طسوتلما قشرل ةيلماعلا ةحصلا ةمظنلم ةيميلقلإا ةنجللا ءاضعأ نادلبلا ةيملاسلإا ناريإ ةيروهجم . ةيبيللا ةيبرعلا ةييرهمالجا . سنوت . نيرحبلا . ناتسكاب . ةدحتلما ةيبرعلا تاراملإا . ناتسناغفأ . ندرلأا صرم . نانبل . تيوكلا . رطق . ينطسلف . نماُع . قارعلا . لاموصلا . نادوسلا . تيوبيج . ةينميلا ةيروهملجا . ةيروسلا ةيبرعلا ةيروهملجا ةيدوعسلا ةيبرعلا ةكلملما . برغلما Subscriptions and Distribution Enquiries regarding subscriptions and distribution of the print edition of EMHJ should be addressed to: Printing and Marketing of Publications at: email: pam@emro.who.int; tel: (+202) 2276 5000; fax: (+202) 2670 2492 or 2670 2494 Permissions Requests for permission to reproduce or translate articles, whether for sale or non-commercial distribution should be addressed to EMHJ at: emhj@emro.who.int Members of the WHO Regional Committee for the Eastern Mediterranean Afghanistan . Bahrain . Djibouti . Egypt . Islamic Republic of Iran . Iraq . Jordan . Kuwait . Lebanon Libyan Arab Jamahiriya . Morocco . Oman . Pakistan . Palestine . Qatar . Saudi Arabia . Somalia Sudan . Syrian Arab Republic . Tunisia . United Arab Emirates . Republic of Yemen Membres du Comité régional de l’OMS pour la Méditerranée orientale Afghanistan . Arabie saoudite . Bahreïn . Djibouti . Égypte . Émirats arabes unis . République islamique d’Iran Iraq . Jamahiriya arabe libyenne . Jordanie . Koweït . Liban . Maroc . Oman . Pakistan . Palestine . Qatar République arabe syrienne . Somalie . Soudan . Tunisie . République du Yémen Correspondence Editor-in-chief EMHJ WHO Regional Office for the Eastern Mediterranean P.O. Box 7608 Nasr City, Cairo 11371 Egypt Tel: (+202) 2276 5000 Fax: (+202) 2670 2492/(+202) 2670 2494 Email: sabrib@emro.who.int/emhj@emro.who.int EASTERN MEDITERRANEAN HEALTH JOURNAL IS the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas, con- cepts, epidemiological data, research findings and other information, with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession, medical and other health educational institutes, interested NGOs, WHO Col- laborating Centres and individuals within and outside the Region. LA REVUE DE SANTÉ DE LA MÉDITERRANÉE ORIENTALE EST une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine des ser-vices de santé ainsi qu’à l’échange d’idées, de concepts, de données épidémiologiques, de résultats de recherches et d’autres informations, se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé, aux membres des instituts médicaux et autres instituts de formation médico-sanitaire, aux ONG, Centres collabora- teurs de l’OMS et personnes concernés au sein et hors de la Région. EMHJ is a trilingual, peer reviewed, open access journal and the full contents are freely available at its website: http://www/emro.who.int/emhj.htm EMHJ is abstracted/indexed in the Index Medicus and MEDLINE (Medical Literature Analysis and Retrieval Systems on Line) and the ExtraMed-Full text on CD-ROM, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), CAB International, Lexis Nexis, Scopus and the Index Medicus for the WHO Eastern Mediterranean Region (IMEMR). ©World Health Organization 2010 All rights reserved Disclaimer 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. 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 express 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. The named authors alone are responsible for the views expressed in this publication. ISSN 1020-3397 Cover designed by Diana Tawadros Internal layout designed by Emad Marji and Diana Tawadros Printed by WHO Regional Office for the Eastern Mediterranean ميدقتل برنم ىهو .ةيلماعلا ةحصلا ةمظنمب طسوتلما قشرل ىميلقلإا بتكلما نع ردصت ىتلا ةيمسرلا ةلجلما ىه ةيئابولا تايطعلماو ميهافلماو ءارلآا لدابتلو ،اله جيوترلاو ةيحصلا تامدلخا فى ةديدلجا تاردابلماو تاسايسلا لك لىإ ةهجوم ىهو .طسوتلما قشر ميلقإب اهنم قلعتي ام ةصاخو ،تامولعلما نم كلذ يرغو ثاحبلأا جئاتنو زكارلماو ،ةينعلما ةيموكلحا يرغ تماظنلما اذكو ،ةيميلعتلا دهاعلما رئاسو ةيبطلا تايلكلاو ،ةيحصلا نهلما ءاضعأ .هجراخو ميلقلإا فى ةحصلاب ينمتهلما دارفلأاو ةيلماعلا ةحصلا ةمظنم عم ةنواعتلما طسوتلما قشرل ةيحصلا ةلجلما Cover 6.indd 2 5/24/2010 11:46:47 AM Contents La Revue de Santé de la Méditerranée orientale Eastern Mediterranean Health Journal Vol. 16 No. 8 8 ددع شرع سداسلا دلجلما• 2010 • Letter from the Editor .................................................................................................................................................................................................................................................................................811 Research articles Characterization of Mycobacterium tuberculosis of Lebanese patients by double-repetitive-element polymerase chain reaction M. Hamze, A. Rahmo and M. Saade .................................................................................................................................................................................................................................................. 812 Characterization of Mycobacterium tuberculosis in Syrian patients by double-repetitive-element polymerase chain reaction A. Rahmo and M. Hamze .......................................................................................................................................................................................................................................................................820 Prevalence and associated factors of persistent diarrhoea in Iranian children admitted to a paediatric hospital N.A. Kermani, F. Jafari, H.N. Mojarad, N. Hoseinkhan and M.R. Zali .................................................................................................................................................................................. 831 Cancer incidence in Jordan, 1996–2005 M. Al-Tarawneh, S. Khatib and K. Arqub ......................................................................................................................................................................................................................................... 837 Epidemiological, clinical and laboratory profile of glucose-6-phosphate dehydrogenase deficiency in the middle and north of Iraq: a comparative study M.D. Al-Mendalawi .................................................................................................................................................................................................................................................................................. 846 Macrovascular complications and their associated risk factors in type 2 diabetic patients in Sana’a city, Yemen A. Al-Khawlani, Z.A. Atef and A. Al-Ansi ......................................................................................................................................................................................................................................... 851 Nutrition knowledge, beliefs and dietary habits among elderly people in Nizwa, Oman: implications for policy A. Al Riyami, S. Al Hadabi, M.A. Abd El Aty, H. Al Kharusi, M. Morsi and S. Jaju .......................................................................................................................................................... 859 Comparing bone mineral density in postmenopausal women with and without vertebral fracture and its value in recognizing high-risk individuals B. Heidari, S. Hoshmand, K. Hajian and P. Heidari ..................................................................................................................................................................................................................... 868 A study on preference and practices of women regarding place of delivery S.S. Mahdi and O.S Habib ...................................................................................................................................................................................................................................................................... 874 Connaissances et pratiques des femmes de la région de Monastir (Tunisie) concernant l’allaitement maternel I. Bouanene, S. ElMhamdi, A. Sriha, A. Bouslah et M. Soltani ................................................................................................................................................................................................... 879 Impact of using essential drug list: analysis of drug use indicators in Gaza Strip R. Fattouh and B. Abu Hamad .............................................................................................................................................................................................................................................................. 886 Correction. Evaluation of effect of silymarin on granulosa cell apoptosis and follicular development in patients undergoing in vitro fertilization. ..............................................................................................................................................................................................................................................................................892 Immunoinflammatory markers and disease activity in systemic lupus erythematosus: something old, something new M.A. Elwy, Z.A. Galal and H.E. Hasan ............................................................................................................................................................................................................................................. 893 HIV-related knowledge and AIDS stigma among college students in Yemen A.M. Badahdah and N. Sayem ............................................................................................................................................................................................................................................................901 Review Burden of HIV/AIDS infection before and during the civil war in Somalia B.H. Ahmed, M.R. Giovagnoli, H. Mahad and G.G. Tarsitani .................................................................................................................................................................................................907 Short communication Public–private partnership scenario in the health care system of Pakistan F. Ahmed and N. Nisar ............................................................................................................................................................................................................................................................................. 910 Case report Primary hydatid cyst of the round ligament: case report M. Akinci, O. Yigitbasi, Z. Ergul,E. Olcucuoglu and H. Kulacoglu ............................................................................................................................................................................................. 913 Belgacem Sabri MD, MPA, MA (Econ), Editor-in-chief Muhammad Afzal MSc, MPhil, PhD, Executive Editor Editorial Board Mohammad Abdur Rab MBBS, DTM&H, MPH&TM, PhD Naeema Al Gasseer MSc, PhD Mohamed M. Ali BSc, MSc, PhD, DTMH Abdulla S. Assaedi MBBS, MPH Mounir Farag MD, DGS, DEmS, DPH Abdul Ghaffar MD, MPH, MHA, PhD Malekafzali Hossein MK, MPH, PhD Jaouad Mahjour MD, MPH Mamunur Rahman Malik MBBS, Dip (Health Economics), MSc, MPhil Kassem Sara MD International Advisory Panel Dr S. Aboulazm. Professor of Orthodontics. Egypt Dr Abdul Rahman Al-Awadi BSc, MD, MPH, Honorary FRCM, Ireland Dr Law, Korea, Honorary FRCS & P, Glasgow, FRCP, Edinbugh. Kuwait Dr Fariba Al-Darazi RN, MSc, PhD. Bahrain Dr M. Al-Nozha, MD, FRCP, FACC, FESC. Professor of Medicine and Consultant Cardiologist. Saudi Arabia Dr Ala’din Alwan MD, FRCP, FFPHM. Iraq Dr F. Azizi. Professor of Internal Medicine and Endocrinology. Islamic Republic of Iran Dr K. Bagchi BSc, MD, PhD. India Professor K. Dawson BA, MD, PhD, FRCP, FRACP, FRCPCH, DObst, RCOG. New Zealand Professor Kaussay Dellagi MD. Tunisia Dr R. Dybkaer MD. Denmark Dr M. Aziz El-Matri. Professor of Medicine. Tunisia Professor F. El-Sabban BSc, MS, PhD. United States of America Dr A.H. El-Shaarawi MSc (Stat), PhD (Stat). Canada Professor N. Fikri-Benbrahim PhD (Pub health) (SocSci). Morocco Professor A.T. Florence BSc (Pharm), PhD, DSc, FRSC, FRPharmS, FRSE. United Kingdom Professor Cheherezade M.K. Ghazi BS (Nursing), MS (Nursing), DPH, MPA. Egypt Professor M.A. Ghoneim MD, MD (Hons). Egypt Dr J.A. Hashmi DTM&H, FRCP. Pakistan Professor J. Jervell MD, PhD. Norway Professor G.J. Johnson MA, MD, BChir, FRCS (C), FRCOphth, DCEH. United Kingdom Dr M. Kassas. Emeritus Professor of Plant Ecology. Egypt Professor M.M. Legnain MBBS, MRCOG, FRCOG. Libyan Arab Jamahiriya Professor El-Sheikh Mahgoub DipBact, PhD, MD, FRCPath. Sudan Professor A.M.A. Mandil MSc (Paediatr), MPH, DrPH. Egypt Professor A.B. Miller MB, FRCP. Canada Professor S.S. Najjar MD. Lebanon Dr Abubaker A. Qirbi BSc, MD (Edin), FRCPC (Can), FRCP FRCPath (UK). Republic of Yemen Professor O.S.E. Rasslan MD, PhD. Egypt Professor W.A. Reinké MBA, PhD. United States of America Professor I.A. Sallam, MD, Dip High Surgery Cairo, Honorary FRCS, PhD (Glasgow), LRCP, MRCS, FRCS (London), ECFMG. Egypt Dr C.Th.S. Sibinga FRCP (Edin), FRCPath. The Netherlands Mr Taoufik Zeribi Eng BSc, MSc. Tunisia Editors Fiona Curlet, Eva Abdin, Alison Bichard, Guy Penet Graphics Suhaib Al Asbahi, Hany Mahrous, Diana Tawadros Administration Nadia Abu-Saleh, Yasmine El Sakhawy المجلة الصحية لشرق المتوسط المجلد السادس عشر العدد الثامن 118 رسالة من المحرر rotidE eht morf retteL لقد ازدادت الجهود الدولية مضاًء وعزمًا لمكافحة فيروس العوز المناعي البشري منذ الإعلان عن المرامي الإنمائية للألفية في عام 0002. وتؤدي منظمة الصحة العالمية دورها الريادي ضمن أسرة الأمم المتحدة باعتبارها السلطة التوجيهية والتنسيقية للصحة في العالم، وذلك بالعمل على تعزيز استجابة القطاع الصحي على الصعيد العالمي للإيدز وللعدوى بفيروسه، وبهذه الصفة، تعدُّ منظمة الصحة العالمية جزءًا من الجهود العالمية لكبح جماح وباء الإيدز والعدوى بفيروسه، وحسر موجات انتشاره. ويوضح الالتزام المتواصل الذي يبديه الشركاء على الصعيد العالمي؛ ومنهم منظمة الصحة العالمية وبرنامج الأمم المتحدة المشتـرك لمكافحة الإيدز وفيروسه، وقادة الدول الثمانية الكبرى، بالإتاحة الشاملة، مدى الحاجة لتسريع وتيرة النهوض بإعداد مضمومة شاملة تضم إجراءات الوقاية من العدوى بفيروس العوز المناعي البشري، ومعالجة مرضاه، وتقديم الرعاية لهم، وللتعزيز السريع لُنُظم الرعاية الصحية. إلا أن الجهود المبذولة للتصّدي للإيدز تضعف بسبب عدم معرفة معظم المعايشين لفيروس الإيدز بوضعهم الصحي. وتعزز برامج منظمة الصحة العالمية لمكافحة الإيدز والعدوى بفيروسه إدراج اختبارات كشف العدوى بفيروس الإيدز ضمن طيٍف واسٍع من الخدمات، من خلال العمل مع الشركاء لتوسيع نطاق الاختبارات، وتقديم المشورة، وذلك من خلال الحملات الإعلامية، والتنسيق، وتوطيد الشراكات، والتوجيه الذي يستند على المعايير والِقَيم، وتقديم الدعم التقني للبلدان. ويهدف البرنامج الإقليمي لشرق المتوسط لمكافحة الإيدز والعدوى بفيروسه ومكافحة العدوى المنقولة جنسيًا إلى تطوير القدرات على الصعيد الوطني في القطاع الصحي، وتعزيز جميع جوانب الوقاية، والمعالجة، والرعاية، والارتقاء بها. ويعمل هذا البرنامج بتعاون وثيق مع الحكومات الوطنية، والمعاهد الأكاديمية، والمجتمع المدني، والمنظمات الدولية الشريكة. وتعتمد كفاءة وفعالية الاستجابة للعدوى بفيروس العوز المناعي البشري على المدى الذي يتم ضمنه قياس التدخلات ذات الأولوية. ويغلب أن تنتشر الوصمة والتمييز المرتبطان بالعدوى بفيروس العوز المناعي البشري ضمن مواقع تقديم الخدمات الصحية، وهو أمر عرف على الدوام على أنه عقبة بالغة الجسامة، تقف في طريق تنفيذ التدخلات التي يقوم بها القطاع الصحي، والانتفاع بها؛ إذ تؤدي الوصمة إلى انخفاض مستوى الإقبال على خدمات الوقاية من العدوى بفيروس العوز المناعي البشري، وعلى الاستفادة من رعاية مرضاه ومعالجتهم. من الممكن التصّدي لكل من الوصمة ومن التمييز الناجم عن العدوى بفيروس العوز المناعي البشري من خلال إجراءات بسيطة وعملية تتخذ ضمن النظام الصحي، مثل تزويد الناس بالمعلومات الصحيحة التي تبدِّ د مخاوفهم، وتصحِّ ح ما لديهم من مفاهيم مغلوطة عن فيروس العوز المناعي البشري، وطرق سرايته. ومما يؤسف له أن هذين الأمرين لا يحظيان بما يستحقانه من استجابة كافية على الصعيد الوطني. فقد كان للقوانين والتشريعات والسياسات المتعلقة بفيروس العوز المناعي البشري أثرًا هامًا على حياة الناس المعايشين لهذا المرض، ويمكن للممارسات التمييزية أن تعّطل حياتهم، وأن تستبعدهم من الحياة، مما يزيد من عبء الوصمة التي تلحق المصابين بهذا الداء الوبيل. ni dehsilbatse erew slaoG tnempoleveD muinnelliM eht ecnis yllaitnatsbus desaercni sah VIH thgfi ot noitazilibom lanoitanretnI gnidael eht syalp )OHW( noitazinagrO htlaeH dlroW eht ,htlaeh lanoitanretni no ytirohtua gnitanidrooc dna gnitcerid eht sA .0002 pots ot troffe labolg a fo trap si OHW yticapac taht nI .SDIA/VIH ot esnopser rotces htlaeh labolg eht no ylimaf NU eht nihtiw elor ,OHW .e.i ,srentrap labolg eht fo tnemtimmoc eht fo noitamrffiaer gniunitnoC .SDIA/VIH fo daerps eht esrever dna fo ssergorp eht VIH fo egakcap evisneherpmoc a fo pu-elacs detarelecca na rof deen eht sthgilhgih ssecca lasrevinu ot ,sredael 8G dna SDIANU .smetsys erac-htlaeh fo gninehtgnerts dipar erom a rof dna ,erac dna tnemtaert ,noitneverp .sutats VIH rieht fo erawanu era VIH htiw gnivil esoht fo ytirojam eht taht tcaf eht yb denimrednu era noitautis eht sserdda ot stroffE ot srentrap htiw gnikrow yb secivres fo egnar daorb a otni gnitset VIH fo noitargetni eht setomorp emmargorP SDIA/VIH OHW eTh lacinhcet dna ecnadiug evitamron ,spihsrentrap fo tnemhsilbatse eht ,noitanidrooc ,ycacovda hguorht gnillesnuoc dna gnitset dnapxe SDIA/VIH( emmargorp snoitcefni dettimsnart yllauxes dna SDIA/VIH lanoigeR naenarretideM nretsaE eTh .seirtnuoc ot troppus .erac dna tnemtaert ,noitneverp fo stcepsa lla pu elacs dna nehtgnerts ot rotces htlaeh eht ni yticapac lanoitan poleved ot smia )ITS dna .snoitazinagro rentrap lanoitanretni dna yteicos livic ,snoitutitsni cimedaca ,stnemnrevog lanoitan htiw ylesolc skrow tI no tnegnitnoc osla si tI .snoitnevretni ytiroirp eht fo noitatnemelpmi fo elacs eht no sdneped esnopser VIH eht fo ssenevitceffe eTh ot tnemtimmoc ytinummoc fo level eht dna ,txetnoc laicos dna larutluc daorb eht ,noisivorp ecivres fo scitsiretcarahc dna ytilauq eht nihtiw tnelaverp nefto era noitanimircsid dna amgits detaler-VIH .noitanimircsid dna amgits retnuoc ot stroffe ni noitapicitrap dna .snoitnevretni rotces htlaeh fo ekatpu dna noisivorp ot selcatsbo lacitirc sa defiitnedi yltnetsisnoc neeb evah dna secivres htlaeh sa hcus ,metsys htlaeh a nihtiw serusaem lacitcarp dna elpmis hguorht delkcat eb nac VIH ot eud noitanimircsid dna amgits htoB .noissimsnart sti dna VIH tuoba snoitpecnocsim rieht slepsid dna sraef rieht syalla taht noitamrofni etarucca htiw elpoep gnidivorp VIH gnidrager seicilop dna selur ,swal s’yrtnuoc A .VIH ot sesnopser lanoitan ni desserdda yletauqeda modles era htob ,yletanutrofnU elpoep edulcxe dna tceffasid nac secitcarp yrotanimircsiD .esaesid eht htiw gnivil elpoep fo sevil eht no tceffe tnacfiingis a evah nac .esaesid eht gnidnuorrus amgits eht gnicrofnier ,VIH htiw gnivil EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 812 Characterization of Mycobacterium tuberculosis of Lebanese patients by double-repetitive-element polymerase chain reaction M. Hamze,1 A. Rahmo 2 and M. Saade3 ABSTRACT Molecular studies have been successfully applied in evaluating epidemiological linkages in tuberculosis. A total of 87 isolates of Mycobacterium tuberculosis were collected from patients in all regions of Lebanon and characterized in terms of drug sensitivity. Double-repetitive-element polymerase chain reaction was used to differentiate between strains. Various correlations related to age, sex, region, sensitivity and genotype were examined. Several genotypes were more common in certain age ranges. Male patients appeared more likely either to be infected by or to develop multi-drug resistant strains. There was also evidence for a distribution of genotype groups indicating some level of geographical isolation and hence separate evolution of M. tuberculosis strains. 1Faculty of Public Health, Lebanese University, Tripoli, Lebanon (Correspondence to M. Hamze: mhamze@ul.edu.lb). 2National Commission for Biotechnology, Damascus, Syria. 3National Tuberculosis Programme, Ministry of Public Health, Beirut, Lebanon. Received: 14/01/08; accepted: 29/06/08 ةجودزلما ةرركتلما صرانعلا يذ زارميلوبلل سلسلسلا لعافتلاب ينينانبللا ضىرلما ىدل ةيلسلا ةرطفتلما صئاصخ لىع ف ُّرعتلا ةداعس سويناطم ،وحمر رداقلا دبع ،ةزحم رذنم اهعجم ةيلسلا تارطفتملل ةدرفتسم 87 عمجب نوثحابلا ماق دقف .لسلا في ةيئابولا تاطباترلا مييقت في حاجنب ةيئيزلجا تاساردلا قبطت :ةـصلالخا لعافتلا نوثحابلا مدختسا دقو .ةيودلأل اهتيساسح ثيح نم ةيلسلا تارطفتلما تافص اوددحو ،ةينانبللا ميلاقلأا عيجم نم ضىرم نم نوثحابلا ،سنلجاو ،رمعلاب ةقلعتلما ةفلتخلما تاقلاعلا اوسردو ،ةيلسلا تارطفتلما يرارذ ينب قيرفتلل ةجودزلما ةرركتلما صرانعلا اذ زارميلوبلل ليسلسلا ًلايم رثكأ روكذلا ضىرلما نأو ،ةيرمعلا تلااجلما ضعب في ًاعويش رثكأ ةديدع ةينيج ًاطمانأ نأ نوثحابلا دجوو .ينيلجا طمنلاو ةيسالحاو ،ةقطنلماو ،فيارغلجا دارفتسلاا ىوتسم لىإ يرشي ةينيلجا طمانلأا تاعوممج عزوت نأ لىع تانيب كانه تناكو .ةددعتم ةيودلأ ةمواقم يرارذ ريوطتل وأ ىودعلل .ةيلسلا تارطفتلما يرارذل لقتسم روطت لىإ لياتلابو Caractérisation de Mycobacterium tuberculosis chez des patients libanais par PCR d’éléments répétitifs doubles RÉSUMÉ Des études moléculaires ont été utilisées avec succès pour évaluer les liens épidémiologiques de la tuberculose. Au total, 87 isolats de Mycobacterium tuberculosis issus de patients de toutes les régions du Liban ont été recueillis et caractérisés en termes de sensibilité aux médicaments. Une PCR d’éléments répétitifs doubles (DRE-PCR) a été utilisée afin de différencier les souches. Différentes corrélations relatives à l’âge, au sexe, à la région, à la sensibilité et au génotype ont été étudiées. Certains génotypes étaient plus fréquents dans certaines tranches d’âge. Il est apparu que les patients de sexe masculin présentaient un risque plus important de développer des souches polypharmacorésistantes ou d’être infectés par de telles souches. Des preuves de distribution des groupes de génotypes, indiquant un certain degré d’isolement géographique et donc une évolution différente des souches de M. tuberculosis, ont également été observées. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 813 Introduction The spread of extensively drug-resistant tuberculosis (TB) poses a serious threat that could reverse recent achievements in TB control [1]. In particular, treat- ment of patients with multidrug resist- ant (MDR) strains is long and costly, and requires the use of drugs which fre- quently cause severe adverse reactions. The treatment outcome is poor, with low cure rates and high fatality ratios [2]. MDR TB cases may remain infec- tious in the community for a prolonged period of time. The emergence of so- called TB “hot-spots” around the world highlights the need for more research and application of current knowledge. Molecular epidemiological studies have been successfully applied in evaluat- ing epidemiological linkages in TB, and the discovery of unexpected ones. They were essential in distinguishing relapse from reinfection in recurrences of TB [3] in establishing evidence of laboratory cross-contaminations (false positives) [4] and in documenting the associa- tion of particular genotypes with hyper- virulence and multi-resistance [5]. The importance of large-scale genotyping of Mycobacterium tuberculosis has prompted countries such as the United States of America to implement large-scale rapid genotyping of all local cases [6]. Various methods have been used for the genotyping of M. tuberculosis TB. The double-repetitive-element polymerase chain reaction (DRE-PCR) method is relatively fast, simple and cost-effective [7,8]. The technique serves as a tailored approach for preliminary genotyping and has the potential for efficient imple- mentation in low-resource countries, where TB is generally widespread and endemic. In this study we isolated various strains of MTB from Lebanese patients in various regions of the country, fol- lowed by characterization of their sensi- tivity to antibiotics and genotyping via a slightly modified DRE-PCR method. Methods Sample Following an agreement with the National Tuberculosis Programme of the Lebanese Ministry of Health, spu- tum samples from newly-detected cases of pulmonary TB (84 samples) and from patients with a past history of the disease who were still under treatment (3 samples) were collected between April 2004 and October 2005 from all Lebanese provinces (muhafazat). Samples were sent refrigerated to the laboratory of the hospital at the Middle East Health Centre in Bsalim/Metin in Lebanon, accompanied by all related in- formation. No information on the HIV status of the patients was obtained. Specimen preparation and culture Specimens were decontaminated by the 2% N-acetyl-L-cysteine NaOH method. After neutralization and cen- trifugation, 0.2 mL of the concentrated specimen was inoculated onto a slant of Lowenstein–Jensen medium (Bec- ton Dickinson Microbiology Systems, Cockeysville, Maryland); 0.5 mL was also inoculated into modified Middle- brook 7H9 broth (BD BBL MGIT, Becton-Dickinson) supplemented with PANTA antibiotic mixture (BBL MGIT PANTA, Becton-Dickinson) and OADC enrichment. The 2 media were incubated at 35–37 °C and the Lowenstein–Jensen slant was exam- ined for growth twice weekly. The BD BBL MGIT tube was read daily with UV light using a positive and a negative control. A positive tube was subcultured and an acid-fast smear prepared. Susceptibility testing Antibiotic susceptibility testing was performed using the BBL mycobacteria growth indicator tube (MGIT) AST system (Becton-Dickinson) based on comparing growth of the Mycobac terium strains in a drug-containing tube with that of a drug-free tube. The day after a positive MGIT tube became positive, final concentrations of antibiotics were added to MGIT tube: streptomycin (STR) (0.8 µg/mL),. isoniazid (INH) (0.1 µg/mL), rifampicin (RIF) (1 μg/ mL and ethambutol (EMB) (3.5 μg/ mL). A control tube was set up for each antibiogram. A control strain of M. tuberculosis (H37 Rv, ACTCC 27294) susceptible to all standard anti- TB drugs was included. The tubes were read with a 365 nm UV transilluminator on the third incubation day [9]. The patterns of antibiotic sensitivity (S) and resistance (R) are described in the text using the notation RRSR, RRRS etc., with the following sequence: rifampin (RIF)–isoniazid (INH)–ethambutol (EMB)–streptomycin (STR). Identification Identity of strains was based on the following biochemical characteristics: production of niacin, nitrate reductase and catalase at laboratory tempera- ture; production of catalase at 68 °C; hydrolysis of Tween 80 in 10 days, urease in 18 hours and arylsulfatase in 3 days [10]. DRE-PCR procedure For DNA extraction, a loopful of each culture was suspended in ATL buffer (0.2 mL) and DNA was extracted using QIAamp DNA blood mini-kit (Qia- gen). The manufacturer’s procedure was adhered to except for the incuba- tion period, which was extended to 3 hours. DNA was eluted in 100 μL PCR water (Gibco). The DRE-PCR proce- dure was followed as reported by Harris [11], a modification of Friedman et al. [12]. The PCR amplification mixture contained 67 mM tris (pH 8.8) 16 mM (NH 4 ) 2 SO 4 , 0.01% tween 20 (1 × reac- tion buffer; Euroclone), 2.5 mM MgCl 2 (Euroclone), 200 μM each deoxynucle- oside triphosphate (MBI Fermentas), 0.5 μM of each of the 4 primers (MWG Biotech, HPSF grade), and 2.5 U of taq polymerase (Euroclone). The sequence of the primers is described in elsewhere EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 814 [11,12]. Then 5 μL of DNA solution was used in the final reaction volume of 50 μL. Amplification was done according to Harris [11], using the Mastercycler thermal cycler (Eppendorf). The ampli- fication products were analysed using parametric analysis of gene set enrich- ment (PAGE), at 10% concentration, stained with ethidium bromide, and visualized under UV light (312 nm). The modifications introduced were: the use of a DNA extraction kit, the inclusion of ammonium sulfate in the reaction mixture and the use of PAGE for band pattern analysis. Statistical analysis SPSS, version 12 was used for analysis. A confidence interval of 95% (2-tailed) was applied. Results The 87 isolates were collected from 62 males, mean age 44 years (range 10–77 years), and 25 females, mean age 30 years (range 16–54 years). Most of the isolates came from patients resident in Mount Lebanon region (33%) followed by Beirut (23%), Tripoli (including Doumia) (20%), Akkar (10%), the South (9%) and Beqaa (5% each). All isolates came from new cases of TB, except for 3 that were from previously treated cases. The isolates included 21 resistant isolates (24.1%) (18 primary-resistant): 4 (4.6%) single-resistant (1R); 11 (12.6%) double-resistant (2R), 4 (4.6%) triple-resistant (3R); and 2 (2.3%) quadruple-resistant (4R) (Table 1). A total of 8 (9.2%) isolates were MDR; 3 of the MDR cases were the previously treated patients (3.5%). The resistance pattern was: RIF 42,9%, INH 81.0%, EMB 19.1%, STR 76.2%. The 87 isolates resulted in 17 differ- ent DRE-PCR patterns, while 12 isolates produced no detectable genotypes and were designated genotype Gx (Table 2). The diversity ratio (i.e. number of genotypes/number of isolates, exclud- ing isolates with no genotype pattern detected) was therefore 0.23 (17/75) (Table 1). A total of 9 clusters were observed, which included 67 isolates; 8 isolates had unique genotypes. The number of different bands was 14 and ranged from 1–3 for each genotype. The genotypes were assigned to 3 groups depending on the total number of bands (I–III). With 1 exception, all genotypes contained a 350 bp band and, with 1 exception, all in genotype group III con- tained the same 2 bands (350 bp, 450 bp) (Table 2). The largest cluster was genotype G3, containing the single band 350 bp, followed by cluster genotypes G9 and G12; together these represented 62% of the isolates (Table 2). The profile of the 3 previously treat- ed cases of TB were as follows: 1 male aged 41 years from Beqaa (genotype Gx, resistance pattern RRSS); 1 male aged 65 years from Beirut (genotype Gx, resistance pattern RRRR); 1 female aged 54 years from Beirut (genotype G1, resistance pattern RRSS). Correlations Various correlations between geno- type, sex, age, resistance and region of collected isolates from the Lebanese population were investigated. Correlations related mainly to sex The general M:F ratio was 2.5 (62/25) considering all isolates. For the Beirut region, it was 4.0 (16/4), while the ratio for the regions outside Beirut taken together was 2.2 (46/21) (OR = 1.83, Table 1 Distribution of Mycobacterium tuberculosis isolates from different regions of Lebanon Variable Total Region Beirut Beqaa South Mount Lebanon Tripoli Akkar Total no. of isolates 87 20 4 8 29 17 9 No. of isolates in cluster genotypesa 67 12 3 8 23 13 8 No. of genotypes represented 17 9 1 2 10 6 3 No. of resistant isolates All 19 + 2Gx 2 + 1Gx 1Gx – 9 5 3 1R 4 – – – 1 3 – 2R 11 1 1 – 4 2 3 3R 4 1 – – 3 – – 4R 2 1 – – 1 – – MDR 6 + 2Gx 2 + 1Gx 1Gx – 4 – – Diversity ratiob 0.23 0.56 0.33 0.25 0.40 0.40 0.38 Gx = no genotype pattern found; – = no isolates. MDR = multidrug resistant. 1R = single-resistant; 2R = double-resistant, 3R = triple-resistant; 4R = quadruple-resistant. aExcluding unknown genotypes, Gx; bDiversity ratio = no. of genotypes/no. of isolates (excluding Gx isolates). طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 815 Ta bl e 2 Se x di st ri bu ti on o f M yc ob ac te ri um tu be rc ul os is is ol at es fr om d iff er en t r eg io ns o f L eb an on a nd b y ge no ty pe G en ot yp e gr ou p/ ba nd s (b p) G en ot yp e To ta l n o. o f is ol at es Re gi on Be ir ut Be qa a So ut h M ou nt L eb an on Tr ip ol i A kk ar A ll M F A ll M F A ll M F A ll M F A ll M F A ll M F G ro up I 35 0 G 3 41 8 7 1 3 3 – 6 2 4 10 6 4 9 5 4 5 2 3 G ro up II 10 0 , 3 0 0 G 1 1 1 – 1 – – – – – – – – – – – – – – – 10 0 , 3 50 G 2 1 – – – – – – – – – – – – 1 – 1 – – – 15 0 , 3 50 G 4 2 1 1 – – – – – – – – – – 1 1 – – – – 20 0 , 3 50 G 5 2 – – – – – – – – – 2 2 – – – – – – – 25 0 , 3 50 G 6 3 – – – – – – – – – 2 2 – – – – 1 1 – 30 0 , 3 50 G 7 2 – – – – – – – – – 1 – 1 1 1 – – – – 35 0 , 4 0 0 G 8 2 1 1 – – – – – – – 1 1 – – – – – – – 35 0 , 4 50 G 9 8 1 – 1 – – – 2 1 1 5 5 – – – – – – – 35 0 , 5 0 0 G 10 1 1 1 – – – – – – – – – – – – – – – – G ro up II I 11 0 , 3 50 , 4 50 G 11 1 – – – – – – – – – 1 1 – – – – – – – 15 0 , 3 50 , 4 50 G 12 5 – – – – – – – – – 1 – 1 2 2 – 2 2 – 27 5, 3 50 , 4 50 G 13 1 1 1 – – – – – – – – – – – – – – – – 27 5, 3 50 , 6 0 0 G 14 1 – – – – – – – – – 1 1 – – – – – – – 35 0 , 4 50 , 6 50 G 15 2 1 1 – – – – – – – 1 1 – – – – – – – 35 0 , 4 50 , 8 0 0 G 16 1 1 1 – – – – – – – – – – – – – – – – 35 0 , 4 50 , 6 0 0 G 17 1 – – – – – – – – – – – – 1 1 – – – – N o ge no ty pe pa tte rn fo un d G x 12 4 3 1 1 1 – – – – 4 3 1 2 1 1 1 1 – To ta l 87 20 16 4 4 4 – 8 3 5 29 22 7 17 11 6 9 6 3 M = n o. o f i so la te s f ro m m al es ; F = n o. o f i so la te s f ro m fe m al es ; G = g en ot yp e (b ol d = cl us te r g en ot yp es ); G x = no g en ot yp e pa tte rn fo un d. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 816 age, which was especially obvious for re- sistance to RIF (Table 4). We observed a greater tendency for the genotype group III to affect older people: 6/12 isolates were from patients in the age range 50–79 years (OR = 3.5, 95% CI: 0.98–12.45, P = 0.055). All cases of MDR, defined as resistance to at least INH and RIF, were concentrated within patients aged 40–69 years, which was true for all genetic groups. Furthermore 75% (6/8) of MDR cases came from the age range 50–69 years (Table 4), even though only 19% of total isolates were from this age range. Correlations related mainly to geno- type and resistance The percentage of resistant isolates to total isolates was 24% (21/87): 25% (17/67) among clustered genotypes and 25% (2/8) for the unique geno- types (Table 4). Nonresistant isolates had a diversity ratio of 0.20 (13/66), while resistant ones had a value of 0.38 (8/21). The diversity ratio for resistant isolates belonging to cluster genotypes (shown in bold font on Table 2) was 0.35 (6/17) and for MDR isolates was 0.83 (5/6). There were 4 genotypes (G1, G5, G15, G17) that appeared exclusively in resistant isolates (OR = 29, 95% CI: 3.24–251.1, P = 0.003), 9 genotypes (G2, G7, G8, G10, G11, G12, G13, G14, G16) appeared exclusively in nonresistant isolates and 4 genotypes (G3, G4, G6, G9) were shared. Some genotypes exhibited no resist- ance to any drugs (e.g. none of the 5 isolates of G12), whereas for genotypes G15 and G5 drug resistance was demon- strated for all the collected isolates. The 2 isolates belonging to genotype G15 demonstrated MDR, while 12 other genotypes, representing 26 isolates, did not include any MDR cases (OR = 34, 95% CI: 3.22–338.8, P = 0.004). These 2 isolates also showed identical resist- ance patterns (Table 4). The percentage of resistant isolates was 20% (8/41) for the genotype group I, and 36% (8/22) and 25% (3/12) respectively for the genotype groups II and III (Table 2). For STR resistance the proportion of resistant isolates de- creased with increasing genotype group number (I > II > III) whereas the op- posite pattern was observed for RIF and INH resistance (I < II < III) (Table 5). Most genotyped MDR cases (5 out of 6) belonged to genotype groups II and III, even though these represented only 45% (34/75) of all typed isolates (OR = 6.9, 95% CI: 0.77–62.2, P = 0.085) (Table 3). Correlations related mainly to region The ratio of resistant to total isolates in Beirut was 0.15 (3/20), while for outside Beirut it was 0.27 (18/67) (OR = 0.48, 95% CI: 0.126–1.82, P = 0.085) (Table 1). Only a few cases of ENB resistance (16% of resistant isolates) were observed (Table 5); and these 95% CI: 0.54–6.14, P = 0.33) (Table 2). The M:F ratio of cluster isolates was 2.4 (47/20), while the ratio for unique genotypes was 3.0 (6/2). The M:F ratio for resistant isolates was 2.5 (15/6); however the specific genotype G3 had 5 resistant isolates from females out of the total of 8 resistant isolates (Table 4). All MDR cases, except for 1, were males, resulting in a M:F ratio of 7.0 (7/1) (OR = 3.1, 95% CI: 1.27–7.39, P = 0.3) (Table 3). The isolates of patients aged 20–49 years produced a M:F ratio of 1.9 (37/20), whereas the ratio for the rest of the age groups was 5.0 (25/5). The M:F ratio was 11.6 (25/16) for genotype group I (single band pat- tern) (OR = 0.33, 95% CI: 0.11–0.97, P = 0.029), 3.4 (17/5) for genotype group II (2-band pattern) and 11.0 (11/1) for genotype group III (3-band pattern) (OR = 5.5, 95% CI: 0.67–45.6, P = 0.11). Correlations related mainly to age A majority of isolates came from pa- tients in the age range 20–49 years. This was mainly true in all regions, with female patients among the collected cases rarely affected after the age of 50 years. The diversity ratio of genotypes within the age range 20–49 years was 0.22 (12/54), excluding unknown genotypes, less than the diversity for the remaining age groups, 0.33 (9/27). There was an apparent increase in the likelihood of resistance proportional to Table 3 Distribution of Mycobacterium tuberculosis isolates (excluding cases where no genotype pattern was found) by patient’s sex and multi-drug resistance for the various designated genotype groups by region of Lebanon Region Total no. of isolates Genotype group I II III All M F MDR All M F MDR All M F MDR Beirut 16 8 7 1 0 5 3 2 1 3 3 0 1 South 8 6 2 4 0 2 1 1 0 0 0 0 0 Beqaa 3 3 3 0 0 0 0 0 0 0 0 0 M. Lebanon 25 10 6 4 1 11 10 1 2 4 3 1 1 Tripoli 15 9 5 4 0 3 2 1 0 3 3 0 0 Akkar 8 5 2 3 0 1 1 0 0 2 2 0 0 Total 75 41 25 16 1 22 17 5 3 12 11 1 2 All = total no. of isolates in genotype group; MDR = no. of multi-drug resistant isolates; M = no. of isolates from males; F = no. of isolates from females. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 817 were restricted to cases from the Mount Lebanon and Tripoli area. Most forms of resistance to drugs involved INH and STR (each covered 79% of resistant genotyped isolates) (Table 4). Of the total of 21 resistant isolates, 17 resist- ance patterns were observed more than once and 9 of these 17 isolates also came from the same regions. However, only 2 of the 9 isolates resulted in the same genotypes (2 were genotype G3, both showing resistance pattern SRSR). We found 4 isolates of identical genotype and resistance pattern (genotype G3, resistance pattern SRSR) that were dis- tributed in 3 regions (Mount Lebanon, Tripoli and Akkar) (Table 4). The vari- ous regions demonstrated similar levels of genotype diversity. The diversity ratio of genotypes for Beirut was 0.56 (9/16) and for outside Beirut was 0.22 (13/59) (Table 1). Mount Lebanon alone included 34% (23/67) of all cluster isolates (Table 2). All the 9 cluster genotypes, except G4, included isolates of patients from Mount Lebanon, while the re- maining 8 unique genotypes included only 2 from the Mount Lebanon area. The cluster genotypes could be divided into 2 categories: clusters in which several isolates belonged to the same region (G3, G6, G9, G12) and clusters that had single isolates belonging to different regions (G4, G7, G8, G15). In the second category all cases involved 1 isolate from Beirut or Mount Lebanon and Tripoli (Table 4); this category also demonstrated a deviation for the Table 4 Distribution of various antibiotic resistance patterns of resistant isolates, including sex of patient and genotype, in different regions of Lebanon by patients’ age group Age group (years) Region Beirut Beqaa Mount Lebanon Tripoli Akkar Pattern Gen.; Sex Pattern Gen.; Sex Pattern Gen.; Sex Pattern Gen.; Sex Pattern Gen.; Sex 10–19 – – – – – – SSRS G3; F – – 20–29 – – – – – – SSSR G3; F SRSR G3; F – – – – – – – – SRSR G3; F – – – – – – – – SRSR G6; M 30–39 – – – – SRSR G3; M – – – – – – – – RSSR G3; M – – – – – – – – SRSR G5; M – – – – – – – – SSSR G9; M – – – – 40–49 – – RRSS Gx; M RRRR G5; M SRSR G3; F – – – – – – SRRR G9; M SRSR G4; M – – – – – – – – SRSS G17; M – – 50–59 RRSS G1; F – – RRSR G3; M – – – – RRSR G15; M – – – – – – – – 60–69 RRRR Gx; M – – RRSS G6; M – – – – – – – – RRSR G15; M – – – – 70–79 – – – – – – – – – – Antibiotic resistance pattern sequence: rifampin (RIF)–isoniazid (INH)– ethambutol (EMB)–streptomycin (STR). R = resistant; S = sensitive. Gen. = genotype; Gx = no genotype pattern found; M = isolates from males; F = isolatea from females; – = no isolates. Table 5 Number of resistant isolates and single resistance contribution associated with the genotype groups Genotype group No. of resistant isolates No. of resistances in each isolate Antibiotic resistances RIF INH EMB STR M F 1R 2R 3R 4R No. % No. % No. % No. % I 3 5 2 5 1 – 2 25 5 63 1 13 7 88 II 7 1 1 5 1 1 3 38 7 88 2 25 6 75 III 3 0 1 – 2 – 2 67 3 100 0 0 2 67 Total 13 6 4 10 4 1 7 37 15 79 3 16 15 79 RIF = rifampin, INH = isoniazid, EMB = ethambutol, STR = streptomycin. M = isolates from males; F = isolates from females. 1R = single-resistant; 2R = double-resistant, 3R = triple-resistant; 4R = quadruple-resistant. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 818 M:F ratio (ratio 7, OR = 3.1, 95% CI: 0.36–26.3, P = 0.31). Discussion The well-documented gender dis- parity for reported TB has been attrib- uted to socioeconomic and cultural barriers in access to health care [13] as well as biological and epidemiological characteristics [14,15]. In this study the higher ratio of males to females that we detected shifted even more towards males when only MDR cases were considered (7:1). Male patients ap- peared more likely either to be infected by MDR strains or to develop MDR. The apparent targeting of males was also confirmed by the very high ratio of males to females (10:1) in isolates belonging to genotypes that were only observed within the age range 20–49 years. The sex ratio for cases from Beirut differed from those from outside Beirut. This, however, is consistent with the prevalence of genotype group I, which had a lower male to female ratio outside Beirut. In general the sex ratio—which may demonstrate a host-sex preference of M. tuberculosis TB—was an average of dissimilar ratios that depended heav- ily on the genotype of the M. tuberculosis TB strains. This was clearly shown when these ratios were calculated individually for each separate genotype group. The clear variation in host-sex preference according to genotype strain holds the potential for determining the genetic factors within M. tuberculosis TB that may underlie this phenomenon. Between July 2002 and April 2004 Araj et al. studied the sensitivity of iso- lates from Lebanon and found 23.8% resistant isolates, almost identical to the 24.1% obtained in the current study [15,16]. The regional distribution of drug resistance varies most clearly with regard to MDR strains, which were con- centrated in the Mount Lebanon area and neighbouring Beirut. The latter was not the case considering resistant strains in general. Again, MDR strains did not behave like the bulk of resist- ant strains. Some forms of resistance were more common than others. The resistance pattern was domi- nated by INH and STR resistance, while few isolates showed resistance to ENB. The 4 isolates with identical resistance and genotype patterns are likely candidates for transmission of resistant strains of M. tuberculosis. It was noted that all these strains shared a common resistance to INH and STR. Considering that the underly- ing genetics of resistance are impor- tant for transmission dynamics [17]; this might affect the distribution of resistance patterns in cluster isolates. In the present study in Lebanon, most TB patients were young adults; 72% were below the age of 50 years and 7% were aged 20 years or less. It appears that several genotypes may be restricted to, or favour, certain age ranges. Some genotypes appeared only in the age range where most cases of TB were obtained, while others were seen only at age ranges where there were fewer isolates. The genotypes belonging to genotype group III showed a tendency to affect older people, a finding which, if con- firmed, could indicate the presence of genetic factors within the strains that are associated with age suscepti- bility of the host [18]. The increased occurrence of specific resistance depending on age was consistent with the elderly patients being most affected by MDR strains. An explana- tion for that shift might be that the elderly are generally too weak to fight successfully against the less fit resist- ant MTB strains [19]. Genotype groups appeared to be slightly selective regarding the pat- tern of drug resistance. The increase in the relative occurrence of RIF and INH resistance from genotype group I through to genotype group III is also consistent with the finding that most cases of MDR belonged to genotype groups II and III. The underly- ing genetic cause of these groupings and the shifts towards specific genotype groups (equivalent to a higher number of bands) could be a consequence of the possible increase in the numbers of the mobile genetic element IS6110; such an increase has been implicated or suspected in genotypic instability that could be associated with drug resistance and adaptation [20]. The higher diversity ratio of resistant isolates 0.42 (8/19) compared with nonresistant ones 0.23 (13/56) and the high ratio seen for MDR isolates 0.83(5/6) could be explained by the proposed lower level of relative fitness of many resistant isolates [17]. Cluster formation of genotypes was seemingly not related to the presence or absence of resistance. However, at the level of individual genotypes, some seemed to be more prone to resistance acquisition, persistence or spread than others. Lebanon is considered an endemic country for TB, with a general incidence estimate for 2005 of 11 per 100 000 for all cases. However, the geographic dis- tribution of the disease varies depend- ing on the region. Studies presented by the Ministry of Health indicate the highest ratio of cases is in the regions of Beirut and the North (Tripoli and Akkar regions) [21]. The observed similarities in the pat- terns suggested a close relationship between most strains. However, the cur- rent study demonstrated that various genotypes tended to be more common in specific regions than others. This se- lective distribution of genotype groups indicates some level of geographic isola- tion and hence separate evolution. It justifies also the initial assignment of the genotypes to major groups depending on the general band pattern. Earlier concerns about a large TB reservoir existing in the larger area of Beirut (which would include many former inhabitants of Mount Leba- non) [21] appear to be validated by طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 819 the presence of isolates from this area in all genotypes forming clusters, sug- gesting an important role for the active spread of TB in Lebanon. The increased relative diversity of genotypes present in the region of Beirut compared with all regions outside Beirut as a whole seems to confirm the epidemic importance of this region, and its role as a major source for the spread of MTB strains. Conclusions The presented study demonstrates the importance of genotype charac- terization of MTB isolates incorporated within the essential framework of an adapted DOTS programme. Low- resource countries can still benefit from a plethora of available molecular tech- niques and adopt a programme that is relatively simple to implement and modest in its required resources. The widespread international incorporation of molecular strain differentiation into TB control programmes, associated with accurate epidemiological tracing, will provide a growing body of clini- cally applicable evidence. It may also shift the balance of control and cure in the battle against the growing threat of virulent MDR strains. Acknowledgements We were able to achieve this project owing to the financial support of the Lebanese University, the Syrian Minis- try of Higher Education, represented by the Syrian High Council of Science, the Syrian National Commission of Bio- technology, and Al-Azm wa Al-Saadeh Society in Tripoli. We would like to express our appreciation to Professor Fawaz Al Azmeh, head of the NCBT, for his cooperation. We also thank Miss Sandy Nasr, Miss Zeina Merhi, Mrs Rana Nader, Mrs Mayssoun Elwi, Mrs. Nibal Qirahkahya, Miss Buthainah Al- Salamah for their efforts. Zigol M et al. Global incidence of multidrug-resistant tubercu-1. losis. Journal of Infectious Diseases, 2006, 194:479–485. Senol G, Komurcuoglu B, Komurcuoglu A. Drug resistance of 2. Mycobacterium tuberculosis in Western Turkey: a retrospective study from 1100-bed teaching hospital. Journal of Infection, 2005, 50(4):306–311. Verver S et al. Rate of reinfection tuberculosis after success-3. ful treatment is higher than rate of new tuberculosis. Ameri- can Journal of Respiratory and Critical Care Medicine, 2005, 171:1430–1435. Martínez M et al. Impact of laboratory cross-contamination 4. on molecular epidemiology studies of tuberculosis. Journal of Clinical Microbiology, 2006, 44(8):2967–2969. European Concerted Action on New Generation Genetic 5. Markers and Techniques for the Epidemiology and Control of Tuberculosis. 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International Journal of Tuberculosis and Lung Disease, 1999, 3(9):774–777. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 820 Characterization of Mycobacterium tuberculosis in Syrian patients by double-repetitive-element polymerase chain reaction A. Rahmo1 and M. Hamze 2 ABSTRACT The role of previous treatment in the dynamics of tuberculosis transmission has not been adequately investigated. Mycobacterium tuberculosis isolates from previously treated patients (n = 88) from all regions of Syrian Arab Republic were characterized in terms of antibiotic sensitivity and genotyping using double-repetitive- element polymerase chain reaction (DRE-PCR) method for the proximity of the repetitive DNA elements IS6110 (a mobile genetic element) and PGRS. The 88 isolates resulted in 59 different DRE-PCR patterns. Correlations related to age, sex, region, sensitivity and genotype were examined. All regions of the country showed high levels of genotype diversity, suggesting a low level of transmission of M. tuberculosis strains in previously treated patients. 1National Commission for Biotechnology, Damascus, Syrian Arab Republic. 2Faculty of Public Health, Lebanese University, Tripoli, Lebanon (Correspondence to M. Hamze: mhamze@ul.edu.lb). Received: 14/01/08; accepted: 29/06/08 ةجودزلما صرانعلل زايرميلوبلل ليسلسلا لعافتلا للاخ نم ينيروسلا ضىرلما ينب ةيلسلا تارطفتلما صئاصخ لىع فرعتلا ةرركتلما ةداعس سويناطم ،وحمر رداقلا دبع ،ةزحم رذنم تارطفتلما تادرفتسم صئاصخ لىع نوثحابلا فرعت دقو .لبق نم ةيفاك ةساردل لسلا ةياسر تايكيمانيد في ةقبسلما ةلجاعلما رود عضيخ لم :ةـصلالخا اهتيساسح ثيح نم كلذو ،ةيروسلا ةيبرعلا ةيروهملجا في قطانلما عيجم لىإ نومتني ،)88 مهددعو( ،اولجوع نأ قبس ضىرم نم ْتَعِ ُمجم يتلا ةيلسلا برق ىدم لىع فرعتلل ،ةرركتلما ةجودزلما صرانعلل زايرميلوبلل ليسلسلا لعافتلا ةقيرط مادختساب ،ةينيلجا اهطمانأ ثيح نمو ،ةيويلحا تاداضملل ًةدرفتسم 88 اهددع غلبي يتلا تادرفتسلما تجتنأ دقو .PGRSو ،)كرحتم ينيج صرنع يهو( IS6110 يه صرانعلا هذهو اندلا لىع ةرركتلما صرانعلا ةنايدلاو رمعلاو سنلجاب ةقلعتلما طباورلا نوثحابلا سرد دقو .ةرركتلما ةجودزلما صرانعلل زايرميلوبلل ةيلسلسلا تلاعافتلا نم ًافلتمخ ًاطمن 59 ةياسر نم ضفخنم ىوتسم لىإ يرشي امم ،ةينيلجا طمانلأا في عونتلا نم ةعفترم تايوتسم ةيروس ءاجرأ عيجم ترهظأ دقو .ينيلجا طمنلاو سسحتلاو .ًاقباس اولجوع نيذلا ضىرلما ىدل ةيلسلا تارطفتلما يرارذ Caractérisation de Mycobacterium tuberculosis par PCR d’éléments répétitifs doubles chez des patients syriens RÉSUMÉ Le rôle des traitements antérieurs dans la dynamique de la transmission de la tuberculose n’a pas été étudié de manière adéquate. Les isolats de Mycobacterium tuberculosis issus de patients précédemment traités (n = 88) provenant de toutes les régions de la République arabe syrienne ont été caractérisés en termes de sensibilité aux antibiotiques et en fonction de leur génotype au moyen de la méthode de PCR d’éléments répétitifs doubles (DRE-PCR) pour la proximité des éléments d’ADN IS6110 répétés (élément génétique mobile) et des séquences répétées PGRS (Polymorphic GC-rich repetitive sequence). Les 88 isolats ont fait apparaître 59 profils DRE-PCR différents. Les corrélations avec l’âge, le sexe, la région, la sensibilité et le génotype ont été étudiées. Une forte diversité des génotypes a été constatée pour toutes les régions du pays, ce qui suggère un faible niveau de transmission des souches de M. tuberculosis chez les patients précédemment traités. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 821 Introduction Patients with a previous history of tuberculosis (TB) treatment have been shown worldwide to have the highest risk of harbouring multidrug- resistant (MDR) and even extensively drug-resistant strains of Mycobacterium tuberculosis. There is some evidence that positive selection of strains occurs within patients [1]. However, the role of previous treatment in the dynamics of M. tuberculosis TB transmission and the multitude of factors underlying treat- ment failure have not been adequately investigated [2]. Molecular studies have been suc- cessfully applied in evaluating epide- miological linkages and in the discovery of unexpected ones. These have been essential for distinguishing relapse from reinfection in recurrences of TB [3] and for establishing evidence of laboratory cross-contaminations (false positives) [4] and the association of particular genotypes with hypervirulence and multi-resistance [5]. Different methods have been used for the genotyping of M. tuberculosis TB. These vary in the time required for testing and their resolution, specificity, typeability, reproducibility, robustness, complexity, cost and amenability to databank construction. The double- repetitive-element polymerase chain reaction (DRE-PCR) genotyping method addresses variations in the proximity presence and the interspace distance separating 2 exceptionally important repetitive DNA elements: insertion sequence (IS) 6110 and poly- morphic GC rich repeat (PGRS). The method is relatively fast, simple and cost-effective [6]. It suffers, however, from a lack of reproducibility due to the occasional absence of low-intensity bands and from only an average level of resolution [7]. At minimum, the technique serves as a tailored approach for preliminary genotyping and has the potential for efficient implementation in a low-resource country, where TB is generally widespread and endemic. The presented study in the Syrian Arab Republic was based on isolating various strains of M. tuberculosis TB from previously treated patients from various regions of the country, followed by char- acterizing their sensitivity to antibiotics and their genotyping through a slightly modified DRE-PCR method. The phe- notypic correlation with the genotypes of various strains, based on adjacency of the 2 repetitive elements IS6110 and PGRS, was examined. Methods Sample Following an agreement with the Syr- ian Ministry of Health, we were able to obtain samples from 88 patients previously treated for pulmonary TB, which included cases of failure after first treatment and of relapse or reinfection. The 88 samples, provided by the Min- istry’s central laboratory, were collected between July 2003 and October 2005 from all Syrian provinces (muhafazat). Samples were shipped, accompanied by the related information, to the biomedical laboratory of the National Commission for Biotechnology in the Syrian Arab Republic. The research was approved by the responsible ethical committee at the Ministry of Higher Education. Specimen preparation and culture Processing of sputum specimens was based on liquefaction and decontamina- tion by 2% N-acetyl-L-cysteine-NaOH. Bacterial culture was performed on solid Lowenstein–Jensen medium [8]. Susceptibility testing Antibiotic susceptibility testing was done using the proportion method of the National Committee for Clinical Laboratory Standards [9] on inoculum preparations of freshly grown colonies from Lowenstein–Jensen medium after transfer and resuspension using beads. The patterns of antibiotic sensitivity (S) and resistance (R) are described in the text using the notation RRSR, RRRS etc., with the following sequence: rifampicin (RIF)–isoniazide (INH)– streptomycin (STR)–ethambutol (EMB). DRE-PCR procedure For DNA extraction, a loopful of each culture was extracted using the QIAamp DNA blood mini kit (Qiagene). The manufacturer’s instructions were adhered to except for the incubation period, which was extended to 3 hours. The DRE-PCR procedure was followed as reported by Harris [10], a modifica- tion of Friedman et al. [11]. The PCR amplification mixture contained 67 mM tris (pH 8.8), 16 mM (NH 4 ) 2 SO 4 , 0.01% tween-20 (1 × reaction buffer; Euroclone), 2.5 mM MgCl 2 (Euro- clone), 200 μM each deoxynucleoside triphosphate (MBI Fermentas), 0.5 μM of each of the 4 primers (MWG Biotech, HPSF grade), and 2.5 U of taq polymer- ase (Euroclone). The sequence of the primers is described elsewhere [10,11]. Amplification was done according to Harris [10], using the Mastercycler thermal cycler (Eppendorf). The ampli- fication products were analysed using parametric analysis of gene set enrich- ment (PAGE), stained with ethidium bromide. The modifications introduced were: the use of a DNA extraction kit, the inclusion of ammonium sulfate in the PCR reaction mixture and the use of PAGE for band pattern analysis. Statistical analysis SPSS, version 12.0 was used. A confi- dence interval of 95% (2-tailed) was applied. Cross-tables that did not fulfil Cochrane rules were tested for significance using the Fisher exact test (2-sided). Unpaired Student t-test was used for continuous variables. Correla- tions were assessed using spearman and Kendall coefficients (rs, τ). EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 822 Results The mean and standard deviation (SD) age of the 88 TB patients was 36.5 (SD 2.7) years, median 34.5, range 17–69 years. There were 63 males, mean age 37.6 (SD 3.2) years (median 35, range 17–69 years) and 25 females, mean age 33.9 (SD 5.0) years (median 35, range 17–62 years) (Table 1). Most isolates belonged to patients in the age range 20–39 years. All patients had been previ- ously treated for M. tuberculosis TB. Of the 88 isolates collected, 85 (96.6%) were resistant; 18 (20.5%) were single-resistant, 12 (13.6%) were poly-resistant and 55 (62.5%) were MDR strains. The resistance pattern was: RIF 69.4%, INH 77.6%, STR 82.4% and EMB 61.2%. The most common resistance pattern was RRRR (resist- ance sequence RIF–INH–STR–EMB) in 45.9% of resistant isolates (39/85). The most common drug resistance was to STR and so the most common single- resistance pattern was SSRS in 16.5% (14/85) of resistant isolates (Table 2). The 88 isolates resulted in 59 differ- ent DRE-PCR patterns, while 6 isolates produced no detectable genotypes. The Hunter–Gaston discrimination index [12] was calculated as D = 0.98. The number of different bands was 24, ranging from 1 to 7 for each genotype (Table 3). We observed 9 clusters, which included 32 isolates. Altogether cluster isolates represented 36% (32) of the isolates (Table 4); unique geno- types were observed for 50 isolates. The largest cluster was genotype G20, containing the single band 300 bp, followed by cluster genotypes G3 and G23. The genotypes were assigned to 7 genotype groups (I–VII) depending on the total number of different bands ob- served (Table 3). Most cluster isolates belonged to genotype group I, and all to I and II. A gradual decrease was observed in the number of isolates with increasing number of bands (Figure 1). Correlations Correlations were investigated between patient’s sex, age and region, the geno- types, and the resistance pattern. Correlations related mainly to sex The general ratio of males to females was 2.5 (63/25) considering all isolates (Ta- ble 1). For the Aleppo region, the ratio was 1.4 (21/15), while the M:F ratio for the rest of the regions taken together was 4.2 (42/10). The M:F ratio of cluster isolates was 5.4 (27/5) (Table 3). The M:F ratio for resistant strains in clusters was 4.6 (23/5), while the M:F ratio for the unique genotypes (all were resistant isolates) was 1.9 (33/17) (Table 2). The general M:F ratio for MDR isolates was 2.6 (40/15) (Table 2), but the ratio was Table 1 Mycobacterium tuberculosis isolates by age, sex and region of the Syrian Arab Republic Variable Total isolates Genotypes Isolates by age (years)a 10–19 20–29 30–39 40–49 50–59 60–69 No. No. No. No. No. No. No. No. Total 88 59 + ctr. 5 24 30 8 15 4 Sex Male 63 42 2 15 + 1Gx 23 + 1Gx 3 13 2 + 1Gx Female 25 22 3 8 5 + 1Gx 4 + 1Gx 1 + 1Gx 1 Region Aleppo 36 30 2 11 9 4 6 + 1Gx 2 + 1Gx Damascus 13 9 1 4 + 1Gx 6 + 1Gx 0 0 0 Deir ez-Zor 9 7 0 1 3 + 1Gx 1 3 0 Rif Dimashq 2 2 1 0 1 0 0 0 Latakia 5 4 0 2 1 1Gx 1 0 Homs 4 4 0 1 1 0 1 1 Al-Hasakah 3 3 0 1 1 0 1 0 Hama 3 3 1 0 1 1 0 0 Al-Qamishli 2 2 0 0 0 0 2 0 Ar-Raqqah 2 2 0 1 1 0 0 0 Abu Kamal 1 1 0 0 0 0 0 0 Adra 1 1 0 0 0 0 0 0 As-Suwayda' 1 1 0 0 1 0 0 0 Quneitra 1 1 0 1 0 0 0 0 Iraq 5 5 0 1 3 1 0 0 aAge was unknown for 2 cases. ctr. = control; Gx = genotype unknown. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 823 Ta bl e 2 A nt ib io ti c re si st an ce p at te rn s of M yc ob ac te ri um tu be rc ul os is g en ot yp es b y pa ti en t’s s ex a nd b y re gi on o f t he S yr ia n A ra b Re pu bl ic Va ri ab le A nt ib io ti c re si st an ce p at te rn a RR RR RR SS RR SR RR RS SS RS SR SS SR RR SR RS RS SS RS RS SR SR SS RR SS SS N o. o f i so la te s M al e 24 5 5 6 8 2 5 2 2 1 0 0 3 Fe m al e 15 0 0 0 6 0 1 0 0 1 1 1 0 To ta l 39 5 5 6 14 2 6 2 2 2 1 1 3 G en ot yp es b y re gi on A le pp o G 10 , G 25 , G 30 , G 44 G 45 , G 47 , G 51 , G 52 G 59 , G 61 , G 67 , G 71 G 72 , G 74 , G 82 , G x G 20 , G 31 G 43 , G 20 – G 3, G 19 , G 23 , G 27 G 28 , G 32 G 39 , G 21 G 23 ; G 49 ; G 70 ; G x G 54 G 57 – G 20 – G 32 D am as cu s G 20 , G 23 , G 29 , G 53 , G 78 , G 81 , G x – – G 20 , G x G 20 – – – G 3 G 55 – – G 45 D ei r e z- Zo r G 20 , G 60 , G x – G 20 G 79 – – G 3 G 42 – – – G 35 G 22 Ri f D im as hq G 23 – – – G 76 – – – – – – – –- La ta ki a G 3, G 38 – – G 62 G x G 48 – – – – – – – H om s G 21 – G 22 – G 80 – – – – G 20 – – – A l-H as ak ah G 40 G 24 – – G 37 – – – – – – – – H am a G 20 – – G 26 G 43 – – – – – – – – A l-Q am is hl i G 36 , G 20 – – – – – – – – – – – A r- Ra qq ah G 50 – – – – – G 56 – – – – – – A bu K am al – G 24 – – – – – – – – – – – A dr a – G 34 – – – – – – – – – – – A s- Su w ay da ’ – – – – G 64 – – – – – – – – Q un ei tr a G 33 – – – – – – – – – – – – Ira q G 69 , G 75 , G 77 – G 22 G 65 – – – – – – – – – a A nt ib io tic re si st an ce p at te rn se qu en ce : r ifa m pi n (R IF )– is on ia zi d (IN H )– st re pt om yc in (S TR )– et ha m bu to l ( EM B) . R = re si st an t; S = se ns iti ve . G = g en ot yp e (b ol d = is ol at es fr om fe m al es ); G x = no g en ot yp e pa tte rn fo un d; – = n o is ol at es . EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 824 17 (17/1) for MDR isolates in clusters (OR = 6.8, 95% CI: 0.67–70.1, P = 0. 1) (Table 2). Most noticeable was the clearly deviating M:F ratio for MDR in Aleppo, 0.8 (9/11) (OR = 0.27, 95% CI: 0.065–1.14, P = 0.075) (Table 2). The diversity ratio (i.e. number of genotypes/number of isolates, exclud- ing isolates with no genotype pattern detected, 3 in males and 3 in females) for isolates from males was 0.7 (42/60) and this was clearly different from the diversity ratio for isolates from females which was 1 (22/22). The dispropor- tionately high number of affected males was obvious for most but not all geno- type groups: The ratio was 9 (27/3) for the genotype group I (OR = 5.7, 95% CI: 1.5–21.4, P = 0.01), while genotype groups VI and VII included only females (OR = 0.09, 95% CI: 0.009–0.818, P = 0.023) (Table 5). Correlations related mainly to age The mean age of patients for cluster iso- lates was 36.6 (SD 4.6) years (median 32, range 17–64 years) and that for cluster genotype G20 was 38.7 (SD 7.9) years (median 32, range 25–64 years); for MDR isolates it was 37.1 (SD 3.4) years (median 35, range 17–65 years) and for MDR cluster isolates 39.1 (SD 6.1) years (median 35, range 17–64 years). Correlations related mainly to geno- type and resistance The largest cluster genotype G20 (11 isolates) had 6 isolates that shared a resistance pattern. The rest had each a unique resistance pattern; genotype G23 had 2 out of 4 and genotype G3 Table 3 Band pattern of the different designated Mycobacterium tuberculosis genotypes and assigned genotype groups by isolate’s resistance and patient’s sex Genotype group/band (bp) Genotype Sensitive strains Resistant strains MDR strains M + F M F No. No. No. No. No. Group I 350 G3 0 4 3 1 1M 250 G19 0 1 1 0 0 300 G20 0 11 10 1 8M 325 G21 0 2 2 0 1M 400 G22 1M 2 2 0 2M 450 G23 0 4 3 1 2M 500 G24 0 2 2 0 2M 550 G25 0 1 1 0 1M 1500 G26 0 1 1 0 1M 2000 G27 0 1 1 0 0 Group II 125, 500 G28 0 1 1 0 0 150, 300 G29 0 1 1 0 1M 150, 325 G30 0 1 0 1 1F 150, 450 G31 0 1 1 0 1M 150, 500 G32 1M 1 0 1 0 150, 750 G33 0 1 1 0 1M 175, 450 G34 0 1 1 0 1M 225, 300 G35 0 1 0 1 0 275, 300 G36 0 1 1 0 1M 275, 325 G37 0 1 0 1 0 300, 400 G38 0 1 0 1 1F 300, 450 G39 0 1 1 0 0 325, 1500 G40 0 1 1 0 1M 350, 500 G10 0 1 0 1 1F 400, 1500 G42 0 1 1 0 0 450, 500 G43 0 2 2 0 1M 450, 600 G44 0 1 1 0 1M 450, 1500 G45 1M 1 0 1 1F طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 825 Table 3 Band pattern of the different designated Mycobacterium tuberculosis genotypes and assigned genotype groups by isolate’s resistance and patient’s sex (concluded) Genotype group/band (bp) Genotype Sensitive strains Resistant strains MDR strains M + F M F No. No. No. No. No. Group III 100, 250, 300 G47 0 1 0 1 1F 150, 500, 1500 G48 0 1 1 0 0 175, 300, 500 G49 0 1 1 0 0 175, 325, 450 G50 0 1 1 0 1M 200, 300, 500 G51 0 1 0 1 1F 225, 325, 450 G52 0 1 0 1 1F 250, 300, 350 G53 0 1 1 0 1M 250, 300, 400 G54 0 1 1 0 0 250, 300, 500 G55 0 1 0 1 0 250, 300, 1000 G56 0 1 0 1 0 250, 300, 1500 G57 0 1 1 0 0 250, 550, 650 G59 0 1 0 1 1F 275, 450, 600 G60 0 1 1 0 1M 300, 400, 450 G61 0 1 1 0 1M 350, 1500, 2000 G62 0 1 1 0 1M 450, 500, 1500 G63 – ctr. – – ctr. 450, 550, 2500 G64 0 1 1 0 0 450, 1500, 2000 G65 0 1 1 0 1M Group IV 175, 250, 300, 550 G67 0 1 1 0 1M 250, 300, 450, 550 G69 0 1 1 0 1M 250, 300, 1000, 1500 G70 0 1 1 0 0 275, 300, 350, 450 G71 0 1 0 1 1F 275, 300, 550, 1500 G72 0 1 0 1 1F 275, 350, 350, 500 G74 0 1 1 0 1M Group V 150, 400, 600, 650, 2000 G75 0 1 1 0 1M 175, 225, 275, 325, 450 G76 0 1 1 0 0 175, 250, 300, 1500, 2000 G77 0 1 0 1 1F 200, + 200, 300, 325, 500 G78 0 1 1 0 1M 300, 350, 450, 500, 1500 G79 0 1 1 0 1M Group VI 175, 200, 225, 350, 450, 550 G80 0 1 0 1 0 275, 300, 350, 400, 500, 2000 G81 0 1 0 1 1F Group VII 125, 225, 275 300, 350, 375, 425 G82 0 1 0 1 1F Total (genotyped) 3M 79 57 22 38M;13F No genotype pattern found Gx 0 6 3 3 2M;2F MDR = multi-drug resistant; M = number of isolates from males; F = number of isolates from females; ctr. = control. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 826 had no islolates that shared the same resistance pattern (Table 1). Genotype groups I, II and III had a combined ratio for MDR strains of 0.59 (40/68), while genotype groups IV, V, VI and VII had a combined ratio of 0.79 (11/14) (OR = 2.6, 95% CI: 0.66–10.1, P = 0.17) (Table 4). The percentage of MDR strains was 63% (55/88), higher in unique genotypes (74%, 37/50) than in cluster genotypes (56%, 18/32). For genotype G20 it was 73% (8/11) (OR = 2.1, 95% CI: 0.46–9.29, P = 0.348). Starting with genotype group IV and going to higher genotype group band numbers, all showed 100% STR resist- ance (Table 6). The STR resistance was most prevalent in unique isolates (94%, 47/50) (OR = 10.1, 95% CI: 2.5–40.7, P < 0.002). However, in cluster isolates, resistance to INH and not to STR was the most common pattern (OR = 1.56, 95% CI: 0.73–3.34, P = 0.25). The fraction of isolates that exhibited the full resistant pattern (RRRR) in the total resistant and in the MDR isolates tended to increase with increasing band number (rs = 0.949, P = 0.026, τ = 0.913, P = 0.035), and this was especially true if only the genotype groups (I, II, III, IV) that included the bulk of isolates (90% of total resistant, 88% of MDR) were considered (rs = 1, P < 0.001, τ = 1, P = 0.021) (Figure 2). Discussion The Syrian Arab Republic is considered an endemic country for TB, with an intermediate burden of disease, an es- timated incidence for all cases in 2006 of 32 per 100 000 population and a TB prevalence of 40 per 100 000 population [13]. However, the geographic distribu- tion of the disease varies depending on the region. No previous studies in the country have been published using molecular epidemiological techniques applied to M. tuberculosis TB. The cur- rent study demonstrates that various genotypes tended to be more common in specific regions than others. The se- lective distribution of genotype groups, in addition to the observed high level of variability, indicated some level of geographic isolation, and hence sepa- rate evolution. It justifies also the initial assignment of the genotypes to major groups according to the general band pattern. All regions of the country showed high levels of genotype diversity, which is consistent with a low level of trans- mission of strains in previously treated patients. However, this requires confir- mation using a larger pool of patients that would include new cases of TB infection. Not a single case of previously treated TB was observed in which a match in genotype, resistance pattern and location was present. The diversity ratio of 1 for isolates from females and < 1 for isolates from males, if confirmed, might suggest that females have a ten- dency not to transmit the disease among their sex, but instead infect and are in- fected by males. One major drawback of using DRE-PCR is the absence of a worldwide accessible databank, mainly due to difficulties of digitizing the results and lack of optimization. Associating obtained patterns with that of digitized genotypes would make future global comparisons of strains possible. The disproportionately high resist- ance in isolates of previously treated patients from the Aleppo region should be a cause for further investigation into local treatment procedures, as well as local strain characteristics, given that 69% of these strains were unique to this region and that there were some indications of deviating characteristics. Furthermore, the generally observed prevalence of STR resistance in Syrian patients suggests a need to reconsider Table 4 Contribution of each drug resistance form to resistant strains of the 32 Mycobacterium tuberculosis isolates in 9 genotype clusters Cluster genotype No. isolates in cluster % of all isolates (n = 88) Single-resistant isolates RIF in INH in EMB in STR in No. %a No. %a No. %a No. %a G20 11 12.5 9 82 9 82 7 64 7 64 G3 4 4.6 2 50 2 50 2 50 3 75 G23 4 4.6 2 50 3 75 3 75 4 100 G22 3 3.4 2 100 2 100 2 100 0 0 G21 2 2.3 1 50 2 100 1 50 1 50 G24 2 2.3 2 100 2 100 0 0 0 0 G32 2 2.3 0 0 0 0 0 0 1 100 G43 2 2.3 1 50 1 50 1 50 1 50 G45 2 2.3 1 100 1 100 1 100 1 100 Total 32 36.4 20 69 22 76 17 59 18 62 aof resistant cluster isolates. RIF = rifampin; INH = isoniazid; EMB = ethambutol; STR = streptomycin. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 827 the inclusion of STR in current first-line drug treatment. The well-documented sex disparity for reported TB has been attributed by some authors to socioeconomic and cultural barriers in access to health care [14], and by others to biological and epidemiological characteristics [15,16]. Some studies were able to detect varia- tions in sex distribution depending on disease category [17,18]. The overall reported ratio of males to females in the Syrian Arab Republic was 1.8 accord- ing to the World Health Organization country TB profile of 2006 [13]. In the current study the higher ratio of males to females was similar whether isolates in general were considered or only resistant ones or only MDR cases. However, the ratio for clustered genotypes was shifted towards males for unique genotypes, and the ratio was highly shifted towards males when MDR cases in clusters were considered. In this pool of patients males appeared more likely to be infected by MDR strains and to develop MDR, and that was true for specific strains. Females of the same pool were more likely to be affected by MDR in the pres- ence of strains with a higher number of bands (e.g. higher designated numbers of genotype groups). The overall sex ratio of 2.5 (males to females)—which seems to reflect a host sex preference of MTB strains—was in fact an aver- age of dissimilar ratios that appeared to depend heavily on the genotype of the MTB strains. Resistance to all 4 drugs (RRRR), was the most common pattern in this pool of previously treated patients. The resistance pattern was generally 50 45 40 35 30 25 20 15 10 5 0 1 2 3 4 5 6 7 N. Band N. MDR female N. female N. MDR male N. male Figure 1 Correlation of patients to number of bands obtained using double-repetitive-elements polymerase chain reaction M M M M M F F F F F F F 4R/tot 4R/MDR1.2 1 0.8 0.6 0.4 0.2 0 1 2 3 4 5 6 7 N. Band 0.5 0.31 0.47 0.75 0.47 0.8 0.8 1 0.75 0.5 0.6 1 1 1 Figure 2 Fraction of fully resistant patients of total and multi-drug resistant (MDR) cases correlated to number of bands obtained using double-repetitive-elements polymerase chain reaction EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 828 dominated by STR resistance, with EMB resistance being the least observed; however this was not the case in cluster isolates, in which INH resistance be- came the dominant form of resistance, whereas RIF and EMB resistance rates did not alter. Association of INH resist- ance with clustering may be explained by the fact that katG 315 mutations are less likely to attenuate bacterial virulence than mutations causing STR resistance [19]. The resistance patterns SSSR, RSSR and RSRR were absent. It is noticeable that these all include resistance to EMB and sensitivity to INH. Considering all observed resistance patterns, resistance to EMB was associated with resistance to INH (and not vice versa). The patterns of concurrent resistance to EMB and INH (4 patterns) involve 51 isolates. The only exception was the pattern SSRR, involving only 1 isolate, which was prob- ably caused by a different mechanism of resistance to EMB. Noticeable also was the fact that all absent resistance patterns (3 patterns) represented EMB resistance and sensitivity to INH. These observa- tions are consistent with both drugs af- fecting the constitution of the cell wall and with the reported pleiotropic effect of EMB resistance, which causes resist- ance to other drugs such as INH [20,21]. EMB and INH are also reported to be targets of an efflux pump which confers tolerance to both drugs [22]. The assigned genotype groups ap- peared to correlate with certain patterns of drug resistance. We observed an in- crease in the relative occurrence of the total resistance pattern RRRR, being low in the genotype group I and high in genotype group VII. MDR was generally more likely to occur when there were a higher number of genotype bands. The underlying genetic cause of these group- ings, and shifts towards specific geno- typic groups, could be a consequence of the possible increase in the number of IS6110 elements; such an increase has been implicated or suspected in genotype instability associated with drug resistance Ta bl e 5 D is tr ib ut io n of M yc ob ac te ri um tu be rc ul os is is ol at es b y pa ti en t’s se x an d m ul ti -d ru g re si st an ce fo r t he v ar io us d es ig na te d ge no ty pe g ro up s b y re gi on o f t he S yr ia n A ra b Re pu bl ic Re gi on To ta l is ol at es G en ot yp e gr ou p I II II I IV V V I V II A ll M D R A ll M D R A ll M D R A ll M D R A ll M D R A ll M D R A ll M D R N o. N o. N o. N o. N o. N o. N o. N o. N o. N o. N o. N o. N o. N o. N o. A le pp o 36 7M ;3 F 3M 6M ;4 F 3M ;3 F 4M ;4 F 1M ;4 F 3M ;2 F 2M ;2 F 0 0 0 0 1F 1F D am as cu s 13 5M 3M 2M 1M 1M ;1 F 1M 0 0 1M 1M 1F 1F 0 0 D ei r e z- Zo r 9 4M 2M 1M ;1 F 0 1M 1M 0 0 1M 1M 0 0 0 0 Ri f D im as hq 2 1M 1M 0 0 0 0 0 0 1M 0 0 0 0 0 La ta ki a 5 1M 1M 1F 1M 2M 1M 0 0 0 0 0 0 0 0 H om s 4 3M 2M 0 0 0 0 0 0 0 0 1F 0 0 0 A l-H as ak ah 3 1M 1M 1M ;1 F 1F 0 0 0 0 0 0 0 0 0 0 H am a 3 2M 2M 1M 0 0 0 0 0 0 0 0 0 0 0 A l-Q am is hl i 2 1M 1M 1M 1M 0 0 0 0 0 0 0 0 0 0 A r- Ra qq ah 2 0 0 0 0 1M ;1 F 1M 0 0 0 0 0 0 0 0 A bu K am al 1 1M 1M 0 0 0 0 0 0 0 0 0 0 0 0 A dr a 1 0 0 1M 1M 0 0 0 0 0 0 0 0 0 0 A s- Su w ay da ' 1 0 0 0 0 1M 0 0 0 0 0 0 0 0 0 Q un ei tr a 1 0 0 1M 1M 0 0 0 0 0 0 0 0 0 0 Ira q 5 1M 1M 0 0 1M 1M 1M 1M 1M ;1 F 1M ;1 F 0 0 0 0 To ta l 88 27 M ;3 F 18 M 14 M ;7 F 8M ;4 F 11 M ;6 F 6M ;4 F 4M ;2 F 3M ;2 F 4M ;1 F 3M ;1 F 2F 1F 1F 1F Al l = to ta l n um be r o f i so la te s i n ge no ty pe g ro up ; M D R = nu m be r o f m ul ti- dr ug re si st an t i so la te s; M = n um be r o f i so la te s f ro m m al es ; F = n um be r o f i so la te s f ro m fe m al es . طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 829 and adaptation [23,24]. Moreover, the IS6110 sequence has been shown to possess a 3ʹ outward directed promoter (OP6110) that is able to upregulate downstream genes [25,26]. Given the importance assigned to the PGRS locus and other nearby genes in the context of virulence [27], multiple adjacency of IS6110, or the increased likelihood of correct positioning in the presence of multiple adjacency, may relate to some of the relevant phenotypic correlations observed and is consistent with the recent importance assigned to strain variations in TB [28,29]. Conclusions The genotyping of M. tuberculosis TB strains, using a slightly modified DRE- PCR, resulted in a Hunter–Gaston dis- crimination index of D = 0.98. The study of strain variations within this pool of previously treated patients found Table 6 Distribution of Mycobacterium tuberculosis isolates by antibiotic resistance for the various designated genotype groups Antibiotic No. resistant isolates Genotype group I II III IV V VI VII No. % No. % No. % No. % No. % No. % No. % RIF 55 20 69 12 63 12 71 5 83 4 80 1 50 1 100 INH 61 22 79 13 68 14 82 6 100 4 80 1 50 1 100 STR 64 19 66 16 84 15 88 6 100 5 100 2 100 1 100 EMB 48 16 55 11 58 10 59 6 100 3 60 1 50 1 100 RIF = rifampin, INH = isoniazid, STR = streptomycin, EMB = ethambutol. a degree of isolation between • M. tuberculosis TB strains in different regions of the Syrian Arab Republic, suggesting evolution of significant strain variations; a gender disparity in the • M. tuberculosis transmission dynamic; distinctive phenotype characteristics • of genotype groups assigned based on the number of obtained bands; phenotypic relevance of the adjacen-• cy of mobile elements IS6110 and PGRS; a correlation between female suscep-• tibility to MDR strains and molecular strain characteristics. The distinction of strains based on loci that contribute to virulence is im- portant for determining the potential causes of disparities in TB incidence and resistance. Routine, large-scale molecular studies are necessary for investigating the transmission dynam- ics and mechanisms of disease in the Syrian Arab Republic and neighbouring countries. Relating various strains to strains obtained in other countries us- ing different genotyping procedures is important. Acknowledgements We would like to thank the reviewers for their thoughtful comments and suggestions. We acknowledge the financial support of the Ministry of Higher Education, represented by the High Council of Science and the Na- tional Commission for Biotechnology in the Syrian Arab Republic. We appre- ciate the cooperation of the Ministry of Health and Professor Fawaz al Azmeh, head of the National Commission for Biotechnology. We also thank Mrs Mayssoun Elwi, Mrs Nibal Qirahkahya and Ms Buthaina Salamah for their efforts. 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Journal of Clini- cal Microbiology, 2007, 45(5):1483–1490. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 831 Prevalence and associated factors of persistent diarrhoea in Iranian children admitted to a paediatric hospital N.A. Kermani,1 F. Jafari,1 H.N. Mojarad,1 N. Hoseinkhan1 and M.R. Zali1 ABSTRACT To identify the frequency and associated factors of persistent diarrhoea in a paediatric hospital in Tehran, Islamic Republic of Iran, children admitted with acute diarrhoea were followed prospectively until resolution of the episode. Persistent diarrhoea developed in 19.6% of the 424 diarrhoea cases. Children with persistent diarrhoea were significantly younger than those with acute diarrhoea (15.3 versus 29.4 months). Enteroaggregative Escherichia coli was the most prevalent pathogen in both groups, but otherwise the profile of symptoms and isolated organisms was similar in the 2 groups. History of dietary change prior to admission and use of antibiotics and anticholinergic drugs in the acute phase were significantly higher in the persistent than acute diarrhoea cases. 1Research Centre for Gastroenterology and Liver Diseases, Shahid Beheshti University, Tehran, Islamic Republic of Iran (Correspondence to N.A. Kermani: nahid_arjmand_k@yahoo.com & arjmand_k@irimc.org). Received: 01/08/08; accepted: 09/11/08 لافطلأا تايفشتسم ىدحإ لىإ اولخدأ نيذلا ينّـِ يناريلإا لافطلأا ىدل هل ةقفارلما لماوعلاو ميدتسلما لاهسلإا راشتنا لدعم لياز اضر دممح ،ناخ ينسح يننزان ،درمج ينيسلحا مظان ناسح ،يرفعج ةتشرف ،نيامرك دنجمرأ ديهان ،ةيملاسلإا ناريإ ةيروهجم في ،نارهط في لافطلأا تايفشتسم ىدحإ لىإ داح لاهسإب مهتباصإ ببسب اولخدأ نيذلا لافطلأا نوثحابلا عبات :ةـصلالخا ميدتسلما لاهسلإا نأ حضتاو .هل ةبحاصلما لماوعلاو ميدتسلما لاهسلإا راركت لىع ف ُّرعتلا فدبه كلذو ،ةمجلها نم مهئافش ىتح ،ةيلابقتسا ةعباتم لافطلأا نم ًايئاصحإ هب دتعي ٍدح لىإ )ًارهش 15.3( ًانس رغصأ ميدتسلما لاهسلإاب نوباصلما لافطلأا ناك دقو ،لاهسإ ةلاح 424 نم %19.6 باصأ دق تناك دقف كلذ نود مايفو ،ًاراشتنا رثكلأا يه ءاعملأل ةيزاغلا ةينولوقلا ةيكيشريلإا تناك ينقيرفلا لاك فيو ،)ًارهش 29.4( دالحا لاهسلإاب ينباصلما مادختساو ىفشتسلما في لاخدلإا لبق يئاذغلا ماظنلا يريغت قباوس نأ نوثحابلا ظحلاو .ينقيرفلا في ةبهاشتم تابوركلما تادرفتسمو ضارعلأا تماس تلااح في هنم ميدتسلما لاهسلإا تلااح ىدل ًايئاصحإ هب دتعي ٍردقب لىعأ ناك دالحا روطلا في ينلوكلا تاداضم نم ةيودلأاو ةيويلحا تاداضلما .دالحا لاهسلإا Prévalence et risques associés de diarrhée persistante chez des enfants iraniens consultant en hôpital pédiatrique RÉSUMÉ Afin d’identifier la fréquence de la diarrhée persistante, et les facteurs associés, au sein d’un hôpital pédiatrique de Téhéran (République islamique d’Iran), des enfants hospitalisés souffrant de diarrhée aiguë ont fait l’objet d’un suivi prospectif jusqu’à résolution de l’épisode. Une diarrhée persistante est apparue dans 19,6 % des 424 cas de diarrhée. Les enfants souffrant de diarrhée persistante étaient nettement plus jeunes que ceux atteints de diarrhée aiguë (15,3 mois contre 29,4). Dans les deux groupes, l’agent pathogène ayant la plus forte prévalence était Escherichia coli entéroaggrégatif. En revanche, le profil des symptômes et des organismes isolés était similaire dans les deux groupes. Les antécédents de changement de régime alimentaire précédant l’hospitalisation et l’utilisation d’antibiotiques et d’anticholinergiques lors de la phase aiguë étaient sensiblement plus élevés dans les cas de diarrhée persistante que dans les cas de diarrhée aiguë. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 832 Introduction Diarrhoea is still an important cause of child morbidity and mortality, caus- ing about 2.2 million deaths annually in the paediatric population [1]. With recent improvements in rehydration therapy programmes, a decline has been observed in deaths associated with acute watery diarrhoea, and thus the problem of persistent diarrhoea has become more concerning. Persistent diarrhoea—defined by the World Health Organization as a diarrhoeal episode with an acute onset and a presumptive infectious etiology lasting ≥ 14 days—comprises only 3%–20% of diarrhoea episodes, but up to 50% of diarrhoea-related deaths [2]. Persistent diarrhoea also imposes a heavy eco- nomic burden on low socioeconomic status countries with its devastating ef- fects on nutritional status, growth and development of children [3,4]. There is little information about per- sistent diarrhoea in the Islamic Republic of Iran. A 7.7% prevalence was reported in a study from the west of the country, and young age, non-breastfeeding, use of antibiotics and presence of mucoid or bloody diarrhoea were factors associ- ated with it [5]. These factors, in addi- tion to malnutrition, were also observed in other studies of Iranian children [6,7]. We conducted the present study to identify the pattern and etiology of persistent diarrhoea among children admitted a paediatric hospital in Tehran and to compare these cases with cases of acute diarrhoea. Methods A cross-sectional prospective study was performed from June 2006 to June 2007 in Mofid Paediatric Hospital, a university-associated referral hospital in Tehran. Sample size Estimated sample size was approximate- ly 400, considering the 7.7% prevalence of persistent diarrhoea in Iranian chil- dren reported in a study with a similar methodology [5], and 95% confidence level and 2.5% acceptable error. Patients The study population was all children below 12 years of age who were ad- mitted for acute diarrhoea during the study period. Previously diagnosed cases of inflammatory bowel disease, coeliac disease and cystic fibrosis were excluded. Also children whose parents were not willing to take part in the study were excluded. Finally, 537 data collec- tion forms were completed. As we were not able to follow up 113 patients due to missing or incorrect contact details or non-response, 424 data collection forms were available for analysis. Data collection Data were collected from the child’s medical record and an interview with the parents. Trained nurses visited all the children admitted to the hospital with gastroenteritis. After a brief expla- nation of the study to one of the parents and acquiring verbal informed consent, a data collection form was completed. This included the demographic char- acteristics of the child and the episode of diarrhoea (duration, signs and symp- toms, changes in diet and any drugs used during the episode). Diarrhoea was defined as the pas- sage of at least 3 non-bloody stools or 1 bloody loose stool per 24 hours. For exclusively breastfed infants, increased frequency or decreased consistency of stool compared with the previous bowel habit of the infant and noticeable by the mother was considered diarrhoea. The duration of the episode of diarrhoea was calculated from the onset of the disease as stated by the parents. Cases were defined as persistent diarrhoea (duration ≥ 14 days) or acute diarrhoea (duration < 14 days). The child’s body weight was measured after rehydration. Weight- for-age z-score was calculated using Epi- info, version 6.01, based on the National Center for Health Statistics (NCHS) ta- bles and was used to categorize the cases as normal weight (z-score ≥ –1.0), mild underweight (–1.0 < z-score ≤ –2.0), moderate underweight (–2.0 < z-score ≤ –3.0) and severe underweight (z- score < –3.0). We analysed nutritional status based on weight-for-age z-score score (to avoid bias, we disregarded height-for-age and weight-for-height scores since we observed mistakes dur- ing height measurements). The patients were followed up until resolution of the diarrhoea episode, even if they were discharged from hospital. Laboratory methods A fresh stool specimen was obtained for laboratory testing during the initial days of the diarrhoea. Each specimen was first examined by a light microscope. A saline and iodine wet-mount preparation was used for detection of amoebae species, Giardia lamblia and Blastocystis hominis, and a formol-ether concentration meth- od for cysts. Trichrome staining and polymerase chain reaction (PCR) was performed to differentiate Entamoeba histolytica/dispar complex from other non-pathogenic intestinal amoeba and E. histolytica from E. dispar respectively. In order to distinguish Cryptosporidium spp., Cyclospora spp. and Isospora belli, a Ziehl–Neelsen acid-fast stained slide was prepared. We used modified tri- chrome stain for Microsporidium spp. Bacterial cultures were done on MacConkey and xylose–lysine– deoxycholate agar plates for Salmonella spp., Shigella spp. and diarrheogenic Escherichia coli. PCR was used to detect isolates that carried the eae and bfp genes for enteropathogenic E. coli (EPEC), pCVD432 plasmid for enteroaggrega- tive E. coli (EAEC), heat-labile (LT) and heat-stable (ST) genes of entero- toxigenic E. coli (ETEC), stx1 and stx2 genes for Shiga-toxin-producing E. coli (STEC), ial and ipaH genes for enter- oinvasive E. coli (EIEC) and Shigella spp., and invA gene for Salmonella spp. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 833 Statistical analysis For comparison of proportions between acute and persistent diarrhoea cases, the χ2 or Fisher exact tests were used and for comparison of means the Student t-test was used. We considered a P-value < 0.05 as statistically significant. Data were analysed using SPSS, version 13.0. Results Patient characteristics A total of 424 children were enrolled in the study. Persistent diarrhoea de- veloped in 83 (19.6%) cases, both hos- pitalized and discharged patients. The mean age of the study population was 26.6 months, and 57.3% of the patients were male. The prevalence of persistent diarrhoea reached 24.4% in the 291 children aged < 2 years and 21.8% in the 372 aged < 5 years. The male to female ratio was not significantly differ- ent between the acute diarrhoea and persistent diarrhoea group (1.4:1 and 1.1:1, respectively). More than 80% of the persistent diarrhoea cases were aged < 18 months. The mean age in the persistent diarrhoea group was 15.3 months compared with 29.4 months in the acute diarrhoea group (P < 0.001). There was also a significant difference in mean age between the 2 groups, when we considered children < 2 years: 12.1 months in the 220 acute diarrhoea cases versus 9.5 months in the 71 persistent diarrhoea cases (P = 0.002). Symptoms and characteristics of the diarrhoeal episodes The mean duration of the diarrhoea episode in the acute diarrhoea group was 5.9 (SD 2.7) days; median 6 days, and in the persistent diarrhoea group 24.9 (SD 18.6) days, median 19 days. Data regarding related symptoms and some characteristics of the diar- rhoeal episodes are summarized in Table 1. Among the symptoms related to diarrhoeal diseases (abdominal pain, nausea and vomiting, loss of appetite and fever) only fever was significantly different between the 2 groups (86.2% in the acute versus 74.7% in the persist- ent diarrhoea group). Defecation times per 24 hours and frequency of bloody or mucoid stool (which may indicate severity of the disease) were not statisti- cally significant between the groups. The frequency of concurrent dis- eases, including other infections and immunodeficiency and gastrointestinal disorders, was similar in acute diarrhoea and persistent diarrhoea cases (21.4% and 20.5%, respectively P = 0.853) (Table 1). A history of major diet change (i.e. introducing complemen- tary food or animal milk, changing the formula brand or introducing wheat to the child) 2 weeks prior to admission was found in 10.6% of acute diarrhoea and 20.5% of persistent diarrhoea cases (P = 0.014). Table 1 Demographic data, related symptoms and some characteristics of children hospitalized with acute and persistent (acute phase) diarrhoea Symptoms and characteristics Acute diarrhoea (n = 341) Persistent diarrhoea (n = 83) P-value No. % No. % Mean (SD) age (months) 29.4 (29.6) 15.3 (17.4) < 0.001 Male:female ratio 1.4 1.1 0.258 Signs and symptoms Abdominal pain 166 48.7 31 37.3 0.063 Nausea and vomiting 256 75.1 57 68.7 0.234 Loss of appetite 261 76.5 58 69.9 0.207 Fever 294 86.2 62 74.7 0.010 Defecation ≥ 6 times per 24 hours 210 61.6 60 72.3 0.069 Bloody stool 80 23.5 21 25.3 0.724 Mucoid stool 13 3.8 6 7.2 0.177 Clinical history Concurrent diseases presenta 73 21.4 17 20.5 0.853 History of previous persistent diarrhoea 18 5.3 7 8.4 0.298 History of major diet change 36 10.6 17 20.5 0.014 Antibiotics 284 83.3 78 94.0 0.013 Anticholinergic drugs 18 5.3 10 12.0 0.026 Breastfedb 144 65.5 46 64.8 0.513 aInfections, immunodeficiency and gastrointestinal disorders. bData for children aged < 2 years only (n = 220 for acute diarrhoea and n = 71 for persistent diarrhoea group). SD = standard deviation. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 834 Antibiotic and anticholinergic drug use during the acute phase was significantly higher in the persistent di- arrhoea than the acute diarrhoea group (Table 1). A summary of medication administered during the acute phase of the diarrhoeal disease (including drugs administered in the hospital before and after admission by parents or other phy- sicians) is shown in Figure 1. The mean of weight-for-age z-score was similar in both groups: –0.76 (SD 1.54) in acute diarrhoea and –0.77 (SD 1.28) in persistent diarrhoea patients. In the age group < 4 months, 20 out of 36 (55.6%) were exclusively breast- fed and in the age group < 6 months 26 out of 73 (35.6%) were exclusively breastfed. The proportion of exclu- sively breastfed infants was significantly higher in the persistent diarrhoea than the acute diarrhoea group, analysing only those aged < 2 years (14.5% versus 4.4%, P = 0.001). There was no differ- ence between the acute and persistent diarrhoea groups in the frequency of breastfed and non-breastfed children (age < 2 years only). Two deaths occurred during this study and both were related to the underlying disease of the patient and not to the diarrhoeal disease. Enteropathogens in stool specimens Laboratory testing of stool specimens for enteropathogens gave a positive result in only 42% of acute and 36% 0f persistent diarrhoea cases (Figure 2). EAEC was the most frequently iso- lated enteropathogen in both groups. No clear difference in the profile of infec- tion was found between cases of acute and persistent diarrhoea (Table 2). Salmonella spp. was the only pathogen with a significantly higher prevalence in persistent diarrhoea (2/83 cases) than acute diarrhoea cases (0/341 cases) (P = 0.038), although the number of cases was very small. Discussion Due to the fact that this was a hospital- based study performed in a referral centre, a high frequency of persistent diarrhoea was expected. The prevalence of persistent diarrhoea (19.6% overall and 21.8% in children aged < 5 years) was higher than that reported in a study from west of Islamic Republic of Iran (7.7%). This may be because of the dif- ference in admission status of the cases (inpatient versus outpatients). The rate of persistent diarrhoea is lower than that from a hospital-based study in Brazil (56.9%) [8] but higher than in Nigeria (11.7%) [9]. Age is a major determi- nant in the development of persistent diarrhoea. Our results showed that diar- rhoea was more likely to be persistent in younger children and this is consistent with the findings of previous studies in Kenya, Peru, Egypt and Guatemala [2,10–13]. Comparing some related symptoms and characteristics of the diarrhoeal disease, we found that the illness was similar in severity in persistent diarrhoea and acute diarrhoea cases. Studies from Nigeria and Egypt have reported similar findings [9,12]. A major dietary change (such as introducing complementary food or animal milk to the child) 2 weeks prior to admission was more common in persistent diarrhoea than the acute di- arrhoea cases. This may underscore the role of non-infectious causes, especially allergies, in the development of persistent Figure 1 Frequency of drug administration to children hospitalized with acute (n =341) and persistent diarrhoea (n = 83) before, during or after hospitalization (any time during acute phase of the diarrhoeal episode) Acute Persistent Drug type % o f c hi ld re n طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 835 diarrhoea. The frequency of exclusive breastfeeding was not very high among the children, so most of them were al- ready exposed to foodborne infections. A diet change such as introducing animal milk or complementary food to an infant who is not exclusive breastfed or chang- ing formula brand may indicate other causes of diarrhoea. Supported by the results of previous studies, we noticed that antibiotic and anticholinergic drug use during the initial days of a diarrhoeal episode was associated with longer dura- tion of the disease [14–17]. Enteropathogens were identified in only 42% of acute and 36% of persist- ent diarrhoea cases. There are several reasons for this relatively low rate. First, we did not exclude patients treated with antibiotics prior to stool exami- nation, which might result in negative bacterial growth. Secondly, we did not test the specimens for some bacterial enteropathogens—e.g. Clostridium dif- ficile, Aeromonas spp. and Campylobacter spp.—or for any viral enteropathogens. Thirdly, a proportion of diarrhoeal episodes may be due to non-infectious causes such as food allergies or chronic non-specific diarrhoea of childhood, as noted by Vernacchio et al. [18]. Several studies from Bangladesh, India and Brazil have recognized EAEC as an important pathogen in develop- ing persistent diarrhoea [19–22]. We also found it as the most prevalent pathogen in cases of both acute and persistent diarrhoea albeit with no significant difference between the 2 groups. Surprisingly, protozoa, especially Cryptosporidium spp. which is pre- sumed to be one of the main etiological agents of persistent diarrhoea, was not associated with prolonged diarrhoea in our study [2,17,23]. Salmonella spp. was the only pathogen with a signifi- cantly higher prevalence in persistent diarrhoea than acute diarrhoea cases in this study, although the numbers were very small. When assessing malnutrition, a demonstrated risk factors for persistent diarrhoea [9,24,25], we found no differ- ence between the 2 groups. Breastfeeding is a protective factor for persistent diarrhoea, as indicated in several studies [5,7,23], but in our study Table 2 Frequency of enteropathogens in stool specimens of children hospitalized with acute and persistent diarrhoea Enteropathogen Acute diarrhoea (n = 341) Persistent diarrhoea (n = 83) P-value No. % No. % Giardia lamblia trophozoite 1 0.3 1 1.2 0.35 Cryptosporidium spp. 6 1.8 1 1.2 1.00 Blastocystis hominis 13 3.8 1 1.2 0.32 Salmonella spp. 0 0.0 2 2.4 0.04 Shigella spp. 7 2.1 2 2.4 0.69 Enteroaggregative Escherichia coli (EAEC) 60 17.6 15 18.1 0.92 Enteropathogenic E. coli (EPEC) 18 5.3 5 6.0 0.79 Shiga-toxin-producing E. coli (STEC) 25 7.3 6 7.2 0.97 Enterotoxigenic E. coli (ETEC) 21 6.2 5 6.0 0.96 Enteroinvasive E. coli (EIEC) 31 9.1 5 6.0 0.37 Figure 2 Number of pathogens isolated from stool specimens of children hospitalized with acute (n = 341) and persistent diarrhoea (n = 83) % o f c hi ld re n Number of pathogens EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 836 the frequency of breastfeeding in chil- dren < 2 years of age was similar in the acute and persistent diarrhoea groups. However, it should be mentioned that the proportion of exclusively breastfed infants was significantly higher in the persistent diarrhoea than the acute di- arrhoea group (14.5% versus 4.4%). We also observed that only 55.6% of infants under 4 months and 35.6% under 6 months of age were exclusively breast- fed. This, along with the fact that moth- ers tend to discontinue breastfeeding during a diarrhoeal episode, implies the need for an extended public health education programme for diarrhoeal disease in the Islamic Republic of Iran. Follow-up of the children showed no deaths associated with acute or per- sistent diarrhoea. This may be a result of good hospital care especially in the case of rehydration and nutritional care. This study presents some data about persistent diarrhoea in a hospital setting and although the findings are not repre- sentative of the community, they clarify some aspects of persistent diarrhoea in Iranian children. Persistent diarrhoea seems to be a benign disease in the Ira- nian paediatric population. Young age, antibiotic and anticholinergic drug use, a history of a significant diet change 2 weeks before the onset of diarrhoea and presence of Salmonella spp. are some factors that may be involved in persist- ent diarrhoea. Acknowledgements The authors wish to thank Ms F. Mola, Ms M. Ghafoori, Dr B. Noorinayer, Dr M.A. Pourhoseingholi and Dr F. Firoozi for their kind assistance. This study was funded by the Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University. Black RE, Morris SS, Bryce J. Where and why are 10 million chil-1. dren dying every year? Lancet, 2003, 361:2226–2234. Persistent diarrhoea in children in developing countries: mem-2. orandum from a WHO meeting. Bulletin of the World Health Organization, 1988, 66:709–717. Bhutta ZA et al. Persistent and chronic diarrhoea and mal-3. absorption: Working Group report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nu- trition. Journal of pediatric gastroenterology and nutrition, 2004, 39(Suppl. 2):S711–716. Ochoa TJ, Salazar-Lindo E, Cleary TG. Management of children 4. with infection–associated persistent diarrhoea. Seminars in Pediatric Infectious Diseases, 2004, 15:229–236. Batebi A et al. A study of effective factors on persistent diar-5. rhoea in under five years old children. Iranian Journal of Public Health, 1997, 26:31–40. Honarpisheh A et al. A study on the relationship between mal-6. nutrition and persistent diarrhea. Journal of Kashan University of Medical Sciences, 1997, 1(1):29–33. Pourahmadi S, Vakili R. Predisposing factors in persistent diar-7. rhoea. Iranian Journal of Pediatrics, 1999, 42:20–24. Lins MD, Silva GA. Doenca diarreica em criancas hospitaliza-8. das - importancia da diarreia persistente [Diarrheal disease in hospitalized children—importance of the persistent diarrhoea]. Jornal de Pediatria, 2000, 76:37–43. Sodeinde O et al. Persistent diarrhoea in Nigerian children 9. aged less than five years: a hospital-based study. Journal of Diarrhoeal Diseases Research, 1997, 15:155–160. Mbori-Ngacha DA et al. Prevalence of persistent diarrhoea in 10. children aged 3–36 months at the Kenyatta National Hospital, Nairobi, Kenya. East African Medical Journal, 1995, 72:711–714. Lanata CF et al. Epidemiologic, clinical, and laboratory char-11. acteristics of acute vs. persistent diarrhoea in periurban Lima, Peru. Journal of Pediatric Gastroenterology and Nutrition, 1991, 12:82–98. Mahmud MA et al. Sociodemographic, environmental and 12. clinical risk factors for developing persistent diarrhoea among infants in a rural community of Egypt. Journal of health, popula- tion, and nutrition, 2001, 19:313–319. References Cruz JR et al. Epidemiology of persistent diarrhoea among 13. Guatemalan rural children. Acta Paediatrica, supplement, 1992, 381:22–26. Karim AS et al. Risk factors of persistent diarrhoea in children 14. below five years of age. Indian Journal of Gastroenterology, 2001, 20:59–61. Shahid NS et al. Risk factors for persistent diarrhoea. 15. British Medical Journal, 1988, 297:1036–1038. Araya M et al. Persistent diarrhoea in the community. Charac-16. teristics and risk factors. Acta Paediatrica, 1991, 80:181–189. Sodemann M et al. Episode-specific risk factors for progression 17. of acute diarrhoea to persistent diarrhoea in West African chil- dren. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1999, 93:65–68. Vernacchio L et al. Characteristics of persistent diarrhoea in a 18. community-based cohort of young US children. Journal of Pedi- atric Gastroenterology and Nutrition, 2006, 43:52–58. Henry FJ et al. Epidemiology of persistent diarrhoea and etio-19. logic agents in Mirzapur, Bangladesh. Acta Paediatrica, supple- ment, 1992, 381:27–31. Fang GD et al. Etiology and epidemiology of persistent diar-20. rhoea in northeastern Brazil: a hospital-based, prospective, case–control study. Journal of Pediatric Gastroenterology and Nutrition, 1995, 21:137–144. Bhatnagar S et al. Enteroaggregative 21. Escherichia coli may be a new pathogen causing acute and persistent diarrhoea. Scandi- navian Journal of Infectious Diseases, 1993, 25:579–583. Bardhan PK et al. Small bowel and fecal microbiology in chil-22. dren suffering from persistent diarrhoea in Bangladesh. Journal of Pediatric Gastroenterology and Nutrition, 1998, 26:9–15. Lima AA et al. Persistent diarrhoea signals a critical period of 23. increased diarrhoea burdens and nutritional shortfalls: a pro- spective cohort study among children in northeastern Brazil. Journal of Infectious Diseases, 2000, 181:1643–1651. Bhandari N et al. Association of antecedent malnutrition with 24. persistent diarrhoea: a case–control study. British Medical Jour- nal, 1989, 298:1284–1287. Black RE, Brown KH, Becker S. Malnutrition is a determining 25. factor in diarrhoea l duration, but not incidence, among young children in a longitudinal study in rural Bangladesh. American Journal of Clinical Nutrition, 1984, 39:87–94. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 837 Cancer incidence in Jordan, 1996–2005 M. Al-Tarawneh,1 S. Khatib 2 and K. Arqub1 ABSTRACT Cancer causes 14% of all deaths in Jordan. This paper presents the incidence of cancer in Jordan from 1996 to 2005. Over the 10-year period there were 33 661 cases of cancer. The average crude incidence rate was 66.2 per 100 000 for males and 70.0 per 100 000 for females (age-standardized rates: 119 per 100 000 adult males and 116 per 100 000 adult females). The 5 most frequently reported cancers among adult males were: lung (10.6%), colorectal (9.8%), leukaemia (9.3%), urinary and bladder (8.6%) and prostate (7.4%). For adult females these were: breast (32.0%), colorectal (9.0%), leukaemia (6.7%), thyroid (4.9%) and corpus uteri (4.6%). Cancer rates have changed little since 1996. 1National Cancer Registry, Amman, Jordan (Correspondence to M. Al-Tarawneh: amman992001@yahoo.com). 2King Hussein Institute for Biotechnology and Cancer, Amman, Jordan. Received: 19/11/08; accepted: 08/01/09 2005 - 1996 ندرلأا في ناطسرلا عوقو لدعم بوقرع وبأ لماك ،بيطلخا دحمأ يماس ،ةنوارطلا لوسر دممح للاخف .2005 لىإ 1996 نم ةدلما في ندرلأا في ناطسرلا عوقو لدعم ةقرولا هذه ضرعتستو .ندرلأا في تايفولا نم %14 ناطسرلا ببسي :ةـصلالخا نم فلأ ةئم لكل 70و روكذلا نم فلأ ةئم لكل 66.2 عوقولل مالخا يطسولا لدعلما ناكو .ناطسر ةلاح 33 661 كانه ناك شرعلا تاونسلا كلت نع غلبلما تاناطسرلا تناكو )ةغلاب ىثنأ فلأ ةئم لكل 116و ،غلاب ركذ فلأ ةئم لكل 119 :ةيرمع ةئف لكب ةصالخا عوقولا تلادعم تناكو( ،ثانلإا ،)%9.3( مدلا ضاضيباو ،)%9.8( ميقتسلماو نولوقلا ناطسرو ،)%10.6( ةئرلا ناطسر :يه ينغلابلا روكذلا ىدل لىولأا سملخا بتارلما لتتح انهأ نولوقلا ناطسرو ،)%32.0( يدثلا ناطسر :يهف تاغلابلا ثانلإل ةبسنلابو ،)%7.4( ةتاتسوبرلا ناطسرو ،)%8.6( ةناثلماو ليوبلا زاهلجا ناطسرو ًا ُّريغت تاناطسرلا تلادعم تيغت دقل .)%4.6( محرلا مسج ناطسرو ،)%4.9( ةيقردلا ناطسرو ،)%6.7( مدلا ضاضيباو ،)%9.0( ميقتسلماو .1996 ماع هيلع تناك ماع ًافيفط Incidence du cancer en Jordanie entre 1996 et 2005 RÉSUMÉ Le cancer est à l’origine de 14 % des décès en Jordanie. Cet article présente l’incidence du cancer en Jordanie entre 1996 et 2005. Au cours de la période de 10 ans sur laquelle a porté l’étude, 33 661 cas de cancer ont été détectés. Le taux d’incidence brut moyen était de 66,2 pour 100 000 chez les hommes et de 70,0 pour 100 000 chez les femmes (taux d’incidence standardisé en fonction de l’âge : 119 pour 100 000 chez les hommes et 116 pour 100 000 chez les femmes). Les cinq cancers les plus fréquents chez les hommes étaient le cancer du poumon (10,6 %), le cancer colorectal (9,8 %), la leucémie (9,3 %), le cancer urinaire et de la vessie (8,6 %) et le cancer de la prostate (7,4 %). Chez les femmes, les cinq cancers les plus fréquemment observés étaient le cancer du sein (32,0 %), le cancer colorectal (9,0 %), la leucémie (6,7 %), le cancer de la thyroïde (4,9 %) et le cancer du corps utérin (4,6 %). Les taux de cancer ont peu évolué depuis 1996. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 838 Introduction Cancer is a major public health problem. In 2005, 7.6 million people died of can- cer out of 58 million deaths worldwide [1]. More than 70% of all cancer deaths occur in low- and middle-income coun- tries, where the resources available for prevention, diagnosis and treatment of cancer are limited or nonexistent. The World Health Organization (WHO) estimates that there will be 20 million new cases and 12 million deaths from cancer alone by the year 2020 [2]. In a study comparing 4 member countries of the Middle East Cancer Consortium (Cyprus, Egypt, Israel and Jordan) with the Surveillance, Epidemi- ology and End Results (SEER) survey in the United States of America (USA), the overall incidence of cancer was substantially higher in the USA and in Israeli Jews than in other Middle East populations [3]. Egyptians and Israeli non-Jews (who are mostly Arabs) had intermediate rates, while the rates in Jordanians were the lowest. A high in- cidence of breast cancer was found in Israeli Jews compared with Arab popu- lations and these differences provide an example of the potential role of lifestyle and genetic factors in the etiology of breast cancer [3]. The implementation of different strategies for the control and prevention of many communicable diseases of childhood, along with rapid improve- ments in socioeconomic status and im- provements in health services in Jordan have led to the emergence of noncom- municable diseases as the dominant source of ill health. Cancer is the second leading cause of death in the country. As cancer incidence rates have not been described in a comprehensive manner in Jordan we present here epidemiological data on cancer cases reported to the national cancer registry during the 10-year period 1996–2005. Methods Background—Jordan cancer registry The Jordan cancer registry (JCR) was established in 1996 as a population- based registry to collect data from all relevant health facilities: public, Royal Medical Services, university and private as well as pathology laboratories. The registry includes all malignant and in situ malignancies diagnosed since January 1996 in people resident in Jordan. The JCR employs a combination of active and passive methods of case- finding. Active collection involves regis- try personnel visiting different facilities on a regular basis and abstracting data onto cancer registry forms. Passive reporting involves trained personnel in the different hospitals abstracting cancer data from patients’ files, completing the notification forms and forwarding them to the registry. Figure 1 shows the cancer statistics for Jordan going back to 1980. The number of cases registered approxi- mately doubled in 1996 when the JCR was transformed from a hospital-based to a population-based registry. All cancer cases are coded using the 3rd revision of the International clas- sification of diseases for oncology (ICD- O-3) [4]. CanReg4 software is used for data entry [5]. Duplicate entries are avoided by checking by name, age, diagnosis and place of residence. JCR relies for the most part on histology or cytology reports when defining incident cases. Data obtained from the pathol- ogy laboratories for all cancer cases are compared with those received from the hospitals. Missing data are sought from the respective institutions. The validity of the data is verified through internal quality checks, external checks and computer checks. Data collection For the current study we extracted and analysed the data on cancer cases regis- tered from January 1996 to December 2005 using a team of trained medical coders who checked the data against the information originally registered. Figure 1 Trend of number of cancer cases, all sites, in the Jordan cancer registry, 1980–2005 Year طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 839 To assess the accuracy of the data we re- captured cases from files and case notes from hospitals and compared it with other data sources. Also visual editing and automated software applications were applied to improve the accuracy of the data and to eliminate duplicate cases. Accuracy was generally high for demographic, diagnostic and treatment details, but less so for grade of differen- tiation, staging variables and dates of treatment. Although the JCR collects data on all cancer cases occurring in Jordan, the present analysis was restricted to people of Jordanian nationality in order to en- sure completeness of data and avoid the difficulty of estimating the age-adjusted rates for non-Jordanian populations. Analysis Jordan had a population in 2000–01 of 5.2 million, approximately 38% of whom were under the age of 15 years and only 3.6% over the age of 65 years. The average crude incidence rates were calculated using the average population for the index years 2000–01. The world standard population [6] was used to obtain age- standardized incidence rates (ASRs). Epi-Info, version 6, was used for statistical analysis. Results Between January 1996 and December 2005, 33 661 cases of cancer in Jordani- ans were reported to the JCR: 16 981 in males and 16 680 in females, a male to female ratio of 1:1.2. Crude incidence rates The highest crude incidence rate for males was 74.7 per 100 000 in 1996 and for females 75.2 per 100 000 in 1997. The highest annual rates were noticed during the early years of establishing the registry at a time when data collection was most active; subsequently the rates stabilized (Figure 2). The average annual crude incidence rate was 66.2 per 100 000 population for males and 70.0 per 100 000 popu- lation for females. When analysed by governorate the highest average crude incidence was in Amman, the capital, at 101.4 per 100 000 population, fol- lowed by Irbid (53.3) (Figure 3). The lowest average crude incidence was in Mafraq governorate (20.1 per 100 000 population). In Jordan lung cancer was the lead- ing cancer among males (10.6%), fol- lowed by colorectal (9.8%), leukaemia (9.3%), urinary and bladder (8.6%) and prostate cancer (7.4%) (Table 1). Among females, breast cancer was the most common malignancy (32.0%), followed by colorectal (9.0%), leukae- mia (6.7%), thyroid (4.9%) and corpus uteri cancer (4.6%) (Table 2). Figure 2 Crude incidence of cancer (per 100 000 population), all sites, 1996–2005 s s Year In ci de nc e .0 . . . . . . . . . . . . . . . . . . . EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 840 Age-specific incidence rates Figure 4 shows the ASRs for all can- cers in males and females. The overall average ASRs for all cancers were 119 per 100 000 adult males and 116 per 100 000 adult females (Table 3). The median age at diagnosis was 56 years for males and 53 years for females. By site of cancer the ASRs per 100 000 population for lung cancer were 16.3 and 3.6 per 100 000 in males and fe- males respectively and for colorectal cancer were 20.1 and 14.6 per 100 000 respectively. The ASR for breast cancer was 39.9 per 100 000 females. The incidence of lung cancer in Jor- dan rose sharply with age, with a first peak of increase of ASR in the age group 40–49 years for both males and females, which continued to rise steadily among males to a peak in the age group 70–74 years (Figure 5). Colorectal cancer was rare under 40 years of age, after which the rates began to rise steadily. By the age of 40–59 years, the rates were 18.7 and 24.3 per 100 000 for males and females respectively (Figure 6). Discussion Cancer is usually considered a disease of industrialized countries. However, increases in life expectancy in most de- veloping countries, even in the least developed [1], together with recent changes in lifestyle, have led to an epi- demic of cancer in developing countries. With current trends it is estimated that by the year 2020 70% of the new cases of cancer will be diagnosed in people living in developing countries [12]. Since the 1970s Jordan has wit- nessed a transition of morbidity and mortality from communicable diseases of childhood to noncommunicable diseases in adults. This is partly due to improvements of the socioeconomic status in the country, the expansion of health services and the strengthening of the primary health care system. With the successful control of most communica- ble diseases of childhood, the leading causes of mortality and morbidity have become cardiovascular diseases, cancer and injuries. The ASR per 100 000 males in Jordan is similar to the rates reported in some other Arab countries such as Kuwait [7], Bahrain [7] and Tunisia [10]. The ASR per 100 000 females in Table 1 Frequency of the 10 most common cancers among Jordanian males, 1996–2005 Rank Cancer site No. (n = 16 981) % 1 Lung 1836 10.6 2 Colorectal 1685 9.8 3 Leukaemia 1602 9.3 4 Urinary & bladder 1481 8.6 5 Prostate 1274 7.4 6 Non melanoma skin 1106 6.4 7 Brain & central nervous system 848 5.2 8 Non-Hodgkin lymphoma 824 4.7 9 Stomach 814 4.7 10 Hodgkin disease 582 3.3 Figure 3 Average crude incidence of cancer (per 100 000 population), all sites, by governorate, Jordan, 1996–2005 .0 .0 In ci de nc e . . . . . . . . . . Governorate طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 841 Jordan is similar to rates among females in Kuwait [7]. comparison with other countries of the REgion is shown in Table 3. The ASRs for all cancers in Jordan, in males and females, were sub- stantially lower than those in the USA (162.7 and 110.4 respectively) and the United Kingdom (173.7 and 121.3 re- spectively) [13]. These differences between Jordan and other countries, particularly indus- trialized countries, can be attributed to many factors, especially differences in lifestyle, which have become more ap- parent only in the past 2 decades. These include smoking and physical inactiv- ity; in the 2005 behavioural risk factor survey 51% of Jordanian males and 7% of females reported being smokers [14]. Fat intake is relatively low compared with industrialized societies and the tra- ditional diet of Jordanians consists of a moderate intake of fruits and vegetables rather than meat [14]. The recent de- mographic changes in Jordan—charac- terized by low infant mortality (22 per 1000 live births), a high total fertility rate (3.7) and life expectancy comparable to that in the developed world (71.5 years for both sexes)—indicate that the elderly population will increase in the future [15]. Breast cancer is the most common cancer in women, with 900 000 new cases occurring annually worldwide [2,12] and is becoming ever more sig- nificant in many developing countries [16,17]. It has been found to be a major- cause of death from cancer, second to lung cancer, in Jordan. Our data indicate that it is the dominant cancer among Jordanian women, with approximately 500–550 new cases occurring annually. The ASR was 39.9 per 100 000 females, higher than that of Saudi Arabia, Oman, Algeria, Bahrain and Tunisia (13.9, 14.9, 16.7, 28.6 and 34.6 respectively), but lower than that in Lebanon, Egypt, Kuwait and the USA SEER population (76.1, 49.6, 46 and 97.3 respectively) [3,18]. Breast cancer arises from a mul- tifactorial process and can be viewed as a disease predominantly influenced by risk factors related to lifestyle, as only about 15% of all breast cancer cases can be attributed to familial and ge- netic influences [19]. Differences in the prevalence of exposure to these lifestyle and genetic risk factors among women from different countries in the Middle East are probably responsible for the Table 2 Frequency of the 10 most common cancers among Jordanian females, 1996–2005 Rank Cancer site No. (n = 16 680) % 1 Breast 5373 32.0 2 Colorectal 1517 9.0 3 Leukaemia 1132 6.7 4 Thyroid 829 4.9 5 Corpus uteri 758 4.6 6 Non melanoma skin 751 4.5 7 Brain & central nervous system 606 3.6 8 Ovary 605 3.3 9 Non-Hodgkin lymphoma 545 3.3 10 Stomach 461 2.7 Figure 4 Average age-specific-incidence rate of cancer (per 100 000 population), all sites, Jordan, 1996–2005 ss Age (years) In ci de nc e EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 842 variability in breast cancer incidence seen between countries in this area [20,21]. Time trends in the prevalence of the lifestyle risk factors can be directly correlated with time trends in breast cancer incidence. Most known risk factors for breast cancer can be linked to the hazardous effects of hormone exposure, although other risk factors such as exposure to ionizing radiation are also relevant in some populations [22,23]. Increasing parity and early age at first parity are protective against breast cancer devel- opment [24]. Women’s breast cancer risk reduces by 4% for every 12 months of breastfeeding [25]. There is clear evidence in the general population that obesity is associated with a significantly higher risk of breast cancer [26]. History of benign breast disease is also related to increased risk of breast cancer. The risk, however, is mostly restricted to women who have undergone biopsies and especially those in whom atypical hyperplasia was found in such biopsies [27]. Most studies have focused on the influence on breast cancer incidence of modern lifestyles such as a high cho- lesterol intake, alcohol consumption and smoking. Dietary fat has been the most investigated food constituent studied in this regard and it is currently believed that a high-fat diet is related to the risk of breast cancer among women with no history of benign breast disease [28]. Active and passive smoking have recently been shown to be related to breast cancer risk [29,30]. Worldwide, colorectal cancer rep- resents 9.4% of all incident cancers in men and 10.1% in women. In Jordan colorectal cancer was the second most common cancer among both males and females, while globally the ASR of colorectal cancer in 2002 was 20.1 per 100 000 males and 14.6 per 100 000 females. There are notable differences in colorectal cancer incidences in more developed versus less developed countries. In the developed parts of the world, the ASR per 100 000 is 40.0 in males and 26.6 in females; in less developed areas the rates are 10.2 and 7.7 respectively. In Jordan, the ASR was 11.5 and 11.2 for males and females Table 3 Age-specific incidence rates (ASR) for all cancers in Jordan compared with other countries of the Eastern Mediterranean Region Country Source All cancers ASR per 100 000 population Males Females Jordan Current study 119 116 Bahrain [7] 118 108 Egypt [8] 152 136 Kuwait [7] 121 120 Lebanon [9] 169 176 Morocco [10] 96 87 Oman [7] 110 93 Qatar [7] 180 152 Saudi Arabia [7] 68 66 Sudan [10] 102 95 Syrian Arab Republic [11] 180 167 Tunisia [] 114 78 United Arab Emirates [7] 78 70 Figure 5 Average age-specific-incidence rate (per 100 000 population), lung cancer, Jordan, 1996–2005 s s In ci de nc e Age (years) طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 843 respectively. The highest ASR in males was observed in Australia/New Zea- land (48.2), followed by North America (44.4) and Western Europe (42.9). At the other end of the scale, the rates in South-Central Asia (4.7) and Central Africa (2.3) were the lowest [10]. In Jordan colorectal cancer was rare under 40 years of age, and the rates began to rise steadily after this age. By the age of 40–59 years, the Jordanian population had rates per 100 000 of 18.7 and 24.3 for males and females respectively. These rates were relatively close to those among Egyptians but lower than the rate of the US SEER population (43.3 and 32.8 for males and females respectively) [3]. In Jor- danians, the rates rose by about 20% for each 5-year period between the ages of 50 and 75 years. Evidence from epidemiological studies seems to show consistently that intake of dietary fat and meat is linked to colorectal cancer. Consumption of animal fat was found to be associated with increased risk of colon cancer [31]. Throughout the world, lung cancer is the most commonly diagnosed can- cer and causes more deaths than any other cancer [10]. In Jordan, 14.7% of cancer deaths are due to lung cancer [3]. International variations in the inci- dence are striking, with ASRs < 10 per 100 000 in parts of Africa, China, and South America and > 100 per 100 000 in the USA [18]. In Jordan the ASR of lung cancer per 100 000 was 16.3 per 100 000 in males, which is similar to that among Egyptians and Kuwaitis (14.0 and 11.3 respectively), but lower than that among Tunisians, Bahrainis and Qataris (27.8, 33.5 and 36.3 re- spectively) [18]. As expected, lung can- cer ASRs increased with age from the youngest age group (< 50 years of age) to the oldest (age 70+ years). The overall ASR of lung cancer in the Jordan population was much lower than in the USA SEER population [3], between one-third and one-quarter of the US SEER rates. In Jordan the lung cancer ASR in females was lower than in males (3.6 versus 16.3 per 100 000 population). Rates of cancer of the lung/ bronchus are similar among Israeli Jews and non-Jews and about twice as high as in Jordanians [32]. Worldwide statistics show that the lung cancer ASRs per 100 000 for males in other Arab coun- tries, such as Algeria (17.1) and Kuwait (11.3), were relatively close to those in Jordan (16.3), while the rate among Jordanian males was lower than that in Tunisia, Bahrain and Qatar (27.8, 33.5 and 36.3 respectively) [18]. However, the rate per 100 000 was lower than in Western countries such as Canada (59.0), Ireland (42.3) and the USA (61.9). All the female populations of the EMR including Jordan, display rates far lower than the USA SEER female population [3]. The ASRs per 100 000 females in Algerians (1.9) and Omanis (2.6) [33] were somewhat lower than in Jordanians (3.5) and Egyptians (3.6), although Kuwaitis (4.1) had a slightly higher rate. By far the most important risk factor in the development of lung cancer is tobacco use. Smoking more than 20 cigarettes per day has been shown to confer a 15- to 25-fold higher risk of lung cancer relative to nonsmokers [34]. Both the duration and intensity of cigarette smoking increases the risk, as does the tar content and the lack of a filter [35]. The risk decreases with time after cessation of smoking, with long- term exsmokers approaching but not reaching the risk of nonsmokers [36]. Other types of tobacco smoking, such Figure 6 Average age-specific-incidence rate (per 100 000 population), colorectal cancer, Jordan, 1996–2005 Age (years) In ci de nc e s s Total EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 844 World health report 2005. Make every mother and child count.1. Geneva, World Health Organization, 2005. Parkin DM et al. Global cancer statistics, 2002. 2. 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Oxford textbook of oncol- ogy. Oxford, Oxford Medical Publications, 1995:1243–1289. Parkin DM, Whelan SL, et al. 18. Cancer incidence in five continents, volume VIII. IARC Scientific Publication, No. 155. Lyon, Interna- tional Agency for Research on Cancer, 2002. Martin AM, Weber BL. Genetic and hormonal risk factors in 19. breast cancer. Journal of the National Cancer Institute, 2000, 92:1126–1135. Chlebowski RT et al. Ethnicity and breast cancer: factors influ-20. encing differences in incidence and outcome. Journal of the National Cancer Institute, 2005, 97:439–448. Bernstein L et al. Ethnicity-related variation in breast cancer risk 21. factors. Cancer, 2003, 97:222–229. Ronckers CM, Erdmann CA, Land CE. Radiation and breast 22. cancer: a review of current evidence. Breast Cancer Research, 2005, 7:21–32. Carmichael A, Sami AS, Dixon JM. Breast cancer risk among the 23. survivors of atomic bomb and patients exposed to therapeutic ionizing radiation. European Journal of Surgical Oncology, 2003, 29:475–479. Antoniou AC et al. parity and breast cancer risk among BRCA1 24. and BRCA2 mutation cancers. Breast Cancer Research, 2006, 8(6):R72. Breast cancer and breast feeding: collaborative reanalysis of in-25. dividual data from 47 epidemiological studies in 30 countries. Lancet, 2002, 360:187–195. Friedenreich CM. Review of anthropometric factors and 26. breast cancer risk. European Journal of Cancer Prevention, 2001:10(1):15–32. Vogel VG. Atypia in the assessment of breast cancer risk: im-27. plications for management. Diagnostic Cytopathology, 2004, 30:151–157. Velie E et al A. Dietary fat, fat subtypes, and breast cancer in 28. postmenopausal women: a prospective cohort study. Journal of the National Cancer Institute, 2000, 92:833–839. Collaborative Group on Hormonal Factors in Breast Cancer. 29. Alcohol, tobacco and breast cancer—collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. British Journal of Cancer, 2002, 87:1234–1245. as pipe, cigar and waterpipe smoking, are also linked to lung cancer, although the relative risks are not as high as for cigarette smoking. Exposure to passive smoking or environmental tobacco smoke is also related to an increased risk of lung cancer, although the relative risk is much lower than in active smok- ers. Worldwide, the incidence of lung cancer among males is much higher than among females, due primarily to the lower prevalence of smoking among females. Several other risk factors for lung cancer have been identified. Occu- pational exposures that increase the risk of lung cancer include asbestos, which also causes an increase in the risk of mesothelioma. Asbestos exposure and cigarette smoking act synergistically, together raising the risk of lung cancer multiplicatively [37]. Conclusion This is the first comprehensive report on cancer incidence in Jordan since the JCR was established in 1996 and expanded its work to cover the entire country. The study was based on data from 33 661 cases diagnosed during a 10-year period. At present, the actual burden of cancer in Jordan remains acceptable, with less than 5000 cases per year. However, as the country undergoes demographic and socioeconomic changes, the burden of cancer may increase in future decades. The pattern of cancer among males and females in Jordan is consistent with the Regional picture, with breast cancer be- ing the most common cancer among females and lung cancer the dominant cancer among males throughout the study period. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 845 Reynolds P et al. Active smoking, household passive smok-30. ing, and breast cancer: evidence from the California Teachers Study. Journal of the National Cancer Institute, 2004, 96:29–37. Boyle P, Langman JS. ABC of colorectal cancer: Epidemiology. 31. Student BMJ, 2000, 8:435–476. Freedman L et al. A comparison of population-based cancer 32. incidence rates in Israel and Jordan. European Journal of Cancer Prevention, 2003, 12:359–365. Blot WJ, Fraumeni JF, eds. 33. Cancer of the lung and pleura. Cancer epidemiology and prevention, 2nd ed. New York, Oxford Uni- versity Press, 1996:637–665. Hammond EC. Smoking in relation to the death rates of one 34. million men and women. National Cancer Institute Monograph, 1966, 19:127–204. Lubin JH et al. Patterns of lung cancer risk according to type 35. of cigarette smoked. International Journal of Cancer, 1984, 33:569–576. Tobacco smoking: monographs on the evaluation of carcinogenic 36. risk of chemicals to man, volume 38. Lyon, International Agency for Research on Cancer, 1986. Berry G, Newhouse ML, Antonis P. Combined effect of asbes-37. tos and smoking on mortality from lung cancer and mesothe- lioma in factory workers. British Journal of Industrial Medicine, 1985, 42:12–18. Towards a strategy for cancer control in the Eastern Mediterranean Region Although the incidence of cancer is still well below that in developed countries, the Eastern Mediterranean Region is expected to experience the highest increase among all WHO regions in the coming two decades. The increasing trend can be attributed to many factors including population ageing and exposure to risk factors such as smoking, unhealthy diet, etc. It is estimated that 40% of cancers can be prevented by risk factor modification; prevention therefore offers the greatest public health potential and the most cost-effective long‐term approach for cancer control. Towards a strategy for cancer control in the Eastern Mediterranean Region was developed in response to the increasing burden of cancer and the need for coordinated action in this regard. This publication reflects a shared commitment to reducing the incidence of cancer and improving the quality of life of those who develop cancer. . Full text is available at: http://www.emro.who.int/dsaf/dsa1002.pdf EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 846 Epidemiological, clinical and laboratory profile of glucose-6-phosphate dehydrogenase deficiency in the middle and north of Iraq: a comparative study M.D. Al-Mendalawi 1 ABSTRACT This study determined the epidemiological, clinical and laboratory profile of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Baghdad (central Iraq) and compared it with previous data from Mosul (northern Iraq). We reviewed the records of 156 under-5-year-olds with G6PD deficiency admitted to 3 hospitals in Baghdad over a 6-year period. A preponderance of males was noted in both Baghdad and Mosul (1.6:1 and 3.4:1 respectively). Family history of G6PD deficiency was positive in 19.2% of patients in Baghdad and 13.6% in Mosul. A majority of patients in Baghdad (69.2%) and Mosul (76.1%) showed haemolysis within 1–3 days of exposure to noxious agents. Similarities in the profiles from Baghdad and Mosul suggest that there are similar G6PD variants and similar exposure to precipitating agents. 1Department of Paediatrics, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq (Correspondence to M.D. Al-Mendalawi: mdalmendalawi@yahoo.com). Received: 21/01/09; accepted: 19/02/09 :قارعلا لماشو طسو في زوكولغ 6-تافسوفلا ينجورديه ةعزان ميزنإ زوعل ةيبرتخلماو ةيريسرلاو ةيئابولا حملالما مسترم ةنراقم ةسارد يولادنلما رهاظ دوممح ،)قارعلا طسو( دادغب في زوكولغ 6-تافسوفلا ينجورديه ةعزان ميزنإ زوعل ةيبرتخلماو ةيريسرلاو ةيئابولا حملالما ةساردلا هذه مسرـت :ةـصلالخا ةعزان ميزنإ زوعب باصم رمعلا نم تاونس 5 نود ًلافط 156 تلاجس ثحابلا عجار دقو .)قارعلا لماش( لصولما نم ةقباس تايطعمب هنراقتو في ثانلإا دادعأ لىع روكذلا دادعأ ةبلغ ظحول دقو .تاونس 6 ةدم للاخ دادغب في تايفشتسم 3 في اولخدأ نمم زوكولغ 6- تافسوفلا ينجورديه %19.2 ىدل ةيبايجإ زوكولغ 6- تافسوفلا ينجورديه ةعزان ميزنإ زوعب ةباصلإل ةيلئاعلا قباوسلا تناك ماك .)1:3.4( لصولماو )1:1.6( دادغب نم لك دعب )%76.1( لصولما فيو )%69.2( دادغب في ضىرلما مظعم ىدل مدلا للاحنا ثدح دقو .لصولما في ضىرلما نم %13.6 ىدلو ،دادغب في ضىرلما نم ينجورديه ةعزان ميزنإ زوعل ةبهاشتم بوضر دوجو لىإ يرشي لصولماو ،دادغب في حملالما مسترم ينب هباشتلا نإ .ةرئاضلا ةدمالل مهضرعت نم مايأ 3-1 .ةببسلما لماوعلل لثماتم ضرعتو زوكولغ 6- تافسوفلا Étude comparative du profil épidémiologique, clinique et biologique du déficit en glucose-6-phosphate déshydrogénase au nord et au centre de l’Iraq RÉSUMÉ La présente étude a permis de déterminer le profil épidémiologique, clinique et biologique de la carence en glucose-6-phosphate déshydrogénase (G6PD) à Bagdad (centre de l’Iraq) et de le comparer avec des données antérieures recueillies à Mossoul (nord de l’Iraq). Nous avons examiné les dossiers de 156 enfants âgés de moins de 5 ans qui présentaient une carence en G6PD, hospitalisés dans trois hopitaux de Bagdad sur une période de six ans. Une prépondérance masculine a été constatée aussi bien à Bagdad qu’à Mossoul (1,6 garçon pour 1 fille et 3,4 garcons pour 1 fille respectivement). Des antécédents familiaux de cette maladie ont été observés chez 19,2 % des patients à Bagdad et 13,6 % de ceux de Mossoul. Dans les deux villes, la majorité des patients présentaient une hémolyse un à trois jours après une exposition à des agents nocifs (69,2 % à Bagdad et à 76,1 % à Mossoul). Des analogies entre les profils de Bagdad et ceux de Mossoul laissent penser qu’il existe des variants similaires de la G6PD et une exposition semblable à des facteurs déclenchants. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 847 Introduction A functional deficiency of glucose-6- phosphate dehydrogenase (G6PD)— which oxidizes glucose-6-phosphate to 6-phosphogluconolactone in the pentose–monophosphate shunt with formation of reduced nicotinamide adenine dinucleotide phosphate (NADPH)—leads to oxidant-induced red-blood cell destruction [1]. It is the most common enzymopathy in the world and it has been estimated that more than 200 million people through- out the world are G6PD deficient. This genetic defect shows sex-linked inher- itance and a marked heterogeneity. More than 300 abnormal variants with deficient biochemical characteristics and about 100 diverse mutations have been identified [2,3]. The most com- mon clinical consequences of G6PD deficiency are neonatal jaundice and sporadic haemolytic crises caused by infections, certain drugs or, in the Medi- terranean variant, by ingestion of fava beans or inhalation of their pollen [1,4]. The study of G6PD deficiency in Iraq dates back to 1963 [5] when the first published study triggered a cascade of research on the problem in the coun- try. The present study aimed to deter- mine the epidemiological, clinical and laboratory profile of G6PD deficiency in Baghdad in the centre of Iraq and com- pare it with previously published data from Mosul in the north of the country. Unfortunately, similar published data from Basra, south of Baghdad, was una- vailable for comparison. Methods The study was conducted on 156 under 5-year-olds with documented G6PD deficiency by G6PD enzyme essay. Data were collected over the period 1 Janu- ary 2000 to 31 December 2006 from the records of patients admitted with a haemolytic episode to one of the 3 hos- pitals in Baghdad city (Al-Khadimyiah paediatric hospital, Al-Karama teaching hospital department of paediatrics and Al-Noor teaching hospital department of paediatrics). Through a review of medical records, data concerning age, sex, clinical presen- tation, onset of haemolysis, past history of neonatal jaundice, family history of G6PD deficiency, laboratory results and final outcome were obtained. The above data were compared with those reported previously in Mosul city [6]. Results Out of 156 patients recruited to the study, 97 (62.2%) were males and 59 (37.8%) were females, a male to female ratio of 1.6:1. The mean age was 2.8 (standard deviation 1.2) years. More than half the patients (58.3%) were in the age group 1–4 years. The characteristics of the study patients are shown in Table 1. Past his- tory of neonatal jaundice was recorded in 11.5% and a positive family history of G6PD deficiency in 19.2%. Recurrent episodes of haemolysis were reported by 10.9% of patients. A majority of patients (69.2%) had experienced haemolytic episodes within 1–3 days of exposure to precipitating agents (usually fava beans and to a lesser extent drugs such as trimethoprime-sulfamethoxazole or nalidixic acid. Clinically, symptoms and signs of dark colour urine and pallor were universal presenting symptoms (100%), whereas jaundice was reported in 82.7% and hepatosplenomegaly in 56.4% of patients. Half the patients (52.6%) had moderate anaemia (5–7 g/dL). Reticulocyte count and total white blood cell counts ranged from 4.5% to 19.6% and 4.9 to 25 × 109/L respectively. The range of total serum bilirubin (mainly indirect type) was 2.6–13.8 mg/dL. Blood urea and serum creatinine ranged from 35 to 47 mg/dL and 0.7 to 1.1 mg/dL respectively. All patients received blood trans- fusions in various amounts and were discharged within 2–4 days of hospitali- zation. No deaths were recorded. Discussion Iraq is situated within a region of a high frequency of G6PD deficiency genotype, with a carrier frequency in the population of 6.3% [7]. Studying the pattern of G6PD deficiency in the population is essential for a number of reasons: the increasing costs of health care associated with frequent hospitali- zations [8]; the substantial morbidity in terms of psychosocial burden and dis- turbed family environment for parents coping with children with chronic ill- ness [9]; and for planning preventive strategies [10]. A preponderance of males was not- ed in both the present study in Baghdad and the previous study in Mosul (1.6:1 and 3.4:1 respectively). The preponder- ance of females noted in some studies in other countries in the Eastern Mediter- ranean Region may be due to high rates of consanguinity, leading to increased numbers of homozygous females in addition to a high frequency of inactiva- tion of the normal X chromosome in female heterozygotes, which leads to disturbances in the Hardy–Weinberg equilibrium. Moreover, the presence of an “enhanced” gene that makes the expression of G6PD deficiency more likely has been suggested [11,12]. A past history of neonatal jaundice was found in similar proportions of chil- dren in this study in Baghdad (11.5%) and the previous study in Mosul (14.8%) [6]. Severe neonatal jaundice, particularly when it requires exchange transfusion, should alert paediatricians to the possibility of G6PD deficiency. Currently, most hospitals routinely test for G6PD when screening neonates before they are discharged from hospi- tal [13]. A positive family history of G6PD deficiency was reported at a higher rate in the Baghdad (19.2%) than in Mosul EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 848 (13.6%). This may be due to the obser- vation that many patients are asymp- tomatic and unaware they are G6PD deficient unless they are investigated or exposed to an oxidizing agent. A majority of patients in Baghdad (69.2%) and Mosul (76.1%) showed haemolysis within 1–3 days of exposure to precipitating agents. This is similar to what has been reported elsewhere [14– 16]. Recurrent haemolytic episodes were recorded in a slightly lower per- centage of children in Baghdad (10.9%) and Mosul (9.1%). Prevention of fur- ther attacks needs awareness of patients and their families to the need to avoid exposure to oxidative stress. Dark colour urine, pallor, jaundice and hepatosplenomegaly were the lead- ing clinical presentations in both areas of Iraq. This observation is consistent with previous studies [14–16]. When liver function is normal, jaundice typically does not occur until more than 50% of erythrocytes have been haemolysed [17]. The size of the spleen and liver in both studies varied from just palpable to 3–4 cm below the costal margin. Fever was documented in 37.8% of the patients in the Baghdad study com- pared with 44.3% in the Mosul study. Many individuals develop fever after the onset of infections such as urinary Table 1 Epidemiological, clinical and laboratory variables of the studied children with glucose-6-phosphate dehydrogenase (G6PD) deficiency in Baghdad and Mosul Variable Baghdad studya (n = 156) Mosul studyb (n = 88) No. % No. % Sex Male 97 62.2 68 77.3 Female 59 37.8 20 22.7 Male:female (ratio ) 1.6:1 3.4:1 Clinical history Positive past history of neonatal jaundice 18 11.5 13 14.8 Positive family history of G6PD deficiency 30 19.2 12 13.6 Recurrent attacks of haemolysis 17 10.9 8 9.1 Onset of haemolysis Few hours 10 6.4 4 4.5 1–3 days 108 69.2 67 76.1 4–7 days 38 24.4 17 19.3 Clinical presentation Dark colour urine 156 100.0 88 100.0 Pallor 156 100.0 88 100.0 Jaundice 129 82.7 69 78.4 Hepatosplenomegaly 88 56.4 55 62.5 Fever 59 37.8 39 44.3 Abdominal pain 33 21.1 14 15.9 Haematological tests Haemoglobin (g/dL) < 5 42 26.9 29 32.9 5–7 82 52.6 39 44.3 7–9 32 20.5 20 22.7 Reticulocyte count (%) 4.5–19.6 3.0–25.0 White blood cell count (/L) 4.9–25.0 × 109 3.9–40.0 × 109 Biochemical tests Total serum bilirubin (mainly indirect) (mg/ dL) 2.6–13.8 1.2–28.2 Blood urea (mg/dL) 35–47 Normal Serum creatinine (mg/dL) 0.7–1.1 Normal Outcome Recovery (days) 2–4 2–3 Mortality rate (%) 0 0 Sources: aPresent study; b[6]. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 849 tract infection, enteric fever and chest infections. The mechanism linking infection and haemolysis is complex and poorly understood. However it has been suggested that during phagocy- tosis leukocytes damage erythrocytes in their vicinity by discharging reactive oxygen species. Moreover, certain infec- tious organisms, such as Plasmodium, Clostridium, Babesia and Bartonella spp., are directly toxic to red blood cells [18]. Recently, it was noted that a mild degree of G6PD deficiency (comparable to the human class III G6PD deficiencies) worsens erythrocyte dysfunction during sepsis. Increased erythrocyte rigidity and a tendency for haemolysis, together with alterations in the interaction between erythrocyte band 3 protein and spectrin, may contribute to the immunomodula- tory effect of G6PD deficiency observed after major trauma and infection in hu- mans [19] .Unfortunately, screening for infectious diseases was not done in either of the Iraqi studies. Variable grades of anaemia, reticu- locytosis and leukocytosis were noted in both studies. A higher rate of mod- erate anaemia (5–7g/dL) was found in Baghdad (52.6%) than in Mosul (44.3%). The oxidized and denaturated haemoglobin forms cross-links and pre- cipitates intracellularly, forming red-cell inclusion bodies that are identified as Heinz bodies on supravital staining of peripheral blood smears. These inclu- sion bodies are removed in the spleen, leaving erythrocytes with a missing sec- tion of cytoplasm. These “bite cells” can be seen in the routine blood smear [1]. Although hyperbilirubinaemia, par- ticularly of the unconjugated type, is the main criterion for the diagnosis of haemolytic anaemia, it is mild and self- limiting when liver function is normal [1]. In the Baghdad and Mosul studies, variable grades of hyperbilirubinaemia particularly the indirect type were seen (2.6–13.8 mg/dL and 1.2–28.2 mg/ dL respectively). The higher range of serum bilirubin in the Mosul study may be attributed to the preponderance of cases of severe neonatal jaundice neces- sitating ultimately phototherapy and/or exchange transfusion. Renal function was preserved in patients in the Baghdad and Mosul studies, as manifested by nearly normal blood urea and serum creatinine levels. Azotaemia can complicate severe intra- vascular haemolysis and oliguria. There- fore, therapy must focus on maintaining a high urine output. All patients in both studies showed uneventful recovery within 2–4 days of hospitalization after receiving various degrees of blood transfusion. No deaths were reported in either study. Deaths reported during acute haemolytic epi- sodes are attributed to severe anaemia causing congestive heart failure, oliguric renal shutdown, malaria and hepatic encephalopathy [20–23]. The epidemiological , c l inical and laboratory picture of G6PD de- ficiency was very similar in patients from Baghdad and Mosul cities. It has been observed that in areas with a high occurrence of red blood cell genetic abnormalities, such as sickle-cell gene, G6PD and α- and β-thalassaemias, vari- ous genes frequently coexist in the same population. Coinheritance of 2 or more abnormal genes in the same individual is frequently encountered, particularly in certain “closed” tribes in which con- sanguineous marriages are the norm. Such genetic interactions modify the clinical presentation of the disease state [24,25]. In conclusion, the similar epidemio- logical, clinical and laboratory profile of G6PD deficiency in the middle and north of Iraq suggest genetic similarities in the G6PD variants and similar ex- posure to precipitating agents. Studies in the other parts of the country par- ticularly the south would further elu- cidate the picture of G6PD deficiency in Iraq, and a national survey is needed to address the exact biochemical and epidemiological variants of G6PD de- ficiency. Further studies would also be useful to determine possible interac- tions between various abnormal red blood cell genotypes notably G6PD, thalassaemia and sickle cell haplotypes. Educational programmes are needed to increase public awareness about G6PD deficiency. Acknowledgements Great thanks are due to the administra- tors of the aforementioned hospitals in Baghdad for their kind help in accom- plishing the study. Beulter E. Glucose-6-phosphate dehydrogenase and other 1. enzyme abnormalities. In: Beutler E et al., eds. William’s hae- matology, 6th ed. New York, McGraw-Hill, 2001. Beulter E. G6PD deficiency. 2. Blood, 1994, 84:3613–3636. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydroge-3. nase deficiency. Lancet, 2008, 371:64–74. Dors N et al. Glucose-6-fosfaatdehydrogenasedeficientie: 4. klinische presentatie en uitlokkende factoren [Glucose-6- phosphate dehydrogenase: clinical presentation and elicit- ing factors]. Nederlands Tijdschrift voor Geneeskunde, 2008, 152(18):1029–1033. References Taj El-Din S, Al-Samarrae A, Al-Abbosi A. Favism in Iraq. 5. Journal of the Faculty of Medicine (Baghdad), 1963, 1:1–7. Omar SK. Clinical profile of children with favism. 6. Annals of the College of Medicine, Mosul, 1998, 24(1&2):27–31. Hilmi FA et al. Red cell glucose-6-phosphate dehydrogenase 7. phenotypes in Iraq. Eastern Mediterranean Health Journal, 2002, 8(1):42–48. Merenstien D, Egleston B, Diener-West M. Lengths of stay and 8. costs associated with children’s hospitals. Pediatrics, 2005, 115(4):839–844. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 850 Genomic Resource Centre The World Health Organization (WHO) is one of several international organizations which have expressed concern about the widening knowledge and technology gap between the more developed and less developed countries, which could lead to the neglect of the health needs of low-income nations. WHO is therefore working to build international networks that involve researchers from all over the world, creating reliable, accessible information and knowledge-sharing tools specifically tailored for middle- to low- income countries. The Genomic Resource Centre (GRC). is an example of such a tool. The Human Genetics Programme has created a comprehensive Internet-based resource on genomics. The GRC’s primary mandate is to consolidate information from a variety of sources and provide links through easily accessible frameworks.This is the first website of its kind dedicated to providing reliable information on genomics and health to developing countries. The mission of the GRC is to enhance the transfer of genomic information, to encourage global networks, to foster informed dialogue, and to improve health services in genetics, especially in low to middleincome countries. Further information on this resource is available at: http://www.who.int/genomics/en/ Rao P, Pradhan PV, Shati H. Psycho-pathology and coping in 9. parents of chronically ill children. Indian Journal of Pediatrics, 2004, 71(8):695–699. Atwood K, Colditz GA, Kawachi I. From public health sci-10. ence to preventive policy: placing science in its social and political contexts. American Journal of Public Health, 1997, 87:1603–1606. Abdulrazzaq YM et al. Diversity in expression of glucose-6-11. phosphate dehydrogenase deficiency in females. Clinical Genetics, 1999; 55(1):13–19. Warsy AS, El-Hazmi MAF. G6PD deficiency, distribution and 12. variants in Saudi Arabia: an overview. Annals of Saudi Medicine. 2001, 21(3–4):174–177. Iwai K et al. A rapid single-step screening method for glucose-13. 6-phosphate dehydrogenase deficiency in field application. Japanese Journal of Tropical Medicine and Hygiene, 2003, 31:93–97. Verle P et al. Glucose-6-phosphate dehydrogenase deficiency 14. in Northern Vietnam. Tropical Medicine and International Health, 2000, 5(3):203–206. Grunfeld A. Acute hemolytic crisis in patients with G6PD de-15. ficiency: a case series. Prehospital and Disaster Medicine, 2001, 16(2):S33. Laosombat V et al. Glucose-6-phosphate dehydrogenase 16. variants associated with favism in Thai children. International Journal of Hematology, 2006, 83(2):139–143. Edwards CQ. Anemia and the liver: hepatobiliary manifesta-17. tions of anemia. Clinical Liver Diseases, 2002, 6:891–897. Berkowitz FE. Hemolysis and infections: categories and mecha-18. nisms of their interrelationship. Reviews of Infectious Diseases. 1991, 13:1151–1162. Spolarics Z et al. Red blood cell dysfunction in septic glu-19. cose-6-phosphate dehydrogenase-deficient mice. American Journal of Physiology. Heart and Circulatory Physiology, 2004, 286(6):H2118–H2126. Sarkar S et al. Acute intravascular hemolysis in glucose-6-phos-20. phate dehydrogenase deficiency. Annals of Tropical Pediatrics. 1993, 13(4):391–394. Ali M et al. Acute viral hepatitis with severe hyperbilirubinemia 21. and massive hemolysis in glucose-6-phosphate dehydroge- nase deficiency. Journal of Clinical Gastroenterology, 2001, 32:461–462. Balaka B et al. Insuffisance renale post-hemolytique chez 22. l’enfant deficient en glucose-6-phosphate deshydrogenase au Centre Hospitalier Universitaire de Lome. [Post-hemolytic renal failure in children with glucose-6-phosphate dehydro- genase deficiency at the university hospital center in Lome.] Medicine Tropicale, 2003, 63(2):151–154. Drout M, Gorgels AP, Bast A. Cardiac failure associated with 23. G6PD deficiency. Circulation Research, 2003, 93(8):e75. Awamy BH. Effect of G6PD deficiency on sickle cell disease in 24. Saudi Arabia. Indian Journal of Pediatrics, 1992, 59(3):331–334. El-Hazmi MAF et al. Genetic compounds—Hb S, thalassaemias 25. and enzymopathies: spectrum of interactions. Journal of Tropi- cal Pediatrics, 1994, 40(3):149–156. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 851 Macrovascular complications and their associated risk factors in type 2 diabetic patients in Sana’a city, Yemen A. Al-Khawlani,1 Z.A. Atef 1 and A. Al-Ansi 1 ABSTRACT A cross-sectional survey in Sana’a city, Yemen, aimed to determine the prevalence of preventable macrovascular complications and their association with glycaemic control and other risk factors in patients with type 2 diabetes mellitus (DM). Some features of macrovascular disease were found in 79 (25.4%) of the 311 patients: 17.8% had coronary heart disease, 9.1% had peripheral vascular disease and 5.8% had cerebrovascular disease. Significant positive associations were found between coronary heart disease and age, duration of DM, systolic blood pressure, diastolic blood pressure and insulin treatment. Peripheral vascular disease was associated with male sex, age, duration of DM and current tobacco smoking. Cerebrovascular disease was associated with systolic blood pressure, diastolic blood pressure and insulin treatment. 1Department of Internal Medicine, Faculty of Medicine, University of Sana’a, Al-Thawra Teaching Hospital, Sana’a, Yemen (Correspondence to A. Al-Khawlani: aalkhawlani@yemen.net.ye). Received: 08/10/08; accepted: 08/01/09 نميلا ،ءاعنص ةنيدم في يرّكسلا نم نياثلا طمنلا ضىرم ىدل راطتخلاا لماوعب اهطابتراو ةيربكلا ةيعولأا في تافعاضلما سينعلا مساق دحمأ ،فطاع دحمأ دياز ،نيلاولخا حلاص دممح ميركلا دبع في اهنم ةياقولا نكمي يتلا تافعاضلما راشتنا لدعم لىع ف ُّرعتلا فدهتسي ،نميلا في ،ءاعنص ةنيدم في ًايضرع ًاحسم نوثحابلا ىرجأ :ةـصلالخا ضعب نوثحابلا ظحلاو .يرّكسلا نم نياثلا طمنلا ضىرم ىدل راطتخلاا لماوع نم اهيرغبو ركسلا ىوتسم طبضب اهطابتراو ،ةيربكلا ةيعولأا %9.1 ىدلو ،ةيجاتلا ينـياشرلا في ضرم مهنم %17.8 ىدل ناك دقف ؛ًاضيرم 311 لصأ نم )%25.4( ًاضيرم 79 ىدل ةيربكلا ةيعولأا ضارمأ حملام يجاتلا بلقلا ضرم ينب ًايئاصحإ هب دتعي ًايبايجإ ًاطبارت نوثحابلا دجو ماك .ًايغامد ًايئاعو ًاضرم مهنم %5.8 ىدلو ،ةيفرطلا ةيعولأاب ًاضرم مهنم ةروكذلاب فيرطلا يئاعولا ضرلما طبترا ماك .ينلوسنلأاب ةلجاعلماو ،يطاسبنلاا مدلا طغضو ،ضيابقنلاا مدلا طغضو ،يرّكسلا ةدمو ،رمعلا ينبو ةلجاعلماو يطاسبنلاا مدلا طغضو ضيابقنلاا مدلا طغضب طبترا دقف يغامدلا يئاعولا ضرلما امأ .غبتلل ليالحا ينخدتلابو ،يركسلا ةدمبو ،رمعلابو .ينلوسنلأاب Complications macrovasculaires et risques associés chez des patients souffrant de diabète de type 2 à Sanaa (République du Yémen) RÉSUMÉ Une étude transversale réalisée à Sanaa (République du Yémen) avait pour objectif de déterminer la prévalence des complications macrovasculaires évitables et leur association avec le contrôle de la glycémie et d’autres facteurs de risque chez des patients souffrant de diabète de type 2. Sur 311 patients, 79 présentaient des signes de maladie macrovasculaire (soit 25,4 %) : 17,8 % souffraient d’une cardiopathie coronarienne, 9,1 % d’une maladie vasculaire périphérique et 5,8 % d’une maladie cérébrovasculaire. Des associations positives significatives ont été constatées entre les cardiopathies coronariennes et l’âge, la durée du diabète de type 2, la pression artérielle systolique, la pression artérielle diastolique et le traitement par insuline. La maladie vasculaire périphérique était associée au sexe masculin, à l’âge, à la durée du diabète de type 2 et la consommation de tabac au moment de l’étude. La maladie cérébrovasculaire était associée à la pression artérielle systolique, la pression artérielle diastolique et au traitement par insuline. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 852 Introduction Diabetes mellitus (DM) is associated with a number of vascular complica- tions. Microvascular complications such as retinopathy, nephropathy and neuropathy are specific to DM, whereas macrovascular complications such as peripheral vascular disease (PVD), coronary heart disease (CHD) and cer- ebrovascular disease (CVD) can occur in the absence of DM [1,2]. Macrovascu- lar complications in DM consist mainly of an accelerated form of atherosclerosis that affects the coronary, carotid and peripheral arteries, thus increasing the risk of myocardial infarction, stroke and diabetic foot disease [3,4]. CHD has been associated with DM in numerous studies, notably the Framingham study [5]. More recent studies have shown that the risk of myocardial infarction in people with DM is equivalent to the risk in nondiabetic patients with a history of previous myocardial infarction [6]. These discoveries have lead to new recommendations by the American Diabetes Association and American Heart Association that DM be con- sidered a coronary artery disease risk equivalent rather than a risk factor [7]. Patients with DM are 2 to 4 times more likely to develop cardiovascular diseases than the general population and have a 2–5-fold greater risk of dying from these diseases [7]. DM is also a strong inde- pendent predictor of the risk of stroke and CVD [8] and patients with type 2 DM have a 150%–400% higher risk of stroke [9]. Similarly, the risk of PVD in DM patients is 4 times higher than normal [10] and patients more com- monly have infrapopliteal arterial oc- clusive disease and vascular calcification than nondiabetic cohorts [11]. DM is known to increase the risk of lower limb amputation by 15–40 times compared with the general population [9]. The prevalence of macrovascular complications among DM patients has not been studied in Yemen. Such data are important given that these complications account for approxi- mately 50% of all deaths among DM patients in industrialized countries [9,10]. The aim of this study was to determine the prevalence of macrov- ascular complications in Yemeni pa- tients with type 2 DM and to identify the role of glycaemic control and other risk factors in patients with and without macrovascular complications. Methods This was a multi-centre, cross-sectional study, conducted from July 2006 to January 2007. The study was approved by the ethics committee of the Faculty of Medicine and Health Sciences at the University of Sana’a. Sample Patients aged ≥ 25 years with type 2 DM were recruited to the study when they visited one of the 2 primary care diabe- tes clinics in Sana’a city or visited the outpatient clinics at, or were admitted to, one of the 2 government hospitals (Al Thawra and Al-Kuwait) in the city. Patients who attend clinics in Sana’a, the capital city of Yemen, come from all regions of the country. Patients were invited to participate in the study by the physicians in the outpatient clinic and were examined according to the study protocol after they had given informed consent. Type 2 DM was diagnosed based on World Health Organization (WHO) criteria [12]. Patients who were diagnosed with gestational diabetes, type 1 DM, ketonuria or autoimmune disease were excluded from the study. Data collection Demographic data and medical history were obtained by a personal interview and by review of the patient’s medical records. Age, sex, duration of DM, type of treatment and family history of DM were recorded. Patients were also asked if they currently smoked tobacco (at least 10 cigarettes per day) or chewed khat leaves (daily). The physicians took the patient’s history of macrovascular complica- tions by interviewing the patients using locally understood terms if necessary. A hospital discharge record was required to certify the event. PVD was diagnosed by manifestations of intermittent clau- dication, ulcers or gangrene or a history of amputation or when one or more foot pulses were absent during medical ex- amination. CHD was diagnosed based on definitive myocardial infarction, ischaemic electrocardiographic changes (Q/QS and ST/T changes) and by a history of angina pectoris, myocardial infarction, coronary artery bypass graft or percutaneous coronary angioplasty. CVD was defined to include both a history of cerebral infarction or transient ischaemic attacks and was diagnosed on the basis of clinical manifestations and findings on computed tomography and a positive answer to the question “Have you ever had a stroke?” Patients with cerebral haemorrhage and embo- lism originating from cardiac thrombi were excluded from this study. Blood pressure was measured on the right arm, with the subject seated after 10 minutes rest, using a standard clinical mercury sphygmomanometer with an appropriate cuff size. Hyper- tension was diagnosed according to WHO criteria [13] if systolic pressure was ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg or if the patient was taking antihypertensive drugs. Height and weight were recorded with the patient wearing clothing and without shoes. Body mass index (BMI) was defined as weight (kg)/height2 (m2). Obesity was classified according to WHO criteria [14]. Blood was drawn after overnight fasting for determination of the levels of fasting plasma glucose, glycosylated haemoglobin (HbA1c) and the lipid profile. A second venous blood sample was taken 2 hours later, to determine the 2-hour postprandial glucose. All bio- chemical measurements were carried out on the same day as blood collection طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 853 using standard laboratory automated techniques. Plasma glucose level was assessed by means of the glucose hex- okinase method (Roche Diagnostic, Mannheim, Germany). Serum total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol and serum triglyc- erides were measured using enzymatic techniques (Boehringer-Mannheim, Germany). Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. The cut-offs were as follows: fasting plasma glucose < 126 mg/dL, 2-hour postprandial glucose < 140mg/dL, total cholesterol > 200 mg/dL, triglycerides > 150 mg/dL, HDL cholesterol < 40 mg/dL and LDL cholesterol > 150 mg/ dL [12,15]. HbA1c level < 7% was taken to indi- cate good glycaemic control. Statistical analysis Statistical analysis was performed using SPSS software, version 15. Mean and standard deviation (SD) were deter- mined for quantitative data. Student t-test was conducted to determine the significance of observed difference be- tween the means of clinical parameters of males and females. Chi-squared tests were used to ascertain the association between macrovascular disease and clinical variables. P < 0.05 was consid- ered significant. Results Patients’ background characteristics A total of 311 patients with type 2 DM were studied. There were 155 males (49.8%) and 156 females (50.2%), mean age 53.9 (SD 10.9) years (range 25–85 years). The duration of DM varied between 1–35 years. Of the total patients 53.4% had hypertension [150 (48.2%) systolic hypertension and 97 (31.2%) diastolic hypertension]. The mean BMI was 24.1 (SD 4.1) kg/m2, and the prevalence of overweight (BMI > 25–< 30 kg/m2) was 34.1% and of obesity (BMI > 30 kg/m2) was 8.7%. HbA1c levels showed that 211 (87.9%) had poor glycaemic control (HbA1c ≥ 7%). DM was being treated with diet alone for 29 patients (9.3%), with oral hypoglycaemic agents for 227 (72.9%) and with insulin in the remaining 55 (17.7%). Table 1 showed the charac- teristic of the DM patients by type of treatment. Insulin-treated patients had a significantly longer duration of disease than individuals on diet or oral hypogly- caemic therapy (P < 0.001). Patients on insulin therapy had a higher prevalence of CHD and PVD compared with pa- tients under oral hypoglycaemic therapy and diet alone, but the difference was only significant for CHD (P < 0.006). Patients on oral hypoglycaemic therapy had a significantly higher prevalence of CVD compared with patients on insulin therapy or controlled with diet alone (P < 0.037). Table 2 shows the demographic, clinical and laboratory findings for the total sample and for males and females. Overall 79 (25.4%) DM patients had symptoms of macrovascular complica- tions: 28 (9.1%) had PVD, 55 (17.8%) had CHD and 18 (5.8%) had CVD. Two patients had all 3 types of mac- rovascular complication, 10 patients had both PVD and CHD, 11 patients had CHD and CVD and 3 patients had PVD and CVD. The prevalence of PVD was significantly higher in men than women (14.1% versus 8.8%, P < 0.001) but there was no significant difference between males and females in the prevalence of CVD (6.5% versus 5.1%, P = 0.07) or CHD (20.6% versus 14.7%, P = 0.17). Overall 21.2% of patients re- ported being current cigarette smokers and 50.8% chewed khat leaves daily. Significantly more men than women were smokers (P = 0.005) and khat users (P < 0.001). Relationship between DM and macrovascular complications The clinical parameters of patients in each subgroup of macrovascular disease—PVD, CHD and CVD— were compared with those without the condition (Tables 3–5). The significant predictive risk factors for PVD were male sex (P < 0.001), age Table 1 Characteristics of patients with type 2 diabetes mellitus (DM) by mode of therapy Variable Insulin (n = 55) Oral hypoglycaemic agents (n = 227) Diet alone (n = 29) P-value Mean SD Mean SD Mean SD Age (years) 55.8 9.3 53.3 11.2 55.6 11.0 0.22 Duration of DM (years)a 11.9 7.3 5.1 5.5 4.9 7.1 < 0.001a No. % No. % No. % Peripheral vascular disease 7 12.0 18 7.9 3 10.3 0.51b Coronary heart disease 16 29.0 37 16.3 2 6.9 0.006b Cerebrovascular disease 1 1.8 17 7.5 0 0.0 0.037b aANOVA test; bChi-squared test. SD = standard deviation. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 854 (P < 0.004), duration of DM (P < 0.001) and smoking (P < 0.015) (Table 3). The significant predictive risk factors for CHD were age (P < 0.001), dura- tion of DM (P < 0.001), systolic blood pressure (P < 0.001), diastolic pressure (P < 0.002) and insulin treatment (P < 0.021) (Table 4). Mean systolic blood pressure (P < 0.028), diastolic blood pressure (P < 0.035) and the propor- tion of patients on insulin treatment (P < 0.037) were significantly higher in patients with CVD than those without it (Table 5). No significant associations were found for glycaemic control, BMI, total cholesterol, triglycerides, HDL- cholesterol, LDL-cholesterol and khat use in any of the 3 categories of macrov- ascular disease. Discussion The present study investigated the prevalence and risk factors of macrov- ascular complications in a sample of Yemeni patients with type 2 DM. Little is known about the prevalence of DM in Yemen, except for a study in 2004 which found a prevalence of DM in the Yemeni population of 4.6% (7.4% in males and 2.0% in females) [16]. Our results strongly suggest that DM is as- sociated with chronic macrovascular complications. The overall prevalence of macrovascular complications among Yemeni patients with type 2 DM was 25.4%: 17.8% had a history of CHD, 9.1% had evidence of PVD and 5.8% were diagnosed with CVD. The rates of macrovascular com- plications in type 2 DM in the present study are consistent with the finding of other studies in the region. A study in the United Arab Emirates (UAE) found similar rates for total macrovascular disease (29.5%), PVD (11.6%), CHD (14.4%) and CVD (3.5%) [17]. In Saudi Arabia the prevalence of acute coronary syndrome (14.8%) and myocardial in- farction (23.1%) were higher than our rate of CHD [18]. The rate of foot infec- tion was 4.3% and amputation was 1.9%; these results were lower than our rate for PVD, while the rate of stroke (10%) was twice a high as our rate for CVD. In Bahrain the rate of PVD reported (11.8%) is consistent with our results [19]. Compared with the rates reported Table 2 Clinical feature of the patients with type 2 diabetes mellitus (DM) by sex Variable All (n = 311) Males (n = 155) Females (n = 156) P-value (males vs females) Mean SD Mean SD Mean SD Age (years) 53.9 10.9 54.7 11.7 53.2 10.0 0.20 Duration of DM (years) 6.3 6.5 6.2 6.9 6.4 6.1 0.76 BMI (kg/m2) 24.1 4.1 24.1 4.2 24.3 4.0 0.61 Glycaemic profile Fasting blood glucose (mg/dL) 211.1 89.5 205.3 85.5 216.7 93.0 0.25 2-hour postprandial blood glucose (mg/dL) 311.2 110.9 306.9 111.5 315.4 110.6 0.50 HbA1c (%) 9.5 2.2 9.3 1.9 9.7 2.4 0.153 Lipid profile Total cholesterol (mg/dL) 189.2 49.1 188.0 48.5 189.8 49.9 0.82 HDL cholesterol (mg/dL) 42.3 28.8 41.7 27.7 42.8 25.8 6.70 LDL cholesterol (mg/dL) 142.2 43.2 141.1 42.4 143.2 451.9 0.67 Triglycerides (mg/dL) 222.5 116.9 233.1 127.9 212.1 104.4 0.12 No. % No. % No. % Macrovascular disease Peripheral vascular disease 28 9.1 22 14.1 6 8.8 < 0.001 Coronary heart disease 55 17.8 32 20.6 28 14.7 0.17 Cerebrovascular disease 18 5.8 10 6.5 8 5.1 0.07 Hypertension Systolic hypertension 150 48.2 71 47.3 79 52.7 0.31 Diastolic hypertension 97 31.2 47 48.5 50 51.6 0.74 Smoking/substance use Smokes tobacco 66 21.2 43 27.7 28 14.7 0.005 Chews khat daily 158 50.8 100 64.5 58 37.2 < 0.001 Family history Family history of DM 188 50.8 76 48.1 82 51.9 0.64 SD = standard deviation; BMI = body mass index; HbA1c = glycosylated haemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 855 by the London follow-up to the WHO multinational study of vascular disease in diabetics [20] the rate of CHD was 3 times lower in our study, the rate of CVD was similar and the rate of PVD was twice as high. In the United States of America (USA), after a mean follow-up of 13 years, the prevalence of CHD in type 2 diabetics was 48.1%, 3-fold higher than the prevalence in our study, and the prevalence of CVD (25.6%) was sev- eral times higher than our rate [21]. The difference in our rate of macrovascular complications among patients with type 2 diabetes and the results mentioned above can be explained by the different study designs, differences in sample size and ethnic variations. Table 3 Characteristics of patients with type 2 diabetes (DM) mellitus with and without peripheral vascular disease Variable Peripheral vascular disease P-value Yes (n = 28) No (n = 282) Mean SD Mean SD Age (years) 59.5 9.4 53.4 10.6 0.004 Duration of DM (years) 11.3 8.8 5.8 6.0 < 0.001 BMI (kg/m2) 23.1 3.8 24.3 4.1 0.13 HbA1c (%) 8.7 1.9 9.5 2.2 0.10 Total cholesterol (mg/dL) 183.3 56.8 189.8 48.3 0.50 HDL cholesterol (mg/dL) 42.2 28.6 42.3 25.5 0.99 LDL cholesterol (mg/dL) 136.0 49.3 142.5 42.6 0.65 Triglycerides (mg/dL) 284.5 112.7 24.3 117.5 0.57 Systolic blood pressure (mmHg) 145.4 24.6 137.9 26.2 0.15 Diastolic blood pressure (mmHg) 88.2 15.1 83.7 12.4 0.08 No. % No. % Insulin treatment 7 25.0 48 17.0 0.51 Smoking tobacco 11 38.2 55 24.2 0.015 Chewing khat leaves 18 64.3 140 49.6 0.14 Family history of DM 13 40.4 144 51.1 0.64 SD = standard deviation; BMI = body mass index; HbA1c = glycosylated haemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein. Table 4 Characteristics of patients with type 2 diabetes (DM) mellitus with and without coronary heart disease Variable Coronary heart disease P-value Yes (n = 55) No (n = 254) Mean SD Mean SD Age (years) 59.3 10.6 52.8 10.6 < 0.001 Duration of DM (years) 9.8 7.8 5.5 5.9 < 0.001 BMI (kg/m2) 24.5 3.8 24.1 4.2 0.48 HbA1c (%) 9.1 2.2 9.6 2.2 0.23 Total cholesterol (mg/dL) 184.7 52.4 190.1 48.5 0.46 HDL cholesterol (mg/dL) 46.6 44.6 41.3 19.5 0.17 LDL cholesterol (mg/dL) 142.8 42.9 142.0 43.4 0.91 Triglycerides (mg/dL) 242.4 155.4 218.5 106.9 0.17 Systolic blood pressure (mmHg) 149.1 28.9 136.3 25.5 < 0.001 Diastolic blood pressure (mmHg) 89.0 15.6 83.1 11.8 0.002 No. % No. % Insulin treatment 16 20.1 88 15.0 0.02 Smoking tobacco 12 21.8 54 21.3 0.93 Chewing khat leaves 30 54.5 128 50.4 0.58 Family history of DM 26 47.3 131 51.6 0.56 SD = standard deviation; BMI = body mass index; HbA1c = glycosylated haemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 856 Analysis of the risk factors in our study showed that systolic hypertension and diastolic hypertension were impor- tant risk factors for CHD and CVD, but not for PVD. Moreover, age and dura- tion of DM were significantly associated with PVD and CHD, but not CVD. Smoking and male sex were significant- ly associated with PVD, while insulin treatment was significantly associated with CVD. These results are consistent with findings elsewhere in the Eastern Mediterranean Region (EMR). For example, in the UAE a cross-sectional study done to determine the prevalence and risk factors of macrovascular com- plications among diabetic patients re- vealed a significant association between macrovascular disease and male sex, age, duration of DM and hypertension [17]. A study in Pakistan showed that subjects with CHD were more likely to have hypertension and be current smokers, and that subjects who had experienced a cerbrovascular accident were more likely to have had DM for more than 5 years and to be current smokers [22]. In the Islamic Republic of Iran, a study revealed that the prevalence of CHD increased with age, BMI, smoking and insulin treatment [23]. Outside the EMR, in the USA, a study revealed that age, fasting glucose levels, smoking and triglyceride levels were independent risk factors for de- velopment of CHD events in type 2 DM, while age, hypertension, glucose and smoking predicted development of CVD [21]. Generally, in our re- sults and the results of other studies mentioned above, the greatest risk fac- tors for macrovascular complications were male sex, age, duration of DM and hypertension. We were not able to detect any association between the presence of macrovascular disease and glycaemic control as determined by HbA1c level. This negative correlation is not unique. Indeed, many longitudinal studies were unable to establish such a link [20,24,25]. The reason may be because ofthe relatively small sample size studied and the small number of patients with complications, or it may be related to the multi-factorial nature of macrovascular disease, as reported in other studies [26]. Furthermore, unlike experience elsewhere [27], our study was unable to demonstrate an associa- tion between BMI and dyslipidaemia in the study population, but this is not uncommon. For example, in Pakistan, macrovascular complications increased with age, duration of DM and were more prevalent in uncontrolled diabet- ics (HbA1c > 8.6%), but macrovascular complications were not associated with BMI or dyslipidaemia [28]. In Saudi Arabia, a study to determine the fre- quency of cardiovascular risk factors in Saudi and non-Saudi diabetics showed that hypertension, hyperlipidaemia and smoking were common CVD risk fac- tors in both Saudis and non-Saudis, while obesity was less common in both groups. Both groups had poor blood glucose control [29]. Smoking was a significant risk factor for PVD but not for CHD or CVD. We also found no significant difference in the rate of macrovascular complica- tions in patients chewing khat in any of the subgroups of CHD, PVD or CVD. Khat leaf chewing is widely practised in Yemen, especially among diabetics, who believe that it reduces blood sugar. Furthermore an association between Table 5 Characteristics of patients with type 2 diabetes (DM) mellitus with and without cerebrovascular disease Variable Cerebrovascular disease P-value Yes (n = 18) No (n = 292) Mean SD Mean SD Age (years) 57.6 12.4 53.8 10.7 0.15 Duration of DM (years) 9.1 4.3 6.2 6.6 0.33 BMI (kg/m2) 23.8 4.3 24.2 4.2 0.69 HbA1c level (%) 9.5 2.5 9.5 2.2 0.98 Total cholesterol (mg/dL) 192.9 50.0 188.9 49.1 0.74 HDL cholesterol (mg/dL) 42.6 19.2 42.3 26.1 0.95 LDL cholesterol (mg/dL) 137.5 42.1 142.4 43.3 0.64 Triglycerides (mg/dL) 255.6 165.1 220.5 113.4 0.22 Systolic blood pressure (mmHg) 151.7 27.1 137.8 28.9 0.028 Diastolic blood pressure (mmHg) 90.3 13.1 83.8 12.7 0.035 No. % No. % Insulin treatment 1 5.6 54 18.5 0.037 Smoking tobacco 5 27.7 61 20.8 0.49 Chewing khat leaves 10 55.5 148 50.7 0.69 Family history of DM 8 44.4 149 51.0 0.59 SD = standard deviation; BMI = body mass index; HbA1c = glycosylated haemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 857 khat chewing and hypertension has been reported previously [30]. The prevalence of CHD in our study was rather low compared with studies in other geographical settings. This may be explained by the fact that patients in our study were slightly younger and had a lower rate of hypertension. The preva- lence of overweight and obesity was considerably lower than the prevalence found in other studies in the region. For example, in a study in Riyadh, obesity was reported in 33% of adult diabetics [31] and in the UAE in 37% [17]. In another study in Saudi Arabia, the mean age of the patients was 58.4 (SD 14.2) years, the prevalence of hypertension was 78% and the rates of overweight and obesity were 39.0% and 44.8% respec- tively [18]. In the Islamic Republic of Iran the study group had a mean age of 62.2 (SD 12.4) years and hypertension was present in 91% [32]. Other studies considered ethnic differences to explain the variation in the risk of cardiovascular disease be- tween populations [33]. Among those, a USA-based study concluded that a substantial part of the risk associated with ethnicity can be attributed to so- cioeconomic status and geographical location rather than ethnicity [33]. The results of our study clearly demonstrate that DM is associated with chronic complications, including PVD, CHD and CVD in this sample of Yemeni dia- betic patients. These findings highlight the need for primary care physicians to be aware of the possible presence of these complications among their patients. The general awareness of the community also needs to be raised about individual risk factors for DM and its complications. Conclusions CHD was the most frequent macrovas- cular complication in this group of type 2 DM patients. The risk was relatively low compared with that seen in patients in other geographical settings. 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El Hazmi MA, Warsy AS. Prevalence of overweight and obes-31. ity in diabetic and non-diabetic Saudis. Eastern Mediterranean Health Journal, 2000, 6(2–3):276–282. Esteghamati et al. Prevalence of diabetes and other cardio-32. vascular risk factors in an Iranian population with acute coro- nary syndrome. Cardiovascular Diabetology, 2006, 5:15 (doi: 10.1186/1475-2840-5-15). Matthews KA et al. Ethnic Differences in cardiovascular burden 33. among middle-aged women’s, health across the nation. Ameri- can Heart Journal, 2005, 149:1066–1072. Second Annual Conference of the Global Diabetes Alliance (GDA 2), Cairo, Egypt, 26–29 October, 2010 Cairo will host the second Global Diabetes Alliance Congress, a very special event whose goal is to unify protocols for epidemiological surveys and prevention and management of diabetes and its related disorders. This Congress will be dedicated to the presentation of updates on the diabetes epidemic in various parts of the world (including the Middle East and Africa) and workshops designed to initiate collaborative research projects among groups of investigators throughout the world. The programme can be accessed from the conference website at: http://conf.global-diabetes. org/index.htm طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 859 Nutrition knowledge, beliefs and dietary habits among elderly people in Nizwa, Oman: implications for policy A. Al Riyami,1 S. Al Hadabi,2 M.A. Abd El Aty,1 H. Al Kharusi,1 M. Morsi1 and S. Jaju1 ABSTRACT The nutritional needs of the ageing population require special attention. We undertook a cross- sectional, community-based, household survey in Nizwa wilayat, Oman to study nutrition-related knowledge and beliefs and self-reported dietary habits among a sample of elderly people. The response rate for the household interview was 99.3% from a total sample of 2041. About 45% of the elderly were overweight or obese. Overall we found poor knowledge of nutrition plus some nutritional imbalances and low levels of physical activity. Significant sex differences existed in elderly peoples’ nutritional knowledge, consumption of fluids, milk and sweets, use of dietary regimens and experience of appetite change. The findings warrant reorientation of the existing health promotion strategy for the elderly. 1Directorate of Research and Studies, Directorate General of Planning, Ministry of Health, Muscat, Oman (Correspondence to A. Al Riyami: asyariyami@gmail.com). 2Directorate of Health Services, Al Dakhliya Region, Nizwa, Oman. Received: 28/10/08; accepted: 12/01/09 ةسايسلا راثآ :نماُع ،ةوزن في يننسلما ىدل ةيئاذغلا تاداعلاو تادقتعلماو فراعلما وجاج ياجنس ،سيرم يدمج ،صيورلخا للاه ،ةيطع دوممح ،بيادلها حلاص ،يمايرلا ايسآ ،ىوزن ةيلاو في عمتجلما لىع زكتري ناكسلل ًايضرع ًاحسم نوثحابلا ىرجأ دقو .ًاصاخ ًامماتها يننسملل ةيوذغتلا تاجايتحلاا بلطتت :ةـصلالخا ةباجتسلاا ةبسن تغلب دقو .يننسلما نم ةنيع ىدل ةيئاذغلا مظنلاو تاداعلا نع تياذلا غلابلإاو ،ةيذغتلا لوح تادقتعلماو فراعلما ةساردل ،نماُع في نع فراعلما نأ نوثحابلا دجوو .ءاندب وأ نزولا يطرفم يننسلما نم %45 ناك دقو .2041 اهددع غلابلا ةنيعلا لماك لصأ نم %99.3 ناكسلا ةلباقلم ينب ًايئاصحإ ابه دتعي تافلاتخا كانه ناكو .ةيندبلا ةيلاعفلا نم ضفخنم ىوتسمو ،يوذغتلا نزاوتلا للاتخا عم ،ةفيعض لياجمإ لكشب ةيذغتلا هِّبنتو .ةيهشلا في ُّريغتلا ةاناعمو ،ةيئاذغلا مظنلا مادختساو ،تايوللحاو ،بيللحاو ،لئاوسلا لوانتو ةيوذغتلا فراعلما ثيح نم يننسلما ىدل ينسنلجا .ينّنسلما ىدل ةحصلا زيزعتل ةيلالحا ةيجيتارـتسلاا في هاتجلاا يـيغت لىإ ةساردلا Connaissances et croyances en nutrition et habitudes alimentaires chez des personnes âgées à Nizwa (Oman) : répercussions sur les politiques RÉSUMÉ Une attention particulière doit être portée aux besoins nutritionnels de la population des personnes âgées. Nous avons réalisé une étude transversale communautaire auprès des ménages de la wilaya de Nizwa (Oman) afin d’étudier les connaissances et croyances en termes de nutrition et les habitudes alimentaires autodéclarées dans un échantillon de personnes âgées. Le taux de réponse des ménages à l’étude a été de 99,3 % pour un échantillon total de 2 041 sujets. Près de 45 % des personnes âgées souffraient de surcharge pondérale ou d’obésité. Dans l’ensemble, les résultats montrent que les personnes âgées avaient de faibles connaissances en nutrition, qu’elles présentaient des déséquilibres alimentaires et qu’elles pratiquaient peu d’activité physique. Des différences significatives liées au sexe ont été observées en termes de connaissances en nutrition, de consommation de liquides, lait et sucreries, de recours aux régimes alimentaires et d’antécédents de modifications de l’appétit. Les résultats justifient une réorientation de la stratégie existante de promotion de la santé destinée aux personnes âgées. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 860 Introduction The World Health Organization (WHO) has acknowledged that age- ing and nutrition is a growing global challenge [1]. Modifying lifestyle fac- tors such as diet can prevent, slow or reverse the onset of many of the chronic diseases associated with ageing. Iden- tifying dietary patterns and specific di- etary components that offer protection against chronic disease is important [2]. Perceptions of healthy eating and food group consumption practices of elderly men are largely unexplored [3]. The Food Habits in Later Life project of the International Union of Nutritional Sciences highlighted the value of rapid assessment procedures for developing food-based dietary guidelines for their aged members [4]. Elderly patients with a compromised nutritional status increase the burden on the existing health care infrastruc- ture. The inpatient burden of elderly people in Oman is around 10% [5]. This study was undertaken to as- sess nutrition-related knowledge and beliefs and self-reported dietary habits among a sample of elderly Omanis and to determine sex differences in their re- sponses. It was hoped that the findings would be utilized for developing health promotion policy. Methods A cross-sectional, community-based, household survey of the profile and needs of non-institutionalized elderly Omanis aged 60 years and above was conducted in the Nizwa wilayat, Al Dakhliya region of Oman in 2005. Sample Our sampling frame was the 2003 cen- sus data [6]. The Ministry of National Economy provided a list of households where elderly people were resident, to- gether with the corresponding enumer- ation area maps for the Nizwa wilayat. Supervisors were involved in updating the maps and numbering the houses. The elderly who had moved to a dif- ferent location in the wilayat and were residing in houses newly built since the census were also traced and recruited. Inhabitants of Jabal Akhdar and remote scattered houses were excluded due to logistic constraints. After updating the list of elderly people we found a total of 1508 houses inhabited by elderly peo- ple, which yielded 2041 elderly people. The response rate for the household interview was 99.3% (n = 2027), while for the clinical examination and investi- gation it was 80.8% (n = 1650). Data collection After approval by the research ethics committee of the Ministry of Health, Oman, informed consent was obtained from the participants. A structured questionnaire to assess 9 different do- mains of health relevant to the elderly in Oman was constructed, based on a literature review and expert opinion; only the nutrition domain is reported in this paper. The data were collected by personal interviews at home. The in- terviewers were health educators from the Ministry of Health and volunteers from community support groups who received 6 days of standardized inten- sive training. A second questionnaire to collect data from clinical examinations and investigations was completed by a medical doctor in the Nizwa com- munity research centre. After the pilot study, data collection was conducted between June and August 2005. The questionnaire collected basic demographic data about respondents: age, sex, marital status, education, oc- cupation, personal income and whether living with their family. The next sec- tion assessed respondents’ knowledge and beliefs about nutrition: whether the quality and quantity of food should change in older ages, what types of food to eat and whether certain food can protect or control diseases in later life. A section on dietary habits asked about number of meals eaten, whether their appetite had changed, the quantities of various food groups that they con- sumed and whether they consumed any special diets, took vitamin/mineral supplements, etc. Currently there are no uniform food guidelines for the Arab region or por- tion size and food composition tables to suit the Arab food habits and culture [7]. For our nutrition analysis we took account of the traditional regional [8] and local dietary habits to establish ap- propriate frequencies of dietary intakes. In the questionnaire the responses were assessed as adequate/inadequate intake. Except for fluids, information about portion sizes was not collected. Adequate consumption of fish/meat/ chicken (animal proteins) was defined as consumption > 3 times per week and inadequate as ≤ 3 times per week. The same criteria were applied for veg- etables, fruits and cereals. Intake of milk and milk products ≤ 3 times per week was classified as less than adequate while 4+ times per week was adequate. Milk and milk products were classified as full-fat if 2 or more items out of milk, yoghurt and laban were reported to be full-fat. Information about portion sizes was not collected. Fluid consumption per day (water, milk, laban, fruit juices and other drinks) ≤ 1500 mL per day (measured by number of oral dehydra- tion solution glasses) was considered inadequate. We also assessed levels of physical activity based on daily chores and walk- ing, with the cut-off set at 30 minutes exercise per day [9]. Body mass index was calculated and underweight, over- weight and obesity were defined based on WHO criteria [10]. Analysis Data entry was done in the region with Epi-Info, version 3.1, and data manage- ment and analysis was done using SPSS, version 9.0. Descriptive analysis of the nutrition-related data was done. Chi-squared tests of significance, with طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 861 P < 0.05 as significant, were used to assess sex differences for the relevant variables. Results Background characteristics The sample of respondents consisted of 51.6% females and 48.4% males (Table 1). There were significantly more women in the 60–69 years age group (59.7% of women, 53.8% of men) and fewer in the 70–79 years group (24.2% of women, 31.3% of men), while the sex distribution of the very elderly (age 80+ years) was similar. A majority of participants resided in urban areas. The illiteracy rate among the women was 95.3%, with only 3.9% having studied up to semi-primary level; the correspond- ing proportions for men were 67.6% and 25.8% respectively. Nearly 7% of men had primary level of education or above, compared with less than 1% of women (P < 0.001). Among men, 91.3% were married and 5.3% widowed compared with 45.1% and 48.7% re- spectively among women (P < 0.001). Occupational status showed that 16.7% of elderly men were work- ing while 98.9% of the women were housewives. Almost three-quarters of women (72.0%) but only one-fifth of men (20.8%) had no personal income. Overall 21.0% earned < 100 Omani rials (OR) per month while 26.0% earned 100–199 OR. The difference in income levels between males and females was significant (P < 0.001). Almost all the men (97.3%) had been resident with the same family for the previous 5 years compared with 93.8% of women (P < 0.001). There was a higher rate of obesity in women (15.7%) than men (10.5%) (P = 0.02) and 31.5% of the total sam- ple was overweight with 7.6% being underweight. Of the total, 49.4% were not physically active, while among the active respondents, more males were physically active than women (21.6% of men versus 14.3% of women took ≥ 30 min exercise/day) (P < 0.001). Nutrition knowledge and beliefs In the assessment of nutrition knowl- edge and beliefs (Table 2), 43.0% of the total sample believed that the quality of nutrition should change with age but only 17.2% believed that the quantity should change, with no significant dif- ference between the sexes. Only 23.5% accepted that they should include some specific types of food with advancing age, while about 26.7% were not certain about this. There was a significant sex difference on this issue, with a higher proportion of men giving affirmative answers. With respect to moderating the consumption of specific food types with age, significantly fewer women gave a negative reply than males, and more women were unsure (P = 0.022). However, a slightly higher proportion of women replied positively to the questions about the need to reduce the intake of sweets/sugar, fat and salt. Respondents’ detailed knowledge about the value of milk and dietary fibreswas quite poor, with 12.3% aware of the value of milk in protecting against osteoporosis while only 1.7% knew it as a rich source of calcium. There were significant sex differences, with fewer women than men having knowledge about milk for osteoporosis prevention (10.1% versus 14.6%) and as a source of calcium (1.1% and 2.4%). Only 7.3% of the total had heard about dietary fibre and, of those, less than 3% knew its im- portance in daily diet. A majority of the elderly did not know which foods were rich in dietary fibre. Significantly fewer women than men (29.4% versus 31.5%) (P = 0.004) were aware that changes in dietary habits could help in prevention and control of health problems. Only 20.4% of the total sample were aware that this could help in hypertension and diabetes, while less than 5% were knowledgeable about the role of dietary habits in other specific illnesses. Nutrition practices The practice of consuming 3 meals per day was reported by 91.4% of the respondents (Table 3). One-third of women (33.5%) compared with 27.3% of men had noticed a change in their ap- petite (P = 0.003). The most common reason was sickness (17.7%), although 12.5% said they had lost their appetite for no reason, with women mentioning these factors more than men. Taking medicines was attributed as a reason by 2.5% of the elderly. Respondents’ self-reported levels of consumption showed that only 16.4% consumed adequate amounts of milk and there was a significant difference be- tween the sexes as regards consumption of milk and milk products, with signifi- cantly fewer women than men (14.1% versus 18.8%) consuming adequate amounts (P = 0.004). Full-fat dairy products were the preference of 38.8% of the sample. Of the total respondents 59.0% consumed adequate amounts of fish/meat/chicken, 83.4% adequate amounts of cereals and 85.0% adequate amounts of fruits. Vegetable intake, however, was inadequate for 88.6% of the total. Proportionately more women did not consume any type of sweets (P = 0.01) but 58.4% of the total sample had a sweet intake 1–3 times a week. There was no sex difference in the ad- equacy of consumption of fish/meat/ chicken, cereals, vegetables or fruits. One-fifth of the sample (19.4%) took additional salt in their diet and 9.3% took vitamin/mineral supplements. Women had significantly lower fluid intake per day (P < 0.001). More women followed a diet regimen (P < 0.001), with 14.0% having fat and cholesterol restriction and around 10% having salt and sugar restrictions. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 862 Table 1 Distribution of background characteristics of elderly respondents by sex Characteristic Males (n = 982) Females (n = 1045) Total P-value No. % No. % % Residence Urban 877 89.3 935 89.5 89.4 > 0.05 Rural 105 10.7 110 10.5 10.6 Age groups (years) 60–69 528 53.8 624 59.7 56.8 0.005 70–79 307 31.3 253 24.2 27.6 80–89 104 10.6 119 11.4 11.0 ≥ 90 43 4.4 49 4.7 4.5 Education Illiterate 662 67.6 996 95.3 81.9 < 0.001 Semi primary 253 25.8 41 3.9 14.5 Primary & above 65 6.6 8 0.8 3.6 Marital status Never married 14 1.4 13 1.2 1.3 < 0.001 Married 896 91.3 471 45.1 67.5 Widowed 52 5.3 509 48.7 27.7 Divorced 19 1.9 52 5.0 3.5 Work status Working 164 16.7 11 1.1 8.6 n/a Not working 818 83.3 0 0.0 40.4 Housewife 0 0.0 1034 98.9 51.0 Personal income (OR/month) 0 204 20.8 752 72.0 47.2 < 0.001 < 100 205 20.9 221 21.1 21.0 100–199 468 47.7 60 5.7 26.0 200–299 63 6.4 4 0.4 3.3 300–399 15 1.5 3 0.3 0.9 400+ 27 2.7 5 0.5 1.6 Living with same family for last 5 years Yes 955 97.3 980 93.8 95.5 < 0.001 No 27 2.7 65 6.2 4.5 BMIa Underweight 55 7.8 53 7.4 7.6 0.020 Normal 358 50.7 325 45.1 47.9 Overweight 219 31.0 230 31.9 31.5 Obese 74 10.5 113 15.7 13.1 Physical activity (min/day) 0 435 44.3 567 54.3 49.4 < 0.001 < 30 335 34.1 329 31.5 32.8 ≥ 30 212 21.6 149 14.3 17.8 aSome data missing. BMI = body mass index. OR = Omani rials. n/a = not applicable. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 863 Table 2 Dietary knowledge and beliefs of the elderly respondents by sex Dietary knowledge/belief Males Females Total P-value (males vs females)No. % No. % % Agree quality of nutrition should change with age 424/966 43.9 434/1030 42.1 43.0 0.617 Agree quantity of nutrition should change with age 177/957 18.5 163/1019 16.0 17.2 0.216 Type of foods to eat at older ages (n = 980) (n = 1043) Certain types of food should be eaten < 0.001 Yes 248 25.3 228 21.9 23.5 No 511 52.1 496 47.6 49.8 Don’t know 221 22.6 319 30.6 26.7 Types of food to eat: Vegetables 107 10.9 113 10.8 10.9 0.952 Fruits 77 7.9 75 7.2 7.5 0.570 Milk 63 6.5 71 6.8 6.6 0.732 Water 87 8.9 83 7.9 8.4 0.456 Moderation of diet at older ages (n = 969) (n = 1031) Certain types of food should be moderated Yes 387 39.9 428 41.5 40.8 0.022 No 375 38.7 343 33.3 35.9 Don’t know 207 21.4 260 25.2 23.4 Types of food to moderate: Protein 37 3.8 33 3.2 3.5 0.453 Cereals/starch 47 4.9 34 3.3 4.1 0.150 Sweets/sugar 206 21.3 239 23.2 22.3 0.302 Fat 210 21.7 238 23.1 22.4 0.449 Milk 6 0.6 11 1.1 0.9 0.276 Eggs/liver/brain 10 1.0 4 0.4 0.7 0.084 Salt 115 11.9 182 17.7 14.9 0.000 Fruits/vegetables 10 1.0 5 0.5 0.8 0.156 Water 1 0.1 0 0.0 0.0 0.302 Benefits of milk at older ages (n = 980) (n = 1043) Rich in calcium 24 2.4 11 1.1 1.7 0.016 Rich in vitamin D 11 1.1 7 0.7 0.9 0.280 Offers protection from osteoporosis 143 14.6 105 10.1 12.3 0.002 Rich in protein 7 0.7 5 0.5 0.6 0.492 Helps to prevent constipation 35 3.6 38 3.6 3.6 0.931 Benefits of dietary fibre at older ages (n = 978) (n = 1042) Heard about dietary fibre 80 8.2 67 6.4 7.3 0.130 Benefits of dietary fibre: Regulates intestinal movements 36 3.7 28 2.7 3.2 0.203 Relieves constipation 17 1.7 10 0.9 1.3 Other uses 27 2.8 26 2.5 2.6 0.709 Foods rich in dietary fibres: Fruits 14 1.4 11 1.0 1.2 0.445 Vegetables 42 4.3 26 2.5 3.3 0.025 Whole cereals 18 1.8 24 2.3 2.1 0.466 Plant proteins 2 0.2 2 0.2 0.2 0.949 EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 864 Discussion This was the first study of nutrition in the elderly conducted in Oman. The high illiteracy rate of respondents can be explained by the fact that all the respondents had reached adulthood before the country’s recent renaissance which began in 1970, at a time when few Omanis had access to education. Females in the Arab world had less opportunity for formal education at that time and this accounts for the sig- nificant sex differences. The same was true for work opportunities and hence the income of the elderly respondents differed significantly between the sexes. Changes in lifestyle and socioeco- nomic status have led to more sedentary lifestyles in Oman and levels of physical activity have decreased sharply in most Arab countries [11]. Half our overall sample took no physical activity and women spent significantly less time in physical activity than men, as most have domestic helpers for daily chores and there is little awareness of the value of walking as exercise. This, along with higher rates of multiparity [11], accounts for the higher prevalence of obesity in women than men (15.7% versus 10.5%). Similar findings on obesity have been noted in elderly women in Egypt [8]. Although the proportion of females among the elderly is generally higher due to their higher survival rates, in this interior region of Al Dakhliya, we found a lower proportion of women in the 70–79 years age range and similar pro- portions in the 80+ years age group. A possible reason could be unavailable or incorrect birth records, leading to mis- classification of age in some cases. There are fewer cultural and social barriers to multiple marriage and remarriage by men, which accounts for a significantly higher proportion of men being married at the time of this study, while a higher percentage of women were widowed. The elderly in our study lacked knowledge about the benefits of nu- tritional foods and a majority of men and women believed that there was no need to change the quantity and qual- ity of nutrition with increasing age. A European study reported that 86% of elderly people believed that they did not need to change their eating habits as they already ate healthily [12]. How- ever, researchers in Assuit governorate in Upper Egypt reported otherwise. They found that 44.0% of men and 63.4% of women in rural settings and 77.3% and 63.8% respectively in urban settings believed that diet should differ with age, either decreasing the amount of food in general or restricting certain types of food [8]. Older people residing outside insti- tutions eat reasonably well [13]. There is ample availability of foodstuff from different parts of the world in Oman. A majority of the elderly in this study lived with their family, and there is a tradi- tion in Arab countries of caring for the elderly. Although there were significant differences between men and women in education and income level and the proportion living with their families, this was not reflected in differences in dietary intake of meat, cereals, fruits and sweets or in the frequency of meals per day Energy intakes fall with advancing age, but average protein intakes remain adequate [13]. High energy intake over decades leads to overweight in both sex- es [14]. There is a shift in the Arab world from consuming traditional foods to more “fast-foods”, which are character- ized by high fat, cholesterol and sodium and low fibre [11]. A high proportion of our sample were overweight or obese. The impact of the promotional activities of the regional health care system and of the WHO Nizwa Healthy City project Table 2 Dietary knowledge and beliefs of the elderly respondents by sex (concluded) Dietary knowledge/belief Males Females Total P-value (males vs females)No. % No. % % Changes in dietary habits at older ages (n = 980) (n = 1043) Changes in diet can protect and control health problems Yes 309 31.5 307 29.4 30.4 0.004 No 355 36.2 328 31.4 33.8 Don’t know 316 32.2 408 39.1 35.8 Diseases that can be controlled by diet: Hypertension 194 19.8 218 20.9 20.4 0.537 Diabetes 200 20.4 203 19.5 19.9 0.595 Hyperlipidaemia 57 5.8 39 3.7 4.7 0.028 Coronary heart disease 35 3.6 27 2.6 3.1 0.200 Obesity 36 3.7 23 2.2 2.9 0.050 Anaemia 13 1.3 10 0.9 1.1 0.436 Gastric/duodenal problems 8 0.8 8 0.8 0.8 0.900 طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 865 on nutrition seems to work positively only for the small proportion of the population who are aware of the health promotion programmes for hyperten- sion and diabetes. A high proportion of older adults in England had little basic nutrition knowledge and this was a barrier to healthier eating. Knowledge of associa- tions between diet and diseases was par- ticularly poor; 90% of subjects were unaware of the benefits of high fruit and vegetable consumption [15]. We found no sex differences in consumption of fruits and vegetables but the lack of knowledge related to fruits and vegeta- bles was reflected in poor consumption of vegetables but not fruits in our study. We noted a significant sex difference for knowledge about the need to eat specific types of food, the need for moderation Table 3 Dietary habits of the elderly respondents by sex Dietary habit Males Females Total P-value (n = 982) (n = 1045) No. % No. % % Meals eaten (per day) 1 15 1.5 11 1.0 1.3 NS 2 67 6.8 81 7.8 7.3 3 900 91.6 953 91.2 91.4 Noticed change in appetite Yes 265 27.3 348 33.5 30.5 0.003 Reasons for change in appetite Sickness 147 15.1 209 20.1 17.7 Taking medicine 26 2.7 24 2.3 2.5 Death of someone close 3 0.3 13 1.3 0.8 No apparent reason 116 11.9 135 13.0 12.5 Adequate consumption of foods(per week Fish/meat/chicken 559 58.4 611 59.6 59.0 NS Cereals 797 83.0 853 83.7 83.4 NS Vegetables 104 10.9 119 11.8 11.4 NS Fruits 810 83.7 885 86.2 85.0 NS Consumption of sweets (times per week) 0 315 38.4 393 44.6 41.6 0.01 1–3 506 61.6 489 55.4 58.4 Consumption of extra salt in diet 194 19.9 197 19.0 19.4 NS Consumption of fluidsa (mL per day) Inadequate 228 23.3 357 34.4 29.0 < 0.001 Adequate 749 76.7 680 65.6 71.0 Consumption of milk & milk products (times per week) Inadequate 796 81.2 896 85.9 83.6 0.004 Adequate 184 18.8 147 14.1 16.4 Types of milk & milk products consumed Low fat/skimmed 534 59.1 591 63.2 61.2 NS Full fat 370 40.9 344 36.8 38.8 Take vitamin/mineral supplements 83 8.6 104 10.0 9.3 NS Follow diet regimen 325 33.3 432 41.6 37.6 < 0.001 Restrict fat and cholesterol 123 12.6 160 15.4 14.0 Restrict sugar 94 9.6 125 12.0 10.9 Restrict salt 84 8.6 130 12.5 10.6 Eat more iron-containing foods 6 0.6 0 0.0 0.3 Eat more fibre 7 0.7 7 0.7 0.7 Totals do not add up to sample size due to missing data; awater, milk, laban, juices, other drinks; NS = not significant. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 866 of certain types of food and whether changes in dietary habits can protect and control health problems at older ages. In another study men were found to have poorer knowledge about nutri- tion than women [16], whereas in our sample women had poorer knowledge. In a study related to fat intake from meat, meat products, dairy products and fried foods, women had higher nutrition knowledge scores and more negative views of fatty foods than did men [17]. More of our women had negative views about specific items such as sweets, fat and salt consumption. However, when it came to actual consumption, only sweets were significantly less fre- quently consumed by women, the other items being consumed equally by both sexes. Although women in our survey knew about the need to moderate their intake of fatty foods, they still consumed these foods, perhaps due to the existing belief systems and attitudes towards such food. Nutritional knowledge about dairy products has been shown to be a better predictor of the type of milk consumed (e.g. lower fat milk to reduce fat intake) than the frequency of milk consumption [18]. We noted similar findings. Knowl- edge about the nutritional value of milk was very poor and women were less informed than men. Overall only 16.4% of the total sample, and significantly fewer women than men, consumed adequate amounts of milk. This shows the poor impact on this age group of the ongoing women’s health programme in Oman. Among those who consumed milk products, 40% used full-fat milk and milk products, which again reflects traditional habits. In the Ageing Nutrition project in Europe a comparative analysis of 36 studies showed that energy intake was too high, especially in some of the “younger old” and seemed not to be adjusted to the energy expenditure, whereas it was considerably lower than recommended in some very old sen- iors in some countries [19]. We cannot comment on the age difference, but energy intake was higher in our sample, which may be inferred from the number of meals per day, the adequacy of food consumption (meat, cereals, sweets and fruits) and the finding that only 7.5% of the total sample was underweight. The prevalence of obesity and overweight were also found to be higher than un- derweight in elderly men and women in Egypt [8]. In contrast to our find- ings, undernutrition in older people is considered to be a significant public health issue in the UK [20]. “Willing- ness to eat” plays a central role with re- gard to appetite among the elderly [21]. In our study decreased appetite noticed by the elderly people themselves was mainly attributed to unexplained fac- tors and sometimes illness and use of medications. Sex differences were found in food choices and energy and nutrient intakes in older British people, especially those aged 65–79 years [22]. Meal frequency has been found to increase in older peo- ple of both sexes, especially men [14]. Women have more regular consump- tion of fruits and vegetables [23], milk and diary products and vitamin supple- ments [14]. Almost all types of meat, eggs, and vegetables are preferred by men and their energy intake also tends to be higher. In both sexes, fat has been shown to represent a higher ratio of en- ergy intake (39%) than recommended [14]. In our study the dietary consump- tion patterns of men and women dif- fered significantly only for milk and milk products, sweets and fluids, with women consuming less of these. The major limitations of our study were that we did not use a validated questionnaire. Also we could not quan- tify the food consumption due to the unavailability of food consumption ta- bles for Oman [24]. Intervention trials demonstrate that there are worthwhile health advantages for older people in changing their risk factors—e.g. weight reduction, sodium restriction, saturated fat reduction—to make their later years healthier, more active and more independent [25]. Effective intervention is required for improving knowledge among the eld- erly in our study. Dietary advice should be based on elderly women’s food preferences and habitual foods [26]. It is important to inform the elderly about known relations between food and disease. This is especially impor- tant for women, who have higher levels of obesity. The WHO Regional Office for the Eastern Mediterranean has addressed the issue of health of the elderly for over a decade and has identified a need for appropriate food and nutrition care for the elderly. However, a draft of the proposed model national policy for the elderly by EMRO does not explic- itly mention the nutrition component [27]. Similarly, the recommendations of the Third Arab Conference on Nu- trition 2007 resulted in the Abu Dhabi Declaration to Promote Healthy Nutrition in the Arab countries [7], but did not specifically address the growing global challenge of ageing and nutrition. Conclusions Our findings that nearly 45% of eld- erly people in Nizwa were overweight or obese, and had poor knowledge of nutrition, along with nutritional imbal- ances and low levels of physical activity, warrants reorientation of the existing health promotion strategy for the eld- erly. The significant sex differences in nutritional knowledge need to be ad- dressed. The above findings need to be incorporated into the awareness and education programme of the national strategy for “Active ageing and self care” proposed by the Ministry of Health and the Ministry of Social Welfare. A further detailed study is necessary in order to prepare a micronutrient supplementa- tion programme for vulnerable groups including the elderly. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 867 Nutrition for older persons1. . World Health Organization [web- site] (http://www.who.int/nutrition/topics/ageing/en/index. html, accessed 18 April 2010). McKevith B. Diet and healthy aging. 2. Journal of the British Meno- pause Society, 2005, 11(4):121–125. Lengyel CO, Tate RB, Bayomi DJ. Food group consumption and 3. self-rated diets of elderly community-dwelling Canadian men. The Manitoba follow-up study. Journal of Nutrition, Health and Aging, 2007, 11(1):8–13. Wahlqvist ML, Wahlqvist ML. “Malnutrition” in the aged: the di-4. etary assessment. Public Health Nutrition, 2002, 5(6A):911–913. Annual health reports.5. MOH hospital inpatients morbidity accord- ing to age groups and disease category. Muscat, Oman, Ministry of Health, Oman, 2003–2007. Census 20036. . Muscat, Oman, Ministry of National Economy, 2003. Abu Dhabi declaration to promote healthy nutrition in the Arab 7. countries. Recommendations of the Third Arab Conference on Nu- trition, Abu Dhabi–UAE, 4–6 December 2007. Abu Dhabi, Arab Center for Nutrition, Abu Dhabi Food Control Authority and Health Authority (http://www.acnut.com/images/stories/ pdf/2ea.pdf, accessed 18 April 2010). Abd El Aty MA. 8. Health profile of the geriatric group in Assuit gover- norate, Upper Egypt [PhD thesis]. Department of Public Health, Faculty of Medicine, University of Assuit, Assuit, Egypt, 1990. Recommended amount of physical activity. Global strategy on diet, 9. physical activity and health. 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New York, Oxford University Press, 1998:499–511. Gustaffson K, Ekblad J, Sidenvall B. Older women and dietary 26. advice: occurrence, comprehension and compliance. Journal of Human Nutrition and Dietetics, 2005, 18(6):421–422. A27. strategy for active, healthy ageing and old age care in the Eastern Mediterranean Region 2006–2015. Annex three. Cairo, World Health Organization, 2006 (WHO-EM/HSG/030/ E/01.06/1000). EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 868 Comparing bone mineral density in postmenopausal women with and without vertebral fracture and its value in recognizing high-risk individuals B. Heidari,1 S. Hoshmand,1 K. Hajian 2 and P. Heidari 3 ABSTRACT Vertebral fracture, the hallmark of osteoporosis, usually occurs in postmenopausal women with low bone mineral density (BMD). The aim this study was to determine which BMD parameter can best predict women at high risk of fracture. BMD values at the spine and femoral neck were compared in 34 women with vertebral fracture and 34 controls. Mean BMD (g/cm2), T-score, and Z-score values at both femoral neck and spine were significantly lower in the fracture than the nonfracture group. Z-score was more sensitive than BMD T-score for detecting low bone mass. T-score was not sensitive enough to identify low BMD in the spine, whereas the femoral neck T-score could recognize women at high risk of fracture with higher accuracy. 1Department of Internal Medicine; 2Department of Social Medicine, Shaheed Beheshti Hospital, Babol University of Medical Sciences, Babol, Islamic Republic of Iran (Correspondence to B. Heidari: heidaribeh@yahoo.com). 3Faculty of Medicine, Islamic Azad University, Tehran, Islamic Republic of Iran. Received: 10/01/09; accepted: 26/02/09 في ةنراقلما ةميقو ،ابه تاباصلما يرغ عم راقفلا في روسكب تاباصلما نم سأيلا نس دعب ءاسنلا ىدل ماظعلل ةيندعلما ةفاثكلا ةنراقم عفترم رطلخ ينضرعلما صاخشلأا لىع ف ُّرعتلا يرديح زانراب ،نايجح ميرك ،دنماشوه نييرش ،يرديح دازبه ةيندعلما ةفاثكلا نيهدل لقت نمم ،سأيلا نس دعب ءاسنلا ىدل ةداع ثديح يذلاو ،ماظعلا لخلختل ةقرافلا تاملاعلا نم ةرقفلا سرك دعي :ةـصلالخا عفترم رطلخ تاضرعلما ءاسنلاب ؤبنتلا نم ءابطلأا ن ِّكتم يتلاو ،ماظعلل ةيندعلما ةفاثكلل ةتباثتلما ميقلا لىع ف ُّرعتلا لىإ ةساردلا هذه فدتهو .ماظعلل ،يرقف سركب تبيصأ ةأرمإ 34 ىدل ذخفلا قنع فيو يرقفلا دومعلا في ماظعلل ةيندعلما ةفاثكلا ميق ينب ةنراقم نوثحابلا ىرجأ دقو .سركلاب ةباصلإل قنع نم لك في Z زرحو ،T زرحو ،)عبرم ترميتنس لكل مارغلاب ةر َّدقم( ماظعلل ةيندعلما ةفاثكلا ميق نأ حضتاو .تادهاشلا ةوسنلا نم 34 ىدل ام ينبو Z زرلحا ناك دقو .روسكلاب تاباصلما يرغ ةعوممج ىدل ماع روسكلاب تاباصلما ةعوممج في ًايئاصحإ هب دتعي رادقمب ضفخأ يرقفلا دومعلا فيو ذخفلا امأ ،تارقفلا في ماظعلل ةيندعلما ةفاثكلا ضافخنا لىع ف ُّرعتلل ةيفاك ةيساسح T زرحلل نكي لمو ،ماظعلل ةيندعلما ةفاثكلل T زرلحا نم ةيساسح رثكأ في .سركلل عفترم رطلخ تاضرعلما ءاسنلا ،ةيلاع ٍةقدب ،فّرعي نأ نكمي T زرلحا نإف ذخفلا قنع في Comparaison de la densité minérale osseuse chez des femmes ménopausées présentant ou non une fracture vertébrale et sa valeur dans l’identification d’individus à haut risque RÉSUMÉ La fracture vertébrale, caractéristique de l’ostéoporose, survient généralement chez la femme ménopausée ayant une faible densité minérale osseuse (DMO). Cette étude visait à déterminer quel paramètre de la DMO était susceptible d’identifier au mieux les femmes qui pourraient être à haut risque de fracture. Des mesures dela DMO réalisées au niveau de la colonne vertébrale et du col du fémur chez 34 femmes présentant une fracture vertébrale et 34 témoins ont été comparées. Par rapport au groupe témoin, les valeurs moyennes de la DMO (g/cm2), du T-score et du Z-score relevées sur le col du fémur et la colonne vertébrale étaient considérablement inférieures chez les femmes souffrant de fractures. Le Z-score s’est avéré plus sensible que le T-score de la DMO pour détecter une faible densité osseuse. Il est apparu que le T-score n’était pas assez sensible pour identifier une faible DMO de la colonne vertébrale, alors qu’il permettait d’identifier avec une meilleure précision les femmes présentant un risque élevé de fracture du col du fémur. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 869 Introduction Vertebral fracture is the most common osteoporotic fracture and also a hall- mark of postmenopausal osteoporosis. It is associated with back pain, disabil- ity, functional limitation and decreased quality of life [1–6]. Bone mineral den- sity (BMD) is an important predictor of future fractures. Low BMD at the spine or femoral neck in postmeno- pausal women has been shown in sev- eral prospective studies to be associated with increased risk of vertebral fracture [7–10]. In the elderly population, how- ever, factors other than BMD, such as age, might play a role in the develop- ment of fracture, because older patients are much more susceptible to fractures at any given BMD than are younger patients, perhaps due to the quality of ageing bone [4,5,11–13]. Several studies have found a relation- ship between increasing risk of vertebral fracture and decreasing BMD values in women [14,15]. There is also a strong association between age and femoral neck BMD with vertebral fracture [16]. Nevertheless, many postmenopausal women with fractured vertebra are not osteoporotic, so BMD measurements cannot accurately predict individuals who will develop fractures. This issue has been attributed to discordance between the site of BMD measurement and the site of fractures; low sensitivity of the BMD T-score criterion; inconsistency between BMD measurement and the time of the fracture; and false elevation of BMD values due to the presence of degenerative changes at the site of BMD measurement [17,18]. Given the bur- den of vertebral fractures in the elderly, detection of low bone mass for preven- tion of fractures is important. At present, the BMD T-score (which measures how much bone mass deviates from the average bone mass of a healthy adult) is used as a tool for evaluation of bone mass as well as for fracture assessment, as recommended by the World Health Organization (WHO) [19]. We hypothesized that the magni- tude of differences in the BMD of spine or femoral neck would be comparable in women with and without fractures irrespective of the BMD parameter used. The aim of this study was to deter- mine which parameter of BMD is more sensitive in diagnosis of low BMD and can more accurately identify women susceptible to vertebral fractures. Methods The study compared postmenopausal women with and without vertebral frac- tures with respect to bone mass at the spine and femoral neck. Sample A sample of 34 postmenopausal women with back pain and vertebral fracture and 34 aged-matched postmenopausal women with back pain but without vertebral fracture entered the study. The study patients attended or were referred to an outpatient medical clinic from the general population of Babol, Islamic Republic of Iran. The women who met the selection criteria were selected se- quentially over a 6-month period from June to December 2007. Only patients with recent back pain who had pain and tenderness at the lumbar spine with symptom duration of less than 6 weeks were included. Those with previous spinal surgery, malignan- cy, traumatic fracture or inflammatory skeletal disease and patients on steroids or anti-osteoporosis treatment were ex- cluded. Patients with fractures at the site of BMD assessment in the lumbar spine were also excluded from the study. This study was approved by the eth- ics committee of Babol University of Medical Sciences. Data collection Data regarding demographic and clinical characteristics were collected by interview and questionnaire. Clinical, radiographic and bone densitometry data were provided by clinical exami- nation, X-ray examination and BMD measurements. At the first visit all patients under- went a complete clinical examination, spinal X-ray, and BMD measurements at the lumbar spine (L2–L4) and femo- ral neck by dual X-ray absorptiometry (DXA) with a single Dorland densi- tometer. BMD was evaluated based on a reference database provided by the manufacturer. The mean duration of back pain prior to spinal radiography and the mean duration between diagnosis of vertebral fracture and BMD measurement was < 2 weeks in about 80% of patients and < 6 weeks in the remainder. Clinical vertebral fracture was diag- nosed by history, clinical examination and spinal X-ray. Vertebral fracture was assessed by the Genant semiquantita- tive method in a lateral-view spinal X- ray by an experienced physician [20]. In this method, the extent of the vertebral height reduction and morphological changes are assessed visually and scored using a grading scale to differentiate fracture from other nonfracture de- formities. Thoracic and lumbar verte- bra from T4–L4 were graded based on the approximate degree of height reduction. Vertebrae with a 20%–25% or greater reduction in anterior, middle and/or posterior height relative to ad- jacent vertebrae of normal appearance were considered as fractured vertebrae. Women with nonosteoporotic verte- bral deformity and traumatic fractures were excluded from the study. Osteoporosis was confirmed ac- cording to WHO criteria [19], defined as BMD value > 2.5 standard deviation (SD) below the young normal mean BMD (T-score < –2.5). Analysis For the statistical analysis patients with vertebral fractures (at least 1 fractured vertebra) were compared with those without fractures in terms of bone EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 870 density values (BMD, T-score and Z- score (which measures how much bone mass deviates from the average bone mass of people the same age and sex), frequency of osteoporosis at the spine or femoral neck regions and duration of menopause. The differences were expressed as mean percentage differ- ence of the fracture group from the nonfracture group. The association between osteo- porosis and vertebral fracture was de- termined by calculation of odds ratio (OR) and its 95% confidence interval (CI) using the chi-squared test. Student t-test was used for comparison of BMD values. Receiver operating characteristics (ROC) curve was applied to evaluate the trade-off between sensitivity and 1–specificity for various cut-off points of BMD values to assess the diagnostic accuracy of BMD parameters and age in discriminating between the fracture and the nonfracture group. Diagnos- tic accuracy of BMD parameters were compared with respect to values of the area under the curve (AUC) and its 95% CI in comparison with the chance level (AUC = 50%). The impact of age on diagnostic accuracy was assessed by comparison of AUC values between 2 age groups (< 65 and ≥ 65 years). Statistical analysis was performed using SPSS software, version 10. Results The mean age of the study patients was 66.6 (SD 8.4) years and the mean dura- tion of menopause was 17.9 (SD 9.2) years. Two-thirds of women (64.7%) were aged over 65 years. Vertebral frac- ture was associated with acute back pain in 84.6% of cases versus 23.5% of those without fractures. As shown in Table 1 the mean age of patients with vertebral fractures was 67.5 (SD 9.7) years and those with- out fractures was 65.6 (SD 7.0) years (not significant). The mean duration of menopause in patients with and with- out fractures was 19.6 (SD 10.4) years and 16.2 (SD 7.7) years respectively (not significant). The mean BMD (g/ cm2), T-score and Z-score values at both the femoral neck and spine regions in the fracture group were significantly lower than in the nonfracture group (Table 1). In the fracture group the mean spine BMD T-score was 35% lower whereas the spine Z-score was 58% lower than in the nonfracture group. The corre- sponding values for femoral neck T- score and Z-score were 24% and 100% respectively. The size of the difference between the 2 groups varied with age and site of BMD measurements. In the fracture group aged < 65 years the cor- responding differences between spine T-score and Z-score were 59% and 92% respectively and in patients ≥ 65 years were 20% and 51%. In the femoral neck the corresponding values for femoral neck T-score and Z-score in women aged < 65 years were 30% and 160% and in women aged ≥ 65 years were 19% and 71% respectively. Vertebral fracture developed in 61.7% of patients with spinal oste- oporosis versus 37.1% patients without spinal osteoporosis (OR = 2.7, 95% CI: 1.3–7.2, P < 0.05). The corresponding values for patients with and without femoral neck osteoporosis were 60.0% and 25.0% respectively (OR = 4.6, 95% CI: 1.4–14.6, P = 0.015). Femoral neck osteoporosis was more strongly associated with vertebral fracture in women aged < 65 years ver- sus those aged ≥ 65 years (OR = 10.0, 95% CI: 1.4–69.2, P = 0.036) whereas the association between spinal oste- oporosis and vertebral fracture was not different comparing patients aged < 65 years with older patients. The presence of osteoporosis at both sites, femoral neck and spine, increased the risk of vertebral fracture by almost 6-fold (OR = 5.8, 95% CI: 1.5–21.9, P < 0.011). Comparison of bone mass at frac- ture and nonfracture sites with BMD T-score and Z-score gave different re- sults with respect to BMD parameters. Based on BMD T-scores, low bone Table 1 Comparison of bone mineral density (BMD) values at the femoral neck and spine in postmenopausal women with and without vertebral fracture Variable Vertebral fracture present (n = 34) Vertebral fracture absent (n = 34) P-valuea Mean SD Mean SD Age (years) 67.0 9.7 65.6 7.0 0.36 Duration of menopause (years) 19.7 10.4 16.2 7.7 0.13 Femoral neck BMD (g/cm2) 0.57 0.09 0.66 0.12 < 0.001 Spine BMD (g/cm2) 0.64 0.12 0.75 0.15 0.003 Femoral neck T-score –3.6 0.76 –2.9 0.83 < 0.001 Spine T-score –2.7 0.79 –2.1 0.95 < 0.001 Femoral neck Z-score –1.5 0.80 –0.8 0.67 < 0.001 Spine Z-score –1.9 0.66 –1.2 0.84 < 0.001 aStudent t-test. SD = standard deviation. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 871 mass (T-score < –2.5, as recommended by WHO) at the femoral neck was more frequent in women with fractures than at the spine (85.3% versus 61.7%, P = 0.007). In contrast, based on BMD Z-score < –1, low bone mass at the spine was more frequent than at the femoral neck (97.0% versus 76.4%, P < 0.015). The overall accuracy of BMD parameters (femoral neck and spine BMD g/cm2, T-score and Z-score) in discriminating high-risk women are presented in Table 2 in terms of the AUC and standard error (SE). All pa- rameters showed a significant ability to recognize high-risk (fracture) patients, but femoral neck BMD Z-score yielded the highest accuracy among all the pa- tients in discriminating fracture from nonfracture patients [AUC 0.77 (SE 0.05), P < 0.001]. This was followed by femoral neck BMD T-score [AUC 0.75 (SE 0.06), P < 0.001] and spine BMD Z-score [AUC 0.74 (SE 0.06), P < 0.001], whereas the spine BMD T-score yielded the lowest accuracy [AUC 0.71 (SE 0.62), P = 0.002]. The accuracy of BMD parameters were compared between the 2 age groups ≥ 65 and < 65 years with respect to AUC values. In patients aged < 65 years, AUC values for femoral neck BMD g/cm2 [AUC 0.87 (SE 0.07), P = 0.002] and femoral neck T-score [AUC 0.82 (SE 0.08), P = 0.007] yielded the highest and spine T-score the lowest predictive accuracy values [AUC 0.77 (SE 0.09), P = 0.007]. However in patients ≥ 65 years the femoral neck T-score [AUC 0.74 (SE 0.07), P = 0.006] yielded the highest accuracy followed by femoral neck Z-score [AUC 0.73 (SE 0.08), P = 0.009]. In patients aged ≥ 65 years the AUC values for spine and femoral neck T- scores decreased by 11.6% and 11.0% respectively compared with those aged < 65 years (P < 0.01), whereas the de- creases in spine and femoral neck BMD Z-score were 7.6% and 7.5% lower respectively(P < 0.01) Discussion The present study found that in postmenopausal women with ver- tebral fracture, BMD values at the fracture as well as nonfracture sites were significantly lower than those without vertebral fractures. Pres- ence of osteoporosis at both spine and femoral neck was associated with an increased risk of vertebral fracture but osteoporosis at the femoral neck was more strongly associated with vertebral fracture than at the spine. However, about 40% of vertebral fractures devel- oped in patients with spine BMD values at the range of osteopenia. In this study, comparison of fracture and nonfracture sites indicated higher bone density val- ues at the fracture site using BMD T-score, whereas based on BMD Z-scores fracture sites demon- strated lower values. Furthermore, the magnitude of spine bone den- sity difference between women with and without fracture was greater using the BMD Z-score than the BMD T-score. Moreo- ver, spine BMD Z-score yielded a larger AUC and higher accuracy in recognizing the fracture group compared with the spine T-score. On the other hand, the BMD T-score yielded higher sensitivity for femoral neck BMD and higher diagnostic accuracy in recognizing women with fracture compared with BMD Z-score, particularly in those aged < 65 years. These findings indicate greater sensitivity of spine BMD Z-score compared with spine BMD T-score in demonstrating low bone mass as well as the extent of bone loss at the spine. At present the BMD T-score is the most widely used parameter for recog- nizing high-risk patients as well as for planning treatment. However, the sensitivity and accuracy of this Ta bl e 2 Pr ed ic ti ve a cc ur ac y of b on e m in er al d en si ty (B M D ) m ea su re m en t p ar am et er s de te rm in ed b y re ce iv er o pe ra ti ng c ha ra ct er is ti c an al ys is a nd a re a un de r t he c ur ve (A U C ) i n re co gn iz in g hi gh -r is k po st m en op au sa l w om en fo r v er te br al fr ac tu re w it h re sp ec t t o ag e gr ou p an d si te o f B M D m ea su re m en t BM D p ar am et er A ge < 6 5 ye ar s A ge ≥ 6 5 ye ar s To ta l A U C SE 95 % C I P- va lu e A U C SE 95 % C I P- va lu e A U C SE 95 % C I P- va lu e Fe m or al n ec k BM D (g /c m 2 ) 0 .8 7 0 .0 7 0 .7 4– 1.0 0 0 .0 0 2 0 .6 7 0 .0 8 0 .5 1– 0 .8 4 0 .0 5 0 .7 4 0 .0 6 0 .6 2– 0 .8 6 < 0 .0 0 1 Sp in e BM D (g /c m 2 ) 0 .7 4 0 .10 0 .5 6– 0 .9 4 0 .0 46 0 .6 8 0 .0 8 0 .5 1– 0 .8 4 0 .0 45 0 .7 0 0 .0 6 0 .5 7– 0 .8 3 0 .0 5 Fe m or al n ec k BM D T -s co re 0 .8 3 0 .0 8 0 .6 6– 0 .9 9 0 .0 0 7 0 .7 4 0 .0 8 0 .5 9– 0 .8 9 0 .0 0 6 0 .7 5 0 .0 6 0 .6 3– 0 .8 7 < 0 .0 0 1 Sp in e BM D T -s co re 0 .7 7 0 .0 9 0 .5 8– 0 .9 6 0 .0 26 0 .6 8 0 .0 8 0 .5 2– 0 .8 4 0 .0 4 0 .7 2 0 .0 6 0 .5 9– 0 .8 3 0 .0 0 2 Fe m or al n ec k BM D Z -s co re 0 .7 9 0 .0 9 0 .6 0 –0 .9 8 0 .0 15 0 .7 3 0 .0 8 0 .5 8– 0 .8 8 0 .0 0 9 0 .7 7 0 .0 5 0 .6 6– 0 .8 8 < 0 .0 0 1 Sp in e BM D Z -s co re 0 .7 8 0 .0 9 0 .6 0 -0 .9 7 0 .0 19 0 .7 2 0 .0 8 0 .5 6– 0 .8 7 0 .0 13 0 .7 4 0 .0 6 0 .6 2– 0 .8 6 < 0 .0 0 1 Ar ea u nd er th e cu rv e w as co m pa re d w ith c ha nc e le ve l. SE = st an da rd e rr or o f A U C ; C I = co nfi de nc e in te rv al . EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 872 parameter varies according to age and site of measurement, whereas BMD Z-score is less affected by age and site. Discordance in BMD T-score between the spine and femoral neck can be explained by the presence of osteoarthritis, which occurs at a higher rate in the spine than femoral neck. Ad- ditionally, accuracy and reproducibility errors which usually occur during BMD measurement may lead to discordance between sites. Spinal osteophytosis falsely elevates BMD T-score without affecting frac- ture risk [17,18]. The impact of vari- ous forms of degenerative diseases on BMD was investigated in a study in which BMD measurement by quantita- tive computed tomography and DXA were compared in 209 postmenopausal women. In that study, the BMD value by posterior–anterior measurement of spine BMD via DXA (PA-DXA) was significantly higher in women with de- generative diseases changes, particularly when osteophytes were present at the vertebral bodies or facet joints, whereas BMD by lateral DXA (L-DXA) was less affected [18]. In cross-sectional stud- ies of postmenopausal women of vari- ous age groups the accuracy of lumbar spine BMD measurement decreased with increasing age because of spinal osteoarthrosis in the elderly popula- tion [21]. The accuracy errors for spine PA-DXA can vary from 4%–10% and the accuracy error for proximal femur DXA measurement was estimated at 6% [22]. The amount of fat to lean body mass surrounding tissues could affect the tissue-density gradient assessed by DXA and influence the accuracy and reproducibility of BMD measurements. Postmenopausal women with greater body weight, mediated by lean body mass or fat body mass, have both higher lumbar spine, hip and femoral neck BMD and lower rate of bone loss [23]. In the present study, disproportionately higher than expected values of BMD T- score in the spine of the fracture group compared to the femoral neck site could be attributed to the higher prevalence of osteoarthritis in the spine compared with the hip. Although we did not de- termine the frequency of osteoarthritis at the spine or hip, a high proportion of degenerative joint disease is expected to be present in our patients based on another study in the Islamic Republic of Iran in which spine degenerative dis- eases were found in 16.6% of the urban population aged 15 years and over, and hip osteoarthritis in only 0.32% of the 10 921 study population [24]. A low prevalence of hip osteoarthritis was also reported in other studies [25,26], whereas arthritis of lumbar facet joints is a common radiographic finding which has been linked to low back pain. In a study of 647 cadaveric human lumbar spines examined by a single examiner, facet arthrosis was a universal finding in 100% of patients aged 60 years and over [27]. Low sensitivity of BMD T-score was also shown in a study of 74 men from the MINOS study. In that study, 27%–47% of incident fractures occurred in men with BMD T-scores –1 and –2, whereas the percentage of incident fractures occurring with BMD T-score < –2 ranged from 13.7%–44.6%. BMD T-score had limited value in determin- ing men at increased risk of fracture and its sensitivity for recognizing high-risk individuals was low [28]. Site-discordant fracture risk, as seen in the present study was also observed in a study of 200 men with mean age of 54.7 years. In that study, a T-score < –2.5 in the femoral neck was associated with a 2.7-fold increase in the risk of vertebral fracture, while a T-score < –2.5 in the spine was associated with only a 2-fold increase in risk. Both femoral neck and spine BMD were significant predictors of the presence of a vertebral fracture but the femoral area was the best site for BMD measurements [16]. The sensitivity and accuracy of BMD parameters have not been compared in any previous studies. The findings of the present study provide new data and extend the evidence-based knowledge about the utility of BMD Z-score in discriminating between the fracture and the nonfracture group. Based on our findings, the BMD Z-score may be a useful tool, not only for BMD assess- ment, but also for recognizing high-risk patients. In addition, our findings are consistent with the results of a previ- ous study concerning the accuracy of femoral neck T-score in recognizing postmenopausal women at high risk for vertebral fracture [16]. The limitations of our study should be considered. The study sample was small and the study design did not per- mit us to perform statistical analysis for prediction of future fractures. However, to compensate for the small sample we employed appropriate tools for charac- terizing the utility of BMD for discrimi- nating fracture and nonfracture sites. Another issue is that the data pro- vided in this study were susceptible to information bias with respect to bone density measurement at the time of vertebral fracture as well as early per- formance of radiographic intervention at the time of presentation with acute back pain. Despite the clinical criteria for sample selection, we could not be certain that the vertebral fractures under review were incident fractures rather than prevalent fractures with symptom exacerbation. However, development of acute back pain and presence of local- ized tenderness at the site of the fracture are evidence in favour of their being incident fractures. The focus of this study was to deter- mine the contributive role of BMD in the development of vertebral fracture, so the influence of other factors that might be responsible for the occurrence of vertebral fractures were not considered in the statistical analysis. On the other hand, since both the fracture and the nonfracture groups were drawn from a population of the same geographic location with similar racial and cultural characteristics, the influence of other طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 873 factors would be expected to affect both fracture and non-fracture groups equally. 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Mahdi1 and O.S Habib 2 ABSTRACT This was a cross-sectional study in Basra, and involved 353 women who had recently given birth drawn from health care institutions. The main objective was to determine the factors that helped determine the women’s choice of place of delivery: hospital or home. Only 16.1% delivered at home, while 83.9% delivered in hospital. The main reasons for choosing hospital delivery were safety and security (96.6% of the women), better hygiene (66.6%) and because of medical advice (63.2%). The main reasons for the choice of home delivery were social support and privacy (98.2%). The women were consistent in their choice of delivery place across different pregnancies (previous, present and future). 1Directorate of Health Services, Basra, Iraq (Correspondence to O.S Habib: omran49_basmed@yahoo.com). 2Department of Community Medicine, College of Medicine, University of Basra, Basra, Iraq. Received: 28/12/08; 15/02/09 ةدلاولا ناكم لوح ءاسنلا تاسراممو ليضفت بيبح ركس نارمع ،يدهم نمالس ةيفص ضرغلا ناك دقو .ةيحصلا ةياعرلا تاسسؤم في ًاثيدح اهدولوم تعضو ةأرما 353 تلمش ،ةصربلا في ةيضرع ةسارد نوثحابلا ىرجأ :ةـصلالخا نأ نوثحابلا ظحلا دقو .تيبلا مأ ىفشتسلما ؛ةدلاولا ناكم ءاقتنا لوح رارقلا ءاسنلا ذاتخا في تدعاس يتلا لماوعلا لىع ف ُّرعتلا ةساردلل سييئرلا ةملاسلاو ناملأا يه ىفشتسلما في ةدلاولا نهرايتخلا ةيسيئرلا بابسلأا نأو ،ىفشتسلما في ندلو نهنم %83.9و ،لزنلما في ندلو طقف نهنم %16.1 يعماتجلاا معدلا يهف لزنلما في ةدلاولا رايتخلا ةيسيئرلا بابسلأا امأ .)%63.2( ةيبط ةزهجأ دوجو ببسبو )%66.6( لضفأ ةفاظنو ،)%96.6( .)ةقحلالاو ةيلالحاو ةقباسلا( ةفلتخلما لوملحا برع نتهدلاو ناكلم ءاسنلا رايتخا في قاستلاا نوثحابلا ظحلا دقو .)%98.2( ةيصوصلخاو Étude portant sur les préférences et les pratiques des femmes quant au lieu d’accouchement RÉSUMÉ Cette étude transversale réalisée à Bassora concernait 353 femmes ayant accouché peu de temps auparavant dans un établissement de soins. L’objectif principal était de déterminer les facteurs ayant influencé le choix de ces femmes en ce qui concerne le lieu d’accouchement : à l’hôpital ou à domicile. Seules 16,1 % des parturientes ont accouché chez elles, contre 83,9 % à l’hôpital. Les principales raisons ayant motivé les femmes à choisir l’hôpital pour accoucher étaient la sûreté et la sécurité (pour 96,6 % d’entre elles), une meilleure hygiène (66,6 %) et les conseils médicaux (63,2 %). Le soutien social et le respect de la vie privée (98,2 %) constituaient les raisons majeures ayant motivé les femmes à accoucher chez elles. Les femmes sont restées fidèles à leur choix concernant le lieu d’accouchement, y compris pour les grossesses à venir. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 875 Introduction One of the issues to be considered in studying the place of delivery for pregnant women is the importance of women’s choice, and the role of tech- nology as a facilitator, allowing choice to be exercised safely [1]. The view of professionals on where women should deliver is mixed [1]. Some consider pregnancy is always as- sociated with risk and hospital delivery is recommended for all pregnant wom- en. Others suggest that home delivery might be safe for women with a low-risk profile and when supervision is made by trained professionals. A third view is in the middle and sees the place of delivery a joint judgement between profession- als and clients. These views illustrate the current differences between the medical and midwifery models of care. The former declares that labour is only ever normal in retrospect (i.e. all labour should be considered a complication), whereas the latter says that most labours are normal and should be treated as such [1]. As a trend, the demand for birth centres and midwifery services varies in different countries. Birth centres and midwifery services grew substantially over the last decades of the 20th century in the United States of America (USA) [2]. In the United Kingdom (UK), after a low point in the mid-1970s, mid- wifery has regained popularity after the wide-spread introduction of midwifery teams with improved continuity and full responsibility for total care in normal cases [1]. In Turkey, home delivery rep- resents only a small fraction of the total reported deliveries [2], while in Tunisia, community health centres staffed by university-educated midwives are well dispersed throughout the country and most deliveries are in these health cen- tres, or in local hospitals or clinics [2]. Utilization of health care services, including maternal services, is deter- mined by complex interacting factors [3–6]. Common determinants are level of need, distance, economic factors, awareness and satisfaction, sociode- mographic characteristics and admin- istrative arrangements. With respect to delivery, these factors definitely operate. Other determinants include traditions, fear of death, the perception of risk on health, the perception of intervention, presence of special problems and com- plications, level of information available to clients and cost of care or family in- come [2,5–8]. Previous field studies carried out in Basra indicated that hospital delivery represented about 76.2% of all reported deliveries. The remaining deliveries took place at home either under the su- pervision of trained midwives (11.4%) or untrained midwives (12.4%) [9, Department of Primary Health Care/ Basra, unpublished report, 2007]. The governmental health care sys- tem in Iraq is the main source of health care. Hospitals and health centres where delivery care is available are staffed by doctors and trained midwives. The sys- tem has been extensively damaged in the past 2 decades [10]. Accordingly, patient interaction with the system might have changed with respect to changed perception of quality of care by consumers. It would be useful there- fore to explore the views of consumers on their preferences regarding specific items of care, such as place of delivery for pregnant women. Understanding the forces behind choice of place of delivery will improve the health services delivery and assist in directing efforts towards better use of resources. Thus this study was carried out to identify the factors affecting the preference of women regarding place of delivery. Methods This was a cross-sectional study to in- vestigate the preference of women in Basra about the place of delivery (hos- pital or home) and factors affecting this preference. The study was carried out in Basra City over a period of 10 months from January to October 2007. The studied women were those who had delivered a baby within 40 days of the interview. They were drawn from 2 sources: Al-Basra Maternity and Children’s Hospital, covereing women admitted with their babies for reasons unrelated to delivery; the second source was primary health care (PHC) cen- tres and included women attending the centres for BCG vaccination of their babies. Four PHC centres were ran- domly selected from a list of 20 PHC centres in the first health sector in Basra. Women were selected from those at- tending the health centres during the morning working hours and who had a baby born within 40 days of the date of the interview. The study included 353 women, 117 from the primary health centres and 236 from the hospital. Of theses, 226 women were from Basra City centre and 127 from outlying dis- tricts and remote areas of Basra gover- norate. A special unvalidated questionnaire form was designed by the researchers to obtain information on sociodemo- graphic characteristics of the women, the distance between the place of residence and nearest official delivery facility, par- ity, place of delivery of present, first, pre- vious and future child when applicable and reasons behind choosing home or hospital delivery. Data were collected through direct interviews of the women by the investigators. The women gave informed verbal consent to participate and there were no refusals. Data were analysed with SPSS, ver- sion 11 and frequencies are presented. Results Demographic characteristics of the women Table 1 shows the age distribution of the women. Women aged 20–29 years rep- resented the highest proportion (56.9%) EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 876 while there were very few women aged 40 years and above, accounting for only 0.8% . Just above one-third (34.3%) of the women had completed primary education, while 37.4% were either il- literate or just able to read and write. Almost 14% had an education above secondary level (Table 1). Most of the women were housewives not working outside the home (90.7%). The majority of the women were from Basra City (64.0%) with far fewer coming from the other 4 areas (Table 1). The great majority (82.4%) needed less than half an hour to reach a place of delivery; only 2.5% needed more than 1 hour. Parity and use of prenatal care Most of the women had had either 2–3 previous births (39.1%) or 1 birth (36.3%) (Table 2). Only 8.2% had par- ity above 5. Just under two-thirds of the women (64.6%) had 5 or more visits to prenatal care clinic. Less than 6% had had no prenatal visits at all. Place of delivery Most previous deliveries of the women took place in hospital (Table 3). Nearly 84% of the present children were delivered at hospital and only 16% were delivered at home. Similarly the place of delivery of the first child and previous child was hospital in 82.2% and 75.1% of women respectively. When women were asked where they would have their next child delivered, 83.3% said they would have it in hospital. Reasons for choice of delivery site The most frequent reason given for preferring a hospital delivery was that the hospital was safe and secure (from the health point of view) (96.6% of the women) (Table 4). The hygiene of hospitals was the reason given by 66.6% of the women. Emergency transfer from midwife to hospital was reported by 5.4% of the women and lack of avail- ability of a midwife by 2.4%. The reasons reported by women who delivered at home for preferring home delivery are also shown in Table 4. Social support and privacy was the predominant reason given by 98.2% of the women who had home delivery of their present child. Fear of interventions and repeated examinations at hospitals was the concern of 71.9% of the women who preferred home delivery. About 17.5% had an unplanned home delivery as a result of quick labour or the secu- rity situation did not allow transfer to hospital. Discussion We attempted to understand some of the factors that influence the choice of women regarding the place of delivery as reported by women themselves. Hospital delivery prevailed among the studied women: 83.9% had their last delivery in hospital and only 16.1% took place at home. This result is similar to the findings reported by primary health care centres in Basra [Depart- ment of Primary Health Care/Basra, unpublished report, 2007] for the years 2004, 2005 and 2006 and showed that Table 1 Distribution of the women according to age, education, occupation, place of residence and time taken to travel to the nearest place of delivery (n = 353) Variable No. % Age (years) < 20 59 16.7 20–29 201 56.9 30–39 90 25.5 ≥ 40 3 0.8 Education Illiterate 85 24.1 Read and write 47 13.3 6 years 121 34.3 7–9 years 39 11.0 10–12 years 12 3.4 ≥ 13 49 13.9 Occupation Housewife 320 90.7 Working outside the home 33 9.3 Place of residence Basra City Centre 226 64.0 Northern Areaa 43 12.2 Western Areab 47 13.3 Southern Areac 28 7.9 Eastern Aread 9 2.5 Travel time to place of delivery (minutes) < 10 31 8.8 10–19 135 38.2 20–29 125 35.4 30–59 53 15.0 ≥ 60 9 2.5 aQurna, Mdaina and Hartha. bZubair, Safwan and Um-Qasr. cAbul-Khasib and Fao. dShatt-Al-Arab. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 877 hospital delivery represented 68.7%, 72.9% and 74.9% respectively. These figures indicate 2 things: first, hospital delivery is common and, second, hospi- tal delivery is increasing with time. Such a high use of hospital delivery care could reflect a high degree of people’s aware- ness of the need for a safe and secure place for delivery where qualified staff and opportunities for medical interven- tion, if needed, are available, unlike the situation in home deliveries. The issue of safety is a matter of judgement. Some studies have shown that home delivery in some communities may be as safe as hospital delivery, for example a study carried out on Nordic women in 1994 [11]. The reasons given by the women for preferring hospital delivery are rational. Safety and security were the reasons be- hind the choice of 96.6% of the women who had a hospital delivery and these are undoubtedly valid. It indicates a high level of awareness among the women of health issues regarding delivery and the value given to their own health and that of their unborn baby. Child birth is not a laboratory project that can be reproduced at will [12] but a natural event that in many situations cannot be predicted in exact time, sequence and ease or difficulty. Hygiene was the second important reason for the choice of hospital deliv- ery, reported by 66.6% of the women. This reflects both the recognition of women of the importance of hygiene for delivery and their expectation of good hygiene standards in hospitals. Medical advice was a common reason for preferring hospital delivery, reported by 63.2% of the women who had hospital delivery. This is an impor- tant point. As the influence of doctors and other health staff increases, as could happen if the family health model is widely adopted, the demand for hospi- tal delivery is likely to increase. Having a hospital delivery be- cause of a recognized risk (high-risk pregnancy) reflects the success of prenatal care in identifying high-risk women and encouraging them to make the appropriate choice for delivery. Similar results have been reported by other studies carried out in the UK [13] and Canada [14] where high-risk pregnancies were more frequent among hospital-delivered women than home- delivered women. As regards personal choice, 71.9% of hospital-delivered women claimed that it was their own personal choice to request hospital as the place for de- livery. This was also reported in a study in Canada in 1999 [7]. The study in Canada also reported the role of the family in determining the place and even the mode of delivery. The predominant reason reported by home-delivered women for prefer- ring home delivery was social support and/or privacy, reported by 98.2% of the women. Social support was through birth attendant, relatives, friends and others, and is a very important factor for reassurance and support in the progress and outcome of labour. This feeling Table 2 Distribution of women according to parity and use of prenatal care (n = 353) Characteristic No. % Parity 1 128 36.3 2–3 138 39.1 4–5 58 16.4 > 5 29 8.2 No. of prenatal visits None 20 5.7 1–2 41 11.6 3–4 64 18.1 Sub-total (inadequate use) 125 35.4 5–6 115 32.6 7–8 56 15.9 9–10 42 11.9 11–12 11 3.1 ≥ 13 4 1.1 Sub-total (adequate use) 228 64.6 Table 3 Distribution of the women according to place of delivery (n = 353) Place of delivery No. % Present child Home 57 16.1 Hospital 296 83.9 First child Home 40 17.8 Hospital 185 82.2 Previous child Home 56 24.9 Hospital 169 75.1 Next child Home 59 16.7 Hospital 294 83.3 EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 878 James DK et al., eds. 1. High risk pregnancy. Management options in labour, 2nd ed. London, WB Saunders, 1999:1071–2. Mother-baby package.2. Implementing safe motherhood in coun- tries. Geneva, World Health Organization, 1994 (WHO/FHE/ MSM/94.11). Habib OS, Vaughan, P. The determinants of health services 3. utilization in Southern Iraq. International Journal of Epidemiol- ogy, 1986, 15:395–403. Habib OS. [4. Health services in Basrah: facts and future perspec- tives]. Basra, Ahmed Al-Ali Press, 2008 [In Arabic]. Ouakrim M, Badr A. Overall view of the health status of women 5. and its determinants in the Eastern Mediterranean Region. Eastern Mediterranean Health Journal, 1996, 2:545–556. Kaartinen L, Diwan V. Mother and child health care in Kabul, 6. Afghanistan with focus on mother: Women’s own perspec- tive. Acta Obestetricia et Gynecologica Scandinavica, 2002, 81(6):491–501. Blais R. Are home births safe? 7. Canadian Medical Association Journal, 1999, 166(30):335–337. Live births by place of delivery and race of mother8. . Atlanta, Cent- ers for Disease Control and Prevention, 1992:246. References Habib OS, Al-Azawi HKF, Ajeel NAH. Household surveys as 9. a source of information to support primary health care: An example from Basrah. Medical Journal of Basrah University, 2000, 18:13–18. Alwan AA. 10. Health in Iraq: A review of the current health situation, challenges facing reconstruction of the health sector and vision for the immediate future. Baghdad, Al-Adib Press, 2004. Olsen O. Hjemmefodsler og videnskabelig tankegang [Home 11. delivery and scientific reasoning]. Tidsskrift for den Norske Laegeforening, 1994, 114(30):3655–3657. The compleat mother12. . Homebirth: as safe as birth gets. (http:// www.compleatmother.com/homebirth/hb_safety.htm, ac- cessed 25 April 2010). Chamberlain G, Wraight A, Crowley P, eds. 13. Home births - The report of the 1994 Confidential Enquiry by the National Birthday Trust Fund. Carnforth, Parthenon Publishing, 1997. Tyson H. Outcome of 1001 midwife attended home birth in 14. Toronto, 1983–1988. Birth, 1991, 18(1):14–19. MacVicar J et al. Simulated home delivery in hospital: A ran-15. domised controlled trial. British Journal of Obstetrics and Gynae- cology, 1993, 100(4):316–323. Olsen O. Meta-analysis of safety of the home birth. 16. Birth, 1997, 24(1):4–13. may make it less feasible to convince such women to have hospital delivery and undermines the view that all labour events should be considered a compli- cation waiting to happen until proved otherwise [1]. The privacy of home does make it a more comfortable place for delivery and if the birth is attended by trained midwives, it may be as safe as hospital delivery [1]. Other studies agree with our finding of the importance of support in home delivery. In the UK, for example, a number of studies found that home delivery provided more than just sympathetic care in a nicely deco- rated room [13,15]. For many women, the benefit of delivering at home comes from the feeling of privacy and being surrounded by family members and friends. Our study also showed that fear Table 4 Reasons given by the women for the choice of hospital or home delivery Reasona No. % Hospital delivery (n = 296) Safe and secure 286 96.6 More hygienic place 197 66.6 On medical advice 187 63.2 Recognized high risk factor 99 33.4 Emergency 16 5.4 Others (No midwife available) 7 2.4 Home delivery (n = 57) Social support and/or privacy 56 98.2 Fear of intervention in hospital 41 71.9 Unplanned (delivery quick or at night) 10 17.5 aMore than one reason could be given. of interventions (medical and surgi- cal) and repeated vaginal examination in hospital was an important factor in avoiding hospital delivery as reported by 71.9% of the women who preferred home delivery. Indeed, a study carried out in Denmark in 1997 on low-risk women planning home or hospital births showed that the planned home birth group had less severe maternal lac- eration, fewer interventions and fewer episiotomies [16]. The results of our study represent the studied women only and we can- not claim to generalize these results to all women in Basra governorate. How- ever, there is no reason to believe that these results do not reflect the general situation in the community of Basra governorate. In conclusion, most of the women in our study preferred a hospital delivery but nearly 1 in 6 pre- ferred home delivery. Both groups had their own expressed justifications for their choices. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 879 Connaissances et pratiques des femmes de la région de Monastir (Tunisie) concernant l’allaitement maternel I. Bouanene,1 S. ElMhamdi,1 A. Sriha,1 A. Bouslah2 et M. Soltani1 RÉSUMÉ Nous avons étudié la prévalence, les connaissances, les pratiques et les facteurs déterminants de l’allaitement maternel auprès de 354 mères amenant leur nourrisson pour la vaccination du sixième mois aux centres de santé de base de la région de Monastir en 2008. L’âge moyen des femmes interrogées était de 30 ans (ET 5,5). La majorité (90,8 %) savait que l’allaitement au sein permet de prévenir les infections chez le bébé mais 38,5 % seulement savaient que le lait maternel peut couvrir à lui seul les besoins de l’enfant jusqu’à l’âge de 6 mois. Alors que 94,4 % des femmes ont allaité au sein à la naissance, uniquement 1,9 % d’entre elles ont poursuivi l’allaitement exclusif jusqu’à l’âge de 6 mois. Les causes d’abandon de l’allaitement maternel étaient principalement l’insuffisance du lait, suivie par la reprise du travail. Une durée d’allaitement maternel exclusif prolongée au-delà de 3 mois était associée au contact peau à peau (OR = 1,93 ; IC 95 % : 1,016-3,69) et aux connaissances des mères des bénéfices du lait maternel (OR = 2,8 ; IC 95 % : 1,2-6,6). Cependant, l’utilisation de la tétine et la prescription de compléments de lait artificiel étaient associées à un sevrage précoce (OR = 0,17 ; IC 95 % : 0,08-0,36 et OR = ,14 ; IC 95 % : 0,05-0,38, respectivement). 1Département de Médecine communautaire, Faculté de Médecine de Monastir, Monastir (Tunisie) (Correspondance à adresser à I. Bouanene : bouaneneines@gmail.com). 2Service régional des Soins de Santé de Base, Monastir (Tunisie). Reçu : 18/10/09; accepté : 08/12/09 )سنوت( يرتسنولما في ءاسنلا ىدل يدثلا نم يعيبطلا عاضرلإا في تاسرمالماو فراعلما نياطلس دممح ،حلاصوب لامآ ،ةيحسر ءماسأ ،يدمحلما ءانس ،نانعوب سانيإ زكارم عجارـت ةأرما 354 ىدل كلذو ،ههاتج نهفقاومو ءاسنلا فراعمو ،هتاددمحو ،يدثلا نم يعيبطلا عاضرلإا راشتنا لدعم نوثحابلا ميق :ةـصلالخا ءلاؤه مظعم نأو ،)5.5 يرايعم فارحناب( ًاماع 30 ةوسنلل يطسولا رمعلا نأ اودجوو ،2008 ماع في يرتسنولما ةقطنم في ةيلولأا ةيحصلا ةياعرلا يدثلا نبل نأ نفرعي طقف نهنم %38.5 نأ لاإ ،ىودعلاب نادلولا ةباصإ نم ةياقولا في دعاسي يدثلا نم يعيبطلا عاضرلإا نأ نفرعي )%90.8( ةوسنلا نهنم طقف %1.9 نإف ،يدثلا نم ننهادلو عاضرإب نأدب دق نهنم 94.4 نأ مغرو .رمعلا نم سداسلا رهشلا غلبي ىتح ماعطلا نم هجاتيح ام ديلولل مدقي ،ٍفاك يرغ يدثلا نبل نأب داقتعلاا يه يدثلا نم ةعاضرلا فاقيلإ ةيسيئرلا بابسلأا تناكو .روهش تس ىتح يدثلا لىع صرتقلما عاضرلإاب رمتسا ،1.93 ةيحجرلأا لدعم( ديلولاو ملأا ينب ميملحا سماتلاب روهش 3 ةدلم يدثلا نم عاضرلإا لىع راصتقلاا قفارـت دقو .لمعلا لىإ ةدوعلا كلذ ولتيو تحوارـتو ،%95 ةقثلا ةلصافو ،2.8 ةيحجرلأا لدعم( يدثلا نبل دئاوف نع ملأا فراعمبو .)3.69و 1.016 ينب ميقلا تحوارـت ذإ ،%95 ةقث ةلصافو ،0.36و 0.08 ينب ميقلا تحوارـتو %95 ةقثلا ةلصافو ،0.17 ةيحجرلأا لدعم( ةياهللا مادختساب ركبلما ماطفلا قلعت دقو .)6.6و 1.2 ينب ميقلا .)0.38و 0.05 ينب ميقلا تحوارـتو 95% ةقثلا ةلصافو ،0.14 ةيحجرلأا لدعم( يدثلا نبل لئادبو Knowledge and practices of women in Monastir, Tunisia regarding breastfeeding ABSTRACT We assessed the prevalence of breastfeeding and its determinants and mothers’ knowledge and practices towards this issue among 354 women attending primary health centres for their child’s 6- month vaccination in the region of Monastir in 2008. The mean age of the women was 30 (SD 5.5) years. Most (90.8%) knew that breastfeeding helped prevent infections in babies but only 38.5% knew that breast milk supplies all infant feeding needs until 6 months of age. While was 94.4% breastfed their babies to start, only 1.9% continued exclusive breastfeeding until 6 months. Main reasons for stopping breastfeeding were perceived breast milk insufficiency followed by return to work. Exclusive breastfeeding over 3 months was associated with skin-to-skin contact (OR = 1.93; 95% CI: 1.016–3.69) and mothers’ knowledge about breast milk benefits (OR = 2.8; 95% CI: 1.2-6.6). Early weaning was related to using pacifiers and breast-milk substitutes (OR = 0.17; 95% CI: 0.08–0.36 and OR = 0.14; 95% CI: 0.05–0.38 respectively). EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 880 Introduction Les vertus de l’allaitement maternel concernent aussi bien la santé de la mère que celle de son enfant, et s’observent à court et à long terme, se traduisant par une réduction de la morbi-mortalité infantile [1,2]. L’OMS recommande un allaite- ment maternel exclusif durant les six premiers mois de vie du bébé [3]. Selon les experts, la poursuite de l’allaitement exclusif pendant six mois permet un développement optimal des nourrissons et doit être encouragée, l’introduction d’une alimentation complémentaire entre quatre et six mois n’apportant aucun bénéfice particulier. En effet, le rôle de l’allaitement maternel exclusif dans la prévention des infections, des al- lergies et des maladies chroniques ainsi que dans le développement cognitif favorable a été mis en exergue dans la littérature scientifique récente [4]. En Tunisie, avant 1960, la pra- tique de l’allaitement maternel était la règle conformément aux normes religieuses et sociales [5]. Par ailleurs, notre pays a vécu, après l’indépendance, l’émancipation des femmes liée à la promulgation du code du statut per- sonnel, permettant à celles-ci l’accès à l’éducation et au travail, avec comme corollaire un abandon précoce de l’allaitement maternel ces dernières an- nées, malgré les nombreuses actions législatives et promotionnelles en faveur de la protection de cette pratique. Les données nationales montrent un recul du pourcentage des enfants al- laités exclusivement au sein jusqu’à l’âge de 6 mois [6]. En effet, ce taux est passé de 46,5 % en 2000 à 6,2 % en 2006. Pour pouvoir mettre en place des interventions visant à promouvoir l’allaitement maternel dans la durée, il est important de connaître les différents déterminants en jeu. C’est dans ce cadre que s’inscrit notre travail qui vise l’étude des connaissances et des pratiques des mères vis-à-vis de l’allaitement maternel et l’identification des facteurs détermi- nants d’un sevrage précoce. Méthodes C’est une étude transversale descriptive exhaustive réalisée durant le deuxième trimestre de l’année 2008, portant sur les connaissances et les pratiques des mères en matière d’allaitement maternel. Notre population d’étude était con- stituée de l’ensemble des femmes qui ont amené leur nourrisson pour la vac- cination du 6e mois (3e prise du DTCP + HBV) aux centres de santé de base de la région sanitaire de Monastir. À partir de cette population et en se basant sur une prévalence d’allaitement maternel de 6,2 % (données du Multiple Indicator Cluster Survey - MICS III [6]) et une précision de 3 %, nous avons étudié un échantillon de 354 mères. Nous avons exclu de cette étude toutes les femmes qui n’ont pas allaité leur bébé à cause d’une maladie de l’enfant entravant cette pratique (mal- formations du tube digestif, anomalie congénitale du métabolisme, hospitali- sation en soins intensifs, etc.), ainsi que toutes les femmes n’ayant pas allaité leur enfant dès l’accouchement à cause d’une maladie contre- indiquant l’allaitement maternel (maladie mammaire, infec- tion par le VIH, hyperprolactinémie majeure, etc.). Le recueil des données était réalisé à l’aide d’une entrevue structurée basée sur un questionnaire préalablement testé et administré aux mères par des enquêteurs formés. Le questionnaire explore les dimen- sions suivantes : le profil socioéconomique et démo-• graphique des mères : âge, origine urbaine ou rurale, niveau d’ins- truction, profession, parité et âge du dernier enfant ; les caractéristiques de la grossesse et • de l’accouchement : suivi et compli- cations éventuelles ; les connaissances et les pratiques • des mères concernant l’allaitement maternel et la diététique infantile : bénéfices du lait maternel, durée d’allaitement maternel exclusif, délai entre l’accouchement et la première tétée, utilisation de tétine, supplé- mentation en lait artificiel et âge de diversification alimentaire ; le rôle du père, de la famille et des • professionnels de santé ; les causes d’arrêt précoce de • l’allaitement maternel. Dans notre travail, nous avons considéré que les mères qui savaient au moins quatre des huit bénéfices de l’allaitement maternel cités dans le questionnaire avaient de bonnes con- naissances. Les données ont été rassem- blées, codées et saisies sur matériel informatique avec le logiciel SPSS 15.0. Les facteurs associés au sevrage précoce ont été recherchés parmi les caractéris- tiques citées ci-dessus. Les comparai- sons ont été réalisées à l’aide des tests statistiques appropriés (test du χ2, test exact de Fischer), au seuil de significa- tion de 5 %. Définitions opérationnelles L’allaitement est exclusif lorsque le nou- veau-né ou le nourrisson reçoit unique- ment du lait maternel à l’exception de tout autre ingestat, solide ou liquide, y compris l’eau. L’allaitement est partiel lorsqu’il est associé à une autre alimen- tation comme des substituts de lait, des céréales, de l’eau sucrée ou non ou toute autre nourriture [3]. Le critère de jugement principal que nous avions choisi pour évaluer les déterminants d’une durée prolongée de cette lactation était le sevrage pré- coce, défini comme étant la cessation de l’allaitement maternel exclusif avant l’âge de 3 mois. Résultats Caractéristiques de la population étudiée L’âge moyen de notre population d’étude était de 30 (écart type [ET] 5,5) ans avec des extrêmes allant de 18 à 46 ans. Les femmes aux âges extrêmes de la procréation (< 20 ans ou ≥ 35 ans) طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 881 représentaient 1,7 % et 21,5 % respec- tivement. Parmi les 354 mères inter - rogées, 329 étaient issues d’un milieu urbain (93,5 %). Près de 60 % des mères (58,8 %) étaient sans profes- sion et 80,8 % avaient un niveau socioéconomique moyen. Un bas niveau d’instruction (analphabète ou de niveau primaire) a été retrouvé chez 36,3 % des cas. La répartition des femmes selon la parité a montré que 24,6 % étaient des primipares et 58,3 % des paucipares (Tableau 1). Connaissances des mères en matière d’allaitement Il ressort de cette étude que 90,8 % des femmes interrogées savaient que le lait maternel assure la prévention des infections chez le bébé. Le rôle de l’allaitement maternel dans le dével- oppement psychoaffectif de l’enfant a été signalé par 43,3 % des mères. Par contre 8,8 % d’entres elles savaient que l’allaitement maternel préserve la santé de la mère (Tableau 2). Selon 99,3 % des femmes, la prise de poids du bébé constituait le signe ma- jeur d’un allaitement maternel efficace chez l’enfant. Et seulement 38,5 % des mères savaient que le lait maternel peut couvrir à lui seul les besoins de l’enfant jusqu’à l’âge de 6 mois. Parmi les 354 femmes de notre série, 67 % ont bénéficié de séances d’éducation sanitaire par les profession- nels de santé en matière d’allaitement maternel . Cette éducation a été pratiquée pendant la grossesse dans 60,8 % des cas . Les médecins représentaient la principale source d’information (72,4 %). Pratiques concernant l’allaitement maternel Près de trois quarts des mères (75,4 %) ont déclaré avoir vécu antérieurement l’expérience d’un allaitement au sein. Le choix du mode d’allaitement a été effectué pendant la grossesse dans 93,8 % des cas. L’encouragement du mari a majoritairement (96,5 %) contribué à la décision des femmes d’allaiter au sein. Le taux d’enfants allaités à la nais- sance était de 94,4 %. Un contact peau à peau entre mère et enfant a eu lieu en salle d’accouchement dans 63,8 % des cas. Concernant le délai de mise au sein après la naissance, 12 % des bébés ont reçu leur première tétée à la première heure de vie, 21 % dans les 2 heures qui suivent la naissance et 67 % à la 3e heure de vie. La durée moyenne de l’allaitement maternel exclusif était de 40 (ET 45) jours avec des extrêmes allant de 1 à 180 jours. Plus de la moitié des femmes (55,6 %) ont allaité leur enfant exclusivement au sein jusqu’à l’âge de 1 mois. À l’âge de 3 mois, 15,3 % des nourrissons bénéficiaient d’un allaitement maternel exclusif. Cette pratique continuait à diminuer pour atteindre 1,9 % à l’âge de six mois(Figure 1). Le recours à la supplémentation Tableau 1 Caractéristiques sociodémographiques de la population d’étude Variables Effectif % Âge (ans) < 25 54 15,3 25-35 224 63,3 > 35 76 21,5 Niveau d’instruction Aucun 15 4,3 Primaire 112 32,0 Secondaire 141 40,3 Supérieur 82 23,4 Origine Urbaine 329 93,5 Rurale 23 6,5 Profession Sans 207 58,8 Ouvrière 83 23,6 Cadre moyen 37 10,5 Cadre supérieur 21 6,0 Étudiante 4 1,1 Niveau socio-économique Bas 44 12,6 Moyen 282 80,8 Élevé 23 6,6 Parité 1 enfant 86 24,6 2-3 enfants 204 58,3 4 enfants et plus 60 17,1 Tableau 2 Connaissances des mères concernant les bénéfices de l’allaitement maternel Bénéfices % Prévention des infections 90,8 Développement psychoaffectif du bébé 43,3 Prévention des allergies 14,0 Préserve la santé de la mère 8,8 Prévention de l’obésité 1,2 Favorise la croissance du bébé 0,3 Prévention du diabète type 1 0,3 Prévention du risque vasculaire 0,0 EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 882 en lait artificiel a été constaté chez 16,7 % des enfants âgés de 3 mois. L’âge moyen d’introduction de ce lait était de 2,6 mois. Les mères étaient 78,9 % à déclarer avoir utilisé une tétine pour leur enfant avant l’âge de 3 mois. La diversification alimentaire pré- coce à partir de l’âge de 3 mois a été rap- portée dans un tiers des cas (33,3 %). Cette supplémentation concernait 61,4 % des nourrissons âgés de 3 à 6 mois. À l’étude des raisons ayant con- duit à une cessation de l’allaitement avant trois mois, on a constaté que la première cause évoquée par les mères pour abandonner l’allaitement materne l é t a i t l e manque de lait (46,4 %), suivi par la reprise du travail (26,2 %) (Tableau 3). Facteurs associés à un allaitement maternel prolongé au-delà de trois mois L’étude des déterminants d’une durée d’allaitement maternel exclusif > 3 mois a fait ressortir une association statis- tiquement significative avec le contact peau à peau (p < 0,03, OR = 1,93 ; IC 95 % : 1,016-3,69) et le niveau des connaissances des mères des bénéfices de l’allaitement maternel (p < 0,02 ; OR = 2,8 ; IC 95 % : 1,2-6,6). À l’inverse, l’utilisation précoce d’une tétine ou d’une sucette (p < 10-4) ou le fait de donner des compléments de lait artificiel (p < 0,003) était défavo- rable à la poursuite de l’allaitement. En effet, ces deux facteurs étaient associés à un sevrage précoce avec OR = 0,17 ; IC 95 % : 0,08-0,36 et OR = 0,14 ; IC 95 % : 0,05-0,38 respectivement (Tableau 4). Discussion Notre étude a porté sur toutes les femmes de la région sanitaire de Mo- nastir ramenant leur enfant pour la vaccination du 6e mois. Ce choix de la population d’étude a permis de dé- terminer la prévalence de l’allaitement maternel exclusif à l’âge de 6 mois tel que recommandé par l’OMS. L’avantage principal du lait mater- nel pour l’enfant est indiscutablement la protection contre les infections. D’autres effets, comme la prévention de l’atopie ou la réduction du risque d’obésité, ren- dent l’allaitement maternel déterminant dans l’état de santé ultérieur de l’enfant. D’après toutes les données de la littéra- ture, une durée supérieure à trois mois est la durée à partir de laquelle tous les bé- néfices précédemment évoqués sont ob- servés. Et il a été démontré que si sa durée Tableau 3 Principales raisons d’un sevrage précoce Causes de sevrage précoce % Manque de lait 46,4 Reprise du travail 26,2 L’enfant ne croît pas bien 16,7 Survenue de complications (crevasse, infection) 9,6 Prise de médicaments 3,6 Survenue de grossesse 3,6 Activité astreignante pour la mère 2,4 Raisons esthétiques 0,0 À la demande du mari 0,0 Autres 13,1 Durée d’allaitment maternel exclusif (mois) % d e fe m m es 60 50 40 30 20 10 0 1 2 3 4 5 6 55.6 15.3 15.3 8.1 3.8 1.9 Figure 1 Répartition des femmes selon la durée d’allaitement maternel exclusif طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 883 est supérieure à trois mois, l’allaitement maternel exclusif diminue l’incidence et la gravité des infections digestives, des infections oto-rhino-laryngologiques (ORL) et respiratoires [7,8]. Pour toutes ces raisons, il nous a paru judicieux d’utiliser comme critère de jugement principal une durée d’allaitement maternel exclusif au-del de 3 mois plutôt que 6 mois pour évaluer les déterminants de cette pratique. Le premier fait notable dans notre étude est que la prévalence de l’allaitement maternel à la naissance était de 94,4 % . Selon différentes en- quêtes nationales réalisées entre 1996 et 2006, la quasi-totalité (93 à 97,5 %) des femmes tunisiennes allaitent leur enfant à la naissance [6,9]. Ces valeurs rejoi- gnent les données de certains pays de l’Europe du Nord [10]. À titre d’exemple, la prévalence de l’allaitement maternel à la naissance est de 90 % en Suède, en Su- isse et au Danemark, et de plus de 95 % en Norvège et en Finlande. À l’opposé, cette prévalence en France est une des plus faibles des pays européens (56 %). Tableau 4 Association des caractéristiques sociodémographiques, des connaissances et des pratiques des femmes à une durée d’allaitement maternel exclusif > 3 mois Variablea Durée d’allaitement maternel exclusif p OR IC95 % < 3 mois > 3 mois Nbre (%) Nbre (%) Âge maternel (ans) (n=339) < 25 4 (16,3) 3 (6,8) 0,151 - - 25-35 187 (63,4) 28 (63,6) ≥ 35 60 (20,3) 13 (29,5) Instruction (n = 335) Néant ou primaire 108 (37,1) 12 (27,3) 0,135 - - Secondaire ou supérieur 183 (62,9) 32 (72,7) Profession (n = 338) Sans 173 (58,9) 26 (59,1) 0,55 - - Avec 121 (41,2) 18 (40,9) Parité (n = 336) 1 enfant 71 (24,3) 10 (22,7) 0,86 - - 2-3 enfants 171 (58,6) 25 (56,8) ≥ 4 enfants 50 (17,1) 9 (20,5) Origine (n = 337) Urbaine 278 (94,6) 39 (90,7) 0,24 - - Rurale 16 (5,4) 4 (9,3) Niveau socio-économique (n = 335) Bas 36 (12,4) 5 (11,4) 0,98 - - Moyen 236 (81,1) 36 (81,8) Élevé 19 (6,5) 3 (6,8) Contact peau à peau (n = 334) Oui 22 (18,6) 195 (90,2) 0,033 1,93 1,016-3,69 Non 96 (81,4) 21 (9,8) Connaissances des mères (n = 313) < 4 bénéfices 247 (96,5) 34 (60) 0,02 2,8 1,2-6,6 ≥ 4 bénéfices 9 (3,5) 23 (40) Utilisation du lait artificiel (n = 216) Oui 46 (17,5) 1 (2,3) 0,003 0,14 0,05-0,38 Non 217 (82,5) 42 (97,7) Utilisation de la tétine (n = 190) < âge de 3 mois 130 (81,8) 11 (52,4) < 10-4 0,17 0,08-0,36 ≥ âge de 3 mois 29 (18,2) 10 (47,6) aLes totaux varient en raison des données manquantes. OR = odds ratio ; IC = intervalle de confiance. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 884 La durée de l’allaitement maternel était très courte dans notre étude : sa durée moyenne a été estimée à 40 jours. L’allaitement à 4 mois a été maintenu dans 8,1 % des cas. Cette prévalence de l’allaitement maternel à l’âge de 4 mois est de plus de 65 % en Suède et en Suisse, 34 % au Canada, 27 % au Royaume-Uni et 5 % en France [11]. Dans notre t rava i l , l e t aux d’allaitement maternel exclusif main- tenu jusqu’à l’âge de 6 mois était très faible (1,9 %). Ce résultat est compatible avec des études menées dans d’autres pays [12,13]. Ainsi, dans notre série, les pratiques des mères demeurent insuffisantes. En témoigne aussi le démarrage précoce de la diversification alimentaire à partir de l’âge de 3 mois qui concernait le tiers des nourrissons. La perception d’une insuffisance de lait semble être la raison majeure amenant les mères à introduire le lait ar- tificiel et/ou à mettre fin à l’allaitement maternel. Cette constatation a été rapportée dans de nombreuses études [14-16]. Or, selon le rapport de l’Agence Nationale d’Accréditation et d’Évaluation en Santé (ANAES), l’insuffisance de lait physiologique est très rare [3]. Dans la majorité des cas, il s’agit soit de la perception d’une insuffisance de lait, qui pourrait être liée à un manque de confiance en soi de la mère, soit d’une insuffisance de lait secondaire à un allaitement mal géré (suite à une fréquence ou à une durée des tétées inadéquate, par exem- ple), à l’introduction de compléments, à une position du bébé incorrecte ou à un problème de succion [14]. Dans notre étude, la reprise du travail était le 2e motif avancé par les mères pour abandonner l’allaitement maternel. Selon Scott et al. [17] et Rojja- nasrirat [18], malgré l’intention de nom- breuses femmes de continuer d’allaiter après le retour au travail, l’emploi de la mère constitue un facteur significative- ment associé à un sevrage précoce. Contrairement à ce qui a été rapporté dans de nombreux travaux [19,20], nous n’avons pas trouvé d’association statis- tiquement significative entre une durée courte d’allaitement maternel et le jeune âge de la mère (< 25 ans). En effet, la tranche d’âge 18-25 ans ne représentait que 15,3 % de notre population d’étude. Ce phénomène peut s’expliquer par le recul de l’âge au mariage. En effet, selon les données du MICS III, la tranche d’âge 40-49 ans représentait 41 % des femmes mariées en âge de reproduction [6]. Dans la littérature, la primiparité était associée à une durée courte de l’allaitement maternel [21,22]. Cette différence entre primipare et multipare serait expliquée par une habilité et une facilité acquise de la multiparité à la mise au sein. Cependant, certains auteurs ont récemment apporté une explication d’ordre physiologique puisque, après un second accouchement, la quantité de lait aurait été retrouvée supérieure à celle produite lors de la première nais- sance [23]. Dans ce travail, la primiparité n’était pas un facteur significatif. Cette consta- tation peut être expliquée par le fait que les femmes primipares représentaient seulement le quart de la population d’étude. Nous avons trouvé que le niveau des connaissances des mères en matière d’allaitement maternel était significative- ment associé à une durée d’allaitement plus longue. Ceci a été rapporté dans les études faites par Gilmour et al. [24] et Baptista et al. [25]. Un manque d’informations sur la durée optimale de l’allaitement maternel est associé à un sevrage plus précoce [16], tandis que la connais- sance de la durée optimale d’allaitement exclusif de six mois (connue par 65 % des mères dans l’étude de Peters et al. [15]) est significativement associée à un allaitement maternel plus long [15]. D’autre part, l’étude de Blyth et al. [14] a montré une relation significa- tive entre l’information et le degré de soutien reçu en prénatal et la durée de l’allaitement. Tout ceci met en exergue l’importance de l’information apportée en prénatal sur le taux et la durée de l’allaitement. Les conséquences des pratiques en salle de naissance sur l’allaitement mater- nel sont connues depuis longtemps. Elles ont été décrites à propos de la première mise au sein [26]. La mise au sein précoce après l’accouchement a été soulignée comme bénéfique sur la durée d’allaitement [15,27], tandis qu’une mise au sein différée semble être un facteur de risque de sevrage plus précoce. Dans la méta-analyse de Bernard- Bonnin et al., quatre des études retenues envisageaient non pas explicitement la mise au sein mais le contact précoce mère-enfant, peau à peau (avec ou sans tétée) : il s’agissait d’un facteur qui fa- vorisait la prolongation de l’allaitement maternel de façon significative [28]. Cette constatation a été retrouvée dans d’autres études plus récentes [29]. Ces données concordent bien avec nos résultats. Par contre, nous avons constaté que l’introduction précoce d’une tétine diminue significativement la durée de l’allaitement maternel. Ce facteur a été retrouvé de façon très fréquente [17]. L’influence de l’utilisation d’une tétine sur l’allaitement maternel ne se limite probablement pas aux interférences avec le mécanisme physiologique de la succion. Il semblerait que l’usage ha- bituel de la tétine soit aussi le témoin de facteurs psychologiques et compor- tementaux maternels (faible confiance en soi, comportement rigide) moins propices à la poursuite de l’allaitement maternel [30]. Dans notre étude, la prescription de compléments de lait artificiel était associée à un risque plus élevé de sevrage précoce. Ceci est conforme à ce qui a été rapporté dans de nombreux travaux [31-33]. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 885 Ip S et al. Breastfeeding and maternal and infant health out-1. comes in developed countries. Evidence Report/Technology Assessessment, (Full Report). 2007, 153:1–186. Horta BL et al. 2. Evidence of the long-term effects of breastfeeding. Geneva, World Health Organization, 2007. Agence Nationale d’Accréditation et d’Évaluation en Santé 3. (ANAES), service recommandations et références profession- nelles. Allaitement maternel : mise en œuvre et poursuite dans les six premiers mois de vie de l’enfant. Recommandations (mai 2002). Gynécologie Obstétrique Fertilité, 2003, 31:481–90. Yngve A, Sjöström M.4. Breastfeeding in countries of the Euro- pean Union and EFTA: current and proposed recommenda- tions, rationale, prevalence, duration and trends. Public Health Nutrition, 2001, 4(6):1306. Khrouf N, Chnaina J, Jebnoun S. Santé maternelle et infantile 5. dans les pays arabes. Revue Maghrébine de Pédiatrie, 1999, n°3. Enquête nationale sur la santé et le bien-être de la mère6. et de l’enfant MICS III (2008). Tunisie, Ministère de la Santé pub- lique/UNICEF/Office National de la Famille et de la Popula- tion, 2008. Bachrach VRG, Scharz E, Bachrach LR. Breastfeeding and the 7. risk of hospitalization for respiratory disease in infancy. A meta- analysis. Archives of Pediatrics and Adolescent Medicine, 2003, 157:237–243. Oddy WH et al. Breast feeding and respiratory morbidity in 8. infancy: a birth cohort study. Archives of Disease in Childhood, 2003, 88:224–228. Enquête nationale9. sur la santé de la mère et de l’enfant PAP CHILD. Tunisie, Ministère de la Santé publique, Direction des Soins de Santé de Base, 1996. Groupe de travail pour la promotion de l’allaitement mater-10. nel dans le Nord. Dossier pour la promotion de l’allaitement maternel dans le département du Nord. Archives de Pédiatrie, 2001, 8:865–874. Castetbon K, Duport N, Hercberg S. Bases épidémiologiques 11. pour la surveillance de l’allaitement maternel en France. Revue d’Épidémiologie et de Santé Publique, 2004, 52:475–480. Oommen A et al. Breastfeeding practices of urban and rural 12. mothers. Indian Pediatrics, 2009, 46(10):891–894. Xu F et al. A comparison of breastfeeding among Han, Uygur 13. and other ethnic groups in Xinjiang, PR China. BMC Public Health, 2006, 6:196. Blyth RJ et al. Breastfeeding duration in an Australian popula-14. tion: the influence of modifiable antenatal factors. Journal of Human Lactation, 2004, 20:30–38. Peters E et al. Breastfeeding duration is determined by only a 15. few factors. European Journal of Public Health, 2006, 16:162– 167. Taveras EM et al. Opinions and practices of clinicians associ-16. ated with continuation of exclusive breastfeeding, Pediatrics, 2004, 113:e283–e290. References Scott JA et al. Predictors of breastfeeding duration: evidence 17. from a cohort study, Pediatrics, 2006, 117:e646–e655. Rojjanasrirat W. Working women’s breastfeeding experi-18. ences, MCN. American Journal of Maternal Child Nursing, 2004, 29:222–227. Thulier D, Mercer J. Variables associated with breastfeeding 19. duration. Journal of Obstetric, Gynecologic and Neonatal Nurs- ing, 2009, 38(3):259–268. Baxter J, Cooklin AR, Smith J. Which mothers wean their babies 20. prematurely from full breastfeeding? An Australian cohort study. Acta Paediatrica. 2009, 98(8):1274–1277. Lebours B 21. et al. L’alimentation du nourrisson jusqu’à quatre mois en Seine-Maritime. Archives Françaises de Pédiatrie, 1991, 48:391–395. Bulk-Bunschoten AM et al. Reluctance to continue breastfeed-22. ing in The Netherlands. Acta Paediatrica, 2001, 90(9):1047– 1053. Ingram J, Woolridge M, Greenwood R. Breastfeeding: it is worth 23. trying with the second baby. Lancet, 2001, 90:1047–1053. Gilmour C et al. Factors associated with early breastfeeding 24. cessation in Frankston, Victoria: a descriptive study. Breastfeed- ing Reviews, 2009, 17(2):13–19. Baptista GH et al. [Factors associated with duration of breast-25. feeding for children of low-income families from southern Curitiba, Paraná State, Brazil]. Cadernos de Saúde Pública, 2009, 25(3):596–604. Righard L, Alade MO. Effect of delivery room routines on suc-26. cess of first breastfeed. Lancet, 1990, 336:1105–1107. Branger B 27. et al. Facteurs influençant la durée de l’allaitement maternel chez 150 femmes. Archives de Pédiatrie, 1998, 5:489– 496 Bernard-Bonnin AC 28. et al. Pratiques hospitalières et durée de l’allaitement maternel : méta-analyse. Revue d’Épidémiologie et de Santé Publique, 1989, 37:217–225. Moore ER, Anderson GC, Bergman N. Early skin-to-skin contact 29. for mothers and their healthy newborn infants. Cochrane Data- base of Systematic Reviews, 2007, 18(3):CD003519. Victora CG et al. Pacifier use and short breastfeeding dura-30. tion: cause, consequence, or coincidence? Pediatrics, 1997, 99:445–453. Asole S et al. Effect of hospital practices on breastfeeding: a 31. survey in the Italian region of Lazio. Journal of Human Lactation, 2009, 25(3):333–340. Declercq E et al. Hospital practices and women’s likelihood 32. of fulfilling their intention to exclusively breastfeed. American Journal of Public Health, 2009, 99(5):929–935. Blomquist HK et al. Supplementary feeding in the maternity 33. ward shortens the duration of breast feeding. Acta Paediatrica, 1994, 83(11):1122–1126. Conclusion Malgré la prévalence élevée de l’allaitement maternel à la naissance, beaucoup d’insuffisances au niveau des connaissances et surtout des pratiques des mères restent à combler. Ceci requiert des stratégies de pro- motion de l’allaitement maternel axées d’une part sur l’information et l’éducation des femmes et d’autre part sur la formation des professionnels de santé au cours de leurs études et pendant la formation continue. De même, certaines initiatives telles que les « Hôpitaux amis des bébés » sont de nature à encourager la promotion de l’allaitement maternel. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 886 Impact of using essential drug list: analysis of drug use indicators in Gaza Strip R. Fattouh1 and B. Abu Hamad 1 ABSTRACT A descriptive cross-sectional study evaluated the compliance of physicians with the Palestinian essential drug list (EDL) in all the government primary care clinics in the Gaza Strip. While 67.4% reported currently using the EDL 51.2% of these physicians reported problems in using it. The mean number of drugs per prescription was 1.92, the percentage of drugs prescribed from the EDL was 97.9% but the percentage of drugs prescribed by generic name was only 5.5%. A copy of the EDL was available in 28.3% of clinics and the availability of key drugs was 82.6%. The compliance of physicians with the EDL was generally good, but more efforts are needed to encourage prescribing by generic name and to ensure the supply of key drugs. 1School of Public Health, Al-Quds University, Gaza, Palestine (Correspondence to R. Fattouh: r_m_11@hotmail.com). Received: 12/10/08; accepted: 13/01/09 ةزغ عاطق في ةيودلأا مادختسا تاشرؤم ليلتح :ةيساسلأا ةيودلأا ةمئاق مادختسا رثأ دحم وبأ ماسب ،حوتف اشر عاطق في ةيموكلحا ةيلولأا ةياعرلا تادايع عيجم في ةيساسلأا ةيودلأا ةمئاقل ءابطلأا لاثتما مييقتل ةيضرع ةيفصو ةسارد ناثحابلا ىرجأ :ةـصلالخا في لكاشلما ضعب اودجو مهنم %51.2 و ضرالحا تقولا في ةيساسلأا ةيودلأا ةمئاق اومدختسي اوناك ءابطلأا نم %67.4 نأ جئاتنلا ترهظأ ماك .ةزغ يتلا ةيودلأل ةيوئلما ةبسنلا تغلبو ،1.92 وه ةدحاولا ةيئاودلا ةفصولا في ةفوصولما ةيودلأا ددع طسوتم نأ جئاتنلا ترهظأ دقف .اله مهمادختسا ةمئاق نم ةخسن تناكو .%5.5 زواجتت نكت لم سينلجا اهمساب فصوت يتلا ةيودلأل ةيوئلما ةبسنلا نأ لاإ ،%97.9 ةيساسلأا ةيودلأا ةمئاق نم فصوت ةمئاقب ءابطلأا لاثتما نأ حضتا اذكهو .%82.6 ةيسيئرلا ةيودلأا رفاوتل ةيوئلما ةبسنلا تناك مايف ،تادايعلا نم %28.3 في ةرفاوتم ةيساسلأا ةيودلأا ةيودلأاب دادملإا نماضلو ،ةسينلجا ءماسلأا فصو لىع عيجشتلل دوهلجا نم ديزلما لذبل ةجاح كانه نكلو ،ماع لكشب ًاديج ناك ةيساسلأا ةيودلأا .ةيسيئرلا Impact de l’utilisation de la liste des médicaments essentiels : analyse des indicateurs d’utilisation des médicaments dans la Bande de Gaza RÉSUMÉ Une étude transversale descriptive a évalué la manière dont les médecins respectaient la liste de médicaments essentiels palestinienne dans l’ensemble des centres de soins de santé primaires publics de la Bande de Gaza. Si 67,4 % des médecins ont affirmé recourir à cette liste, 51,2 % d’entre eux ont déclaré rencontrer des problèmes lors de son utilisation. Le nombre moyen de médicaments par prescription était de 1,92 ; le pourcentage de médicaments prescrits à partir de la liste était de 97,9 %, mais le pourcentage de médicaments prescrits par nom générique atteignait seulement 5,5 %. Un exemplaire de la liste était disponible dans 28,3 % des centres et les principaux médicaments étaient disponibles à 82,6 %. En général, les médecins se conformaient bien à la liste des médicaments essentiels, mais des efforts supplémentaires pour encourager la prescription de médicaments par leur nom générique et pour assurer l’approvisionnement en principaux médicaments essentiels doivent être réalisés. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 887 Introduction Since 1994, there have been 4 major players involved in the health services of the Palestinian territories: the Ministry of Health (MOH), the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA), various nongovernmental organiza- tions (NGOs) and the private sector. The MOH is responsible for provid- ing a significant portion of the primary health care (PHC), secondary care and some tertiary care [1]. In 2005, the MOH spent 17.9% of its total budget on pharmaceuticals [1]. Research findings indicate that over-prescribing, irrational prescribing and prescribing expensive brand-name drugs are common in Pal- estinian health facilities [2]. The development of the Palestinian essential drug list (EDL) in 2000 was an important step towards rational pre- scribing [3]. In line with World Health Organization (WHO) suggestions, the present study was designed to pro- vide guidelines for updating the EDL. Uniquely, the study explored physicians’ compliance with the EDL within the Palestinian context, which is character- ized by diverse socioeconomic, political and managerial challenges. The general objective of the study was to evaluate the compliance of physicians with the Palestinian EDL in government PHC facilities in order to highlight measures to improve the utilization of the EDL, thus contributing to health system efficiency and effective- ness. The specific objectives were to assess physicians’ prescribing practices with reference to selected WHO indica- tors; to appraise physicians’ attitudes and practices regarding the Palestinian EDL; to examine the relationship be- tween prescribing practices and other variables; and to identify strengths and weaknesses in physicians’ prescribing practices with reference to compliance with the EDL. Methods This was a cross-sectional descriptive analytical study with a self-administered questionnaire to physicians and an analysis of prescriptions collected from PHC clinics. Sample Because the study population is small, all 276 physicians working in govern- ment PHC clinics in Gaza Strip were recruited for the questionnaire survey. For the prescribing analysis a retro- spective multi-stage random sample of 1656 prescriptions from the previous 6 months were selected. In compliance with WHO guidelines, 36 prescriptions were taken from each of the 46 clinics [4]. Because the study included all the clinics, the time-scale for the study was limited and it was difficult to access older prescriptions, therefore a time interval of 6 months was judged to be sufficient to monitor prescriptions, based on the WHO guidelines [4]. Be- cause drug availability varies across the days of the month, 3 prescriptions were randomly drawn from each month and for each group (< 3 years and ≥ 3 years): 1 from the first 10 days of the month, 1 from the middle 10 days and 1 from the last 10 days. Data collection Two instruments were used. The first was a self-administered questionnaire distributed to physicians to collect some relevant organizational and personal data and to assess their attitudes and practices towards the EDL. The second was a checklist using the WHO recommended format to record selected WHO drug use indicators [4]. The researcher and 2 trained assistants filled the checklist. The mean number of drugs prescribed per encounter, the percentage of drugs prescribed by generic name and the percentage of drugs prescribed from the EDL or local formulary were calculated using standard methods [5]. The survey also checked the percentage availability of 12 key drugs in the surveyed clinics and whether a copy of the EDL or formulary was available at the health facilities. The short-list of key drugs that are essential to treat common health problems were drawn up after discussions with key stakeholders and policy-makers [6]. The researcher reviewed the filled ques- tionnaires and checklists and entered them into the database. Official approval to conduct the study was obtained from the research ethics committee in the Gaza Strip. Ad- ditionally, the MOH officially approved conducting the study and provided ac- cess to the study population. Data analysis Prescribing indicators were analysed by patient’s age group, time of the month, governorate and by health care facility level. Because the local health system treats patients who are younger than 3 years in a different way from older patients, the prescriptions from each month in each clinic were divided into 2 groups: patients aged < 3 years (treated free-of-charge) and patients aged ≥ 3 years (medical insurance required) [4]. The health care levels were defined as follows: level 1 (clinic has a community health worker and a nurse all weekdays and is visited twice per week by a physi- cian); level 2 (physician and full-time nurse work in the clinic all weekdays); level 3 (physicians and nurses work all weekdays and the clinic provides basic laboratory services, X-ray, dental care and emergency care 12 hours daily); level 4 (full-time physicians, nurses, laboratory services, ultrasound, X-ray, family planning and emergency care 24 hours daily in addition to some specialty services). Data entry, cleaning and analysis was done using SPSS software, version 11. Descriptive analysis and then inferential analysis were done based on the nature of the study variables. Means and stand- ard deviations (SD) were computed for EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 888 the continuous numeric variables fol- lowed by recoding of certain variables. The selected WHO drug use indicators were computed using the statistical for- mulae developed by WHO. In order to explore the potential relationships between the study variables, advanced statistical analysis were conducted, in- cluding independent t-test, 1-way analy- sis of variance and the chi-squared test for categorical variables. P-value < 0.05 was considered statistically significant. Results Physicians’ knowledge, attitudes and practices A total of 242 out of 276 physicians completed the questionnaire, a response rate of 87.7%. Only 2.8% of respondents had been involved in the preparation of the EDL, 34.4% had attended training courses on the EDL and 88.9% were interested in having further training (Table 1). Only two-thirds of physicians (67.4%) reported currently using the EDL, and around half of this subgroup (51.2%) said they faced many problems in using the EDL, especially concerning inad- equate supplies of the listed drugs. Table 2 shows the responses of phy- sicians according to whether they were using the EDL or not. As expected, phy- sicians who reported that EDL drugs were exclusively available in their clinics (94.1%) were using EDL drugs more than the others and the differences be- tween the 2 groups were statistically significant (P < 0.001) (Table 2). Table 2 also shows that 83.1% of physicians who had undergone an evaluation of their prescribing practices were currently using the EDL. Similarly, 83.3% of those who received written feedback about their prescribing prac- tices were using the EDL. Physicians who had attended train- ing courses on EDL were currently us- ing it (83.1%), a higher proportion than those who had not had training (58.6%) and the differences between the 2 groups were statistically significant (P < 0.001). Moreover, significantly more physicians who found the EDL easy to use were currently using it (91.3%) compared with those who perceived its use as difficult (57.9%) (P < 0.001) (Table 2). Fewer physicians who agreed that they were strongly influenced by clients’ requests for drugs were using the EDL (55.6%) than those who reported never being influenced by clients’ requests for drugs (72.4%). The difference between the groups was statistically significant (P = 0.013). WHO drug use indicators The mean number of drugs prescribed per encounter was 1.92 (SD 0.99), with a median of 2 (range 1–8). Table 3 shows the drug use indica- tors by patient’s age group. The 2 age groups of patients (< 3 years and ≥ 3 years) had similar mean scores in all drug use indicators, and no statistically significant differences were found be- tween them. As shown in Table 4, there were statistically significant differences be- tween the number of drugs prescribed per prescription with regard to the time of the month (P < 0.001), with the high- est mean number (2.03) in the first 10 days of the month. The mean percentage of drugs prescribed by generic name was 5.4% (SD 0.4%), range 0%–10.8% (Table 5). However, as illustrated in Table 6 there were statistically significant dif- ferences between the rates of generic prescribing across governorates, with the highest percentage in Gaza gover- norate (10.8%). The mean percentage of drugs prescribed from the EDL or the for- mulary was 97.8% (SD 0.97), range 94.4%–100% (Table 5). Table 1 Attitudes and practices of physicians in Gaza Strip towards the essential drugs list (EDL) Variable No. % Use EDL in prescribing Use it currently 155 67.4 Used in the past 22 9.6 Don’t use 53 23.0 Total 230 100.0 Experience problems in using EDL (if used) Yes, many 88 51.2 Yes, a few 54 31.8 None 28 17.0 Total 170 100.0 Attended training courses on EDL Yes 77 34.4 No 147 65.6 Total 224 100.0 Involved in preparation of EDL Yes 6 2.8 No 206 97.2 Total 212 100.0 Interested in attending other training courses on EDL Yes 200 88.9 No 25 11.1 Total 225 100.0 طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 889 Less than 30% of surveyed facilities were able to show the research team a copy of the EDL (Table 5). Interest- ingly, more PHC clinics at level 3 had copies than other level clinics and this difference was statistically significant (P = 0.001). Differences in the availability of the EDL across governorates were also statistically significant (P = 0.001) (Table 6). The mean proportion of the 12 key drugs available at clinics was 82.6% (SD 15.2%), range 41.6%–100% (Ta- ble 5). The researcher validated the availability of drugs listed in the EDL Table 2 Attitudes and practices of physicians in Gaza Strip towards the essential drugs list (EDL) by current use of the list Variable Currently using EDL Used in the past Not used at all χ2-value P-value No. % No. % No. % Influence on physicians of clients’ request for drugs Very strong 10 55.6 4 22.2 4 22.2 16.13 0.013 To some extent 52 74.3 2 2.9 16 22.9 Weak 45 58.4 14 18.2 18 23.4 Never 42 72.4 2 3.4 14 24.1 Physicians have evaluation for their prescribing practices Yes 49 83.1 4 6.8 6 10.2 13.22 0.01 No 69 58.0 15 12.6 35 29.4 Don’t know 33 73.3 2 4.4 10 22.2 Physicians receive feedback about their prescribing practices Yes, written 15 83.3 2 11.1 1 5.6 5.89 0.208 Yes, verbal 55 71.4 4 5.2 18 23.4 None 79 63.2 14 11.2 32 25.6 Ease of use of EDL Yes, easy 136 91.3 13 8.7 n/a – 17.17 0.001 No, not easy 11 57.9 8 42.1 n/a – Availability of EDL drugs in the pharmacy Exclusively present 16 94.1 1 5.9 0 0.0 27.33 0.001 Partially present 118 73.3 15 9.3 28 17.4 No 14 48.3 4 13.8 11 37.9 Don’t know 3 23.1 2 15.4 8 61.5 Attended training course on EDL Yes 64 83.1 8 10.4 5 6.5 19.03 0.001 No 85 58.6 13 9.0 47 32.4 n/a = not applicable. Table 3 Drug use indicators from clinics in Gaza Strip by patient’s age (i.e. treatment category) Drug use indicator Age of patient t-value P-value ≥ 3 years (insurance required) (n = 849) < 3 years (qualify for free treatment) (n = 807) Mean SD Mean SD No. of drugs per prescription 1.93 1.09 1.91 0.87 0.458 0.647 % of drugs prescribed by generic name 5.2 0.3 5.8 0.4 –1.020 0.308 % of drugs prescribed from EDL 97.4 1.07 98.4 0.9 0.004 0.997 n = number of prescriptions analysed; EDL = essential drugs list; SD = standard deviation. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 890 by checking clinic pharmacies and confirmed subjects’ responses, revealing availability of all 12 drugs in only 7.7% of the clinics surveyed and partial avail- ability of the list in 73.4%. Physicians reported different reasons for drug shortages, including inadequate sup- plies of drugs at the MOH central store (66.2%), inaccurate estimation of the quantities of drugs required (35.1%), management problems and bureauc- racy (22.5%) and a lack of financial resources (21.2%). Discussion Physicians who reported that EDL drugs were exclusively available in their clinics were using EDL drugs significantly more than the others. This is a clear indication that the availabil- ity of EDL drugs in clinics encourages physicians to comply with the EDL and this stimulates the MOH to exert more efforts to ensure continuous avail- ability of drugs. It was noticed that in some facilities, although the EDL was available, physicians used Medic (the Israeli drugs guide) in their prescribing, despite of the fact that Medic contains many brand-name drugs that are nei- ther listed in the Palestinian EDL nor present in the clinic pharmacies. More of the physicians who had undergone an evaluation of their pre- scribing practices (83.1%) or who had received written feedback about their prescribing practices (83.3%) were cur- rently using the EDL than the overall percentage (67.4%). This points to the importance of monitoring and super- vision as the distribution of the EDL is not adequate by itself. Physicians who found the EDL easy to use were significantly more likely to use it than those who perceived its use as difficult. Therefore health managers and other stakeholders should organize periodic assessments of the EDL and regularly update it to produce more user-friendly versions [7]. The mean number of drugs prescribed per encounter (1.92) is consistent with the international stand- ard recommended by the WHO (below 2) [8]. It was also close to the average in Egypt, the United Arab Emirates and Morocco (2 drugs per encounter) [9–11]. There were statistically significant differences between the numbers of drugs per prescription at different times of the month. Drug orders are distributed to PHC clinics within the first 10 days of the month. As a result, patients became aware of this and tend to go to the clinics more within these days to ensure that they will receive the needed drugs. Moreover, physicians also become familiar with that situation and prescribe drugs more within the first 10 days of the month. Needless to say, there are many factors potentially contributing to the above results. In the Gaza Strip, clients have access to other health providers who freely pro- vide drugs. Additionally, there is the phenomenon of prescribing drugs on informal prescriptions to be dispensed from private pharmacies. Table 4 Drug use indicators of clinics in Gaza Strip by time of the month in which the prescriptions were prescribed Drug use indicator Time of month F-valuea P-value First 10 days (n = 552) Days 11 to 20 (n = 550) Last 10 days (n = 554) Mean Mean Mean No. of drugs per prescription 2.03 1.92 1.81 7.25 0.001 % of drugs prescribed by generic name 6.4 4.7 5.5 1.93 0.145 % of drugs prescribed from EDL 97.0 97.3 98.3 5.38 0.005 % of key drugs available in clinics 84.4 79.4 83.3 0.49 0.617 a1-way ANOVA. n = number of prescriptions analysed; EDL = essential drugs list. Table 5 Drug use indicators of clinics in Gaza Strip by level of primary health care (PHC) facility Drug use indicator Overall PHC level F-value P-value Level 2 (n = 540) Level 3 (n = 828) Level 4 (n = 288) Mean Mean Mean No. of drugs per prescription 1.92 1.99 1.90 1.84 2.419 0.089 % of drugs prescribed by generic name 5.4 2.0 7.9 4.9 17.47 0.001 % of drugs prescribed from EDL 97.8 97.9 97.3 98.9 2.596 0.750 % of key drugs available in clinics 82.6 89.4 79.3 79.1 2.391 0.104 % of clinics with copy of EDL 28.3 16.3 34.2 33.6 4.615 0.015 n = number of prescriptions analysed; EDL = essential drugs list. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 891 The percentage of drugs prescribed by generic name is an important ele- ment of the essential drugs concept. The rate of generic prescribing of 5.5% in our study is very low compared to the standard WHO value (100%) [8]. Decision-makers should put more ef- fort into increasing the knowledge of physicians about the positive impact of generic prescribing. The MOH also needs to promote generic drugs in all aspects of the commodity management cycle (procurement, selection and or- dering). Another factor contributing to the tendency of physicians to prescribe brand-name drugs is the false impres- sion of the public, and of physicians, that generic drugs are of poorer quality and efficacy [12]. There were significant differences between the rates of generic prescribing across governorates, with the highest rate in Gaza governorate. This could be attributed to the proximity effect, as the pharmacy management centre is based in Gaza governorate where all the implementation and training for the EDL takes place before it is rolled out to other governorates. Also, there are some PHC facilities in Gaza governo- rate which independently held training courses for their physicians [13]. The overall percentage of drugs prescribed from the EDL (97.9%) is one of the highest in the world as it is near the standard value of 100% [8]. This result shows a positive result for implementation of EDL and physician compliance with it. This was achieved was mainly as a result of managerial interventions, by which all drugs pro- vided to facilities are from the EDL. Drugs prescribed from outside the EDL were donated ones. It is therefore essential to apply WHO guidelines for drug donation, emphasizing that all drug donations should comply with the local EDL. It is worth noting that donat- ed drugs represent an important drug resource in Palestine [14]. Ironically, the researcher noted that physicians prescribed drugs not from the EDL on informal prescriptions. This may indicate that physicians’ compliance is mainly based on drug availability, regardless of whether these drugs are from the EDL or not. The fact that the MOH only provides drugs on the EDL list forces physicians to prescribe these available drugs without being fully aware of the value of the EDL. This calls for additional training programmes with follow-up and monitoring. Less than 30% of surveyed facilities had a copy of the EDL, a rate much lower than the standard (100%) [8]. This highlights the need for an appropri- ate dissemination plan for the EDL, fol- lowed by monitoring and supervision. Although the presence of the EDL is es- sential for compliance, it is not enough by itself to ensure it [15]. Dissemination of the EDL should be accompanied by training on it content and use. The availability of key drugs was 82.6%, which is low compared with the standard value advised by WHO (100%) [8]. The lack of availabil- ity of key drugs reflects problems in the MOH which are frequently manifested by drug shortages in clinics [1]. Possible factors leading to drug shortages are insufficient financial resources for drug procurement, the overuse of drugs by physicians, pharmacists and patients and Israeli border closures, which delay the arrival of drugs. Additionally, most of the MOH drugs are funded by the World Bank through lengthy proce- dures which cause delay, particularly in the unstable and unpredictable po- litical situation in the area [1]. Rational drug use here plays an important role in overcoming drug shortages; therefore, training and awareness, appropriate regulations and supervision physicians and dispensers are essential, particularly in relation to the rational use of drugs and its impact. Conclusions and Recommendations The compliance level of PHC physi- cians was generally good and could be explained mainly by managerial/regula- tory factors affecting the provision of drugs that are listed on the EDL. The results of WHO drug use indicators were positive in certain aspects such as Table 6 Drug use indicators of clinics in Gaza Strip by governorate Drug use indicator Governorate F-value P-value North (n = 252) Gaza (n = 504) Mid-Zone (n = 468) Khanyounis (n = 324) Rafah (n = 108) Mean Mean Mean Mean Mean No. of drugs per prescription 2.07 1.99 1.86 1.87 1.62 5.291 0.001 % of drugs prescribed by generic name 5.8 10.8 3.2 1.1 0.0 24.01 0.001 % of drugs prescribed from EDL 94.2 96.4 100.0 100.0 100.0 2.531 0.039 % of key drugs available in clinics 82.1 73.2 80.1 96.2 97.2 5.53 0.001 % of clinics with copy of EDL 42.9 42.9 15.4 0.0 66.7 2.49 0.058 n = number of prescriptions analysed; EDL = essential drugs list. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 892 Health status in Palestine. Annual report.1. Ramalla, Palestine, Ministry of Health, Palestinian National Authority, 2005. Obeidallah W et al. 2. Drug situation analysis for the West Bank and Gaza Strip. Geneva, World Health Organization, 2000 (EDM/ DAP/2000.1). Palestinian drug formulary3. , 1st ed. Ramalla, Palestine, General Directorate of Pharmacy, Ministry of Health, Palestinian Na- tional Authority, 2002. How to investigate drug use in health facilities4. . Geneva, World Health Organization, 1993 (WHO/DAP). Quality assurance of pharmaceuticals. A compendium of guide-5. lines and related materials. Volume 1. Geneva, World Health Organization, 1997. How to use applied qualitative methods to design drug use inter-6. ventions. Geneva, World Health Organization, 2000. How to develop and implement a national drug policy7. . Geneva, World Health Organization, 2001. Dumoulin J. 8. Guide to drug financing mechanisms. Geneva, World Health Organization, 1998. Zaki A et al. The use of medication in infants in Alexandria, 9. Egypt. Eastern Mediterranean Health Journal, 1999, 5(2):320– 327. References Hasan M, Das M, Mourad F. Drug utilization and antibiotic use 10. in primary health care centres in Sharjah. Eastern Mediterranean Health Journal, 1997, 3:444–451. Simon N et al. Drug prescription and utilization in Morocco. 11. Therapies Journal, 1998, 53(2):113–120. Medical and pharmaceutical situation inside the West Bank in 12. primary health care. Ramalla, Palestine, Pharmaciens Sans Frontieres, 2003. Essential drugs list and Palestinian national formulary training 13. course report. Quality improvement program. Ramalla, Palestine, Palestinian National Authority, Ministry of Health, 2001. Kousa M et al.14. West Bank and Gaza Update: World Bank report on impact of intifada. A quarterly publication of the West Bank and Gaza Office. Ramalla, Palestine, World Bank, 2003. Grimshaw J, Russell I. Effect of clinical guidelines on medical 15. practice: a systematic review of rigorous evaluations. Lancet, 1993, 342:1317–1322. Management Science for Health and World Health Organiza-16. tion. Managing drug supply, 2nd ed. West Hartford, Connecti- cut, Kumarian Press, 1997. Practical guidelines on pharmaceutical procurement for countries 17. with small procurement agencies. Manila, Philippines, World Health Organization Regional Office for the Western Pacific, 2002. Correction Evaluation of effect of silymarin on granulosa cell apoptosis and follicular development in patients undergoing in vitro fertilization. N. Moosavifar,1 A.H. Mohammadpour,2,3 M. Jallali,1 G. Karimi 2,4 and H. Saberi 2Eastern Mediterranean health journal, 2010, 16(6):642–650. The affiliation for the fourth authori should be changed from G. Karimi 2,4 to G. Karimi 3,4. 1Women’s Health Research Centre; 2Pharmaceutical Research Centre ; 3School of Pharmacy; 4Medical Toxicology Resarch Centre, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran. the low rate of polypharmacy (1.92), but negative in others such as the low rate of prescribing by generic name (5.5%). Efforts are needed to improve the use of generic names on prescrip- tions, the availability of key drugs and the availability of the EDL document at clinics. Developing an effective dissemi- nation plan for the EDL with appropriate follow up and supervision is essential, and policy-makers need to improve the drug management cycle at PHC facilities, with special attention to ensuring the availability of essential drugs [16,17]. Further research is needed to evaluate prescribing practices in other settings and sectors. Follow-up assessments are also recommended in the future. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 893 Immunoinflammatory markers and disease activity in systemic lupus erythematosus: something old, something new M.A. Elwy,1 Z.A. Galal2 and H.E. Hasan3 ABSTRACT This study assessed the utility of some novel inflammatory markers compared with traditional laboratory markers in patients with systemic lupus erythematosus (SLE). In a cohort of 43 SLE patients (19 with inactive and 24 with active SLE) and 20 healthy controls, serial measures of soluble vascular cell adhesion molecule (sVCAM-1) were significantly associated with SLE disease activity, scored using the British Isles Lupus Assessment Group index. Inflammatory markers neopterin and soluble intercellular adhesion molecule (sICAM-1) appeared to be clinically useful for isolated assessments of disease activity. Both antibodies to double-stranded DNA (anti- dsDNA) and sVCAM-1 were relatively good markers of disease activity and could help to predict remission or monitor the therapeutic response in SLE. 1Department of Rheumatology and Rehabilitation; 2Department of Clinical Pathology; 3Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt (Correspondence to M.A. Elwy: elwy.mohamed@yahoo.com). Received: 27/03/08; accepted: 06/05/08 ميدق اهضعبو ديدج اهضعب :ةيعومجلما ةيممالحا ةبئذلا في ةيضرلما ةيلاعفلاو ةيباهتللاا ةيعانلما تماساولا نسح نانح ،للاج بنيز ،يولع دممح ةيممالحا ةبئذلا ضىرم ىدل ةيديلقتلا ةيبرتخلما تماساولاب انهونراقيو ،ةديدلجا ةيباهتللاا تماساولا ضعب ةساردلا هذه في نوثحابلا مِّيقي :ةـصلالخا بناج لىإ ،)لاعفلا روطلا في مهنم 24و لاعفلا يرغ روطلا في مهنم 19( ،ةيزاهلجا ةيممالحا ةبئذلاب ًاضيرم 43 نم ًابارتأ نوثحابلا سرد دقو .ةيعومجلما ةيلاعف عم ًايئاصحإ هب دتعي ًاطبارـت طبارـتي با َّوذلا يئاعولا يوللخا يقصلاتلا ءيزجلل ةيلاتتلما تاسايقلا نأ اودجوو .ءاحصلأا دهاوشلا نم 20 ءيزلجاو نيتربوين ْنيَيباهتللاا يمساولا نأ ادب مايف .ةبئذلا مييقتل ةيناطيبرلا رزلجا ةعوممج بسنم زارحأ مادختساب كلذو ،ةيزاهلجا ةيممالحا ةبئذلا ءاد ءيزجللو ،قاطلا جودزلما اندلل دادضلأا نم ًلاك نأ ماك .ءادلا ةيلاعفل ةلزعنلما تماييقتلا في ةيريسر ةدئاف ماله با َّوذلا يوللخا لخاد يقصلاتلا ةباجتسلاا ةبقارم في وأ ،ضرلما ةأدبه ؤبنتلا في دعاست نأ اهنكميو ،ضرلما ةيلاعفل ةديج تماساوك ناديفم با َّوذلا يئاعولا يوللخا يقصلاتلا .هل ةلجاعملل Marqueurs immuno-inflammatoires - anciens et nouveaux - et évolutivité du lupus érythémateux disséminé RÉSUMÉ La présente étude a évalué l’utilité de nouveaux marqueurs immuno-inflammatoires par rapport aux marqueurs de laboratoire conventionnels chez des patients atteints de lupus érythémateux disséminé (LED). Dans une cohorte de 43 patients atteints de lupus érythémateux disséminé (19 présentant un lupus érythémateux disséminé stable et 24 un lupus érythémateux disséminé évolutif) et un groupe témoin comprenant 20 sujets sains, la présence répétée de molécules d’adhésion des cellules vasculaires sous forme soluble (sVCAM-1) était associée de manière significative à l’activité du lupus érythémateux disséminé. Ces mesures ont été effectuées selon l’indice du British Isles Lupus Assessment Group (Groupe d’évaluation du lupus des îles britanniques). Les marqueurs inflammatoires comme la néoptérine et la molécule d’adhésion intercellulaire (sICAM-1) se sont révélés utiles sur le plan clinique pour réaliser des évaluations isolées de l’activité de la maladie. Les anticorps anti-ADN double brin (anti-dsDNA) ainsi que les sVCAM-1 se sont avérés être de bons marqueurs d’activité de la maladie contribuant à prévoir une rémission ou à surveiller la réponse thérapeutique du lupus érythémateux disséminé. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 894 Introduction Systemic lupus erythematosus (SLE) is a progressive autoimmune disorder associated with chronic stimulation of various components of the immune system, affecting the skin, joints, kidneys, heart and nervous and haematopoietic systems. The etiology of SLE is unknown and its clinical course is highly variable, with periods of flare-ups and remission [1,2]. A characteristic feature of SLE is that the pattern of organ involvement differs from one patient to another, suggesting differences in pathogenic mechanisms, a hypothesis supported by differences in the autoantibody profiles that correlate with involvement of differ- ent organs [2–4]. The clinical evaluation of the disease still lacks a reliable marker that is both sensitive and specific for the diagnosis as well as for the measurement of disease activity [5,6]. The accepted measures of disease activity in SLE include erythrocyte sedi- mentation rate (ESR), plasma/serum complement component 3 (C3) and component 4 (C4) and presence of antibodies to double-stranded DNA (anti-dsDNA). Some patients, however, have abnormalities in these tests for con- siderable periods yet show few clinical symptoms or functional deterioration of a major organ; others are markedly symptomatic with only minor aberra- tions in these test results [4,7,8]. The utility of some relatively new markers of SLE disease activity are still disputed [2]. Neopterin is specifically produced by human macrophages when stimulated by interferon-gamma released from activated T-lymphocytes, and is therefore an indirect marker of the up- regulation of the cellular immune system [9,10]. Intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin supergene family and play a central role in cell-to-cell and in cell-to-extracellular matrix-mediated immune responses [11]. During exac- erbations of SLE, endothelial cells are activated to increase their expression of adhesion molecules [12,13]. The objectives of this study were to compare some of the newer markers (neopterin, sICAM-1, sVCAM-1) with conventional laboratory measures (anti- dsDNA, C3 and C4) and the nonspe- cific inflammatory marker C-reactive protein (CRP), using a standard index of disease activity, and to investigate whether certain variables correlated with any type of specific organ involve- ment in an unselected group of patients with SLE. Methods Sample The study group were patients who were regular attendees at the outpatient clinics of the rheumatology units of the department of internal medicine and the department of rheumatology and rehabilitation at Ain Shams University Hospitals, Cairo, Egypt between August 2005 and March 2007. A convenience sample of 43 patients (40 females and 3 males) who were present at the time of the researchers’ visit and who agreed to participant were selected. All of them fulfilled 4 or more of the 1982 revised American Rheumatism Association (ARA) criteria for the classification of SLE [14]. Their mean age was 41.0 [standard deviation (SD)] 13.2 years and the mean disease duration of the patients at the time of recruitment was 10.7 (SD 9.4) years. A control group of 20 age- and sex-matched, apparently healthy individuals (18 females and 2 males) was also selected for the study; their mean age was 38.1 (SD 9.3) years. All participants were informed and will- ing to be included in the study. Data collection Clinical All the patients had documented medi- cal histories of SLE and were subjected to a full history-taking and thorough clinical examination for this study by qualified internists. Case documenta- tion, assessment of disease activity, damage events and therapeutic inter- ventions were made by the same group of rheumatologists throughout. In this study the overall disease ac- tivity was scored using the British Isles Lupus Assessment Group (BILAG) index of disease activity [15] to assess lupus activity in the major organ systems (mucocutaneous, musculoskeletal, re- nal, nervous, cardiovascular, vasculitis and haematological) and general con- stitutional manifestations. All the organ systems were graded A to E and then to obtain a global BILAG score the com- ponent scores were assigned numerical values [A (most active disease) = 9, B (intermediate activity) = 3, C (mild and stable disease activity) = 1, D (inactive disease) = 0 and E (no activity ever) = 0], resulting in a potential global score ranging from 0 to 72. This numerical score as well as the total BILAG score have been shown to be valid [10,16]. SLE patients were arbitrarily categorized into 2 groups: active disease (BILAG score > 5) and inactive disease (BILAG ≤ 5). A total BILAG score > 5 usually consists of at least 1 organ score of 3 (which signifies 1 organ system with a minor flare-up). Renal lesions were classified histo- logically according to the World Health Organization (WHO) classification for lupus glomerulonephritis [17]. Hyper- tension was also diagnosed according to WHO definitions. Systolic and diastolic blood pressure (BP) were determined using an average of 2 consecutive sit- ting BP readings taken 5 minutes apart. Patients were considered to be hyper- tensive if over the study period they had mean systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg and/or were taking antihypertensive drugs. None of the patients or controls had a concomitant viral or bacterial infec- tion or other disorders such as diabetes mellitus, liver or thyroid disease at the time of the study. Subsequent follow-up supported this clinical opinion. None طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 895 of the participants was pregnant or had drug-induced lupus erythematosus at the time of the study. Laboratory methods The following laboratory investigations were completed for all the participants: ESR and complete blood count • (CBC) using standard methods. Serum creatinine, blood urea, liver • function tests, fasting lipid profiles and fasting blood sugar were deter- mined using an autoanalyser (Syn- chron CX-7, Beckman). Complete urine analysis for the pres-• ence of red blood cells (RBCs), pus cells, albumin and urinary casts (ei- ther granular, hyaline, tubular and/or mixed type). CRP detected by ELISA technique • (Active Diagnostic Systems), with normal levels defined as < 6 mg/L. Antinuclear antibodies (ANA) and • anti-dsDNA were detected by indi- rect immunofluorescent assay on mouse kidney and stomach slides and Crithidia luciliae slides (Immco Di- agnostics). The slides were analysed with a Nikon epifluorescent micro- scope. A titre ≥ 1:80 was considered positive for ANA and > 1:40 IU/mL for anti-dsDNA detection. Complement C3 and C4 were • determined by single radial im- munodiffusion plates (Diffu-Plate, Biocientifica). Soluble VCAM-1 and ICAM-1 were • quantified with an immunoassay kit (R & D Systems), with normal levels for sICAM-1 defined as 115–306 ng/ mL [mean 211 (SD 2SD) ng/mL] and for sVCAM-1 as 349–991 ng/ mL [mean 557 (SD 139.6) ng/mL]. Detection of serum neopterin was • performed using an enzyme immu- noassay kit (DRG Instruments), following the basic principles of com- petitive ELISA. The serum neopterin normal value was < 10 nmol/L (< 2.5 ng/mL), with the range of normal values 3–9 nmol/mL. Blood and urine samples from SLE patients and controls were obtained at the time of recruitment to the study. All blood specimens were collected under aseptic conditions and were allowed to clot for about 30 min at room tempera- ture. Sera were obtained after centrifu- gation, and routine laboratory tests were carried out immediately. The remaining sera were stored frozen in aliquots at –20 °C for the subsequent assays and thawed only once. Grossly haemolytic, icteric or grossly lipaemic specimens were discarded to avoid aberrant re- sults; repeated freeze–thaw cycles were avoided. Stored samples were protected from light. Urinary sediment analysis was carried out by routine microscopy. The samples of the SLE cohort and controls were analysed together at the same time to avoid methodological er- rors. All markers and the disease activity index were measured at 3 time points over 6 months, at the beginning (the baseline measurement) and 3 and 6 months after joining the study. Data analysis Statistical analysis of the data was per- formed with SPSS, version 11.0 software, and continuous variables were pre- sented as means and SD. Comparisons between the SLE disease groups and the control group were carried out using the Mann–Whitney test. The relationship between inflammatory markers levels and clinical parameters was determined using the Spearman correlation analysis and the linear regression method. P- values < 0.05 were considered to be statistically significant. Results Background characteristics of patients Using the BILAG score cutoff > 5 to separate active from inactive SLE, 24 (55.8%) patients were classified with ac- tive disease at the time of investigation and 19 (44.2%) with inactive disease. Of the 24 patients with active dis- ease, 16 patients had active extrarenal disease and 8 had active renal disease defined by the presence of: persistent proteinuria > 0.5 g/day or dipstick proteinuria > 3+ if measurement was not performed; or cellular urinary casts (haeme, granular, red cell or mixed) and cells present (> 5 RBCs or WBCs per high-power field); or unexplained rise in serum creatinine (> 1.5 mg/dL). Of these 8 patients, 5 patients had a renal biopsy: 3 were diagnosed with diffuse proliferative nephritis (class IV) and 2 with focal segmental nephritis (class III). Of the remaining 3 patients with active renal disease, 1 had thrombocy- topenia that was not considered safe for the biopsy procedure and 2 had lupus nephritis with clear clinical and labora- tory findings. A total of 39 (90.7%) patients were receiving drugs at the time of assess- ment: 13 were on low-dose corticoster- oids (prednisone 47.5 mg/day), 4 on antimalarials, 3 on methotrexate and 1 on azathioprine as the single treat- ment. The remaining 18 patients were receiving combined drug treatments: 2 were on antimalarials plus low-dose corticosteroid, 1 on methotrexate plus corticosteroid (> 7.5 mg/day), 6 on azathioprine plus corticosteroid (> 7.5 mg/day), 5 on cyclophosphamide plus corticosteroid (> 7.5 mg/day) and 4 on cyclosporin A plus corticosteroid (> 7.5 mg/day). All the 5 patients treated with cyclo- phosphamide had active lupus nephritis: 2 were classified as IV.B and 1 was III.B according to the WHO classification. A renal biopsy was not performed on 2 pa- tients, but their kidney involvement was obvious from the clinical and laboratory findings (proteinuria > 1 g/day). Of the 4 patients treated with cyclosporin A, lupus nephritis was present in 3, and was documented by histology in 2 cases (1 III.A and 1 IV.B); in 1 of them the presence of lupus nephritis was clear from the clinical and laboratory find- ings. There were 3 patients treated with EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 896 cyclophosphamide and 1 treated with cyclosporine A, who received immuno- suppressive therapy before inclusion in the study. Organ system involvement Of the 24 patients with active disease, 15 (62.5%) had involvement of only 1 organ system and 9 (37.5%) had in- volvement of more than 1 organ system. Large variations in disease activity were found. On average, 38% of the patients showed no activity ever in at least 1 of the organ systems (category E). The ac- tive and inactive SLE groups did not dif- fer significantly in terms of age, disease duration and number of ARA criteria fulfilled (Student t-test) (Table 1). In this study more patients had activity (categories A to C) in the musculoskel- etal, mucocutaneous and haematologi- cal systems (22, 21 and 19 respectively) as compared with the renal, neurological and cardiovascular systems (10, 4 and 5 respectively) (Table 2). Laboratory markers Table 3 shows the data for the con- ventional laboratory measures of inflammation and SLE disease activ- ity (elevated CRP level, positive anti- dsDNA titre and C3 and C4 levels) compared with the novel immunoin- flammatory markers. As expected, the proportion of patients with elevated CRP level was significantly different between SLE patients and the control group and between inactive and active SLE patients (P < 0.001). The percent- age of anti-dsDNA-positive patients was not significantly different between the 2 SLE groups. None of the controls had anti-dsDNA antibodies in their sera. No significant differences were found in the mean serum levels of the complement C3 and C4 in those with inactive versus active SLE. The mean levels of neopterin, sICAM-1 and sVCAM-1 were higher in SLE patients compared with controls (P < 0.01). Mean levels of neopterin and sVCAM-1 were significantly differ- ent comparing active and inactive SLE groups (P < 0.05). Correlations between different laboratory markers Significant positive correlations be- tween the different markers are shown on Table 4. There were significant cor- relations between neopterin and CRP levels (P < 0.05), between neopterin and dsDNA antibody level (P < 0.001) and between neopterin and sVCAM-1 levels (P < 0.001). In addition, correlations were calcu- lated between the different serological markers and the total BILAG score. There was a significant correlation between total BILAG score and CRP level (P < 0.001), but not between total BILAG score and anti-dsDNA or C3 and C4 levels. Also, no correlation was found between total BILAG score and sICAM-1 levels, but significant cor- relations were found with sVCAM-1 (P < 0.01) and neopterin (P < 0.05) levels (Table 4). To calculate the correlations be- tween the serological markers and dis- ease activity of different BILAG organ systems, we chose the 3 organ systems where the number of patients with a BILAG score > 3 was high enough (n > 9) for a statistical analysis (i.e. muco- cutaneous, musculoskeletal and renal involvement). No positive correlation was found between any of the tested Table 1 Characteristics of patients with active and inactive systemic lupus erythematosus (SLE) Variable Active SLE (n = 24) Inactive SLE (n = 19) Mean (SD) age (years) 42.3 (14.7) 40.1 (11.9) Mean (SD) disease duration (years) 11.1 (7.1) 10.4 (9.1) No. of ARA criteria 6.4 5.2 SD = standard deviation; ARA = American Rheumatism Association. Table 2 Disease activity by organ system of patients with systemic lupus erythematosus (SLE) as assessed by the British Isles Lupus Assessment Group index scores Organ system SLE disease activity (no. of patients) A Strong B Moderate C Low D None presently E None ever Musculoskeletal 1 4 17 15 6 Mucocutaneous 1 9 11 14 8 Haematological 0 3 16 14 10 Vasculitis 0 0 13 12 18 Renal 1 6 3 13 20 General 1 0 4 23 15 Nervous system 0 0 4 8 31 Cardiovascular/ respiratory 0 0 5 15 23 طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 897 markers and the disease activity of dif- ferent BILAG organ systems. Higher levels of neopterin and sVCAM-1 were identified in patients with lupus nephritis (mean 14.8 nmol/L and 1780 nmol/L respectively) compared with patients without kidney impairment (mean 13.7 (ng/mL) and 1710 (ng/ mL) respectively). Serial measurements of markers and disease activity index Among the 43 SLE patients complete follow-up data were only available for 22 patients who were included in the next step, in which all markers and disease activity index were measured at 3 time points over 6 months, at the be- ginning (the baseline measurement) and after 3 and 6 months. They were divided into 3 subgroups (active with flare-ups, active with remission and inactive patients). Patients with lupus nephritis were present in both active subgroups with initially high disease activity. However, they were not ho- mogeneous enough to be included in the final evaluation as a separate subgroup. The descriptive statistics for anti-dsDNA, complement C3 and C4, neopterin, sICAM-1 and sVCAM-1 levels in the subgroups over the 6 months are shown in Table 5. The serum levels of anti-dsDNA antibodies were the lowest in the inactive subgroup. A significant differ- ence in anti-dsDNA levels was found between the inactive subgroup and the subgroup with active flare-ups at baseline, 3 months and 6 months (P < 0.001). The inactive subgroup and the active with remission subgroup differed significantly in the baseline measurements (P < 0.001). Among the subgroup who were active with remission a significant difference was found between measures at baseline and 6 months (P > 0.01). The serum levels of C3 were the highest in the inactive subgroup, but differences between the subgroups did not reach significant levels, nor were there significant differences within the subgroups over the 3 measurements. The highest levels of C4 were in the inactive subgroup, but the differences were not statistically significant. Chang- es in C4 levels at follow-up within each subgroup were not significant. The differences in serum neopterin levels were significant comparing the inactive subgroup and both active sub- groups at baseline and at 6 months (P < 0.01and P < 0.001 respectively). There were no significant differences between the active subgroups when compared with each other or when the changes within each subgroup were compared. The highest levels of sVCAM-1 were in the subgroup with active flare- ups at baseline. Although the differences between active subgroups were not sig- nificant statistically, significant decreas- es between baseline and the 6-month measurements of sVCAM-1 levels were Table 3 Frequency of elevated traditional laboratory parameters and mean levels of inflammatory markers in the control group and in subgroups of patients with systemic lupus erythematosus (SLE) Marker Controls (n = 20) Active SLEa (n = 24) Inactive SLE (n = 19) P-value Elevated CRP level [no. (%) of patients] 1 (5.0) 17 (70.8) 5 (26.3) < 0.05b,c Positive anti-dsDNA [no. (%) of patients] 0 (0.0) 15 (62.5) 9 (47.3) < 0.05b Mean C3 level (g/L) 1.23 0.64 0.89 < 0.05b Mean C4 level (g/L) 0.31 0.16 0.15 < 0.05b Mean neopterin level (nmol/L) 6.7 14.3 10.1 < 0.05b,c Mean sICAM-1 level (ng/mL) 275.1 669.7 490.6 < 0.05b Mean sVCAM-1 level (ng/mL) 782 1721 1465 < 0.05b,c aTotal BILAG score > 5. b P < 0.05 between SLE patients and controls; cP < 0.05 between active and inactive SLE patients. CRP = C-reactive protein; anti-dsDNA = antibodies to double-stranded DNA; C3 and C4 = complement components 3 and 4; sICAM-1 = soluble intercellular adhesion molecule; sVCAM-1 = soluble vascular cell adhesion molecule. Table 4 Significant positive correlations between inflammatory markers in patients with systemic lupus erythematosus Marker Marker CRP anti-dsDNA Neopterin sICAM-1 sVCAM-1 C3 CRP 1 – – – – – anti-dsDNA – 1 – – – – Neopterin < 0.05 < 0.001 1 – – – sICAM-1 – – – 1 – – sVCAM-1 – – < 0.001 – 1 – C3 – – – – – 1 BILAG score < 0.001 – < 0.05 – < 0.01 – CRP = C-reactive protein; anti-dsDNA = antibodies to double-stranded DNA; sICAM-1 = soluble intercellular adhesion molecule; sVCAM-1 = soluble vascular cell adhesion molecule; C3= complement component 3; BILAG = British Isles Lupus Assessment Group index. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 898 found within all subgroups (P < 0.001, P < 0.001 and P < 0.01 respectively). No significant differences in sICAM-1 levels were found among subgroups or within subgroups. Discussion Levels of complement C3 and C4, and dsDNA antibodies, classic laboratory markers for disease activity in SLE, did not differentiate between active and inactive disease in our patient cohort. This was in agreement with other stud- ies suggesting that serum neopterin [2,18,19] and sVCAM-1 [2,13,20,21] are more sensitive markers of disease activity. Levels of anti-dsDNA antibod- ies are a widely accepted measure for evaluating disease activity in SLE. How- ever, anti-dsDNA does not necessar- ily fluctuate with disease activity and a substantial proportion of SLE patients are anti-dsDNA negative [4]. SLE is characterized by hyperactivity of B cells and by the production of organ non-specific autoantibodies. Levels of anti-dsDNA antibodies are very specific tests, particularly in diagnosis [7,8]. In this study, the correlation of anti-dsD- NA with the disease activity index was weaker than in the case of sVCAM-1. In some studies the limited value of serial measurement of anti-dsDNA antibod- ies for the prediction of lupus relapse has been discussed [2,13]. The complement components C3 and C4 are also traditional markers of disease activity and their use reflects the important role that the comple- ment system plays in SLE pathogenesis [5,6]. An impaired complement system might affect the clearance of apoptotic material and thus enhance the vicious circle in SLE, but the clinical measure- ment of complement components is not sensitive enough to detect disease activity in SLE [2,18]. According to the results of our study, their levels did not correlate significantly with the disease activity index. C3 and C4 did Table 5 Mean serum levels of selected markers in subgroups of patients with systemic lupus erythematosus (SLE) at baseline and after 3 and 6 months Marker Active SLE with flare-ups (n = 10) Active SLE with remission (n = 8) Inactive SLE (n = 4) Mean (SD) Mean (SD) Mean (SD) Anti-dsDNA (IU/mL) Baseline 71.5 (67.6)*a 86.3 (55.1)*a 33.2 (35.3) 3 months 86.1 (67.3)*a 52.3 (56.8) 29.9 (25.8) 6 months 68.2 (51.9)*a 32.4 (51.2)*a,b 24.1 (11.5) C3 (g/L) Baseline 0.63 (0.17) 0.54 (0.14) 0.72 (0.22) 3 months 0.62 (0.15) 0.59 (0.19) 0.76 (0.19) 6 months 0.57 (0.19) 0.60 (0.16) 0.69 (0.20) C4 (g/L) Baseline 0.16 (0.07) 0.15 (0.08) 0.19 (0.08) 3 months 0.15 (0.06) 0.17 (0.06) 0.16 (0.06) 6 months 0.13 (0.05) 0.16 (0.07) 0.16 (0.05) Neopterin (nmol/mL) Baseline 14.1 (8.3)*a 13.9 (9.4)*a 10.5 (8.4) 3 months 13.3 (8.7)*a 12.7 (7.6) 10.8 (9.6) 6 months 12.8 (7.2)*a 10.2 (6.1)*a 8.7 (6.7) sICAM-1 (ng/mL) Baseline 724 (236) 662 (173) 529 (252) 3 months 628 (152) 636 (152) 538 (156) 6 months 645 (273) 611 (139) 501 (134) sVCAM-1 (ng/mL) Baseline 2105 (312)*a 1722 (426) 1564 (385) 3 months 1662 (325)*a 1347 (374) 1456 (491) 6 months 1265 (296)*a,b 961 (463)*a,b 1057 (269)*a,b *aP < 0.05 versus inactive subgroup; *bP < 0.05 versus baseline measurement. SD = standard deviation; anti-dsDNA = antibodies to double-stranded DNA; C3 and C4 = complement components 3 and 4; sICAM-1 = soluble intercellular adhesion molecule; sVCAM-1 = soluble vascular cell adhesion molecule. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 899 not decrease significantly during SLE disease flare-ups in individual patients, even though their levels correlated (but not significantly) with the BILAG score. Furthermore, their levels did not change significantly and rapidly enough with the declining activity over the period of the follow-up in the subgroup with declining BILAG index. Their utility as a reliable marker of disease activity and therapy response is therefore limited [18]. In accordance with some earlier studies, sICAM-1 levels were elevated above the normal range in all our pa- tients but did not differ significantly between patients with active and inac- tive disease [2,6,18,22]. It is noteworthy that neither the values of the C3 and C4 nor the levels sICAM-1 correlated significantly with the disease activity index and this agrees with other studies [16,22]. These results contrast with data reported in other studies [16,23]. Of all the immunoinflammatory variables we investigated, CRP, neop- terin and sVCAM-1 correlated best with disease activity measured by the total BILAG score. Interestingly, sev- eral studies of CRP autoantibodies have claimed that serum levels of CRP often remain low despite high disease activity and despite high levels of other acute phase proteins [24], suggesting that the presence of low CRP levels may not reflect the presence of antibodies to CRP which may play an important role in SLE pathogenesis [25]. The important question is whether the involvement of different organ systems in SLE correlates with differ- ent patterns of immunoinflammatory markers. This is likely, as it is well known that anti-dsDNA correlates with renal disease, but not with musculoskeletal involvement in SLE [6]. We chose the BILAG scoring scale because it gives an accurate organ- specific measurement of disease ac- tivity, and would allow correlation of immunoinflammatory markers with disease activity in the different organs involved. However, we could not es- tablish a relationship between any of the tested markers and organ-specific BILAG scores. This may have been be- cause of the limited numbers of patients in each group and the wide variety of organ-specific BILAG groups included in our study (7 groups). Our results contrast with other studies where, for example, changes in anti-dsDNA and complement concen- trations were reported predominately to accompany flare-ups of lupus nephritis [20,26,27]. Significant correlations have been found between other biological laboratory markers and some BILAG organ system scores, such as between interleukin-1 receptor antagonist (IL- 1ra), and the musculoskeletal score [7] and between soluble tumour necrosis factor receptors p55 and p75 (sTNFR- 55/sTNFR-75) and renal BILAG score [6]. Their findings, but not ours, support the hypothesis of different pathologi- cal mechanisms in the different organ systems. Although we found higher values of sVCAM-1 in patients with lupus nephritis compared with patients with- out kidney impairment the differences were not statistically significant, a result that agrees with other studies [27–29]. However, another study showed that the serum level of sVCAM-1 was sig- nificantly higher in patients with active lupus nephritis (WHO classes III and IV) than in patients in inactive lupus nephritis and there was a positive cor- relation between sVCAM-1 and SLE disease activity, which decreased during remission [20]. Similarly, an increased level of neopterin was reported with lupus nephritis [10]. In this study, time-series modelling was adopted to investigate if serial meas- urements of some inflammatory mark- ers could predict the BILAG score and hence SLE disease activity in individual patients. Time-series analysis showed that sVICAM-1 increased significantly during flare-ups in SLE disease activ- ity. Similarly, a significant decrease in concentrations was observed in patients with active SLE who went into disease remission, as shown in another study [20]. In those patients whose disease remained active or in remission on the third successive assessment, concentra- tions were found to be correspondingly greater or smaller compared with initial values. Levels of sICAM-1 were predomi- nantly within the baseline range dur- ing maximal disease activity and did not change in the time period before remission. These findings might in part be explained by binding of the func- tionally active soluble molecules to their respective ligands on activated leukocytes [13]. The present finding of high sVCAM-l levels, however, conflicts with this hypothesis, although it might be explained by an excess of released molecules compared with the number of accessible molecules [13,23,29,30]. Generally, none of the other study pa- rameters was found to mirror SLE dis- ease activity as effectively as sVCAM-1 using both single time-point and time- series analyses. In conclusion, this study indi- cates that serial concentrations of sVCAM-1 are significantly associated with SLE disease activity scored using the BILAG index. Measurement of neopterin and sVCAM-1 appeared to be clinically useful for isolated as- sessments of disease activity. Both anti-dsDNA and sVCAM-1 were rela- tively good markers of disease activity in SLE. It seems that both are suitable for the monitoring of disease activity and could help to predict remission or to monitor the therapeutic response. Assessment of the possible advantages of sVCAM-1 over anti-dsDNA re- quires additional information from future studies. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 900 De Leeuw K et al. Traditional and non-traditional risk factors 1. contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus. Lupus, 2006, 15(10):675–682. Horak P et al. Clinical utility of selected disease activity markers 2. in patients with systemic lupus erythematosus. Clinical Rheu- matology, 2001, 20(5):337–434. Kaplanski G et al. Increased soluble vascular cell adhesion 3. molecule 1 concentrations in patients with primary or systemic lupus erythematosus-related antiphospholipid syndrome: correlations with the severity of thrombosis. 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Journal of Rheumatology, 2001, 28(3):514–519. Ho CY et al. Elevated plasma concentrations of nitric oxide, 29. soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus. Rheumatology (Oxford), 2003, 42(1):117–122. Mason JC, Kapahi P, Haskard DO. Detection of increased 30. levels of circulating intercellular adhesion molecule 1 in some patients with rheumatoid arthritis but not in patients with systemic lupus erythematosus. Lack of correlation with levels of circulating vascular cell adhesion molecule 1. Arthritis and Rheumatism, 1993, 36(4):519–527. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 901 HIV-related knowledge and AIDS stigma among college students in Yemen A.M. Badahdah 1 and N. Sayem 2 ABSTRACT The present study analysed data from 501 Yemeni university students to examine their knowledge about HIV and their attitudes towards people with HIV/AIDS. The findings indicate that participants had several serious misunderstandings about HIV/AIDS and held negative attitudes toward people living with HIV/ AIDS. Although female students were less knowledgeable about HIV/AIDS than were male students, they held more positive attitudes toward people with HIV/AIDS. An overwhelming number of students expressed their willingness to get tested for HIV and recognized that AIDS is a serious issue facing their country. The study provides suggestions for HIV prevention efforts and ideas for future studies in Yemen. 1Department of Sociology, University of North Dakota, Grand Forks, North Dakota, United States of America (Correspondence to A.M. Badahdah: abdallah.badahdah@und.edu). 2Department of Psychology, University of Sana’a, Sana’a, Yemen. Received: 31/10/08; accepted: 14/01/09 نميلا في تاعمالجا بلاط ينب زديلإا ةمصوو يشربلا يعانلما زوعلا سويرف لوح فراعلما ليلخ مئاص ةاجن ،حدحداب دممح للها دبع يعانلما زوعلا سويرف لوح مهفراعم لىع فرعتلا دصقب ةينميلا ةعمالجا نم ًابلاط 501 لوح تايطعلما ةساردلا هذه في ناثحابلا للح :ةـصلالخا يرطخ مهف ءوس ةساردلا في ينكراشلما ىدل نأ لىإ ناثحابلا اهيلع لصح يتلا جئاتنلا تراشأ دقو .زديلإا سويرفل ينشياعلما نم مهفقاومو ،يشربلا زديلإا لىع ًاعلاّطا لقأ تابلاطلا نأ مغرو .زديلإا سويرفل ينشياعلما هاتج ةيبلس فقاوم نوفقي منهأو ،هسويرفب ىودعلاو زديلإا نع بناولجا ددعتمو فشك رابتخا ءارجإب مهبيحرـت نع بلاطلا نم ةيرفغ دادعأ تبرعأ دقو .زديلإا سويرفل ينشياعلما هاتج ةيبايجإ رثكأ فقاوم نفقي ننهإف ،بلاطلا نم سويرفب ىودعلا نم ةياقولا دوهلج تاحارـتقا ةساردلا مدقتو .مهدلب هجاوت ةيرطخ ةيضق زديلإا نأ نوكردي مهو ،يشربلا يعانلما زوعلا سويرف .نميلا في ةيلبقتسم تاسارد ءارجإ نع ًاراكفأو ،زديلإا Connaissances en termes de VIH et stigmatisation associée au sida chez des étudiants en République du Yémen RÉSUMÉ La présente étude a analysé des informations recueillies auprès de 501 étudiants yéménites afin d’évaluer leurs connaissances sur le VIH et leur attitude vis-à-vis des personnes atteintes du VIH/sida. Les résultats montrent que les répondants présentaient de graves lacunes en termes de connaissances du VIH/sida et qu’ils réagissaient de manière négative envers les personnes infectées. Si les étudiantes étaient moins bien informées que les étudiants, elles adoptaient toutefois une attitude plus positive envers les personnes atteintes du VIH/sida. Un nombre considérable d’étudiants a exprimé le désir de bénéficier d’un test de dépistage du VIH et a admis que le sida représentait un grave problème auquel leur pays devait faire face. L’étude présente des propositions relatives aux efforts de prévention du VIH et des idées pour de futures études à réaliser en République du Yémen. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 902 Introduction HIV/AIDS prevention strategies aspire to reduce HIV infection by changing the perceptions and behaviours that in- crease the likelihood of people becom- ing infected and altering the underlying structural arrangements that shape or constrain people’s behaviours, such as poverty and gender inequality [1]. One of the structural factors that has been the target of HIV prevention efforts is stigma [2–4]. Since the beginning of the AIDS epidemic, AIDS-related stigma has been globally acknowledged as detrimental to the well-being of people living with HIV/AIDS (PLWHA) and a significant obstacle to HIV prevention programmes [2]. Stigma interferes with individuals’ desire to seek treatment, disclose their health status, adhere to antiretroviral therapy or seek support. Some countries have made progress towards understanding AIDS-related stigma, its prevalence and its impact on the lives of PLWHA and their signifi- cant others. The few studies available on HIV/AIDS in countries of the Arab world, however, show the existence of various misconceptions about HIV/ AIDS and the pervasiveness of the stig- matization of individuals with HIV/ AIDS [5–7]. Although HIV/AIDS prevalence rates in the Eastern Mediterranean Region are low, the Region has one of the fastest-growing HIV infection rates in the world [8]. Djibouti and Sudan have the highest prevalence rates in the Arab world and are facing a generalized epidemic. Other countries, such as Mo- rocco and the Libyan Arab Jamahiriya, are experiencing a localized epidemic. The main route of infection in the Arab world is unprotected heterosexual in- tercourse. However, in some countries injecting drugs is the major cause of HIV infection. Although considerable success has been achieved in slowing the spread of AIDS, HIV rates continue to increase rapidly in some countries, including Yemen. Yemen is a conservative and tribal state of 23 million people with a median age of 16.7 years and high rates of illiteracy, poverty and unem- ployment; it is one of the poorest and least-developed countries in the Arab world [9]. The World Health Organiza- tion (WHO) has estimated that there are approximately 24 000 HIV-infected individuals in Yemen [10]. During the 1990s the majority of the infected peo- ple in Yemen were men; in 1995 for every 4 HIV-infected men there was 1 HIV-infected woman. However, the risk of HIV infection among Yemeni women has increased and in 2005 it was reported that as many women as men were infected [9]. Yemen lacks the basic tools to halt the spread of HIV. To illustrate this, only 107 patients are receiving antiret- roviral therapy [11], and testing and counselling facilities are limited [12]. With this in mind, we were able to lo- cate only 2 published empirical studies about HIV/AIDS in Yemen, one that examined individuals’ knowledge and perceptions of individuals with HIV/ AIDS [13] and another that assessed Yemenis’ attitudes toward the use of condoms as a means of HIV prevention [14]. The purpose of the present paper was to assess Yemeni students’ knowl- edge of HIV/AIDS and the stigmatiza- tion of PLWHA. This is the first study to focus exclusively on young Yemenis, who represent 21.4% of the country’s population [15]. Methods Sample To determine the sample size for the study, the proportion of students who held positive attitudes toward PLWHA and had accurate knowledge about HIV/AIDS was assumed to be 50%. The sample size was estimated to be around 400 students. To minimize problems associated with unusable questionnaires we increased the sample size by 25%. A convenience sample was selected con- sisting of 501 undergraduate students who attended a large public university in Sana’a, the capital of Yemen. Uninten- tionally, the sample size was divided al- most equally between men and women (251 males and 250 females). Data collection The data were collected via a question- naire that was distributed to students in psychology classes. The items for this study were selected from previous studies conducted by the first author in several countries in the Arab world [5] and from a study conducted in Yemen to develop an AIDS-related stigma scale [16]. The questionnaire contained several items about HIV/AIDS knowl- edge, AIDS-related stigma and other items related to HIV prevention. For the knowledge index, 11 state- ments (e.g. “There is a cure for AIDS”) were generated to assess students’ general knowledge about HIV and its transmission. Students could choose from 3 options for each question: “cor- rect”, “wrong” and “don’t know”. The “don’t know” answers were treated as wrong answers in the analysis. An index of AIDS knowledge was created that ranged from 0 to 11, with higher scores indicating greater knowledge of HIV. AIDS-related stigma was measured by 11 items that indicated the beliefs (e.g. “AIDS is a punishment from God”), emotional responses (e.g. “Peo- ple with AIDS make me angry”) and behavioural reactions towards PLWHA (e.g. “People with AIDS should be fired from jobs”). Participants responded to each statement on a Likert-type scale with possible responses ranging from 1 (very strongly agree) to 6 (very strongly disagree). Cronbach alpha was used to assess the internal consistency of the items of the AIDS stigma measure. The coefficient of reliability indicated that the 11 items were highly consistent (α = 0.81). Students were also asked about their willingness to take an HIV test طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 903 and whether they knew someone with AIDS. To understand students’ percep- tions of the AIDS situation in Yemen, we asked them if they thought that HIV was an issue in Yemen and whether the media had exaggerated its prevalence. Data analysis SPSS, version 17 was used to analyse the data for this study. The mean and standard deviation (SD) were used as well as Student t-test, Spearman correla- tion and Cronbach alpha to assess the reliability of the stigma scale. The level of significance was P < 0.05. Results The students’ ages ranged from 17 to 29 years, mean 22 (SD 2.22) years, and the majority (83.8%) were single. An over- whelming proportion of the participants (82.6%) reported that they had grown up in a middle-income family The mean score of students’ knowl- edge about HIV transmission on the 11-item index was 6.70 (SD 1.87) (Table 1). Four out of 11 items were answered incorrectly by half or more of the students. Specifically, 69.2% of the participants either did not know or thought that there was a cure for AIDS and 51.8% either did not know or believed that mothers cannot transmit HIV through breastfeeding. Only a fraction of the participants (28.9%) knew that mosquito bites cannot trans- mit HIV. A third of the students (36.3%) knew that condoms are effective in pre- venting sexually transmitted diseases such as HIV. Only a few students (8.2%) knew that they could not identify a person with AIDS by looking at him/ her, and 33.9% lacked knowledge or provided the wrong answer when asked whether the HIV virus infects only homosexuals. Female students were less knowledgeable about HIV [mean score 6.50 (SD 1.85)] than were male students [mean score 6.90 (SD 1.87)]. This gender difference was statistically significant (t = 2.40, P < 0.05). Yemeni students’ perceptions of PLWHA were slightly below the mid- point of the scale [mean score 3.48 (SD 1.01)]. More than half the respondents (52.1%) agreed that “people with AIDS should be ashamed of themselves” and 56.5% said they would be ashamed if one of their relatives got AIDS (Table 2). Similarly, 66.3% believed that it is shameful to have people with AIDS in Yemen. Other AIDS-related emotional statements that a large proportion of participants endorsed were about sym- pathy and anger: 48.5% agreed that they find it personally difficult to sympathize with people with AIDS, and 42.7% ex- pressed anger toward people with AIDS. Although 60.3% of the students agreed that “AIDS is a punishment from God”, many also thought that individuals with AIDS were not responsible for their infection (63.1%). Statements about isolating PLWHA by dismissing them from their jobs or quarantining them were endorsed by 39.9% and 39.7% of the students respectively. Female students overall expressed more positive attitudes towards PLWHA than did male students [mean score 3.82 (SD 0.90) versus 3.14 (SD 0.99)] (t =7.87, P < 0.001) (Table 2). Students who had greater knowledge about HIV/AIDS also had higher at- titude scores towards PLWHA than students who had some misconcep- tions about HIV (r = 0.11, P < 0.05). Just over 85% of the participants indicated their willingness to take an HIV test. These students expressed more positive attitudes toward PLWHA than those who were not interested in taking the test [score 3.55 (SD 1.00) versus 3.25 (SD 1.10)] (t = 2.36, P < 0.05). Twenty (20) students (4.0%) reported knowing someone with HIV/AIDS. The majority of the students agreed that HIV is a problem facing their country (84.3%) and that the issue is accurately presented in the media (77.6%). Table 1 HIV/AIDS knowledge among students in Sana’a, Yemen (n = 501) AIDS-related knowledge item Correct response Incorrect responsea No. % No. % Can tell if someone has AIDS by looking at him/her 41 8.2 286b 57.1 Only homosexuals get AIDS 75 15.0 331b 66.1 HIV lives in human body for years without symptoms 383b 76.4 52 10.4 There is a cure for AIDS 149 29.7 154b 30.7 Pregnant women can transmit HIV to their unborn babies 426b 85.0 19 3.8 Can get HIV by touching someone with AIDS 59 11.8 392b 78.2 Can get HIV by using public phone 17 3.4 407b 81.2 HIV can be transmitted through breastfeeding 241b 48.1 94 18.8 Mosquito bites can transmit AIDS 183 36.5 145b 28.9 Condoms reduce the probability of getting HIV 182b 36.3 78 15.6 AIDS virus can be found in semen 410b 81.8 12 2.4 aDon’t know responses are not shown; bIndicates the expected answer. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 904 Discussion This study examined the misconcep- tions about HIV and the stigmatiza- tion of PLWHA in Yemen, a country that to date has been largely outside the realm of AIDS research. We found specific deficiencies in Yemeni students’ knowledge about HIV. Most students erroneously believed that HIV cannot be transmitted via breastfeeding, that mosquito bites can infect people with HIV, that condom use is ineffective in preventing HIV infection and that there is a cure for AIDS. Al-Serouri et al. noted similar findings in their study in Yemen: 86% of the participants agreed that one can get infected with the AIDS virus from mosquito bites [13]. This misconception is probably due to the high prevalence of malaria in Yemen. According to the WHO “approximately 60% of the population live in areas with malaria transmission” [17]. Two knowledge items deserve close examination because of the significant role they play in HIV prevention. The first is about the effectiveness of condom use in preventing HIV infection. Only 36.3% of the participants were well in- formed about the role of condoms in re- ducing the probability of HIV infection. Unfortunately, this figure is lower than that of Busulwa et al., who found in a household survey that 46% of Yemenis knew that condoms protect against sexually transmitted infections [14]. This lack of knowledge among young college students is disturbing because they are at a stage in their lives where they may be tempted to experiment with extramarital sex and drugs. One explanation for this deficiency in our sample, which we did not test directly, may be that our college students do not consider themselves at risk of acquiring HIV; hence knowledge about condoms is irrelevant. Although they acknowledge the seriousness of AIDS in Yemen, they might believe that AIDS is an issue among older adults or promiscuous individuals. Another interpretation, which we believe is also applicable to the findings of Busulwa et al., is that most public health establishments in the Arab world do not advocate the use of condoms as a preventive measure in the fight against AIDS in their educational and preven- tion programmes [14]. This attitude is motivated by the misconception that promoting condom use is against the teaching of Islam and would encour- age people to engage in unlawful sex [18]. This attitude was illustrated by a female college student who stated, “No, we should not encourage the use of condom[s] or the spread of condom[s] because this can cause the spread of dis- eases and other dangerous behaviour. No, it is forbidden. It is not allowed.” [14]. The other knowledge item was about the availability of a cure for AIDS. Al Serouri et al. reported that 17% of the participants in their study in Yem- en assumed that there was a cure for AIDS [13]. Unexpectedly, in our study a larger percentage of students were either unsure (39.5%) or thought that a treatment did exist (29.7%). Perhaps the students were not educated enough about HIV to be able to distinguish between antiretroviral therapy and a cure for AIDS. Another possible source of confusion is the claim made by Abdul Majeed Al-Zandani, a well-known Yem- eni religious figure, who said he can cure people with AIDS. Such a false claim being publicized by a figure well-known in the country is dangerous to the public health of Yemenis, and trivializes HIV prevention efforts in Yemen. Another important finding of this study is the gender gap in HIV knowl- edge, with Yemeni males being more knowledgeable about HIV/AIDS than Table 2 Sex differences in attitudes towards people with HIV/AIDS among students in Sana’a, Yemen Attitude item Males (n = 251) Females (n = 250) t-value P-value Mean scorea SD Mean scorea SD People with AIDS should be fired from their jobs 3.21 1.91 4.14 1.62 5.87 < 0.05 It is difficult to sympathize with people with AIDS 3.29 1.62 3.86 1.52 3.99 < 0.05 I would be ashamed if a relative of mine got AIDS 2.96 1.75 3.41 1.76 2.87 < 0.05 People with AIDS should be quarantined 3.21 1.88 4.25 1.63 6.61 < 0.05 If a friend of mine got HIV I would continue being friends with him/her 3.69 1.69 4.08 1.56 2.74 < 0.05 People with AIDS make me angry 3.33 1.70 3.93 1.61 4.01 < 0.05 People with AIDS should be ashamed of themselves 2.96 1.66 3.70 1.74 4.80 < 0.05 It does not bother me if my classmate has AIDS 3.27 1.63 4.01 1.49 5.32 < 0.05 People with AIDS are responsible for getting AIDS 3.54 1.85 4.30 1.69 4.80 < 0.05 It is shameful to have people with AIDS in Yemen 2.57 1.63 3.00 1.76 2.88 < 0.05 AIDS is a punishment from God 2.61 1.72 3.34 1.74 4.70 < 0.05 aHigher scores = more positive attitudes. SD = standard deviation. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 905 their female counterparts. Although a gender gap was noted in other studies in Yemen [13] and the United Arab Emir- ates [19], our study pointed to 2 serious misconceptions that Yemeni female college students had about AIDS. We found that more males (43.0%) than females (29.6%) knew that condoms are effective in reducing the likelihood of HIV infection. Also more males (88.8%) than females (74.8%) knew that HIV can be transmitted through se- men. This gap is grave and needs urgent attention from public health officials in Yemen because the limited data that exist suggest that the majority of HIV- positive Arab women have contracted it from their husbands [20]. Yemeni students’ overall percep- tion of PLWHA was not encouraging. The results suggest that students were divided equally in their emotional reactions and negative beliefs about PLWHA. At the behavioural level, around 40% of the students endorsed 2 statements about the need to socially isolate PLWHA. This tendency may be motivated by the students’ perception that AIDS is a punishment from God. Studies from around the world and the Eastern Mediterranean Region have found similar attitudes [21–24]. For example, 23.2% of those between the ages of 11 and 83 years from Eskisehir, Turkey [22], 14% of those living in Te- hran, Islamic Republic of Iran [23] and 28% of high-school students in Tunisia [24] supported such a statement. One of most encouraging results of this study was the finding that correct knowledge about HIV/AIDS was as- sociated with holding a positive image of PLWHA. Another one was that most students were willing to get tested for HIV, although such a desire may not be fulfilled because of the lack of re- sources in Yemen. Students’ awareness of the magnitude of the AIDS problem in their country is a positive step that would facilitate HIV prevention efforts in Yemen. Health care professionals and nongovernmental organizations in Yemen should capitalize on these posi- tive orientations and try to provide test- ing and counselling for young Yemenis. Only 4.0% of tudents reported that they knew someone with AIDS. This is less than the number reported by a sample of rural and urban residents in Yemen in which 15% of the 1400 participants said they knew someone with AIDS [25]. Despite the valuable contribution of this study, several limitations should be mentioned. The findings cannot be gen- eralized to all college students in Yemen because the sample was conveniently collected from 1 university in 1 city. Furthermore, because no standardized AIDS-stigma scale has been developed exclusively for Yemenis or Arabs in gen- eral, we used a collection of items that the first author had used in previous studies. At this juncture, we believe that there is a need to construct an AIDS stigma scale that is appropriate to the Arab culture. Conclusion Our findings demonstrate the benefit of furnishing Yemeni students with accu- rate information about HIV/AIDS as a strategy to eliminate the stigma of AIDS. Educational campaigns in Yemen need to present AIDS as a health issue rather than a moral failure and find a way to incorporate condom use into HIV pre- vention efforts. Coates TJ, Richter L, Caceres C. Behavioural strategies to re-1. duce HIV transmission: how to make them work better. Lancet, 2008, 372:669–684. Heijnders M, Van Der Meij S. The fight against stigma: an 2. overview of the stigma-reduction strategies and interventions. Psychology, Health and Medicine, 2006, 11:353–363. Goffman E. 3. Stigma: notes on the management of a spoiled iden- tity. Englewoods Cliffs, New Jersey, Spectrum, 1963, Link B, Phelan JC. Conceptualizing stigma. 4. Annual Review of Sociology, 2001, 27:363–385. Badahdah AM. Saudi attitudes toward people with HIV/AIDS. 5. International Journal of STD and AIDS, 2005, 16:837–838. Musso S, Fanget D, Cherabi K. Religion and education for HIV/6. AIDS prevention: an Arab-Islamic view. Prospective, 2002, 32:207–213. Roudi-Fahimi F. 7. Time to intervene: preventing the spread of HIV/ AIDS in the Middle East and North Africa. Washington DC, Popu- lation Reference Bureau, 2007. AIDS epidemic update8. . Geneva, United Nations Joint Pro- gramme on HIV/AIDS, 2007. Akala FA, El-Saharty S. Public health challenges in the Middle 9. East and North Africa. Lancet, 2006, 367:961–964. References Yemen. HIV/AIDS treatment scale-up. Summary country profiles.10. World Health Organization, 2005 (http://www.who.int/hiv/ HIVCP_YEM.pdf, accessed 27 April 2010). Towards universal access. Scaling up priority HIV/AIDS interven-11. tions in the health sector: progress report 2008. Geneva, World Health Organization, 2008. Botswana: Champion of ART scale up in Africa. Country Sto-12. ries Fact Sheet for Media. World Health Organization, 2006 (http://www.who.int/hiv/countrystories.pdf, accessed 27 April 2010). AlSerouri AW et al. Knowledge, attitudes and beliefs about 13. HIV/AIDS in Sana’a, Yemen. Eastern Mediterranean Health Journal, 2002, 8:706–715. Busulwa R et al. Perpcetions of the condoms as a method of 14. HIV prevention in Yemen. Eastern Mediterranean Health Jour- nal, 2006, 12:64–77. Country profiles for population and reproductive health: policy 15. developments and indicators 2005. New York, United Nations Population Fund and Population Reference Bureau, 2005. Badahdah AM, Sayem N, Foote CE. Development of a Yemeni 16. AIDS stigma scale. AIDS Care, 2009, 21:1–6. Yemen: country profile.17. Overview of malaria control activities and programme progress. Geneva, World Health Organization, EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 906 International Conference on Opportunistic Pathogens, New Delhi, India, 27–30 September 2010 Topics of concern and interest which will be addressed at the International Conference on Opportunistic Pathogens include: contracting opportunistic infections, resistance to anti-retroviral drugs, co-pathogens of HIV, receptor attachment, neuropathology, tissue tropism, testing guidelines, universal testing strategies, and future vaccine candidates against HIV. Further information on the conference can be found at: http://icopa-india.org/default.htm 2005 (http://rbm.who.int/wmr2005/profiles/yemen.pdf, ac- cessed 27 April 2010). Madani T et al. Epidemiology of the human immunodeficiency 18. virus in Saudi Arabia; 18-years surveillance results and preven- tion from an Islamic perspective. BMC Infectious Diseases, 2004, 4:1–8. Ganczak M et al. Break the silence: HIV/AIDS knowledge, at-19. titudes, and educational needs among Arab university students in United Arab Emirates. Journal of Adolescent Health, 2007, 40: 572.e1–572.e8 (doi:10.1016/j.jadohealth.2007.01.0112). Alrajhi A, Halim M, Al-Abdely H. Mode of transmission of HIV-1 20. in Saudi Arabia. AIDS, 2004, 18:1478–1480. Kopelman LM. If HIV/AIDS is punishment, who is bad? 21. Journal of Medicine and Philosophy, 2002, 27:231–243. Ayranci U. AIDS knowledge and attitudes in a Turkish popu-22. lation: an epidemiological study. BMC Public Health, 2005, 13:1–10. Montazeri A. AIDS knowledge and attitudes in Iran: results 23. from a population-based survey in Tehran. Patient Education and Counseling, 2004, 57:199–203. Tebourski F, Ben Alaya D. Knowledge and attitudes of high 24. school students regarding HIV/AIDS in Tunisia: does more knowledge lead to more positive attitudes? Journal of Adoles- cent Health, 2004, 34:161–162. Common misconceptions about HIV increase discrimination. 25. Yemen Times, 12 August, 2009 (http://yementimes.com/arti- cle.shtml?i=1180&p=health&a=2, accessed 27 April 2010). طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 907 Review Burden of HIV/AIDS infection before and during the civil war in Somalia B.H. Ahmed,1 M.R. Giovagnoli,1 H. Mahad 2 and G.G. Tarsitani 1 ABSTRACT Somalia has suffered a massive internal population displacement and exodus that began in 1988 and is still ongoing during the prolonged and intermittent civil war. This review looks at the burden of HIV infection in Somali and the impact of civil war on its epidemiology. Serosurveys have indicated that HIV was not present in Somalia before the civil war and to date Somalia has had an HIV prevalence markedly below that of its neighbours. However, due to the ongoing war HIV sentinel surveillance cannot reach most of the affected areas in Somalia and the current HIV infection problem may be greater than the figures indicate. 1School of Medicine, Sapienza University of Rome, Rome, Italy (Correspondence to: Gianfranco.tarsitani@uniroma1.it). 2Adolphus College, St Peter, Minnesota, United States of America. Received: 20/08/08; accepted: 24/12/08 لاموصلا في ةيلهلأا برلحا ءانثأو لبق زديلإا/يشربلا يعانلما زَوَعلا سويرفب ىودعلا ءبع نياتيسرت وكنارفنايج ،دهم نسح ،ليونافويج ايراسورايرام ،دحمأ نسحوهارب دملأا ةليوطلا ةيلهلأا برلحا للاخ ةرمتسم لازتلاو 1988 ماع في تأدب ةرجه عم ناكسلل ميسج ليخاد حوزن نم لاموصلا نياعت :ةـصلالخا .اله ةيئابولا تماسلا لىع ةيلهلأا برلحا رثأو ،لاموصلا في يشربلا يعانلما زَوَعلا سويرفب ىودعلا ءبع ةقرولا هذه في ناثحابلا سرديو .ةعطقتلماو راشتنا لدعم نأو ،ةيلهلأا برلحا لبق لاموصلا في ًادوجوم نكي لم يشربلا يعانلما زَوَعلا سويرف نأ لىإ )ةيلصلما( ةيجولويرسلا تاحوسلما يرشت ذإ د ُّصترلا نإف برلحا رارمتسلا ًارظن هنأ لاإ .ةرواجلما لودلا في هيلع وه امم ضفخأ ليالحا تقولا ىتح لازيلا لاموصلا في يشربلا يعانلما زَوَعلا سويرف يرشت امم ةروطخ رثكأ اذبه ىودعلا ةلكشم نوكت دقو ،لاموصلا في ةرضرتلما قطانلما مظعم لىإ لصي نأ نكمي لا يشربلا يعانلما زَوَعلا سويرفل رفالخا .ماقرلأا هيلإ Charge de l’infection par le VIH/sida avant et pendant la guerre civile en Somalie RÉSUMÉ Depuis 1988, la Somalie est confrontée à un déplacement massif de population à l’intérieur du pays et à un exode qui perdurent au cours de la guerre civile épisodique auquelle elle est confrontée de longue date. La présente analyse étudie la charge de l’infection par le VIH en Somalie et l’impact de la guerre civile sur son épidémiologie. Des enquêtes sérologiques ont révélé que le VIH n’était pas présent en Somalie avant la guerre civile et qu’à ce jour, la prévalence du VIH en Somalie était nettement inférieure à celle des pays voisins. Toutefois, en raison de la guerre qui sévit actuellement, la surveillance sentinelle du VIH ne peut accéder à la plupart des zones touchées en Somalie et le problème actuel relatif à l’infection au VIH pourrait être plus important que ce que les chiffres laissent entendre. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 908 Introduction Somalia, situated on the Horn of Africa, has suffered a massive internal popu- lation displacement and exodus that began in 1988 with the rebellion in the north of the country, causing refugees to flee to camps in Ethiopia and Kenya. Other refugees from the north were resettled in Mogadishu, the capitol of Somalia, located on the central-southern coast. In 1991, armed militia overthrew the Somali central government. The population shift has continued during the ensuing prolonged and intermittent civil war. The conflict was still ongoing as of March 2008 [1]. In this review we look at the burden of human im- munodeficiency virus (HIV) infection in Somalia and the impact of civil war on its epidemiology. Methods To review the HIV epidemic before and during the civil war in Somalia, the data in this article were identified from a search using the PubMed search engine and the keywords “East Africa”, “Soma- lia” “HIV” and “AIDS”. United Nations (UN) reports and articles published in international journals not indexed by PubMed were also included. The selection was based on original research articles and critical reviews by major investigators. Key issues related to the HIV epidemic in Somalia from early studies collected in different sites were summarized, including a serosurveil- lance survey conducted by the World Health Organization (WHO) in 3 dif- ferent zones: South-Central Somalia, Puntland and Somaliland. Results Before the civil war, some early HIV/ AIDS surveys were carried out in Somalia. Different population groups were tested, using serum collected from female sex workers, patients attending sexually transmitted disease (STD) clinics and patients with tuberculosis in Mogadishu and 2 other southern cities. Between 1978 and January 1987, anti- bodies against HIV were not detected in any of these groups [2–5]. A seroepi- demiological survey was conducted in 1989 Mogadishu, the urban capital, and the rural areas of Marko, Qoryoley and Kismayo [6]. There were 1269 study subjects, including 57 female sex work- ers, 79 patients attending STD clinics and 1133 others, including hospital- ized patients, outpatients, people from rehabilitation camps, secondary-school pupils and immigrants from Ethiopia. The people tested were suffering from leprosy, tuberculosis and other infec- tious diseases. The results showed that none of them tested positive for HIV-1 and HIV-2. Further studies were carried out in July and August 1985 and January 1986 on 471 serum samples, from 3 different groups of women aged 14–48 years, including pregnant women admitted to hospital and their newborn babies, women with higher education (physi- cians, nurses, university students and administrative staff) and sex workers. All were negative for HIV antibodies [7]. The first HIV-antibody positive sample in Somalia was found in 1987 among serum samples collected from 287 female sex workers in Mogadishu and reported first by Burans at the IVth International Conference on AIDS, Stockholm, in 1988 and later published by Ahmed et al. [8]. Another 4 cases of HIV were reported in Somalia in 1989. The numbers increased to 13 in 1991 [6,9]. A follow-up study carried out in 1991 showed that the seroprevalence of HIV-1 antibodies was 3% among female sex workers in Mogadishu, Merca and Kisimayo [10]. However, HIV infection was still rare in 1990 in Somalia, perhaps due to the low level of trade activity between Somalia and the rest of Africa [11]. By 2000, the figures reported for Somalia were still much lower than those reported from neighbouring countries [12,13]. In Kenya, Ethiopia and Djibouti the HIV epidemic reached double-digit rates of infection, as reported by the UN Joint Programme on HIV/AIDS in 2000 [14,15]. According to a WHO HIV surveillance report in 2004 in 3 regional zones (South-Central Somalia, Punt- land and Somaliland), out of a total of 4732 people tested, 44 were positive for HIV (0.9%). A follow-up report in 2007 indicated that the prevalence of HIV had increased to 2.2% in Bosaso, and 2.7% in Berbera [16]. Based on the 2005 WHO estimate of the HIV status of So- malis, there were 40 000 Somali adults living with HIV infection and 4200 new infections. The estimated death toll due to AIDS was 970 [17]. Discussion Serosurveys have indicated that HIV was not present in Somalia before the civil war started. Other studies carried out during the war indicated that HIV was present at a low rate, although the prevalence has subsequently risen steadily to reach a maximum of 2.7%, the latest figure recorded in the north of the country in 2007 [16]. The re- sults of other studies emphasize that conflict is a risk factor for HIV transmis- sion [1,16,18]. Somalia’s population, still sporadically at war, is vulnerable to further exposure to HIV infection. Factors such as promiscuity, polygamy, high incidence of STD, malnutrition, poverty and the continued presence of some traditional practices such as the use of nonsterile tools for minor surgery are high risk for HIV transmis- sion. Longstanding conflict and forced displacement can change the behaviour of a society and increase the risk of HIV [17]. Surveys conducted on the Somali population indicate that there is a lack of understanding and awareness of طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 909 basic information about HIV, including mechanisms of prevention of transmis- sion. Added to this are factors such as the widespread stigma attached to HIV infection; reluctance to disclose infor- mation to family and partners; gender inequalities that increase the vulner- ability of women and girls; transfusion of unsafe blood; and the widespread use of qat which may be associated with high-risk behaviour [18]. Because of the ongoing war HIV sentinel surveillance cannot reach most of the affected areas in Somalia. The current HIV infection problem may be higher than the figures indicate. To date, Somalia has had an HIV infection rate markedly below that of its neigh- bours. This is most likely related to the cultural traditions and behavioural norms practised by Somalis, such as discouragement of extramarital sex and prostitution. This is in danger of change due the continued civil unrest in the country. Another practice which helped Somalis avoid the scourge of HIV may be male circumcision. Male circumcision has been suggested as a reason for the low prevalence of HIV in many communities which practise it in sub-Saharan Africa [19–21]. WHO has reported that male circumcision re- duces the risk of HIV by approximately 60%. The mechanism is thought to be that the HIV virus targets immune cells such as Langerhan cells, CD4+, T-cells and macrophages that are located in the mucosal side of the foreskin and that these are reduced in circumcised men. Furthermore, circumcision, by forming a thick layer of squamous epithelial cells, may act as a barrier to HIV uptake in the underlying target cells [22]. Special attention to HIV prevention and education, including more media information, is needed for the Somali population, who are still being dispersed by an ongoing war. Because of the lack of a central authority in the country, both surveillance programmes and pos- sible interventions should be addressed in a decentralized way. Gisselquist D. 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Male circumcision for HIV 22. prevention: a prospective study of complications in clinical and traditional settings in Bungoma, Kenya. Bulletin of the World Health Organization, 2008, 86(9):669–677. EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 910 Short communication Public–private partnership scenario in the health care system of Pakistan F. Ahmed 1 and N. Nisar 2 ABSTRACT Public–private partnerships (PPP) in basic health services delivery aim to improve service provision, such as better coverage, quality and infrastructure of health care, as well as raising the demand for health by the community. This paper outlines some examples of public–private partnerships in Pakistan and examines barriers to further development of such initiatives. We argue that to meet the challenges of globalization and achievement of the Millennium Development Goals, Pakistan needs to improve the health status of its society by promoting and practising PPP in providing health care services. 1Institute of Health Sciences, Baqai Medical University, Karachi, Pakistan (Correspondence to F. Ahmed: fah_khan@yahoo.com). 2Department of Community Medicine, Dow University of Health Sciences, Karachi, Pakistan. Received: 28/12/08; accepted: 08/03/09 ناتسكاب في ةيحصلا ةياعرلا ماظن في صالخاو ماعلا عاطقلا ينب ةكاشرلا ويرانيس رازن تهجن ،دحمأ ميهف ،لضفأ ٍوحن لىع ةيطغتلا لثم ،تامدلخا ميدقت ينستح لىإ ةيساسلأا ةيحصلا تامدلخا ءاتيإ في صالخاو ماعلا عاطقلا ينب ةكاشرلا فدته :ةـصلالخا تاكاشرلا نع ةلثملأا ضعب ةقرولا هذه فصتو .ةحصلا لىع عمتجلما في بلطلا ةدايز بناج لىإ ،ةيحصلا ةياعرلل ةيتتح ةينب نمضو ،ةيلاع ةدوجبو ينستح ناتسكاب لىع يغبني هنأ ناثحابلا ىريو .تاردابلما هذله م ُّدقتلا نم ديزلما قيعت يتلا زجاولحا ضرعتستو ،ناتسكاب في صالخاو ماعلا عاطقلا ينب عاطقلا ينب تاكاشرلا زيزعتب كلذ نوكيو ،ةيفللأل ةيئمانلإا يمارلما قيقحتلو ةلموعلا اهضرفت يتلا تاي ِّدحتلل ي ِّدصتلل عمتجلما في ةيحصلا اهعاضوأ .ةيحصلا ةياعرلا تامدخ ءاتيإ في اتهاسراممو ،صالخاو ماعلا Projet de partenariat public-privé dans le système de santé du Pakistan RÉSUMÉ Les partenariats public-privé relatifs à la prestation de services de santé de base visent à améliorer les services fournis, notamment en développant la couverture et la qualité des soins de santé et les infrastructures correspondantes. Ils ont également pour objectif d’accroître la demande de la communauté en termes de santé. Cet article présente brièvement quelques exemples de partenariats public-privé au Pakistan et évalue les obstacles au développement futur de telles initiatives. Nous pensons que, pour relever les défis liés à la mondialisation et la réalisation des objectifs du Millénaire pour le développement, le Pakistan doit améliorer l’état de santé de sa population par la promotion et l’établissement de partenariats public-privé relatifs à la prestation de services de santé. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 911 Background The concept of co-operation between public and private provision of health care was instituted in Pakistan in nation- al health policy in 1960 and started as a model of corporate social responsibility to serve the nation’s health needs. Pub- lic–private partnerships (PPP), as they are now called, are a health sector reform to create long-term, task-oriented and formal relationships among the public and private sectors in sharing their core competency and resources, including some degree of joint decision-making and innovative interaction to provide sustainable improvements in the provi- sion and enhanced utilization of health care services and also to address emerg- ing health challenges for the benefit of society. A core set of objectives of PPP in basic health services delivery relate to improving service provision, such as coverage, quality and infrastructure, as well as raising the demand for health by the community. The 1973 Constitution of Pakistan, Article 38(d), guarantees that the State shall provide the basic necessities of life, including the provision of health care. Yet, the apparent priority given national security over human develop- ment means that the government seems unable to fulfil its constitutional promise to bring reforms to the health sector of Pakistan. The provision of basic health services in Pakistan is inadequate and is a major obstacle to human develop- ment. Pakistan is facing a double burden of disease. Not only is the country failing to overcome infectious diseases such as poliomyelitis that others have tack- led, but it is also facing the challenge of chronic noncommunicable diseases. As far as health indicators are concerned the infant and maternal mortality rates for Pakistan are very high compared even with other developing countries, at around 100 per 1000 live births and 340 per 100 000 live births respectively. Barriers to public– private partnership Privatization policies in Pakistan remain largely unexamined and insensitive to the need for basic health services that are accessible, available, affordable and of acceptable quality. This could be due mainly to downsizing of social capital and inadequate financial resources or to disparities in power and lack of trust between the public and private sectors that inhibits collaboration at the policy and operational level in provision of health care in Pakistan. As a result, the health sector in Pakistan is far from developing a consistent form of interac- tion between the public and private sectors, and suffers from a persisting political polarization along 3 major, intersecting faultlines—bureaucrats, technocrats and the military—that have been evident in Pakistan since the partition of the Indian subcontinent in 1947. This in turn is reflected in a high burden of disease, lack of health care staff, staff absenteeism and poor access to health facilities for patients [1]. According to the Pakistan National Health Policy 2001, primary health care in Pakistan is currently functioning mainly in the private sector through contracting out of health services, which means handing over of un- and under- utilized government health facilities, such as basic health units, rural health centres and hospitals to the private sector. This is supposed to provide support for awareness raising and the management of clinical and nonclinical services in the community [2]. This was implemented through a rural support programme. Pilot programmes Pilot programmes were established in 8 districts of Punjab in 2005. About 104 basic health units in one district, Rahim Yar Khan, were handed over to a large nongovernmental organization on a pilot initiative to provide primary health care services to overcome the inability of the health care services delivery system to tackle diseases at basic health units. The World Bank has been a catalyst for such contracting out in Rahim Yar Khan district, which includes providing funds and technical support. However, the Sustainable Development Policy Institute, in cooperation with the Uni- versity of Birmingham in the United Kingdom, recently conducted a study and found that the PPP results in Rahim Yar Khan district were disappointing, due to lack of a preventive approach, disparities in power and other factors. While the overall utilization of facilities had increased, insufficient numbers of patients were attending basic health units. In this district—where the poor- est of the poor are still socially excluded, live in inaccessible areas, lack confidence and information and are unable to pay for services—the services provided remain un-utilized [3]. The government of Pakistan has decided to scale-up the programme to the national level but the benefits of this have not yet become apparent in the general population in terms of improved public health. Examples of public– private partnership The goals of PPP are to create a financially sustainable system, capac- ity reform and management reform in the public–private sector which may lead to increased health care delivery and utilization, preventing unintended outcomes of private sector growth in health, control health care costs and cre- ate improvements in the health status of society, thus facilitating socioeconomic development. In Pakistan there are some examples of successful public– private collaborations in health care provision: a mobile doctors programme run by • a tobacco company since 1980 in the tobacco cultivation areas and at their EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 912 factories as a part of their corporate social responsibility strategy (Paki- stan Tobacco Company, 2005); the national programmes for malaria, • tuberculosis and HIV/AIDS control implemented through a collaboration of government and private health care providers, including the Ministry of Health and the GreenStar Network, the Asia Foundation and HealthNet International; the World Health Organization (WHO), United Na- tions Development Programme and World Bank support all providers in the services; the Ministry of Finance, Government of Pakistan, subsidizes the insecticide-treated bednets. a public sector mother and child • hospital in Shikarpur district in Sindh province whose management is handed over to a private practi- tioner; the Health and Nutrition Develop-• ment Society (HANDS), an NGO in partnership with Sindh government to provide primary health care serv- ices at basic health units in Karachi; the Aga Khan University Karachi, • Pakistan, a private sector partnership with Sindh Government to provide primary health care services in rural and urban slum communities for dis- ease surveillance, vaccines and drug trials; Heartfile, an NGO in partnership with • government, the International Vac- cine Institute (South Korea), WHO, Save the Children and UNICEF, is the supporting agency in a policy development initiative to control noncommunicable diseases; a Ministry of Population Welfare and • United States Agency for Internation- al Development partnership estab- lished a social marketing programme from the GreenStar Network in Paki- stan to enhance contraceptive use; a private company that educates • young mothers about healthy baby-care practices and teaches 5–9-year-old children about basic hygiene habits using these activities in the company’s marketing strategy (Procter and Gamble) [4]. Challenges PPP are considered to be a successful model of health reform in the health sector of other countries [5–7]. So the challenge ahead is for Pakistan to facilitate the implementation of vari- ous components of health sector pro- grammes, including establishing norms, tackling morality and accountability issues, building a legislative framework, defining operational strategies, as well as safeguarding the Consumer Protection Act to safeguard the interest of consum- ers. The issues we are facing to facilitate implementation of partnerships in providing and encouraging utilization of health care services include a lack of appropriate monitoring and reporting mechanisms, a lack of clarity in policies and low efficiency of the private sector in taking care of the poorest sectors of society. The research in the field of establish- ing effectiveness of PPP in providing and raising demand of health care services in the community in Pakistan is limited to rare cases. Furthermore the data to pro- mote health sector reform in Pakistan are unavailable or unpublished. PPP is a multidisciplinary and multi-sectoral approach, which needs significant insti- tutional development, monitoring and evaluations systems. The government of Pakistan is com- mitted to achieving the Millennium Development Goals for eradicating poverty, providing health and education facilities, ensuring gender equality and combating HIV by 2015 in partnership with the World Health Organization and the World Bank. To meet the chal- lenges of globalization and achieving a prosperous Pakistan in the 21st century we need to promote and practise PPP in providing health care services to im- prove the health status of our society. The state of the worlds’ children1. . New York, United Nations Chil- dren’s Fund, 2001. National Health Policy 2001. The way forward. Agenda for 2. health sector reform. Karachi, Ministry of Health, Government of Pakistan, 2001 (http://www.nacp.gov.pk/introduction/ national_health_policy/NationalHealthPolicy-2001.pdf, ac- cessed 26 May 2010). Siegmann KA, Shaheen N. Joining hands for better health care. 3. SDPI Research and News Bulletin, 2006, 13(4 & 5):10–15. Siegmann KA, Shaheen N, Shah S. 4. Collaboration between state and non-state providers of basic services in Pakistan. Islamabad, Pakistan, Sustainable Development Policy Institute, 2006. References Allen G. The private finance initiative. 5. House of Commons Library Economic Policy and Statistics Section Research Paper, 2001, 01/117. Nayani P, White F, Nanan D. Public–private partnership as 6. a success factor for health systems. Medicine Today, 2006, 4(4):135–142. Nikolic IA, Maikisch H. 7. Public–private partnerships and col- laboration in the health sector. An overview with case studies from recent European experience. Health, Nutrition, and Population Family discussion paper. Washington DC, World Bank Human Development Network, 2006. طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 913 Case report Primary hydatid cyst of the round ligament: case report M. Akinci,1 O. Yigitbasi,2 Z. Ergul,1 E. Olcucuoglu1 and H. Kulacoglu1 1Department of General Surgery; 2Department of Urology, Ankara Diskapi Teaching and Research Hospital, Ankara, Turkey (Correspondence to M. Akinci: melihakinci@yahoo.com). Received: 18/07/08; accepted: 11/09/08 Introduction Echinococcosis is a zoonotic infection in which the liver is the organ most fre- quently involved, followed by the lung and sometimes the heart, spleen, kidney and brain [1]. Hydatid cyst can be seen in almost every part of the human body [2–5]. Despite the common involve- ment of the liver in terms of location, only 2 cases of isolated hydatid cyst of the round ligament of the liver have been reported, first in 1985 in Italian [6] and then in 1993 in Spanish [7]. We present here the third case of round ligament hydatid cyst. Case report A 24-year-old male was admitted to the department of general surgery with an epigastric mass that he had noticed 3 months previously. He complained of abdominal fullness and vague pain. The patient had no other systemic disorder and no history of surgery or use of medi- cal drug therapy. Physical examination of the patient revealed a semifixed 6 cm mass on the abdominal epigastric area adjacent to the right inferior ribs. There were no other positive findings at physical examination. Abdominal ultrasound demon- strated a 6 × 4 cm cystic mass between the anterior abdominal wall and ante- rior surface of the left hepatic lobe. There were no vesicles or necrotic areas in the cystic mass. It was reported that the lesion could be originating from the left lobe of the liver. Ultrasound also revealed a left renopelvic dilatation. Abdominal com- puterized tomography showed a 7 × 4 cm capsulated cystic mass that was being compressed by the hepatic left lobe and abdominal wall. A clear border between the liver and mass was visualized. No other lesions were seen in any part of the abdominal cavity (Figure 1). The patient’s routine laboratory tests were normal and the echinococcosis immune haemagglutination test (Dade Behring, Margurg, Germany) was nega- tive. Before making a decision about the treatment of the cyst, the patient was referred to the department of urology. There he stated that he had recently started to experience left lumbar pain. In the urological evaluation an intrave- nous pyelogram confirmed dilatation of the left renal pelvis and calyx, and renal scintigraphy revealed left ureteropelvic stenosis. This ureteropelvic junction stenosis was considered to be symp- tomatic by the urologists and an open surgical treatment was planned. First, the urologists performed a dismembered pyeloplasty, then the cystic lesion was approached by the Figure 1 Hydatid cyst (6 × 4 cm) between the anterior abdominal wall and the liver. A clear border is seen between the cyst and the liver (R = right rectus abdominis muscle) EMHJ • Vol. 16 No. 8 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale 914 general surgery team via a 10 cm long upper midline incision. The cyst was found to originate directly from the round ligament of the liver (ligamentum teres hepatis). The round ligament was ligated and divided and then the mass was totally excised from the abdominal wall with 1 cm free borders. It was a 6.5 × 4 × 4 cm cystic mass filled with serous fluid. The capsule was creamy-white in colour with a well-circumscribed shape. The histopathological examination con- firmed a hydatid cyst by demonstrating protoscolex within. The patient’s postoperative course was uneventful and he was discharged on the fourth postoperative day. Alben- dazole was prescribed with a dose of 2 × 400 mg/day. Discussion Hydatid disease, caused by the larval stage of Echinococcus granulosus, is recognized as a public health problem [8]. Turkey is an endemic region for this disease. Besides the liver and lungs, hydatid cysts with unusual locations (e.g. pancreas, spleen, kidney, intra-abdominal cavity, ovary, breast, mediastinum, chest wall, muscle, adrenal, lung, thyroid gland, anterior abdominal wall, thigh, presacral space, brain, cavernous sinus, submandibular gland, heart, pleura, retrocrural tissue, inguinal canal, bone, bile duct, soft tissue and retroperitoneum) have previously been reported from this country [2–5]. When the present case presented with an anterior mass, the lesion was considered as a possible hydatid cyst since hydatid disease is very common in Turkey and anterior abdominal hydatid cysts have been reported several times [9–11]. However, the tomographic examination noted a deeper lesion beneath the anterior abdominal wall. Therefore a pancreatic cyst, parasitic or not, was a diagnostic possibility [12]. In 2003, the World Health Organiza- tion Informal Working Group on Echi- nococcosis (WHO-IWGE) proposed a standardized ultrasound classification based on the active–transitional–inac- tive status of the cyst as suggested by its sonographic appearance [13]. In our case, ultrasonography and tomography revealed a simple cyst with well-defined borders and uniform anechoic contents. This description, according to WHO- IWGE classification, is not pathogno- monic for echinococcal cysts because nonparasitic cysts may have the same appearance. In addition, the haemag- glutination test did not support a diag- nosis of hydatid disease. However, while haemagglutination displays a very good specificity with few false positive results, it has a low sensitivity of just 50% [14]. In fact hydatid cyst of the round liga- ment of the liver is a very rare presenta- tion of echinococcosis. Only 2 cases have been reported to date [6,7]. There is no doubt that the ideal treatment of a cystic or solid mass is total excision. However, this choice is quite aggressive and rarely possible in hydatid cysts of the liver, and partial excision of the (peri)cyst with or without omentoplasty usually results in a better clinical response [15], while radical resections are still the treatment of choice for hepatic hydatid disease [16]. Unlike in hepatic hydatid cysts, total excision is technically easier for intra-abdominal nonhepatic hydatid cysts involving the omentam or free peritoneal cysts [17]. The present case was treated by perform- ing a total cystectomy. Surgery for hydatid cysts is rarely ac- companied by an unrelated abdominal surgery. Generally, surgeons are not will- ing to add an extra surgical procedure during a hydatid cyst operation because of its unclean nature. In our case, the hydatid cyst of the round ligament was totally excised without any spillage and no risk of infection was added to the elective urological procedure. Interestingly, a pal- pable abdominal lesion made it possible to diagnose and treat a hidden urinary pa- thology in an early stage. A Medline search found several reports using the keywords “ureteral obstruction” and “hydatid”, but those obstructions were secondary to renal hydatid disease [18]. Moreover, to the best of our knowledge, no reports have been found in the literature describ- ing such a combined surgery. Medical therapy in the form of ben- zimidazole carbamates, alone or in com- bination with praziquantel, has been advocated for the treatment of hydatid disease [19–21]. However, it is gener- ally accepted that systemic albendazole treatment is not an alternative to surgi- cal treatment [22]. Albendazole may be given as an adjuvant to surgery to avoid recurrence and to suppress subcenti- metre lesions not visible by ultrasound. Therefore, despite the fact that the first scan for any concomitant cysts was negative and that a total cyst excision was achieved, we put the patient on a prophylactic albendazole regimen with a dose of 2 × 400 mg/day. We report here a very rare presenta- tion of hydatid disease that originated from the round ligament of the liver. Hydatid cysts should be considered in the differential diagnosis of intra- abdominal masses, particularly in endemic regions or in patients who have emigrated from endemic countries, even when serological tests are negative. Tiseo D et al. Cystic echinococcosis in humans: our clinic expe-1. rience. Parassitologia, 2004, 46:45–51. Yuksel M et al. Hydatid disease involving some rare locations in 2. the body: a pictorial essay. Korean Journal of Radiology, 2007, 8:531–540. Yildirim M, Erkan N, Vardar E. Hydatid cysts with unusual locali-3. zations: diagnostic and treatment dilemmas for surgeons. An- nals of Tropical Medicine and Parasitology, 2006, 100:137–142. Kireşi DA et al. Uncommon locations of hydatid cysts. 4. Acta Radiological, 2003, 44:622–636. References طسوتلما قشرل ةيحصلا ةلجلماشرع سداسلا دلجلما نماثلا ددعلا 915 Engin G et al. Hydatid disease with unusual localization. 5. Euro- pean Radiology, 2000, 10:1904–1912. Vadalà G et al. Su un caso di cisti da echinococco del lega-6. mento rotondo del fegato. Nota preliminare [A case of echino- coccal cyst in the round ligament of the liver: preliminary note]. Minerva Medica, 1985, 76:647–649. Fernández Ballesteros A et al. Quiste hidatidico en el ligamento 7. redondo. Una presentacion excepcional. [Hydatid cyst in the round ligament. An unusual presentation.] Anales de Medicina Interna, 1993, 10:619–620. Moro PL, Gonzalez AE, Gilman RH. Cystic hydatid disease. In: 8. Hunter GW, Strickland GT, Magill AJ, eds. Hunter’s Tropical Medicine and Emerging Infectious diseases. Philadelphia, WB Saunders, 2000:866–871. Durakbasa CU et al. An audit on pediatric hydatid disease 9. of uncommon localization: incidence, diagnosis, surgical approach, and outcome. Journal of Pediatric Surgery, 2006, 41:1457–1463. Hamamci EO, Besim H, Korkmaz A. Unusual locations of hy-10. datid disease and surgical approach. ANZ Journal of Surgery, 2004, 74:356–360. Ozoilo KN et al. Anterior abdominal wall hydatid cyst: an 11. unusual presentation. Nigerian Journal of Medicine, 2007, 16:181–182. Moosavi SR, Kermany HK. Epigastric mass due to a hydatid 12. cyst of the pancreas. A case report and review of the literature. Journal of the Pancreas, 2007, 8(2):232–234. WHO Informal Working Group. International classification of 13. ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Tropica, 2003, 85(2):253–261. Gonlugur U et al. The role of Casoni’s skin test and indirect 14. haemagglutination test in the diagnosis of hydatid disease. Parasitology Research, 2005, 97:395–398. Uravic M et al. Diagnosis and treatment of liver hydatid disease. 15. Hepatogastroenterology, 1998, 45:2265–2269. Aydin U et al. The optimal treatment of hydatid cyst of the liver: 16. radical surgery with a significant reduced risk of recurrence. Turkish Journal of Gastroenterology, 2008, 19:33–39. Türkyilmaz Z et al. Conservative surgery for treatment of 17. hydatid cysts in children. World journal of Surgery, 2004, 28:597–601. Yaycioglu O et al. Isolated renal hydatid disease causing ure-18. teropelvic junction obstruction and massive destruction of kidney parenchyma. Urology, 2006, 67:1290.e15–17. Teggi A, Lastilla MG, De Rosa F. Therapy of human hydatid dis-19. ease with mebendazole and albendazole. Antimicrobial Agents and Chemotherapy, 1993, 37:1679–1684. Silva MA et al. Treatment of hydatid disease of the liver. Evalua-20. tion of a UK experience. Digestive Surgery, 2004, 21:227–233. Koulas SG et al. A fifteen years experience (1988–2003) on 21. the management of liver hydatidosis in northwestern Greece. International Surgery, 2006, 91:112–116. Kapan S et al. Albendazole is not effective for primary treat-22. ment of hepatic hydatid cysts. Journal of Gastrointestinal Sur- gery, 2008, 12:867–871. طسوتلما قشرل ةيلماعلا ةحصلا ةمظنلم ةيميلقلإا ةنجللا ءاضعأ نادلبلا ةيملاسلإا ناريإ ةيروهجم . ةيبيللا ةيبرعلا ةييرهمالجا . سنوت . نيرحبلا . ناتسكاب . ةدحتلما ةيبرعلا تاراملإا . ناتسناغفأ . ندرلأا صرم . نانبل . تيوكلا . رطق . ينطسلف . نماُع . قارعلا . لاموصلا . نادوسلا . تيوبيج . ةينميلا ةيروهملجا . ةيروسلا ةيبرعلا ةيروهملجا ةيدوعسلا ةيبرعلا ةكلملما . برغلما Subscriptions and Distribution Enquiries regarding subscriptions and distribution of the print edition of EMHJ should be addressed to: Printing and Marketing of Publications at: email: pam@emro.who.int; tel: (+202) 2276 5000; fax: (+202) 2670 2492 or 2670 2494 Permissions Requests for permission to reproduce or translate articles, whether for sale or non-commercial distribution should be addressed to EMHJ at: emhj@emro.who.int Members of the WHO Regional Committee for the Eastern Mediterranean Afghanistan . Bahrain . Djibouti . Egypt . Islamic Republic of Iran . Iraq . Jordan . 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ISSN 1020-3397 Cover designed by Diana Tawadros Internal layout designed by Emad Marji and Diana Tawadros Printed by WHO Regional Office for the Eastern Mediterranean ميدقتل برنم ىهو .ةيلماعلا ةحصلا ةمظنمب طسوتلما قشرل ىميلقلإا بتكلما نع ردصت ىتلا ةيمسرلا ةلجلما ىه ةيئابولا تايطعلماو ميهافلماو ءارلآا لدابتلو ،اله جيوترلاو ةيحصلا تامدلخا فى ةديدلجا تاردابلماو تاسايسلا لك لىإ ةهجوم ىهو .طسوتلما قشر ميلقإب اهنم قلعتي ام ةصاخو ،تامولعلما نم كلذ يرغو ثاحبلأا جئاتنو زكارلماو ،ةينعلما ةيموكلحا يرغ تماظنلما اذكو ،ةيميلعتلا دهاعلما رئاسو ةيبطلا تايلكلاو ،ةيحصلا نهلما ءاضعأ .هجراخو ميلقلإا فى ةحصلاب ينمتهلما دارفلأاو ةيلماعلا ةحصلا ةمظنم عم ةنواعتلما طسوتلما قشرل ةيحصلا ةلجلما Cover 6.indd 2 5/24/2010 11:46:47 AM
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Eastern Mediterranean Health Journal [2010; Vol.16, Issue 8]
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Organisation mondiale de la santé (OMS)
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