subgroup addressed a particular content area) were chosen based on their experience in providing or organizing clinical care in resource-limited settings and their up-to-date knowledge of both the relevant literature and the public health approach to delivering HIV, TB, and other adult medical services through strengthened district networks. Most external experts are either global content experts from academic institutions or active clinicians with in-depth expertise in their content areas. Selection of experts was also based on recommendations from collaborating WHO departments and the academic publications of experts, especially aiming to identify those who have experience with supporting implementation of services at district hospitals and health centres in countries with high HIV and TB burdens. Experts were drawn from all WHO regions. Preference was given to those familiar with the realities of working with a limited drug formulary and with limited laboratory and equipment at the district hospital level in limited-resource settings. The subgroups also include WHO medical ofﬁcers. Moreover, the manual reﬂects a broader collaboration of medical and technical ofﬁcers from multiple WHO Departments, themselves advised by expert groups, who contributed their updated normative guidelines and operational tools. Whenever possible, the expert subgroups simpliﬁed and operationalized existing evidence-based WHO normative guidelines. Treatment recommendations are consistent with the WHO Formulary unless superseded by more up-to-date WHO guidelines or evidence. The relevant WHO normative guidelines are listed in footnotes in each Section, including, where available, an indication of when these will next be revised.

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Drafts of the sections were developed in the following manner: Writers from the expert subgroups, WHO medical ofﬁcers, or consultants produced ﬁrst drafts of each Section. Wherever available, they based the Sections on WHO guidelines from various departments. When evidence-based WHO guidelines had not yet been developed, they added to these initial drafts on the basis of evidence and expert consensus. These drafts were then circulated for peer review and comment, revised, and then circulated again. This iterative improvement entailed multiple cycles of review and discussion for each Section. Each Section was sent for review to the relevant WHO departments, while the general reviewers reviewed all sections. Each Section thus reﬂects evidence reviews of the literature combined with practical experience and/or constitutes operationalized derivatives of WHO evidence-based normative guidelines, which themselves often have been developed to reﬂect a public health and clinical care approach feasible in limitedresource settings. Expert subgroups also contributed to the evidence reviews, suggested best practice approaches, discussed drafts, reached consensus through discussion in meetings and by email, and assisted in preparing draft sections for ﬁeld-testing and with the ﬁeld-testing itself. The core group members identiﬁed other experts for consultation when necessary. For many of the conditions considered, there was a lack of evidence from limitedresource settings with limited diagnostic capabilities; thus, evidence reviews often identiﬁed evidence predominantly from developed-country settings. Although this is indirect evidence, it was used to inform decisions, while taking into account the experts’ extensive clinical and programme experience that suggested modiﬁcations based on feasibility, cost, and other resource considerations. Two initial developmental meetings were held in Geneva, in March and October 2006.

Development of speciﬁc sections in Volume 1 Section 2 (Quick Check and emergency treatments) was developed to be compatible with the existing emergency triage assessment and treatment guidelines for paediatrics (ETAT), for pregnant women (from IMPAC PCPNC), and for adults (from IMAI Acute Care). Section 3, Approach to the severely ill patient, draws on WHO formulary recommendations, the evidence review described below, and input from the emergency, pulmonary, and sepsis expert subgroups. The WHO departments of HIV/AIDS (IMAI team), GAR, and GIP initially constituted these as separate subgroups but then combined them to work together, as the WHO Working Group on Critical Care in Limited-Resource Settings, to develop the emergency guidance on management of septic shock and severe respiratory distress (and other severe illnesses). In 2009 expert meetings were held in March (Geneva, Switzerland), April (Addis Ababa, Ethiopia), June (Geneva), and September (Florence, Italy). This Group was composed of highly qualiﬁed professionals who have expertise and experience in the areas of pneumonia, acute lung injury, septic shock, inﬂuenza, and the treatment of critically ill patients in general. The recommendations provide both guidance to countries experiencing outbreaks of febrile disease causing critical illness (including, but not limited to, pandemic inﬂuenza) where local resources are not able to provide mechanical ventilation for medical patients and the full spectrum of «ICU-level care» and guidance for the management of patients severely ill from HIV/AIDS, TB, severe malaria, maternal sepsis, dengue, and other endemic diseases. On an emergency basis, an extract of these guidelines for management of severe complications of inﬂuenza H1N1 was released.

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The mental health recommendations in Section 3 (and Section 10.11) were developed by an expert group that originally met during the March and December 2006 second-level learning programme meetings in Geneva and then shared drafts and references by email and teleconferences. Several members of the expert subgroup met in November 2008 to ﬁnish the Section and to review the mental health content of all other sections. In view of the limited evidence in this ﬁeld from resource-limited settings and the often relatively neglected mental health and psychiatric services in many developing country settings, the Section was written using evidence from resource-rich countries, with adaptations to developing country settings. To ensure that the recommendations are feasible, the Section was further reviewed and adapted by psychiatrists and psychologists who have signiﬁcant expertise in adapting mental health interventions to developing country settings. The WHO mhGap GRADE reviews were completed in late 2009, and all recommendations on mental health, neurology, and substance use in the Manual were then made fully compatible with the mhGAP recommendations. Various treatment recommendations in the Quick Check, Section 3.10 Burns, Section 4 Trauma (management of the acutely injured patient) were adapted from Surgical care at the district hospital (SCDH) (WHO, 2003), with updates based on the expert meeting in Addis Ababa in April 2009 (convened collaboratively by the IMAI and IMEESC teams). These sections then underwent the evidence check detailed below. Review of Section 3.8, on poisoning, was organized by the WHO International Programme on Chemical Safety, Evidence & Policy on Environmental Health (EPE). A panel of clinical toxicologists reviewed the ﬁrst draft by email. The revised draft was submitted to an evidence check as described below. The management recommendations for speciﬁc substances, together with the outcomes of the evidence check, were then distributed to individual clinical toxicologists to check for completeness and to comment on questions raised by the evidence check. The outcome of this process was tabulated and reviewed once again by a guideline panel of clinical toxicologists convened by EPE in July 2010 in Edinburgh, Scotland.

Process of evidence check In 2009–2010 an additional check of the evidence was carried out based on a protocol agreed with the WHO Guideline Review Committee for each treatment recommendation in the manual, unless these recommendations came from a current WHO guideline. A team of reviewers was contracted to perform these evidence reviews. The process was used as an opportunity to build capacity in evidence-based medicine; thus, a considerable portion of the evidence reviews were done by reviewers from Ethiopia and South Africa. A two-week training course was held in Addis Ababa in 2009 on the review protocol and topics such as assessing the quality of evidence and data extraction. The evidence check process aimed to be fully transparent and replicable. Thus, several steps were taken to enhance standardization of the processes used by the review team. These included use of a protocol outlining the pre-speciﬁed review methods and having an overall coordinator responsible for overseeing the evidence review (Matthew Chersich, assisted by Janet Diaz). Each step, including the listing of treatment recommendations, searches made, and the results of evidence identiﬁcation and evidence retrieval, was stipulated in the evidence review protocol. Details of each search strategy were documented in an evidence review log, together with the date that the ﬁnal search was done and the evidence located

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for each recommendation. Review questions were formulated as an “answerable review question”, containing the components of the PICO acronym: the target population (P), the intervention (I), the intervention it is compared with (C), and the outcome of interest (O). The full detailed evidence summary logs are posted on the IMAI EZcollab site and are available to the public on request. The outputs from the evidence review will also be used to inform adaptation of the manual to the circumstances in different countries. Evidence retrieval addressed only treatment recommendations and not prevention or counselling messages. Economic evaluations were not systematically reviewed. The WHO Library & Information Networks for Knowledge Database (WHOLIS, http://dosei.who.int) was searched to locate existing WHO normative or policy recommendations; these were assessed to determine if they were current and valid guidelines and their state of revision. The reviewer then assessed whether recommendations in the IMAI manual were fully consistent with recommendations in current WHO guidelines. For some topics WHO guidelines have recently been developed and cover all the treatment recommendations within a Section of the IMAI manual. In these instances – after cross-checking that all treatment recommendations in the Manual Section are consistent with the WHO guideline – no evidence summaries were made. The WHO Model Formulary (http://apps. who.int/emlib/Medicines.aspx?Language=EN) was searched for all treatment recommendations that involve administration of drug therapy. Treatment recommendations located in the WHO Model Formulary were checked for consistency with the manual and other evidence, and the reviewer documented this in the evidence log. If drugs are mentioned in the IMAI manual and not included in the WHO Formulary, then evidence for their effectiveness was sought, as with all other interventions. These drugs are in italics in Section 8 Medicines/therapies. When no WHO guidelines currently address a treatment recommendation in the manual, selected national-level authorities were searched. These authorities were chosen because they develop guidelines using clearly documented methodology, including conducting systematic reviews. The sources searched were: the UK National Institute for Clinical Excellence (NICE, http://guidance.nice.org.uk), the Scottish Intercollegiate Guidelines Network (SIGN, http://www.sign.ac.uk), and the US AIDSInfo Clinical Guidelines Portal (http://www.aidsinfo.nih.gov/guidelines). Some of these authorities make use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in developing their guidelines. When a treatment recommendation was located in a national authority guideline, a reviewer determined whether the national-level guideline is consistent with the WHO treatment recommendation and extracted information from the guideline to complete the evidence log form. If the intervention and population in the district clinician manual recommendation were not located in a national-level guideline, then evidence-based medicine sources were searched, provided they use acceptable systematic methods: namely, British Medical Journal Clinical Evidence (http://clinicalevidence.bmj. com), the Cochrane Collaboration (http://www.thecochranelibrary.org), and the Database of Abstracts of Reviews of Effects (http://www.crd.york.ac.uk/CRDWeb), which systematically identiﬁes and assesses the quality of systematic reviews. UpToDate (http://www.utdol.com) was searched only if no systematic reviews were identiﬁed in the other sources. As the next step in the hierarchical system, a reviewer searched for systematic reviews of evidence in the MEDLINE database, using the PubMed interface. A search strategy was developed using a validated search ﬁlter for systematic reviews. An evidence summary of systematic review ﬁndings was made, as applicable. Where independent systematic reviews were

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not located, randomized controlled trials were sought on MEDLINE and, if located, summarized in a table in the evidence logs. Once the evidence summaries were completed for a Section, the evidence review team then searched the log forms to identify the new WHO recommendations in the manual and instances where the evidence check showed a discrepancy between new WHO recommendations and recommendations in the manual. WHO then organized small, unconﬂicted guideline panels to consider each of these new or discrepant recommendations. Members of these ﬁnal unconﬂicted guideline panels are included in the related expert groups in the table of expert writers and reviewers, below, with a superscript designating the guideline panel they participated in. Reports can be found on the EZcollab site under “Y expert panel report.” These panellists assessed the evidence extracted from the evidence-based medicine sources or primary evidence located by the review and considered the overall balance of risks and beneﬁts (including such considerations as feasibility, resource constraints, and diversity of values and preferences). Each guideline panel then decided if the evidence review findings were applicable – most importantly, the directness (or external validity) of the evidence with respect to the populations, the interventions, and the settings where the proposed intervention will be used. For example, the panels considered whether the recommendation required modiﬁcation to limited-resource settings, based on the level of technology available in these settings. When review ﬁndings were not directly applicable to limited-resource settings, the experts had to decide whether this indirectness introduced important uncertainty as to whether the effectiveness of an intervention is likely to differ according to setting. It was necessary, at times, to modify recommendations based on appropriate technology use in limited-resource settings, as the diagnostic process and treatment protocols in this manual assume that only the minimum essential laboratory tests are available. Through consensus techniques, the expert panels agreed whether the recommendation required modiﬁcation to make it relevant and feasible in resource-constrained settings or to leave the recommendation unchanged if the difference with the evidence check was due to resource implications of alternative recommendations, which may include health system implications, such as training and supervision requirements, referral support, equipment and infrastructure requirements. Because the recommendations for septic shock, severe pneumonia, and acute pulmonary oedema might be used in caring for adult patients whose conditions reﬂect different etiologies, (e.g. maternal sepsis, disseminated TB, severe malaria, severe inﬂuenza, and dengue), the appropriateness of the recommendations for these conditions was reviewed against current WHO condition-speciﬁc guidelines (for TB, dengue, and malaria). In addition, two guideline panels discussed their appropriateness for pregnant or postpartum patients and those with severe malaria.

Field-testing of the manual Field-testing of the entire draft manual was carried out with representatives of the intended audience in 6 countries – Uganda, Rwanda, Ethiopia, India, Zambia, and Tanzania – in 2009–2010, in parallel with the evidence check. Field-testing provided valuable feedback on feasibility and utility of the manual and on district clinicians’ preferences, as well as practical suggestions to improve the relevance and presentation of the manual. The Quick Check and the guidelines on severe respiratory distress and septic shock were ﬁeld-tested with a training course in

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Uganda, Rwanda, Ethiopia, and Malawi in the same period. A second ﬁeld test was conducted in the same 6 countries after the district clinicians had used the manual for more than a year. Over the course of ﬁeld-testing, a detailed survey in Survey Monkey and focus group discussions provided speciﬁc information on the usefulness and adaptability of the various Sections of the manual, based on district clinicians’ use of the ﬁrst version and then review of the new version. Country and Principle Investigator in country for the ﬁeld tests Ethiopia Ghion Tirsite Mengistu, WHO John Stephen, St. John's Medical College Ashwin Vasan, Chadi Cortas, Partners In Health District clinician representative at external review meeting Tekle Beyene Weldemeskel, Dibrhe Birhane Hospital Preethy Harrison, Snehadaan Hospital Chadi Cortas, Partners In Health

Completed second ﬁeld test survery Seblewengel Eshetu, Daniel Zewde, Zemen Hassen, Merid Mersha Preethy Harrison, Prathana, Sr. Anies, Rajendar Prasad Vincent Cubaka, Alfred Rutagengwa, Rene Kabera, Michael Miller, Rogers Musaﬁri, Gabriel Kabilwa, Vedaste Nkurunziza, Theoneste Rubanzabigwi, Alain Uwumugambi, Issaka Biximana, Richard Bmark, Jean Dieudonnee Damascene, Maaike Flinkenﬂogel, Emile Karinganire, Jean Paul Kimenyi, Anaclet Mugali, Sebibibi Munyamaliza, Jean Bosco Ndacyaliho, Jean Paul De Charles Umurungi

India Rwanda

Tanzania Uganda

Jan van den Homberg, Pharmaccess Patrick Banura, Masaka Regional Hospital; Leah Thayer, Infectious Disease Institute, Makerere University Eleanor Turnbull, Stewart Reid, CIDRZ

Sixtus Assey, Turiani Hospital Patrick Banura, Masaka Richard Kyakuwa, Edwig Namwanga, Resty Mukwaya, Justine Nakatumba

Zambia

Keith Mweebo, Ministry of Health

Final steps in development of the manual Modiﬁcations in format, ﬂow, and clarity, based on the results of ﬁeld-testing, further review suggestions by expanded expert subgroups, and internal WHO review after submission to the WHO Guideline Review Committee (GRC), and the decisions of the ﬁnal guideline panels were incorporated into the manual Sections. The GRC chair and DGO referred the manual to an external review prior to its publication. The members of the external review group, which met 20–22 June 2011, are listed in the table below. Technical recommendations from this review were incorporated into the manual.

Plans for updates It is important that this manual remains consistent with new WHO guidelines as these are updated or newly developed. Within 3 months of the revision or release of a relevant WHO normative guideline, an updated Section of the manual will be posted on the manual web site (IMAI second-level EZcollab web site). Revisions will also take into account further ﬁeld-testing and experience from closely monitored

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early use. The updated Sections of the IMAI manual will be incorporated into an annual revision of each Volume, which will be reprinted yearly. Before adapting the manual, users are advised to check for the most up-to-date Sections on the EZcollab site.

Declarations of interest Declarations of interest were received from the contributors to Volume 1. Nine of the contributors declared an interest, two of which were relevant to the development of the IMAI District Clinician Manual. Drs Moore and Jacob had conﬂicts of interest related to the manual. They received funding from Pﬁzer™ through grants to their institutions for a research training programme for students and fellows and for a study of ﬂuid resuscitation, PRISM-U2. For those contributors with potential conflicts of interest, declarations are summarized below: 1. Dr Ortiz received a travel allowance from Merck to attend the American Thoracic award conference. 2. Dr Runyon received funds from Abbot Tanzania for developing an emergency department and a training programme at Muhimbili Hospital in Dar es Salaam. 3. Dr Molyneux received a 2–3 year grant for malaria research in Malawi from The Leverhulme Trust. 4. Dr Bukham received a grant for equipment from Sonosite Inc. 5. Dr Vuylsteke received a grant from iMDsoft Fukuda Denshi, a software developer, for research on application in a clinical environment. 6. Dr Cruz received honoraria for lectures from GSK, Mantecorp, LIBBS, Astrazencea, and Novartis and a further donation from Novartis for public work in a health facility and donations from Mantecorp, CHIESI, Novartis, and Ache for NGO work in Brazil. 7. Dr Dawson received funds from Wellcome Trust for capacity-building in the management of poisoning and for research on activated charcoal and gastric decontamination. All of the above were considered unconﬂicted. Declarations of potential conﬂicts of interest were also received from all participants of the ﬁnal expert review meeting. Dr David Cohn declared having received funds from NIAID and CDC for research on HIV and TB when employed by Denver Health Hospital Authority, from which he retired in 2011. His past participation in publicly funded research was not considered to constitute a conﬂict of interest. Dr Michael Runyon declared that his institution has been reimbursed by Abbott Fund Tanzania for his work on the development of and support to an emergency department at Muhimbili Hospital in Dar Es Salaam in the United Republic of Tanzania. He was considered unconﬂicted.

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External Review Members David Cohn, Chair University of Colorado School of Medicine, Denver, CO, USA Andrea Atzori,* Walter Inojosa, Gianpiero Pellizer, Bruno Turri, Vinicio Manfrin Yusuf Ahmed** John Saunders Medici con l'Africa CUAMM, Padova, Italy University Teaching Hospital, Lusaka, Zambia Youth Substance Abuse Research, University of Queensland and Faculty of Medicine, Sydney Medical School, University of Sydney, Australia Swiss Tropical and Public Health Institute, Basel Department of Pharmacology and Pharmacy, Faculty of Medicine, University of Colombo, Sri Lanka Infectious Diseases Institute. Makerere University, Kampala, Uganda Axum St Mary Hospital, Axum, Ethiopia Consultant, sabbatical, Paris, France Shree Hindu Mandal Hospital, Tanzania Carolinas Medical Center, University of North Carolina, USA, and Muhimbili Hospital, Dar es Salaam, Tanzania Associate Professor, Dept of Psychiatry, College of Health Sciences, Addis Ababa University, and Consultant Psychiatrist, Amanuel Hospital Cervical cancer screening research, University of Zimbabwe Makerere University, College of Health Sciences, Kampala, Uganda School of Medicine, Addis Ababa University, and Tikur Ambassa Hospital, Addis Ababa, Ethiopia

Valérie D'Acremont,* Christoph Hatz, Johannes Blum, P. Kocher Rohini Fernadopulle Concepta Merry** Tewodros Haile Gebremariam Veronique Bortolotti Ramaiya Kaushik Michael Runyon Abebaw Fekadu

Tsitsi Magure Elizabeth Sentongo Abebaw Fekadu Wassie**

*Attended the meeting and represented other reviewers from same institution **Attended by teleconference and emailed comments

Expert writers and reviewers for Volume 1 Superscript numbers refer to involvement in ﬁnal guideline panels as shown below. Writers’ names appear in boldface. 1 Shock 2 Pulmonary 3 Trauma/surgery 5 Burns 6 Maternal 7 Malaria 8 Delirium 9 Seizures 10 Electrolyte abnormalities 11 Altered consciousness/diabetes 12 Poisoning

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Critical care expert group Emergency expert group Chris Curry John Kennedy University of Western Australia New South Wales Medical Retrieval Services, Australia Carolinas Medical Center, USA University of Washington, USA Universidade de la Republica, Uruguay Division of Emergency Medicine, University of Witwatersrand, South Africa Crusader Health, Ghana University of Colorado, USA Queen Elizabeth Hospital, Malawi Liverpool School of Tropical Medicine, UK PATH, USA WHO AFRO Partners In Health, Rwanda Northern Territory Health, Australia Pulmonary expert group Phil Hopewell2 Alvaro Cruz UCSF/SFGH, USA Allen Cheng Universidade Federal da Bahia, Brazil University of Washington, USA Julian Bion1 Stephen Gordon, Jamie Rylance Patrick Lee Salah Ottmani Paul Torzillo2 Anthony Harries, Chen Yuen Chaing Clement Yeh, Luke Davis, Adithya Cattmanchi, Anh Innes Neill Adhikari1,2 Liverpool School of Tropical Medicine, UK Partners In Health WHO StopTB, Switzerland University of Sydney, Australia International Union Against TB and Lung Disease UCSF/SFGH, USA Alain Vuylsteke Shevin Jacob Satish Bhagwanjee1 School of Health Research, Australia Oxford University Clinical Research Unit, Viet Nam University Dept of Anaesthesia & Intensive Care Medicine, Queen Elizabeth Hospital, Birmingham, UK Anaesthesiology, University of Witwatersrand, South Africa Cambridge University Health Partners, UK Division of Allergy and Infectious Diseases, University of Washington, USA Médicins Sans Frontière, Belgium Masaka Regional Hospital, Uganda Department of Medicine, University of Virginia, USA WHO GAR, Switzerland Sepsis working group convened by WHO GAR

Jeremy Farrar

Len Hudson

Michael Runyon Eric Walter, Eoin West Amalia Laborde Walter Kloeck

Mark Blaylock Eric Simoes Elizabeth Molyneux Ruth Suckling

Sunnybrook Health Sciences Centre, Toronto, Canada Partners In Health and Harvard Brigham and Women's Hospital, USA UCSF/SFGH, USA

Natalie Van Meerbeeck Patrick Banura Christopher Moore

Justin Ortiz2 Olive Chifefe Kobusingye Gene Buckham Melanie Little

Kwonjune Seung

Phil Hopewell2

Matthew Lim1

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Clinical reasoning, approach to lab investigations Chris Mathews Chris Behrens10 Fareed Ramzi Asfour Valérie D'Acremont UCSD, USA ITech, University of Washington, USA WHO IMAI; then private infectious diseases practice, USA Swiss Tropical and Public Health Institute

Malaria (11.40) Andrew Brent7 Nicholas White 7

KEMRI–Wellcome Trust Research Programme, Kenya Mahidol University, Thailand College of Medicine, University of Malawi WHO GMP, Switzerland

Malcolm Molyneux7 Peter Olumese Marian Warsame Andrea Bosman

Burns (3.10) Richard Gosselin3 Massey Beveridge5 Remy Zilliox 5

University of California Berkeley, USA University of Toronto, Canada Université Hôpital, Lyon, France Iﬁkara Health Institute, Tanzania WHO EHT, Switzerland

Gebreegziabher Tekie5 Anthony Magoda5 Meena Nathan Cherian

Surgery/trauma (Quick Check, 4) Richard Gosselin3 Aberra A. Gobezie Pascience Kibatala3 N. Mkandawire Hillary Cohen1,3,5 Lawrence Sherman David Speigel3 Charles Mock Meena Nathan Cherian 3

University of California Berkeley, USA Awassa University, Ethiopia Iﬁkara Health Institute, Tanzania Maimonides Medical Center, USA Ministry of Health, Liberia Children’s Hospital, Philadelphia, USA WHO Violence and Injury Prevention, Switzerland WHO EHT – IMEESC team leader, Switzerland

Neurology (Quick Check, 3.4, 10.10) Corrado Barbui8 Charles Newton 9

University of Verona, Italy Kenya Medical Research Institute, Kenya Chikankata Hospital, Zambia

Gretchen Birbeck9

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Zenebe Melaku Yirsaw Chris Mathews Elijah Chaila Penny Lewthwaite Theo Smart Martin Dedicoat Kevin Robertson Miriam Taegtmaeyer Tarun Dua Chris Duncombe

International Center for AIDS Care and Treatment Programs (ICAP), Ethiopia UCSD, USA The Adelaide & Meath Hospital, Ireland University of Liverpool, UK HIV AIDS Treatment in Practice, South Africa Africa Centre and Hlabisa Hospital, South Africa University of North Carolina, USA LSTM, UK WHO, MSD, Switzerland WHO HIV,, Switzerland

Mental health (Quick Check, 3.4, 10.11) Francine Cournos8 Mark Halman8 Julie Maggi Joseph K. Mbatia Helen McColl John Palen Melvyn Freeman Zoe Rush Rita Thom MaryAnn Vitello Vikram Patel Jose Manuel Bertolote Jose Catalan Pamela Collins Shekhar Saxena, Tarun Dua Columbia University, USA Saint Michael's Hospital, University of Toronto, Canada Ministry of Health and Social Welfare, Tanzania Pattison Centre, UK USAID, USA Department of Health, South Africa Johns Hopkins University, USA University of Witwatersrand, South Africa International Training and Education Centre on HIV, (I-Tech), University of Washington London School of Tropical Medicine, UK WHO MSD, retired. Imperial College, UK Columbia University, USA WHO MSD, Switzerland

Diabetes and hypoglycaemia (Quick Check, 3.4) Ayesha Motala11 Bahendeka K. Silver11 Ramu Ramachandran11 Sidartawan Soegondo Gojka Roglic 11

Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, South Africa Chair, International Diabetes Federation Africa Region, Uganda India Diabetes Research Foundation, India SS Diabetes Care, Indonesia WHO CHP, Switzerland

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Pregnant and postpartum severely ill patients Jean Anderson6 Kisore Pichamuthu6 Michael Gravett Yusuf Ahmed6 Binila Chacko 6 6

Johns Hopkins University, USA Christian Medical College and Hospital, Vellore, India University of Washington, USA University Teaching Hospital, Lusaka, Zambia Christian Medical College and Hospital, Vellore, India WHO MPS, Switzerland

Matthews Mathai

Electrolytes and calcium Lut Lynen10 Chris Behrens 10

Institute of Tropical Medicine, Antwerp, Belgium ITech, University of Washington, USA

Infection control (6) Sergey Eremin Daniel Chemtob Eyerusalem Negussie WHO GAR, Switzerland WHO STB, Switzerland WHO HIV, Switzerland

Procedures (7) Kiran Joshi Mark Blaylock WHO IMAI consultant, USA Crusader Health, Ghana

Poisoning (3.8) Andrew Dawson Tareq Al Refai12 Randall Bond Amalia Laborde Reza Afshari Clare Roberts Winai Wananukul12 Bob Hoffman Knut-Erik Hovda Nadeem Al Duaij Lynn Panganiban 12 12

South Asian Clinical Toxicology Research Collaboration, Sri Lanka Syrian Poison Information Centre, Damascus, Syria Cincinnati Children's Hospital, USA Departamento de Toxicología, Centro de Información y Asesoramiento Toxicológico, Montevideo, Uruguay Medical Toxicology Centre, Imam Reza Hospital, Iran Poisons Information Centre, School of Child and Adolescent Health, Red Cross War Memorial Hospital, South Africa Ramathibodi Poisons Centre, Thailand Division of Medical Toxicology, New York University School of Medicine, USA Department of Acute Medicine, Ullevaal University Hospital, Norway Harvard School of Public Health, USA National Poison Management & Control Centre, Philippines

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Verrol Simmons12 Robertas Badaras12 Ismail Afandiyev12 Naima Rhalem Joy Veale12 Indika Gawarammana Surjit Singh12 Barbara Groszek12 John Fountain12 Nick Bateman12 Joanna Tempowski Alexander Fleishmann 12 12

Poison Information Centre, University of the West Indies, Trinidad and Tobago Poisons Control & Information Bureau, Lithuania Azeri Toxicologists Professional Society, Azerbaijan Centre Antipoison et Pharmacovigilance de Maroc, Morocco Department of Pharmacology, University of Stellenbosch, South Africa South Asian Clinical Toxicology Research Collaboration, Sri Lanka Dept of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India Department of Toxicology, Collegium Medicum, Jagiellonian University, Poland New Zealand National Poisons Centre, New Zealand National Poisons Information Service (Edinburgh Centre), UK WHO EPE, Switzerland WHO MSD, Switzerland

Medicines and therapeutics – Mona Shah, WHO consultant, USA; Kristin Lunghi, UCSF/SFGH, USA; Julia Lord, The Alfred, Australia; Rohini Fernandopulle, Department of Pharmacology and Pharmacy, University of Colombo, Sri Lanka; Shevin Jacob, University of Washington, USA; and Neill Adhikari, University of Toronto, Canada. Illustrations: Robert Thatcher Ultrasound: Sachita Shah, PIH, and Adriana Velazquez Berumen, WHO EHT. Graphics and layout: Susan Stickler and L’IV Com Sàrl. Administrative and EZcollab web site support: Jane Ndanareh Evidence review: The following contributed to the evidence check of Volume 1, under the direction of Matthew Chersich and Janet Diaz: Hillary Cohen, Laura Diamondstone, Araya Giday, Helene van Gorsel, Senbeta Guteta, Kiran Joshi, Stanley Luchters, Rudzani Muloiwa, Priya Shete, Hildred Sarah Rochon, and Admasu Tenna Mamuye. WHO acknowledges the specific funding support from USAID towards the development of this manual. This development has also beneﬁted from the active collaboration of HIV/AIDS and other WHO departments. We would like to thank the donors supporting these departments and making this possible.

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Organizational abbreviations CDC Centers for Disease Control and Prevention, Atlanta, USA KEMRI Kenya Medical Research Institute LSTM Liverpool School of Tropical Medicine USAID United States Agency for International Development UCSD University of California San Diego UCSF/SFGH University of California San Francisco/San Francisco General Hospital WHO AFRO WHO Regional Ofﬁce for Africa WHO CHP WHO Department of Chronic Diseases and Health Promotion WHO EHT WHO Department of Essential Health Technologies WHO GAR WHO Global Alert Response WHO GMP WHO Global Malaria Programme WHO MPS WHO Department of Making Pregnancy Safer WHO MSD WHO Department of Mental Health and Substance Use WHO EPE WHO Evidence & Policy on Environmental Health

For further information please contact: IMAI Team Department of HIV/AIDS World Health Organisation Avenue Appia, 20 CH–1211 Geneva 27 Switzerland imaimail@who.int www.who.int/hiv/capacity/en

Informations clés

Organisation Organisation mondiale de la santé (OMS)

Type de document Publications

Date d'adoption 11 décembre 2012

Source Organisation mondiale de la santé