Neuropsychiatric aspects of HIV-1 infection: data collection instrument for a WHO cross-cultural study.

WHO News and activities Blood-borne pathogens can be transmitted from an infected person to uninfected individuals through contaminated equipment. WHO estimates that the risk from skin punctures with hypodermic needles contaminated with blood that is positive for human immunodeficiency virus (HIV) is 0.13-0.50%. Blood sampling by venepuncture therefore entails this risk, while, by inference, finger-pricking could also expose the blood sample donor to infection.e The risk of transmission of hepatitis virus B in this way is higher (estimated to be 6-30% in unvaccin- ated persons).J Several other diseases, e.g., Chagas disease, syphilis and malaria, can be transmitted by the same route, albeit probably more rarely. The precautions needed for preventing transmission of HIV are the same as those that should always be used with any of the blood-related diseases. When invasive techniques are needed, the sterility of the material used should be ensured and, equally, its proper disposal carefully planned and executed. WHO has produced guidelines on steril- ization and disinfection methods that are effective against HIV, which are available in English, French, and Spanish.9 It must be considered the responsibil- ity of officers in charge of malaria control program- mes that all blood collection activities carried out for control purposes be performed with the necessary precautions against HIV infection. It is strongly recommended that persons with national responsi- bility for malaria elaborate a set of rules for work with blood based on the above-mentioned WHO guidelines. Generally, the precautions needed to minimize the risk of HIV infection in malaria work do not differ from those that apply in other clinical settings. The specific aspects outlined below nevertheless merit some comments. * For capillary (e.g., finger-prick) blood sampling, only single-use disposable lancets should be em- ployed. * When, for economic or operational reasons, it is absolutely necessary to re-use such lancets, they must be sterilized by standard methods. When this is not possible, e.g., in the field, disinfection should be carried out by boiling them in water for at least 20 minutes. * Biosafety guidelines for diagnostic and research laboratories working with HIV. Geneva, World Health Organization (In press). ' Guidelines for prevention of transmission of human immunode- ficiency virus to health-care and public-safety workers. Morbidity and mortality weekly report, 38 (S-6) (1988). 9 Guidelines on sterilization methods effective against human immunodeficiency virus (HIV). 2nd edition. Geneva, World Health Organization, 1989 (WHO AIDS Series No. 2). * Irrespective of whether lancets are re-used or not, their disposal and destruction must be planned in detail by supervisory staff, according to local circum- stances. * Nurses, ancillary staff, and microscopists need to be informed about the risks that they and individuals who are pricked are exposed to, if rules are not followed. * Even dried blood films may contain HIV. In practice, the risk of infection by handling them is probably minimal, but laboratory workers should be aware of the theoretical risk, so that they avoid handling slides with blood films if, for example, they have a wound on a finger. * In some anti-malaria programmes, it has been customary to prepare thick films from four or five individuals on one slide, with the risk of undried blood from one sample contaminating the finger of the next person who deposits blood on the slide. Clearly, this is unacceptable. * Field-workers may have made a habit of using the same piece of dry cotton-wool for several patients to wipe the first drop of blood after a finger-prick. Continued efforts need to be made to ensure that such practices do not occur and to enforce proper disposal of all blood-contaminated objects. * Some malaria control programmes that are deeply entrenched in the traditions of eradication programmes may take more blood samples than are actually necessary. Consideration of the risk of transmission of blood-borne pathogens may there- fore be a good opportunity for reviewing the objectives and scope of blood collections. In some situations, whole population surveys might be re- placed by representative sample surveys, which are easier to supervise adequately. Good biosafety practices can virtually eliminate the risk of HIV transmission through blood collec- tions, but in the less controllable circumstances of field-work the risk cannot be reduced to zero. This must be weighed against the potential benefits of these blood collections. Neuropsychiatric aspects of HIV-1 infection: data collection instrument for a WHO cross-cultural studyh It is well established that neurological and psy- chiatric disorders are a frequent occurrence in subjects with AIDS-related complex (ARC) and h Contributed by M. Maj, F. Starace & N. Sartorius. WHO Bulletin OMS. Vol 69. 1991. 243 WHO News and activities AIDS. Furthermore, it has been repeatedly re- ported that acute stress reactions and adjustment disorders are common in otherwise asymptomatic HIV-1 infected subjects, especially immediately after discovery of seropositivity.' Several gaps still exist, however, in our knowl- edge of the neuropsychiatric aspects of HIV-1 infection. In particular, almost all studies in this area have been carried out in Western populations and on samples of well-educated, mostly white, homo- sexual or bisexual men. The generalizability of the results of these investigations to other geographic and cultural contexts and to different at-risk popula- tions is uncertain. The World Health Organization, ac- knowledging the important health care and policy implications of studies concerning HIV-1-associated neuropsychiatric disorders, has recently launched a large cross-cultural study, aiming to verify in a broader context the research findings obtained in Western populations.i The study is currently ongo- ing in six centres (Bangkok, Thailand; Kinshasa, Zaire; Los Angeles, CA, USA; Munich, Germany; Nairobi, Kenya; and Sao Paulo, Brazil). Data collection instrument The data collection instrument consists of seven modules: I) Socio-demographic survey, which collects in- formation on sex, race, age, present work status, educational level, and first language. II) Cognitive/neuropsychological assessment, which includes (a) a brief questionnaire on subjective complaints concerning cognitive functioning; (b) a battery of neuropsycholo- gical tests (see below); (c) a modified version of a structured interview for the objec- tive evaluation of cognitive performance (SIDAM),k which incorporates algorithms for the diagnosis of dementia according to the classifications of mental disorders provided by WHO (ICD-10) and by the American Psy- chiatric Association (DSM-III-R); and (d) a rating scale for the evaluation of functioning in daily living activities (ADL). Maj, M. Psychiatric aspects of HIV-1 infection and AIDS. Psychological medicine, 20: 547-563 (1990). i See: Bulletin of the World Health Organization, 68 (5): 671- 673 (1990). k Zaudig, M. et al. SIDAM-a structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct demen- tia and dementias of other etiology according to ICD-10 and DSM-III-R. Psychological medicine, (In press). III) Psychiatric assessment, which includes (a) a modified version of a WHO structured inter- view (CIDI),' which incorporates algorithms for psychiatric diagnoses according to ICD-10 and DSM-III-R; (b) a global psychiatric rating scale, the 18-item version of the Brief Psychiatric Rating Scale (BPRS);' and (c) a rating scale for depression, the Montgomery- Asberg Depression Rating Scale (MADRS).n IV) Neurological assessment, which includes (a) a screening neurological examination (covering level of consciousness, cranial nerve function- ing, wiggles, muscle strength, coordination, involuntary movements, reflexes, sensory functioning, gait); (b) a detailed neurological examination (with sections on cranial nerve functioning, involuntary movements, muscu- lar tone, motor functioning, coordination and sensory functioning); (c) a neurological his- tory; and (d) a neurological summary. V) Physical assessment, which includes (a) a brief physical examination (collecting infor- mation for staging of HIV-1 infection accord- ing to the Centers for Disease Control (CDC) and WHO criteria); (b) a questionnaire for recording subjective symptomatology; and (c) a general medical history. VI) Laboratory tests, which include HIV-1 sero- logy (both ELISA and Western blot), CD4 and CD8 lymphocyte count and VDRL as mandatory tests, and several optional diag- nostic tests. VII) Summary sheet, which summarizes informa- tion on HIV-1 serostatus, HIV-1 infection staging according to CDC and WHO criteria, diagnosis of HIV-1-associated neuropsy- chiatric disorders according to WHO opera- tional criteria, other psychiatric diagnosis, other psychiatric symptoms or signs, other neurological diagnosis, and other neurolo- gical symptoms and signs. The neuropsychological battery includes the following tests: Timed Gait, Finger Tapping (domi- nant and non-dominant), WHO/UCLA Auditory Verbal Learning Test, Color Trails 1 and 2, the Composite International Diagnostic Interview (CIDI). Unpubl- ished WHO document MNH/NAT/89.5, Rev. 3,1989. m Overall, J.E. & Gorham, D.R. The Brief Psychiatric Rating Scale. Psychological reports, 10: 799-812 (1962). n Montgomery, S. & Asberg, M. A new depression scale designed to be sensitive to change. British journal of psychiatry, 134: 382-389 (1979). 244 WHO Bulletin OMS. Vol 69. 1991. WHO News and activities Block Design subtest of the EIWA (Spanish version of the Wechsler Adult Intelligence Scale),' the Digit Symbol subtest of the EIWA, Grooved Pegboard (dominant and non-dominant), Verbal Fluency (animals and first names), Trail Making A, WHO/UCLA Picture Memory and Interference test.P Four of these tests (the WHO/UCLA Audit- ory Verbal Learning Test, the Color Trails 1 and 2, and the WHO/UCLA Picture Memory and Interfer- ence Test) were specifically developed for the present study, and were validated by means of a pre-pilot investigation. The functional domains covered in the neuro- psychological battery include (a) motor speed and fine motor control (Timed Gait, Finger Tapping, Color Trails 1 and 2, EIWA Block Design, EIWA Digit Symbol, Grooved Pegboard, Trail Making A); (b) rapid visual search (Color Trails 1 and 2, EIWA Digit Symbol, Trail Making A); (c) sustained attention (Color Trails 1 and 2, Trail Making A); (d) selective attention (Color Trails 2, EIWA Digit Symbol); (e) cognitive flexibility (Color Trails 2, EIWA Digit Symbol); (f) perceptual-motor analysis (EIWA Block Design); (g) verbal memory (WHO/UCLA Auditory Verbal Learning Test); (h) visual memory (WHO/UCLA Picture Memory and Interference Test); and (i) verbal fluency (Verbal Fluency Test, animals and first names).P Inter-centre and intra-centre reliability Data on the inter-centre reliability in the use of the SIDAM and of the psychiatric rating scales, and in the application of the neurological examination, were obtained by all the researchers involved in the study in the different centres using a series of live and videotaped interviews and clinical examinations of patients with HIV-1-related symptoms and signs. The mean percentage agreement score was 97.6% o Wechsler, D. Manual para la Escala de Inteligencia Wechsler para adultos (adaptation by Green, R.F. & Martinez, J.N.). Cleveland, The Psychological Corporation, 1968 (in Spanish) P Details on these tests (in English only) may be obtained by writing to Division of Mental Health, World Health Organization, 1211 Geneva 27, Switzerland. for the SIDAM, 89.9% for the BPRS, 96.6% for the MADRS, and 95.0% for the neurological examina- tion. Data on the intra-centre reliability in the use of these instruments were obtained by the joint inde- pendent assessment of at least five patients with HIV-1-associated neuropsychiatric manifestations within each centre. The overall mean percentage agreement score was 97.8% for the SIDAM (range 80.0-100%), 92.8% for the BPRS (range 86.0- 100%), 88.8% for the MADRS (range 79.0-100%), and 94.0% for the neurological examination (range 90.0-100%). Comment The need for instruments allowing the assessment of HIV-1-associated neuropsychiatric abnormalities in different cultural and socioeconomic settings, regardless of education and linguistic background, has been stressed by a number of authors. This WHO cross-cultural study attempts to address the above need by developing a compre- hensive instrument for the collection of neuropsy- chiatric data, including a battery of neuropsycholo- gical tests suitable for use in both developing and developed countries. This instrument has been shown to facilitate the early detection of HIV-1- associated neuropsychiatric abnormalities even in settings with a very limited availability of labora- tory diagnostic tools. The development and use of a set of neuropsy- chological tests in several different cultures, as in this study, could pave the way for the investigation of cognitive abnormalities occurring in other infec- tious or non-infectious diseases which affect the central nervous system and are highly prevalent in developing countries. WHO Bulletin OMS. Vol 69. 1991. 245 Notes et activit6s OMS * I1 est possible que certains programmes de lutte antipaludique, impregnes des habitudes des pro- grammes d'eradication, prelevent plus d'echantil- lons de sang qu'il n'est necessaire. La perspective du risque de transmission d'agents pathogenes par voie sanguine peut etre l'occasion de revoir les objectifs et les possibilit6s des prelevements de sang. Dans certains cas, au lieu d'enquetes couvrant toute une population, il pourra etre preferable de se limiter a des sondages sur des echantillons representatifs plus faciles a supervi- ser. Des m6thodes assurant une bonne securite biologique peuvent eliminer virtuellement le risque de transmission du VIH lors du prelevement d'echantillons sanguins, mais sur le terrain, oiu les conditions de travail sont moins bien contr6lables, le risque ne peut etre completement elimine. I1 faut donc l'evaluer par rapport aux avantages potentiels des prelements sanguins. Les aspects neuropsychiatriques de l'infection a VIH: le recueil des donnees pour l'etude transculturelle realisee par I'OMSh I1 est bien etabli que le pr6-sida (ou parasida ou ARC) et le sida s'accompagnent fretquemment de troubles neurologiques et psychiatriques. Les reac- tions aigues aux facteurs de stress et les troubles de l'adaptation sont en outre frequents chez les sujets infectes par le VIH-1 mais asymptomatiques, plus particulierement dans la periode qui suit immediate- ment la decouverte de la seropositivite..' Notre connaissance des aspects neuropsychia- triques de l'infection a VIH-1 reste cependant tres lacunaire. En effet, les etudes realisees dans ce domaine portent pour la plupart sur des populations occidentales et sur des echantillons d'homosexuels ou de bisexuels le plus souvent de race blanche ayant un niveau d'etudes eleve. La generalisation des resultats de telles investigations et leur application a d'autres contextes geographiques et culturels et a d'autres populations a risque est discutable. Les etudes sur les troubles neuropsychiatriques associes au VIH-1 influent sur les politiques de sante et la prestation de soins. Consciente de leur impor- tance, l'Organisation mondiale de la Sante vient d'entreprendre une etude transculturelle de grande hpar M. Maj, F. Starace et N. Sartorius. Maj, M. Psychiatric Aspects of HIV-1 infection and AIDS. Psychological medicine, 20: 547-563 (1990). envergure dont le but est de verifier dans un contexte plus large les resultats des recherches obtenues chez les populations occidentales. i L'dtude a d6butd dans six centres (Bangkok, Thaflande; Kinshasa, Zaire; Los Angeles, CA, Etats-Unis d'Amerique; Munich, Allemagne; Nairobi, Kenya; Sao Paulo, Bresil). L'instrument de collecte des donn6es Sept modules constituent l'instrument de collecte des donndes: I) L'enquete socio-demographique, qui doit re- cueillir les donnees sur le sexe, la race, l'age, la situation professionnelle, le niveau d' 'tudes et la langue maternelle. II) L'e'valuation cognitive/neuropsychologique, qui comporte a) un petit questionnaire sur les plaintes du sujet A propos de ses fonctions cognitives; b) une batterie de tests neuropsy- chologiques (voir ci-dessous); c) une variante de l'interrogatoire structure permettant une evaluation objective des performances cogni- tives (SIDAM),k avec des algorithmes pour le diagnostic de la demence suivant les classifica- tions des troubles mentaux de l'OMS (CIM-10) et de l'American Psychiatric Asso- ciation (DSMIIIR); d) une echelle d'6valua- tion fonctionnelle des activites quotidiennes (ADL). III) L'evaluation psychiatrique, qui comprend a) une variante de l'interrogatoire structure OMS (CIDI),' avec des algorithmes pour les diagnostics psychiatriques suivant la CIM-10 et le DSMIIIR; b) une echelle d'evaluation psychiatrique globale, variante en 18 item de l'echelle abregee d'6valuation psychiatrique (BPRS)m et c) une echelle d'Wvaluation de la depression, la Montgomery-Asberg Depres- sion Rating Scale (MADRS).n Voir Bulletin de lOrganisation mondiale de la Sante, 68 (5): 671-673 (1990). kZaudig, N. et al. SIDAM-a structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct demen- tia and dementias of other etiology according to ICD-10 and DSM-III-R. Psychological medicine (sous presse). Organisation mondiale de la Sante. Composite Intemational Diagnostic Interview (CIDI). Document interne WHO/MNH/ NAT/89.5, Rev. 3, 1989 (en anglais). m Overall, J.E. et Gorham, D.R. The Brief Psychiatric Rating Scale. Psychological reports, 10: 799-812 (1962). n Montgomery, S. et Asberg, M. A new depression scale designed to be sensitive to change. British journal of psychiatry, 134: 382-389 (1979). 250 WHO Bulletin OMS. Vol 691991. Notes et activit6s OMS IV) L'evaluation neurologique, qui comporte a) un examen de d6pistage neurologique (etu- diant le niveau de conscience, le fonctionne- ment des nerfs craniens, l'6tat d'agitation, la force musculaire, la coordination, les mouve- ments involontaires, les reflexes, le fonction- nement sensoriel et la demarche); b) un examen neurologique detaill (etudiant le fonctionnement des nerfs craniens, les mou- vements involontaires, le tonus musculaire, le fonctionnement moteur, la coordination et les fonctions sensorielles); c) une etude des antdcddents neurologiques et d) un resume de l'etat neurologique. V) L'evaluation physique, qui comprend a) un bref examen physique (pour determiner le stade de l'infection a VIH-1 suivant les critbres des Centers for Disease Control (CDC) et de l'OMS; b) un questionnaire pour l'enregistrement des symptomes et c) une etude de l'histoire medicale generale. VI) Les analyses de laboratoire, avec serologie VIH-1 (par ELISA et Western blot), num6ra- tion des lymphocytes CD4 et CD8 et VDRL obligatoires ainsi que divers tests diagnosti- ques facultatifs. VII) Un formulaire resume, qui reprend les infor- mations essentielles sur la serologie VIH-1, le stade de l'infection a VIH-1 ddfini d'apres les criteres des CDC et de l'OMS, le diagnostic de troubles neuropsychiatriques associes au VIH-1 d'apres les criteres operationnels defi- nis par l'OMS, les autres diagnostics et tableaux psychiatriques, les autres symptomes et diagnostics neurologiques. La batterie de tests neuropsychologiques com- porte: marche chronometree, "tapping" (dominant et non dominant), le test OMS/UCLA de memorisa- tion verbale, les tests de sequence avec couleurs 1 et 2, le test de construction geometrique figurant dans la version espagnole de l'echelle d'intelligence de Wechsler pour l'adulte (EIWA),° le test de symboli- sation de chiffres de cette meme echelle, le test de la planche a chevilles (dominant et non dominant), le test de facilite verbale (animaux et prenoms), le test de sequence numeral A, le test OMS/UCLA de memorisation visuelle avec interf6rence.P Parmi ces tests, quatre (les deux developpes en collaboration o Wechsler, D. Manual para la Escala de Inteligencia Wechsler para adultos (adaptation by Green, R.F. & Martinez, J.N.). Cleveland, The Psychological Corporation, 1968 (en espagnol). avec l'UCLA et les tests de sequence avec couleurs 1 et 2) ont ete specialement mis au point pour les besoins de cette etude dans une pre-enquete pilote. Les domaines fonctionnels couverts par cette batterie de tests neuropsychologiques sont: a) la vitesse motrice et le contr6le de I'activite motrice fine (marche chronometree, "tapping", les tests de couleurs 1 et 2, les tests de construction et de symbolisation des chiffres de 1'echelle EIWA, la planche a chevilles, le test de sequence numeral A); b) la recherche visuelle rapide (tests de couleurs 1 et 2, symbolisation des chiffres de 1'echelle EIWA, test de sequence numeral A); c) la capacite d'attention soutenue (tests de couleurs 1 et 2, test de sequence numeral A); d) la selectivite de I'attention (tests de couleurs 2, symbolisation des chiffres de 1'echelle EIWA); e) la flexibilite cognitive (tests de couleurs 2, symbolisation des chiffres de 1'echelle EIWA); f) la capacite d'analyse perceptivo-motrice (test de construction de 1'echelle EIWA); g) la memoire verbale (test OMS/UCLA de memorisation auditive et verbale); h) la memoire visuelle (test OMS/U- CLA de memoire visuelle avec interference); i) la facilite verbale (test de facilite verbale, animaux et prenoms) . P Fiabilite intercentre et intracentre La fiabilit6 intercentre du SIDAM, des echelles d'evaluation psychiatrique et de 1'examen neurologi- que a e testee par la totalite des chercheurs impliqu6s dans 1'etude dans les differents centres, sur une serie d'entretiens et d'examens cliniques de patients porteurs de symptomes Uies au VIH-1, directement observes et enregistres en vid6o. La mesure de I'accord donne des pourcentages moyens de 97,6% pour le SIDAM, 89,9% pour le BPRS, 96,6% pour le MADRS et 95,0% pour 1'examen neurologique. La fiabilite intracentre de l'utilisation de ces instruments a fait l'objet d'une evaluation conjointe independante, sur au moins cinq patients atteints de manifestations neuropsychiatriques associees au VIH-1 par centre. Globalement, la mesure de I'accord exprimee en pourcentage moyen est de 97,8% pour le SIDAM (extremes 80,0-100%), 92,8% pour le BPRS (extremes 86,0-100%), 88,8% pour le MADRS (extremes 79,0-100%) et 94,0% pour 1'examen neurologique (extremes 90,0-100%). P Des pr6cisions sur ces tests peuvent etre obtenues (en anglais seulement) en s'adressant a la Division de la Sante mentale, Organisation mondiale de la Sante, 1211 Geneve 27 (Suisse). WHO Bulletin OMS. Vol 69 1991. 251 Notes et activit6s OMS Discussion Un certain nombre d'auteurs ont souligne la neces- site de disposer d'instruments permettant 1'evalua- tion des anomalies neuropsychiatriques associees au VIH-1 dans des milieux socio-economiques et cultu- rels divers, independamment du niveau de scolarisa- tion et du contexte linguistique. Cette etude transculturelle de l'OMS tente de repondre au besoin expose ci-dessus par la mise au point d'un instrument global de collecte des donnees neuropsychiatriques, et notamment d'une batterie de tests neuropsychologiques pouvant etre utilisee dans les pays en developpement comme dans les pays developpes. Cet instrument a montre qu'il pouvait faciliter le depistage precoce des anomalies neuropsychiatriques associees au VIH-1, meme quand les methodes diagnostiques de laboratoire sont tres limitees. La mise au point et l'utilisation d'un ensemble de tests neuropsychologiques dans plusieurs cultures differentes, comme c'est le cas dans cette etude, devraient faciliter l'investigation d'anomalies cogni- tives accompagnant d'autres maladies, infectieuses ou non, qui touchent le systeme nerveux central et sont tres presentes dans les pays en developpement. WHO Bulletin OMS. Vol 69 1991.252