Eastern Mediterranean Health Journal [2004; Vol.10, Issue 1-2]

J.a .. d .. __,:.llJ_,.. '",J~_)tl~f:::&t\ Regional Office for the Eastern Mediterranean Bureau regional de la Mediterranee orientale , rranee rielltale q L-J I~~~ I;: l; :... World Health Organization Organisation mondiale de la Sante J-JJ.1 Jr-l ~I 41$.1 ..:.,L...,l:-)I ~ili .fa' -/' J .a.J.Wi .,_,..]1 ~- .1... y:1I J .r-1 ~'jl ~I y- J..i...,.; JI ~ )I ~I ab;i -/' .!Jj~ _.,.); J ..!J~\11 ~l:i J 4,14_,ll ..:.,~IJ ~WIJ "IJ \Ii J~l,::] J ,t.. ~JJ-llJ ~I ..:.,L,..ij.l ij 0--4.l:l,.i dJ~W.IJ ~I ..:.,L.$JIJ ,~I .:,t--1I "~i JS' J! 4.p.-y -/'J . .1...y:1I J__,.:. ~~ 4:,-, ~ L. ...,.l,,:.J ,..:.,L._,L.ll ,:.r ~I ~l_;-i\JIJ ;_,,.l.WI ;__,.._,.JI ~C;' .,;J\..dl _.fl}IJ ,~I a,,..pI _.,.); ..:.,l.J:i;.ll l..i.S"J ,~I..uoWI Jl,,,J ."->.-Jl,,:. J ~'ii J .,_,..i4 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, concepts, 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 Collaborating Centres and individuals within and outside the Region. LA REVUE DE SANTE DE LAMEDITERRANEE ORIENTALE EST une revue de sante officielle publiee par le Bureau regional de !'Organisation mondiale de la Sante pour la Mediterranee orientale. Elle offre une tribune pour la presentation et la promotion de nouvelles politiques et initiatives dans le domaine des services de sante ainsi qu'a l'echange d'idees, de concepts, de donnees epidemiologiques, de resultats de recherches et d'autres informations, se rapportant plus particulierement a la Region de la Mediterranee orientale. Elle s'adresse a taus Jes professionnels de la sante, aux membres des instituts medicaux et autres instituts de formation medico-saniaire, aux ONG, Centres collaborateurs de l'OMS et personnes concernes au sein et hors de la Region. The Eastern Mediterranean Health Journal is abstracted/indexed in the Index Medicus and MEDLIN£ (Medical Literature Analysis and Retrieval Systems on Line) and the ExtraMed-Ful/ text on CD-ROM, the Cumulative Index to Nursing and Allied Health Literature (CJNAHL), CAB International, Lexis Nexis™ and the Index Medicus for the WHO Eastern Mediterranean Region (IMEMR). EMHJ is also available on the World Wide Web: http://www/emro.who.int/emhj.htm ALL ARTICLES ARE PEER REVIEWED ISSN 1020-3397 © WORLD HEALTH ORGANIZATION, 2005 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved. 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 Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitations of its frontiers or boundaries. 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. The authors alone are responsible for the views expressed, which do not necessarily reflect the opinion of the World Health Organization or of its Member States. COVER: Remote sensing image of the area of the world that includes the Eastern Mediterranean Region. Cover image produced by the Canada Centre for Remote Sensing, Ottawa, Canada. (NOAA AVHRR Composite) Reproduced with permission Cover designed by Ahmed Hassanein, EMRO Printed on acid-free paper Printed by Dar Mourad for Printing, Cairo, Egypt ,)'~lv m~ tt _. ' UI f. ,1 . . . Eastern Mediterranean Health Journal Vol. 1 0 Nos 1/2 January/Janvier 2004 March/Mars La Revue de Sante de la Mediterranee orientale J\i.11 iJ j~ / .1-L.,t 'I'/' IJ\~.WI , .,,..!,lall .ili,l,1 J1,H I ..r JL.o Contents Letter from the Editor ................................................................................................................................... 4 Research articles Hepatitis B infection among Iraqi children: the impact of sanctions H.Y.M. Ali ................................................................................................................................................................ 6 Correction. Relationship between depression and non-adherence to anticoagulant therapy after valve replacement ................................................................................................................................................. 11 Supplementary feeding of malnourished children in northern Iraq S.Y. Agha ............................................................................................................................................................... 12 Pakistan's experience of a bioterrorism-related anthrax scare K. Ahmad, A.S. Di/, B.M. Kazi, N. Us-Saba, J. Ansari and K. Nomani ........................................................ 19 Anthrax: pathological aspects in autopsy cases in Shiraz, Islamic Republic oflran, 1960-2001 S.Z. Tabei, A. Amin, A. Mow/a, S.A. Nabavizadeh and A. Razmkon ............................................................ 2 7 Cout des soins de sante de base dans une circonscription sanitaire en Tunisie A. Nouira, A. Bchir, M. Njah, B. Yazid et S. Bou Ali ....................................................................................... 3 7 Life expectancy and cause of death in the Kuwaiti population 1987-2000 M. El-Shaz/y, G. Makboul and A. El-Sayed ..................................................................................................... 45 Capture-recapture methods for estimation of fertility and mortality in a rural district of Turkey D. Asian, H. Ozcebe, M. Bertan and E. Karaaoaoolu .................................................................................... 5 6 Adolescents' use of health services in Alexandria, Egypt: association with mental health problems M. Afifi ................................................................................................................................................................... 64 Practice and awareness of health risk behaviour among Egyptian university students A. Rejaat ................................................................................................................................................................ 72 Opioid use in patients presenting with pain in Zahedan, Islamic Republic of Iran V. Rahimi-Movaghar, F. Rakhshani, M. Mohammadi and A. Rahimi-Movaghar ..................................... 82 Right heart haemodynamic values and respiratory function test parameters in chronic smokers M. Gulbaran, T. Cagatay, T. Gurmen and P. Cagatay ................................................................................... 90 Detection of cotinine in neonate meconium as a marker for nicotine exposure in utero N.A. Sherif, S.M. Kamel, O.S. Al-Ashkar, O.A. Sharaki, E.A. Seif and E.A. Hegazy .................................. 96 Growth charts of Egyptian children with Down syndrome (0-36 months) N.A. Meguid, A.I.S. El-Kotoury, G.M.H. Abdel-Salam, M.O. El-Ruby and H.H. A/i.fi ................ I 06 Fragile X syndrome: a clinico-genetic study of mentally retarded patients in Kuwait L.A. Bastaki, F. Hegazy, M.M. Al-Heneidi, N. Turki, A.S. Azab and K.K. Naguib ...... .. ............. I 16 Apolipoprotein B gene polymorphisms in people in the East Mediterranean area of Turkey L. Tamer, K. Tanriverdi, B. Ercan, A. Unlu, N. Sucu, H. Pekdemir and U. Atik ..................................... 12 5 Improved serum HDL cholesterol profile among Bangladeshi male students during Ramadan fasting M. Rahman, M. Rashid, S. Basher, S. Sultana and M.Z.A. Nomani ......................................................... I 31 Ischaemic stroke in Jordan: a 2-year hospital-based study of subtypes and risk factors Y. Bahou, H. Hamid and A. Hadidi ................................................................................. .. Prevalence of atrial fibrillation in a primary health care centre in Fars province, Islamic Republic of Iran 138 F. Habibzadeh, M. Yadollahie, M. Roshanipoor and A. Boroomand Haghighi ............. ........................ 14 7 Frequency of Yersinia species infection in paediatric acute diarrhoea in Tehran M.M. So/tan-Dalla/ and K. Moezardalan ...................................................................................................... 152 Quinine therapy in severe Plasmodiumfalciparum malaria during pregnancy in Sudan I. Adam, O.A. Mirghani, O.K. Saed, S.M. Ahmed, A.A. Mohamadani, H.M. Ahmed, C.D. Mackenzie, MM.A. Homeida and M./. Elbashir ................................................................................. 159 Anopheles arabiensis: abundance and insecticide resistance in an irrigated area of eastern Sudan Y. El-S. Himeidan, M.Y. Dukeen, El-A. El-Rayah and I. Adam ................................................................. 167 Characteristics of tuberculosis patients in Yazd province, Islamic Republic of Iran, 1997-99 M.H. Safari and A.B. Kalantari .. .... .. .. .. .. .. .. .. . .. .. .. .. .... .. .. .. .. .. .. .. . .. .. .. .. .. .. .. .. .. .. .. .... .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .... .. .. .. .... . 1 7 5 La fievre typhoi'de au nord du Li ban : etude sur 8 ans ( 1992-1999) utilisant le test de Wida! M. Hamze et P. Vincent .................................................................................................................................... 180 Visual outcome of extracapsular cataract extraction and intraocular lens replacement in leprosy patients A. Derakhshan .................................................................................................................................................. 187 Distichiasis and dysplastic eyelashes in trachomatous trichiasis cases in Oman: a case series R. Khandekar, S. Kidiyur and A. Al-Raisi ...................................................................................................... 192 Reviews ..J' )1 ..:,il.Q$.W:,.o) ~I lk,:. .,j_:,! ~I ..:,iL..., J',,.J.I ::,~ ~ ..'.i.11-\.? .::, ................................................................................................................................ 198 The district health system: a challenge that remains B.T. Shaikh and F. Rabbani ............................................................................................................................ 208 Report Development of the Regional Malaria Training Centre in Bandar-e Abbas, Islamic Republic oflran H. Vatandoost, A.R. Mesdaihinia, G. Zamani, R. Madjdzadeh, K. Holakouie, B. Sadrizadeh, H. Atta and P.F. Beales .................................................................................................................................... 21 5 Case reports Rothmund-Thomson syndrome in a young man without cataract involvement I. E.ljandiarpoor, S. Shamsadini and S. Farajzadeh .................................................................................. 2 2 5 Molecular basis of RhD-positive/D-negative chimerism in two patients S.S. Eid ............................................................................................................................................................... 228 Guidelines for authors .............................................................................................................................. 242 WHO sales and discount policy ............................................................................................................... 246 Eastern Mediterranean Health Journal M. Haytham Khayat MD, FRSH, Editor-in-chief Ahmed Ezzat Abdou BSc, DPH, PhD, Executive Editor Editorial Board Ibrahim M. Abdel Rahim MBBS, MPH&TM, MRCP Houssain Abouzaid MS (Chem Eng), MS (Sanit Eng), DrS Zuhair Hallaj MD, DPH, DrPH Mohamed Hussein M. Khalil MD, MPH, PhD (Biostat) Belgacem Sabri MD, MPA, MA (Econ) Abdel Aziz Saleh Dip (Hosp Pharm), Dip (Indus Pharm), PhD Kassem Sara MD, MAM Anna Verster MBBS, Dip Nutr M. Helmy Wahdan MD, DPH, PhD International Advisory Panel Dr S. Aboulazm. Professor of Orthodontics. Egypt Professor Y.H. Ahmed MA (Resp dis), MA (Pub health/ Com med). Somalia Dr Abdul Rahman AI-Awadi BSc, MD, MPH, Honorary FRCM, Ireland, Honorary Dr. Law, Korea, Honorary FRCS & P, Glasgow, FRCP, Edinbugh. Kuwait Dr Fariba AI-Darazi RN, MSc, PhD. Bahrain Dr M. AI-Nozha. 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 EI-Matri. Professor of Medicine. Tunisia Professor F. EI-Sabban BSc, MS, PhD. United States of America Dr A.H. EI-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. Reink0 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 DrC.Th.S. Sibinga FRCP (Edin), FRCPath. The Netherlands Mr Taoufik Zeribi Eng BSc, MSc. Tunisia Editorial: Fiona Curiel, Marie-France Roux, Alison Bichard 4 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Letter from the Editor The devastating earthquake in Barn, Islamic Republic of Iran on 26 De- cember 2003 was a profound tragedy inflicting great loss and suffering on the people. The world responded with help and Dr Hussein A. Gezairy, the Regional Director for the WHO Eastern Mediterranean Regional Office affirmed the commitment of WHO to provide necessary technical and material support to the Islamic Republic of Iran. This disaster served to illustrate what little control we often have, but at the same time emphasized the need to be prepared. Unfortunately, it is often the actions of people themselves that affect the health and well-being of others. In this issue we present two papers on the impact of sanctions on the health of children in Iraq. While sanctions are no longer an issue, sadly the beleaguered people of Iraq are now expe- riencing other health dangers as a result of the ongoing fighting within the country. It is to be hoped they will come through these troubled times and come to enjoy peace and stability. WHO continues to work to assist the country in its provision of health care for its people. Today we also face the man-made threat of bioterrorism and included here are two papers on anthrax, which has already been used as an agent for bioterrorism and remains a potential threat. Not only do people suffer from risks from outside, but they can endan- ger their own well-being by their actions and life styles. On this aspect, this issue contains papers on risky health behaviour among university stu- dents in Egypt, opioid use in the Islamic Republic of Iran, and respiratory function in chronic smokers in Turkey. It is reported that 7 million children around the world are born annually with severe genetic disorders or birth defects and 90% of infants born with such disorders are found in developing countries. Thus included here are a number of papers concerned with genetic conditions such as Down syndrome, fragile X syndrome and Rothmund Thomson syndrome and an Arabic paper on handicapped and mute children. These are just some of the papers published in this first issue of Volume 10. Other areas covered are communicable diseases (such as malaria, tu- berculosis, hepatitis, typhoid fever and leprosy), health systems and popu- lation health data. As ever, therefore, EMHJ presents an eclectic mix of papers from many countries both within and outside the Region, and we hope our read- ers will find much to inform and stimulate interest. --< . "' --< .!.. C· £ \. ~ t ·C:. ~ [ f. r 't::- (., ~ t t ~ c -t;.. i: 1 r c· c ·" · G, f ~· ~ t 1"· v. ~- i;. <;.: ,r- ~· r ~· ~ 1-~ .L: re:_. .'f,.. t f_ ·':: ·':: I. ~ 1). {, - '- \ L \r \ )0 ti_ y f [ "-· ~ ,:- -: ·,. - 'tr- 'tr- 'f \- \ Jo" ·G f· - ~: 'y..... --;· ~, "' r,. - "' - i- - .;::.. \ t (• ~. ~. -.L: ~ ;t: ,_ .~ 1- [ - ~ i' r. ~!) f' ~- r· c. ·,'t,c:.,: '!'_. '.L:.L: - - ~-~i: - t.'1....' c:..: { ,:;· -:~· ,. (..• ~ ', { C, - L· (:,: .C .~ ,~ ~' , - !;, . L t' -• t, '- ~ 0 t c_.. ' I.... C- . ' ~" ._ . 0 - l--· \t. ~· ,c,.. r . [ t -• G, f,\ -. - (<;; " I.... E ' ( . ... -~ . I.... x- 'L - :- .L: ~ r; . ' -:- "'- V C' 1· "' - f ,. (._ ' . !! 't .... ' "' ~ f O f. ,. - r, 1- 0 ·t ~ ~" ( r "' '[ ~ "' " ~ -t \ Yi- t .r -t '. " '- ·C " ,._. v --:· . -~ . .,, t ~ - . 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CD 3 s::: CD a. m iil ::::, CD !l) ::::, I CD !l) § '-0 C 3 ~ Q: p z 0 [/) ~ I\) I\) 0 0 .j:s. U1 6 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Hepatitis B infection among Iraqi children: the impact of sanctions H. Y.M. A/17 -$"" __,paili -½--()1 ..,_,'..pl .!.1 _,..1,:,- J-""' J J\.,JI -4-<J1 ..,..4--11 C t.:i.! jl y .J.s- .:.,'-!_,.'WI ~ ~ J::, :L..,,iJ,-1 .r' i a_i ;..U1 ..::Jl-J ,2001 _,,i Y-/ :.J\_,._:r J 2000 ~ Y-/ ~I J!. r"' J.:.! o _juill -J .,!.:J~ J ,..:,~I _,.]I Ji_..i.::,)'1 J.:.! ;jl:JI .,1 r-l-1 ..:.LJ., _, Jt.Y -.>-½--<Ji ..,.,4-=11 J _,,.. ~l:.-l.l J-.-- ,11 .J 9 _,....,.J• a........:Ji y J J;J.r. ,y....U, ~ )' ~1_, ~I ylf=l',i ~I ~I ,.;~ (1;:,l)i'} r-t/:14 .k;,;)1 ~ 9-\..;J.1 .3....tl.il1 .:.,l) .. :,-:,..1 J-".,.. _,l.1 JW..l.,,,1 ..,,. 74 ~1;..U' ~....J:. ..u; ,.J'yl -.,.;$Ji ..... Lr!")IJ .>W1; .JY' 4J• ..,..4-<l")J ._:'),\;JI t,___.i .,":Jj-J> .. :.,-~ 0-" J ·,/\.)', -;.i.,5:.11 ...... ~)lj ~· ~ u.,.. ~i .}S- 1996-1994 ,$'Is, ~ l L...,i ,..lo.l.!1 ._,. ,ii,.l;,-1~ --'r le. .l,w ~ 21 I--• ,~I -$'1..,.- o.)I..!.=...)' ~I;--;• ~l,1 J 62 \ ~ i...,.. i_., -' ~ '1 ...,------- I'" ~ I. .#I, ' . ,cJ.l wl...,;1 \U"i ..LS'J1 .___,I .•i)l \')',_;JI .wa:..J,1 ;J\5', ,,.-'w.JL ._,. l,,=. .,.,._ 4.,: 1.-. i •. ~J.1 ._,. ~~s.o 41 -~ .., "' •• ...s . . . ....... "'-: ...... l w' ., - ~ .... ,7~ ...... ~- ....... • .... Jw.1 ..;..;IS J .(l'.80.7} ~ .:i:,-' ,.s..l.l l.,i~: jWI ;;..L$J1 ..... ~")'J ,)W:,11 .J'S"_, (!'.14.5) JW..i ~ ~ .;.,...U • ,d·, ~I a!-11 j ,..:..t.,..WJI .-al; ..,; .; ~ .i_;, _ ,_il:;ll ~ ~.uJ l.... ·~.JJ< J1 ._.. 12 1.,,.1.1,! _ ;Ji ,- .) ~- _r•·-·····- - "-" -,- ./ I ,/ ........ 1, _. 't •• ....... J •-..,r " ~ .. ,},]1 ...J..;; o;..L..o! ._sjjl 986 Jl ~I _ w..:i ..IA, .;> ,.!lb, ._. •;...U.I ..:.,)1L,l,..t i...: '-' .. .r-t..r---,- -- .I .., ABSTRACT Effect of sanctions on hepatitis B vaccine availability and occurrence of viral hepatitis B among Iraqi children was studied. Between June 2000 and June 2001, families of patients attending the Public Health Laboratory, Mosul, for hepatitis B follow-up were screened. Enzyme-linked immunosorbent assay was used totastforHBsAg, HBaAg and anti-Hl3a. Wadiagnosed 74children born 1994-1998.as HBs.A.gcarriers. For 62 of 74 cases, parents had consulted vaccine centres promptly: 41 were not vaccinated and 21 had only one vaccine dose. HBeAg marker was positive lor9 (14.5%) and anti-HBefor 50 (80.7%). Parental reluc- tance was the reason for non-vaccination for 12. Vaccine shortages during the birth years of cases were documented, even after implementation of United Nations Security Council Resolution 966. L'infection par le virus de l'hepatite B chez les enfants lraqulens : Impact des sanctions RESUME L:effet des sanctions sur la disponibilite du vaccin contre l'hepalite Bet la survenue de l'hepatite virale B chez les enfants iraquiens a ete etudie. Entre juin 2000 et juin 2001, les famines des patients consultant au Laboratoire de sante publique de Mosoul pour le suivi d'une hepatite B ont fait 1'objet d'un depistage. La technique ELISA apermis la recherche de l'AgHBs, de l'AgHBeetde l'anti-HBe. Nous avons diagnostique 74 enfants nes entre 1994 et 1998 comme porteurs de l'AgHBs. Pour 62 des 74 cas, les parents avaient consults dans des centres de vaccination rapidement: 41 n'etaient pas vaccines et 21 n·avalent r~u qu·une dose cte vaccin. Le rntm,iutiur dll l'AyHBtH~tall po5ilir puur 9 patie11ll> (14,5 %) 1:1l l'anti- HBe pour 50 (80, 7 %). La reticence des parents etait la raison de la non-vaccination pour 12 enfants. Les penuries de vaccins durant les annees de naissance des cas etaient documentees, meme apres !'application de la Resolution 986 du Conseil de Securite des Nations Unies. 'Depal1ment of Microbiology and Immunology. College of Medicine, University of Mosul, Ninevah, Iraq {halsinde@yahoo.com). Received: 22110/02; accepted: 17103/03 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 7 Introduction Infection with hepatitis B virus (lIBV) is of global importance and is one of the major diseases of humankind. The scale of public health problems posed by HBV is large and over 250 million carriers exist worldwide. In developing countries, infants and chil- dren form carrier pools and infection oc- curs through mother-child transmission or close contact among children [/]. The probability of becoming a chronic carrier is substantially greater following infection during infancy and early childhood with in- creases in incidence of HBV-induccd seri- ous liver sequelac [2]. Hepatitis B vaccine has an outstanding record of satety and ef- fectiveness. The vaccine has been licensed since 1982 and the World Health Organiza- tion strongly urges all countries to use it in national immunization programmes. The cost of the vaccine, wars and sanctions have been obstacles to its introduction and to shortages in many countries. Before 1990, Iraq was a middle-income country with integrated public health ser- vices. The Gulf War and the subsequent sanctions imposed upon Iraq in August 1990 created a humanitarian crisis from the massive degradation of the country's infra- structure and the deciine in public health services [3]. Infectious disease control programmes were disabled and shortages of medicines and vaccines became com- mon because of che sanc-tions. Millions of people, especially children, women and the elderly, are still suffering from its conse- quences. The lifestyle of the Iraqi people has changed and a significant number of families have moved to rural areas to work in agriculture, where public health services are insufficient and shortages of medicines and vaccines are evidem. The oil for food programme was implemented by United Nations Security Council Resolution 986 in December 1996 to correct the humanitari- an crisis created by the sanctions imposed on Iraq since 1990. Mosul is the second biggest city in Iraq with a population of approximately 2 mil- lion. The main vaccine store of the Health Directory of Mosul is responsible for vac- cine delivery to the primary health care centres that vaccinate infants and children. The amount of vaccine received by the city depends on the amount present in the stores of the Ministry of Health. The de- mand of hepatitis H vaccine in Mosul is es- timated to be 250 000 doses per year according to local health records. A human- itarian crisis has been created by the sanc- tions imposed on Iraq since 1990 and infection control measures have been greatly damaged [ 4,5]. Health authorities are still working, however, through the screening of blood donors and other blood products to prevent parenteral routes of spreading IIBV. This has led to the diagno- sis of many acute or chronic carrier cases. The screening of contacts and relatives of infected cases has enabled us to identify more carrier cases. The aim of this study was to investigate the effect of sanctions in Mosul on the availability of hepatitis B vaccine for chil- dren and its impact on the occurrence ot viral hepatitis B cases among children there. Methods From June 2000 to June 2001, 74 hepatitis B surface antigen (HBsAg) positive carrier children were identified and evaluated. All were born during sanctions, between 1994-1998, and their age range was 2-7 years. It is policy at the blood banks to register the addresses of all blood donors and to 8 La Revue ae same ae 1a MM11erranee or1ema1e, vo1. 1u, N° ,r~. :.!UU4 notify positive cases of HBV infection for further evaluation. Health authorities also si.:1c1;11 i.:uul11,i.:ls am.I family 1111;:mlu;;rs uf these cases. Among 419 contacts and fam- ily members of 76 cases of HBsAg carrier blood donors and other high-risk groups whu iillt:mlt:J lht: Puulii.; Ht:<1llh La!Ju1alu1y, Virology Centre. in Mosul, North Iraq, the main viral hepatitis referral centre in that area, 254 children were screened for HBV iufc:1,;liu11. f1um thc:m, 74 HB:sAg pu:silivc: carrier children were identified and evaluat- ed. The vaccine cards of HBV-infected children were inspected and their parents wc:n: inlt:i-vicwt:d abuul lht:ir cu11:suhalium; at vaccine centres at the recommended time of vaccination. We recorded their rea- sons why the children had not been proper- ly v,41,;l;i11i1,Li.;u, Di1-Lo4 n,;g;,-.udiug Lin; amuuul ofHB vaccine in the main vaccine store and the number ofHB vaccine recipients during the birth years of our cases were also col- kctcd. The enzyme-linked immunosorbent assay technique was performed to test for HBsAg, HBeAg and anti-HBe markers. We u:scd Biotc:st kit:1 (Biotc:1t AG, Drcieich, Gennany) for HBsAg and Hepanostika kits (Organon Teknika. Boxtel, the Nether- lands) for hepatitis Be antigen (HBeAg) and a.nti-hcpatiti:1 Be (auti-HBe). The a.:1:1a.ys were perfonned according to the manufac- turer's instructions. Results In our study, 74 of 254 screened children (29.1%} were HBsAg positive. There was documentation that for 62 of our 74 cases (83.5%) parents had visited the vaccine centre at the recommended time of vacci- nation: 41 (66. l %) were not vaccinated and 21 (33.9%) had only 1 vaccine dose. Parental reluctance was responsible for non-vaccination in 12 of74 cases (16.2%). HBeAg marker was positive for 9 of 62 (14.5%) and anti-HBe for 50 of 62 cases (80.7%). Scrulugk slalus, birth year and cause of HB vaccine noncompliance for the 62 cases were compared to the quantity of vaccine receivea in Mosul during each birth yt:i-11 uf infoi..:Lcd d1iluren (Tablt:: 1 ). More children who were HBsAg positive were born in years with severe vaccine shortag- es fo Mosul (Figure l). Furthermore, the 11umbt:1 uf HB Vi1-l:cine doses that rcai..:hi.;d the city spiked in 1997, the year of the first shipment of food and medicines into Iraq following the implementation of UN Secu- rity Cuundl Reimluliun 986; there were Table 1 Serologlc status, vaccination uptake 1:md birth y•11rs uf 02 HDsAg carrier chlldren and number of hepatitis B vaccine doses received during 1994-1998" Variable HBsAg carrier children No. % Sero/ogle status HBeAg 9 14.5 Anti-HBe 50 80.7 Vaccination status Not vaccinated 41 55.4 Low uptake 21 28.4 Rirthy=r 1994 10 16.1 1995 17 27.4 1996 12 19.5 1997 8 12.9 1998 15 24.2 HB vaccine doses received in: 1994 40000 1995 6000 1996 80000 1997 130 000 1998 20000 • The city of Mosul demand of hepatitis 8 vaccine per year was 250 000 child doses. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 9 18 ! 1400000 16 /\ 1200000 14 I I 12 ~ 1000000 10 \ 800000 8 ~ 600000 6 \ ; 400000 --, ~ 4, ' " i 200000 I t 2 ... ! 0 0 1994 1995 1990 1997 1990 Birth years of HBsAg carrier children D No. of HBsAg carrier children .... Hepatitis B vaccine doses received per year Figure 1 Number of vaccine doses received during the birth years of 62 HBsAg carrier children (1994-199B). Annual demand of hepatitis B vaccine was 250 000 child doses. United Nations Resolution 9B6 was implemented in December 1996. fewer H BsAg positive children born in that year than in any other year between 1994 and J()QR (Figure l) Hnwever, the numher of vaccine doses received fell in 1998, the second year of sanctions. resulting in more HBsAg carrier children being born in that y~Rr Discussion Iraq is an area of intermediate endemicity of HBV infection f 6l. Prevalence rates of HBV infection have been studied through- out the country and among different occu- pations and the primary routes of transmission that have been proposed are intrafamilial, non-sexual and non-parenteral [7-9]. Among adults, the annual sporadic cases of acute and carrier hepatitis H have been mostly from unpredictable sources [9]. The HBsAg carrier rate among the nor- mal population was estimated to be 4.3% and the prevalence of anti-HBs was 30%. The frequency of HBeAg and anti-HBe among carriers was estimated to be 20% and 65% respectively f / 01; the majority represent a state of childhood infection with persistence into adulthood rat.her than new exposure to the virus [8-9]. High car- rier rates were detected among hospital workers and foodhandlers with the detec- tinn nf rlP.ltB hcpatiti!<. vira I infection among some carriers [II, 12]. HB V status among Iraqi children is not well studied but is thought to be similar to other Middle East- ern cnuntrics in that HBsAg carrier rates are high between I and 2 years of age and IIBeAg positivity peaks around the age of 5 years [7,13]. lraq was a pioneer among Middle East- em countries jn introducing the hepatitis B vaccine. The Iraqi Viral Hepatitis Commit- tee hoped that this vaccine together with other strategic,;. would control hepatitis R infection The importation of sufficient amounts of vaccines in the early 1980s al- lowed for the vaccination of high-risk ernnps. In the late I 9k0s. hepatitis R vacci- nation was introduced as a 'routine vacci- nation' as part of the Expanded Programme 10 La Revue ae sante ae 1a Mea1terranee orrentale, Vol. 10, Nu 112, 2004 on Immunization. Children who escaped vaccination or who did not complete the vi:11,;1,;im1.Liu11 ~i.:111.:<lult: l1ad 1:1 vt:ry low chance of vaccination later in life, because adult vaccination was obligatory only in certain high-risk groups. Aflc1 sa:nctiom;, crfurts wt:rt! made to maintain childhood vaccination pro- grammes, including hepatitis B vaccination, to prevent infectious disease occurrence t1111u11g children using tht! availabk: vaccine doses in the main stores. The breakdown of vaccination programmes was inevitable with the prolonged years of sanctions. Thcn:;forc, many childnm art: t:ither not vaccinated against hepatitis B or have es- caped one or two doses. Because of this situation, a new susceptible pool of chil- dren [1t1~ ueen <11.kJ.cu tu Lilt! existing ft!St:r- voir of adult carriers of hepatitis B. We found that HBV child carrier cases accumulated during sanctions. Our finding is supported by data documeutiug the dras- tic shortages of vaccine doses reaching Mosul in the birth years of infected chil- dren, especially before and after the launching of UN Security Cuu11i.;i] Rc:.ulu- tion 986. We have included only cases iden- tified through the policy of screening family members and contacts of infected blood donor:.; thi.; problem mi~ht be found to be more serious if a large-scale study were to audit hepatitis B vaccine uptake among children in the years of vaccine shortages. Non-completion of other vac- cine types was also recorded. Parental re- luctance may play only a small part in these escapes, and perhaps they are also the re- su It of sanctions because of the need to work in rural areas, far from vaccination centres, and not because parents were un- willing to vaccinate their children. More- over, the presence of HBeAg carrier children carries high risk for the develop- ment of serious liver sequelae and the in- creased tendency for transmission to other contacts. Some of these cases will become carrier mothers themselves and perpetuate the cycle of perinatal transmission, subse- quently expanding acute and carrier states and increasing the burden of liver disease in the country. In conclusion, the present humanitarian crisis in Iraq continues to smoulder, and takt:s a heavy Lo11 in human lives and health conditions. The oil for food programme designed by UN Security Council Resolu- tion 986 and implemented in December 1996 111<1y hav~ improvt:d the availability of some drugs and certain medical equipment but has not relieved the humanitarian crisis in Iraq. These economic sanctions for this prnlong~d p1;:riuc.l appc:ar to have devastaL- ing consequences. References 1. Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gas- trocntcrology c!inlca of North America, 1994, 23:437-55. 2. Beasley RP. Hepatitis B virus as the etio- logic agent in hepatocellular carcinoma: 1;:1µiuerniulogic considerations. Hepat- ology, 1982, 2:2Is-65s. 3. Popal GA. Impact of sanctions on the population of Iraq. Eastern Mediterra- nean htu1lth journal, 2000, 6(4);791-5. 4. Nutritional status survey at primary health care centres during Polio Immuni- zation Days in Iraq. Iraq, Ministry of Health/Un11ea Nations Children·s t-und/ World Food Programme, 1998. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 11 5. Report on nutritional status assessment mission to Iraq. Rome, Food and Agricul- ture Organization of the United Nations, 1993. a Report on the second intercountry scien- tific oroup meetin_q on liver diseases. Al- exandria, Egypt, World Health Organi- zation, East Mediterranean Regional Of- fice, 1984. 7 Trnik,m All et al. The epidemiology of hepatitis B virus among family members in the Middle East. American 1ournal of epidemiology, 1990, 132: 220-32. 8. Toukan AU. Hepatitis B in the MirtrllA East: Aspects of epidemiology and liver disease after infection. Gut, 1996, 38(suppl 2):S2-S4. 9. Ali HYM. Adult HBoAg carriorc: the pos- sible risk to carriers, family members and the community. Journal of the Bahrain Medical Society, 2001, 13(3):124. Correction 10. Omer AR, AI-Douri S. Viral hepatitis in Iraq (abstract). Sixth International Con- gress for VIroIogy, 1-1 Septemoer 1984, Sendai, Japan. 1984:23--6 11. Alwan AS, Omer AR, AI-Ani FS. Preva- lence of hepatitis B surface antigen and anti-HBs in health care personnel in Baghdad. Arab Journal of medicine, 1986, 5(5):4-6. 12. Ali HYM, Vassen SHA. Prevalence of hepatitis B and delta infections among hospital personnel in Mosul, Iraq. Qatar medical Journal, 2001, 10(2):51-3. 1 :1 AI-Faleh FZ et al. Seroeoidemiolooical of hepatitis B virus infection in Saudi Ara- bian children: a baseline survey for mass vaccination against hepatitis B. Journal of infection, 1992, 24:197-206. Relationship between depression and non-adherence to anticoagulant therapy after .. alve replacement. A.S. EI-Gatit and M. Haw. F,a~tern Mediterranean Health Journal, 2002, VuL 9 l\os 1/2, pages 12-19, The name of the first author ,houlcl read: A.M. Fl-Gatil in En~li,h and ..w,:. ~I ~I in Arabic. 12 La Revue de Sante de la Mediterranee orientale, Vol. 1 0, N° 1 /2, 2004 Supplementary feeding of malnourished children in northern Iraq S. Y. Agha' jl.,,J! J~ ~ 4.!.ik.JI ~ ~1..AI.I Jt.il,'JJ ~\ r~~\ jj,j ~ J, .i.,._. j2:, ,1 ..... i:.1 __ .1.1 -~ •• i_1,; A_L_Gr..:'J1 ,. ,--- -"'""'1......-!.\ . (~Su __l__._(~1 ... L..l. '..:l __..~ __ . ~~ ~- .: ~~~1 ..,:; .;:; i"' .,, .,_ _, ,.I UTI ~ - ' ........ _, - ..,;. - ', ' ...:.... _., M I "" I )jJ .:,:_ ... <._ JI Ll;.J..!I ,,) JLlb,)'1 ~l..1J'. .,.,,1.A.< ,:..,.)S _ij) ,-,1_,J1 JL...t. !,)J..,,~ ..WL.:. J ..;.;1_,,:..- 3J )-*"' 6 I _I . \1 ,t3,1 ' ' - --'1 ·, ' - . ·, ;, I • - ,, • " ' ,. . I ·t I_, 'I C:·-"_;p) _J ~'-=>' ['J~! I.J., -~) ·r' ) .:.:·:-,:J-,A-A ~"'!-_r' .)..l.tl- ..:;_r ~'-; -;;;-,,..;.I ..J_j_,--1 ..:," y ~'-"4-J - ' ' ._:,-_;i _:;)L; ~~' ~J,.s.__J1 ,j ~ jlo.'.o,':,11 ,.:_:,~- J ).Jr~ 7 ,_,_i_. ._r- -~I.;;,. J) 2001 _,;~/.,.,_;~I J ,_]~ .i:.,. ...::..,;l{"_~ .~i.:;.i\ ~~-')• .l-,b, 4J..._d1 jy, ~y ~-, ",i_rl-:0- .....,,__ __ \,G ~~ _),.,..; ~ .J,'·JI ~I,_) l,j\.4..!IJ L......._..'-;, ',Llb½l~-.5.J.l-;__;.h,..J.u,.J·,\11._..,.;\,'I ...,!,)'I,.~!~ ;1<JL.w)'',~')'µ, ... ) - ..I ..... ~- ..... .,I .J _,, • ,,~ ½ *, ,,_ ~ -· J" ~-,.A J-,::.- _)..i; ~! ~.:,~ \._L ~1L.ib~-. _...J ~J ~\e-L~ _,. J_: ._~""'"--·1 .J -..,:._1;l_~_:l'1 ~ ... ~ J.i,.. -~-)~fl ~,I J •~<o._)~\ o~ ~ ~l J~ ~-~ '½)~ .,i ,U~ \\~\ .:_.17"-t ..Lt! ,:.L.,\;..0 11 ~r"' ~1....ib~rl ~~ I I ~ • '1...l, -1.k _ ,. \] •, II / 11 n • ·~ ..... ~:Lr;_..~~--:,...,,:_,-.. ) . L'"'IJ ~ '~ ---~J_,,t-:-~· ~1- ~: .... ~'-..,.._...._~_} t}_) .... ~ ~.: ABSTRACT The effectiveness of the supplementary feeding programme for malnourished children aged 6 month:s to 3 years in Dohull. µiuvir ''-''-', , ,ur U 11:m, Iraq was evaluated_ Tne enrolment cntenon was child weight ~ 2 standard deviations below standard weight-tor-age. Children enrolled in the programme in January 2001were followed over 7 months. Children received high-protein high-energy biscuits in the first month and a monthly child ration for preparing soyabean mix throughout. Their families received food rations in the first 4 months. Improvement was noticP.rl for flil r:hilrlri:m, r,::rrtir1Jlarly in th,:, fin;:t month, Problems with tho rationc and within the growth monitoring units resulted in significant drop-out. Use of standard growth charts may be a way to overcome this problem. High-protein biscuits should be distributed throughout instead of the mix. t.:alimentatlon supplemenlaire des enfants malnutrls dans le nord de l'lraq RESUME L:efficacite des programmes d'alimentalion supplementaire pour les enfants malnutris ages de 6 mois a trois ans dans la province de Dohouk (nord de l'lraq) a ete evaluee. Le critere d'admission etait un poids de l'enfant en dessous du rapport po1ds-age standard de 2 ecarts-types au plus. Les enfants inscrits au programme en janvier 2001 ont fail l'objet d'un suivi pendant sept mots. Les enfants ont re-;:u des biscuits a ha.ute 1.,, ,.,u, r,.,rut8ir 1iqut< el energetlque penaam 1e prem rer mo1s et une ration mensuelle pour la preparation d'un melange de graines de soja pendant toute la periode. Les families ont re9u des rations ali mentaires pendant les quatre premiers mois. Une amelioration a ete notee chez taus les enfants, notamment au cours du premier mois. Des problemes avec les rations et au sein des services de surveillance de la croissance ant entraine d'import.intes rlAfP.ctirm<: I 'utili-;gtion cle oourbos dg croissance standard peut ctro un moyen de surmonter ce probleme. Des biscuits a haute teneur en proteines devraient etre distribues pendant toute la periode au lieu du melange. 'Department of Public Health, College of Medicine, University of Dohuk, Dohuk, Iraq. Received. 26/06/02; accepted 20107/03 Eastern Mediterranean Health Journal, Vol 1 O. Nos 1 /2, 2004 13 Introduction lmprnvcmcnt in the nutritinnal status nf young children reduces morbidity and mor- tality f J,2]. Recognizing this fact, in 1994 the World Food Programme, in coordina- tion with UN!CCr and the dircctorntcs of health in Northern Iraq, initiated a supple- mentary feeding programme (Si-:P} for children under 5. Si nee then the pro- gramme has 61.:cn evaluated through a nu- trition surveillance system set up in all the primary health care centres involved in the SFP as we!! as through UNICEF-sponsored Regional nutrition surveys conducted every 6- 12 months l3J. This study is aimed at the -::valuation of the SFP in Dohuk province. Methods The study was conducted at the primary health care level under the supervision of the Dlrcctorute of Health and UNICEF. Af- ter the simple random selection of 9 (15%) of 62 primary health care centres which have growth monitoring units, the evalua- tion study started in Dohuk province on l January 200 l. Two of the 9 units were lo- cated in urban areas, the rest in rural areas. The growth monitoring staff of these cen- tres, plus I supervisory mobile nutrition team, were retrained in a 3-day UNICEF- sponsored course. Retraining of growth monitoring staff is a routine process, done almost every year. The SFP routinely consists of assessing the nutritional status of children aged 6 months to 3 years according to weight-for- age criteria. Children are weighed wearing light underclothing and without shoes. Readings arc taken to the nearest 100 g. Standard scales, model MP25, were sup- plied by UN lCEF. If weight is ;:::: 2 standard deviations (SD) below the standard weight- for-agc, then the child receives a wcckly ration of high-protein high-energy biscuit (0.8 kg/week) for the next month. The bis- cuit contains \\'heat flour, soyabeans, glu- cose, vegetable oil, multivitamins and minerals. At the same time, the child is reg- istered to rccchc, over the next 7 months, a monthly child ration of 5 kg soyabean flour plus vegetable oi! (0.6 kg) and sugar (0.6 kg) for making a high-protein high-energy mix. The family should, theoretically, also receive 4.5 kg vegetable oil, 3 kg sugar, 3 kg pulses and 13 kg rice monthly. This family ration is for the first 4 months only. Food rations are received from a ration agent and not from the gro,vth moniroring unit. At least once monthly, before distribut- ing any rations, the staff of the growth monitoring unit should sec all the children who arc enrolled and record follow-up in- formation, in particular the child's weight. Staff arc also supposed to give health and nutrition education to the mothers. The su- pervisory team and the author monitored and supervised staff throughout the period of the study. Height was measured for every mal- nourished child enrolled in this study (if a child\ weight is :::, 3 SD below standard weight-for-age, height is measured routine- ly). Children ·0 2 years were mea$ured lying dovm, and those :::, 2 years were measured standing, all without shoes. Shore infant/ child length/height measuring boards sup- plied by UNICEF were used. Readings were taken to the nearest 0.1 cm. If weight is 2: 3 SD below standard weight-for- hcight, then the child is referred to a hospi- tal nmritional rehabilitat.ion centre and admitted and given therapeutic milk plus medical care. During the current evaluation study, the growth monitoring staff werc requested w routinely record monthly height measure- ments for every malnourished child en- 14 La Hevue de ~ante de la Med1terranee onentale, VoL 10, N° 1/2, 2004 rolled in the SFP according to v.·eight-tor- age criteria. \V1;igh1-ror-agc, wcigh1-ror-hcigh1 and height-for-age standards used were those of the World Health Organization [ 4,5]. with unequal variances (SPSS, version 10) was used to determine the increase in wclgh1 or children rccdving high-protein high-energy biscuits compared to controls. Another aspect of the current evaluation was a 1-momh field trial w srudy chc in- crease in the weight of a sample of 27 mal- nourished children who were receiving high-protein high-energy biscuits. They were compared with 27 normal comrol children in the same age range (6 months to 3 years). The control children were visiting the primary health care centres for routine immunization or growth monitoring. Par- ticipants were selected by taking the first 3 malnourished and the first 3 healthy chil- dren who presented to the primary health care cernrcs involved in rhc smcty atler 20 .I une 200 I . In formed consent was obtained orally from parents, and there were no re- fusals. After 1 month, 2 malnourished chil- dren and 3 cornrols were losr to tollmv-up. Unpaired t-test for 2 independent samples Results Malnourished children enrolled in the SFP in January 2001 were followed up till July 2001. There was sil!nifi cant drop-out. par- ticularly in the last 2 months (Table 1). Throughout the study, we saw few children with weight ~ 2 SD below stan- dard weight-for-height or height ~ 2 SD below standard for age. The ,vasting or stunting in those children, therefore, shov..-cd no significant changes. Since the SFP basically uses the weight-for-age in- dex for the purposes of enrolling children, results of follow-up were constructed us- ing weight-for-age criteria (Table 2 and Figure 1). Eighteen children had been intro- duced erroneously into the programme, i.e. Table 1 Reduction in number of children attending the supplementary feeding programme at primary health care centres in Dohuk provi nee, Iraq, 2001 Primarv Januarv April Mav Julv health No. No. % No. % No. % care centre children children children children enrolled covered covered covered Barda rash 16 14 875 11 68.8 3 18.8 Seen 21 20 95.2 19 90.5 10 47.6 HoJava 9 9 100 9 100 8 88.9 Mangesh 16 15 93.8 14 87.5 4 25.0 Razgary 13 13 100 10 76.9 2 15.4 Dairabon 13 13 100 9 69.2 1 7.7 Moqibla 7 7 too 5 71.4 6 85.7 ();i,;mk 4"l 41 ~1.0 :1S 814 xi fi1S Heizel 39 36 92.3 26 66.7 0 0.0 Total 177 167 94.4 138 78.0 57 32.2 Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 15 180 7 "O 150 I ~ a, .cc "' 120 ~ ·;::; :, 0 I C: 90 ~ Q) "O ' C: 60 :, ci 30 z 0 Jan Feb Mar Apr May Jun Jul Figure i Number of underweight children more than 2 standard deviations below standard weight-for-age, January-July 2001 {numbers represent only children on the programme ;,- 2 standard deviations below normal weight-for-age at dates indicated, excluding drop-outs and the 18 initially normal chl tdren) they initially had normal weight-for-age med5ure111ents. and therefore "vcrc exclud- ed from the results in Table 2 and Figure I. The mean increase in weight for 25 children who received the biscuits for 1 month was 440 g, compared lo 315 g in- crease in the controls, a mean difference of 125 g (95%, Cl: -18.6 to 269.5). The t-val- ue was 1.772, therefore the difference was not statistically significant (P > 0.05). However, scrutiny of the data reveals that for 1 child enrolled in Sccri, weight de- crcascd 200 g over the first month while he was receiving the high-protein high-energy biscuit. The follow-up data showed that he was having persistent diarrhoea. Exclusion of this child from analysis makes the differ- ence statistically significant (mean differ- ence in weight increase of 152. l g, 950,.:~ Cl: 16.4 to 287.8, t-value 2.241, P ·< 0.05). Discussion The household nutritional stah1s survey of 1994 revealed a high prevalence of malnu- trition in Northern Iraq, with 25.8~10 of chil- dren being underweight (2 2 SD below standard weight-for-age) [ 6]. Since 1994, there has been a general improvement in the nutritional situation [3]. The nutritional sta- Table 2 Progress of 159 children enrolled in January 2001 on the supplementary feeding programme according to wi.,iyl11-rur-c1yi., criltni1:1 Month Weight below normal for age (standard deviations) <2.0 2.0-2.9 2> 3.0 Total no. No. % No. %, No, % January 0 0.0 150 94.3 9 5.7 159 February 51 34.4 92 62.2 5 3.4 148 March 37 29.1 60 thl.O 10 7.9 127 April 6:3 40.6 79 51.0 13 8.4 155 May 62 512 49 40.5 10 8.3 121 June 45 57,Q 28 35.4 6 7.6 79 July 31 59,6 17 32.7 4 7.7 52 Eighteen children were excluded as they were mitial/y normal weight bur had been erroneously enrol/eel m tile programme. .,, .. ~ ,1'-\ Jb.W' ,,.,;;,\...JI .J~I ,.,,!.l,..il ,~\1 ~. ,.k..,,_p.1 Jp ~I ;,J_.,1 16 La Revue de Sante de la Mediterranee orientale, Vol. 10, N" 1/2, 2004 tus survey of November I 999 indicated prevalence of underweight of 9,5%i [7). The same trend of general improvement is shown by the nutrition survei!lance data compiled by the directorates of health for growth monitoring units throughout North- ern Iraq l8]. Distribution of rations by UNICEF and the directorates of health nu- trition programme ·with the World Food Programme has contributed to improve- ments in the nutritional status of children [3]. However, the current evaluation re- veals, more specificaUy, the difficulties ex- perienced in improving the nutritional status of malnourished children through the existing SFP. The most prominent feature of the present study i:-. the significant drop-out, starting in May 200 I. and becoming quite significant in June and July . .From May on- wards, the family ration was no longer giv- en and families ~1f enrolled children were only receiving the small child ration, the value of which is much lower than the ex- pense of the trip from many villages to pri- mary health care centres. Despite the existence or good general food rations, families had become dependent on this ra- tion to justify their visit to the primary health care centre. Providing the special ra- tion for a malnourished child and ignoring the family may decrease food availability within the family, and make the mother less capable of breast-feeding her child. An important factor in causing drop-out from the SFP may have bc\'.'.n the poor pal- atability and difficult preparation method of the soyabean mix, the main item of the child ration. These were repeatedly men- tioned by parents during the course of the study. Some families used to feed the mix to poultry rather than their children. Another factor which contributed to drop-out from the SFP. was the instruction given by World Food Programme and Di- rectorate or Health mobile teams to the growth mnnitorin2 <;;t:iff to ,,.,·eigh i.:hildrc-n and n:cord monthly daia only if the ration arrived. Due to the irregular arrival of the ration, such instructions resulted in an in- terruption of the monitnring proccs~. Defi- ciencies and changes in the staff. coupled with overcrmvding in some primary health care centres, e.g. Heizel and Seeri, also contrihuted to thP dmp-rn.,l. In Hei:zcl, for instance, a trained female staff member took a long "motherhOl)d leave" and was replaced by an untrained health worker. Growth monilorine: nf Pnrol!c-d children and all other children was carried out not more than once or nvice weekly. The result was that. despite SLtpervision, :-.uch problems with the staff IPrl tn thP Prronc-ot1s enrol- ment of 18 children in the SFP. This is the reason for different totals in Tables 1 and 2. Other factors that could have increased the drop-out rate inrlndr: thP hot ,,veather of June and July, which may have discour- aged families from travelling. These months also coincide with the harvest sea- son. when rura 1 fami I ie~ ~rf' tno hm:y to bring their children to the growth monitor- ing units (hgurc I). The current child ration (apart from the hiJ.,:h-protein high-energy his:r11 it given in the first month) lacks adequate comple- mentary fnnd items like animal protein and micronutricnts, in particular iron and vita- min A [9L Iron deficiency :rn:iPmi:< :ind vi- tamin A dcficirncy arc considered significant health problems in the region [10.ll]. There Vias a relatively sk~p d.-,cline in the number nf underweight children more than 2 SD belov,· standard weight-for-age during the first month of the SFP (Table 2. Figure 1). This may he attrih11terl tn thP ef- fect of the high-protein high-energy bis- cuit. Apart from the first month, follO\v-up of malnourished children showed a gradual Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 17 and slow, rather than dramatic. improve- mf'nt in nutritional status. This is obvious for the period from February to May (Tabk 2 and Figure 1 ). Afterwards, the attendance rate to the growth monitoring units was too lnw fnr a l'.onclusion to he drawn. It may be concluded from the current study that the soyabean mix has less effect on weight gain than the biscuits, as the rate of decline in malm1tritinn was slower after the first month. Further evidence for the effectiveness of the high-protein high-energy biscuit ('.nmcs from the short follow-up study. Af- ter excluding I child who had persistent di- arrhoea. children receiving the biscuits over l month displayed significantly higher wcir:ht garn than c!mtrnl:c.. Lack of remarkable improvement, ex- cept for the first month of the SFP, could also reflect the emphasis by the growth monitoring staff on just giving the food ra- tion. Other activities, in particular health education. seemed to be considered of less importance, taking into consideration the difficulties they encountered. It is known that nutritional problems are multi-factorial with roots in many sectors of development such as health, education, demography. agriculture and rural develop- ment l2, 12]. Lack of a widely based inter- sectoral approach toward malnutrition may explain the slow trend of improvement. Recommendations Weighing of children enrolled in the pro- gramme and n:cortling or data musl us: done monthly, even if the ration arrives late. This wiH compensate for the incom- plete registration of follow-up data and re- duce the drop-out rate. Families should be educated on how to caITy out the process. Since neither the growth monitoring staff nor the families used the small growth chart present on the immunization card, its importance should be emphasized for mon- itoring the growth of every child under 5. Children enrolled in the SFP should preferably be given high-protein high- energy biscuits throughout the period of enrolment instead of the soyabean mix. It would then be possible to reduce the period of enrolment to 4 or 5 months because of the more rapid catch-up in growth. Staff at primary health care centres, particularly growth monitoring staff, can be very useful in providing health and nutri- tion education to all caregivers provided they are well trained and retrained, super- vised, supported and motivated. A broad intersectoral and integrated ap- proach involving all sectors of development is needed to tackle nutritional problems. Community participation programmes, us- ing for example the Women's Union and traditional birth attendants, arc needed to educate families on the use of growth charts and supplementary food items to tackle malnutrition. Acknowledgement The author is grateful to UNICEF Northern Iraq for supporting this research and allow- iug Ll1t: puLlicution Qf thi:s :study. References 1. King FS, Burgess A. Nutrition for deve/- op;ng countries, 2nd ed. New York, Ox- ford University Press, 1993:209-21. 2. Lucas AO. Gilles HM. Preventive medi- cine for the tropics, 3rd ed. London, Ed- ward Arnold, 1990: 216-42. 18 La RevLie de Sante de la Mediterranee orientale, Vol_ 10, N° 1/2, 2004 3. Programme review 1990-2000: sector review report, Notthem Iraq, health and nutrmon. Baghdad, UNtt;l:::t- Iraq, 2001. 4. Beaton G et at. Appropriate uses of an- thropometric indices in children. Geneva, United Nations System Stand- ing Committee on Nutrition, 1990 (ACC/ SCN State-of-the-art series, Nutrition policy discussion paper No. 7). 5. Measuring change in nutritional status: guidelines for assessing the nutritional impact of supplementary feeding pro- grammes. Geneva, World Health Orga- nization, 1983. 6. Annual report. Baghdad, UNICEF Iraq, 1994. 7. Nutritional status of children under five. Frbil, UNICEF Northsrn Iraq, 1999. 8. UNICEF Northern Iraq - Nutrition sec- tion. Analysis of Directorates of Health monthly statistics. UNICEF Northern Iraq nutrition surveillance bulletin, 2001, 5:3. 9. Complementary feeding: family foods tor breast-fed children. Geneva, World Health Organization, 2000. 10. Vasconcelos S. Anaemia in Northern Iraq. UNICEF Northern Iraq nutrition sur- veillance bulletin. 2000. 4:2_ 11. Othman Q. Studies on vitamin A defi- ciency in Northern Iraq. UNICEF North- ern Iraq nutrition surveillance bulletin, ?001, 5:3. 12. Park K. Park's textbook of preventive and social medicine, 16th ed. Jabalpur. India, Banarsidas Bhanot Publishers, 2000, 403 51. Training work5hop to develop nut.-ilio11 ::.urveillanc;e c;apabllitle.s of Member States to improve the monitoring and evaluation capaci· ties in nutrition programmes The World Health· Organization organized the above-mentioned training worksnop at the nigh institute ot r'ublic nealth, Alexandria University, Alexandria, Egypt from 7 to 15 March 2004 In order to develop nutrition survelllance capabilities of Member States and im- prove the monitoring and evaluation capacities in nutrition pro- gramme;i. The ODJecnve of the workshop was to prepare Member States to establish national nutrition surveillance systems with fo- cus on mlcronutrient deficiencies_ Participants from Bahrain, Islamic Republic of Iran, Jordan, Kuwait, Morocco, Oman attended this work- ::,t10p as well as representatives from me centers for Disease con- trol and Prevention, Atlanta and the United Nations Children's Fund. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2.2004 Pakistan's experience of a bioterrorism-related anthrax scare K. Ahmad, 1 A.S. Oil, 1 B.M. Kazi, 1 N. Us-Saba, 1 J. Ansari' and K. Nomam"I 19 ,_/'{ y _,,.)1 yl.A .i1/4 ~ ;., ;i•_,;1..1 o _,J:1 ,y J J,-1 _; IJ~~ i _?" ..J~ ..llGc- ,._.;). • .a,r J.-~ 1.i· ...... J./ JY ,..;j!S _,,,. :r- ._....,,.--"' ,J.:,-¼'-- ;1.n , ......... i µ ;.,,.,... 2001 _.,..j_,.:,/ .)U.:l ~-<_,.!.. .:.,.,,, ,; ;,ill ._!')'..:,,:.. JL; .. S\ .~1.,1 !"')'-! J '---4iJ ...,,~ _,]I .._...l1 ~ :u~I , . . .~ .:.,l.,:.i ... u_: -¥1 • .,...;,., ,:_1.,} JI.!,:,~ Ub: 1;..l...a.o 194 ,_;,,,.,- ~ 230 .2002 ...,-)<>/J1~1_: .st .... J1 ~ 1..;,,,.; -,,..0, ..,.L,,;..,.:,\'1 .,.. •• ~; ; ......,!,.1 . ~ ..s .::.1.. 1 .:L -...;;.!-I :, , ~. ~i...) .,.. .::.,LA.!1 - J .., _, -~ -- _.,, -· ..F--· -...5"- _7- ...... ,,J~....i'li,,, ........ j' _., 1_,;4 ,.?}' ~ 1.J-' ~ 141 ~I ,j1)-1, ~~ J\.s.\11 j.s- d+I ~ 1Jj .,S..U J -4!.-¼_,J\ ;_:_,,k]IJ ,____ " • fS- ~\ ,i ._s' ..,:__,, .,_.,'j, JL-:....): _,: ..-... lh 1,')\...:.',;1 ._.,,U. l:,. .::.,1.....:!l ~ ~L..a.,;. .,.,. uj'~\J .,::.A, ...,,,,Ji ... .. r - ~ _,, ~ ... ":""" ~ ....... . .. I..,, ..,. - - .. r-- ~, ~ .;.,I.:: ..;:_l·, ._,. 62 ,.._..\ J..u ,~i .i. :,/J.; . .__; _ill .:..,\:, ;-_........J ~I ~W-1 , ....... ;1.,.,_ . U 1...,,:, ._.,."" \,, ~--- .,,-------- -· .J- ·, J ., J r--- .. ~ - _, .., ., . .. ?,, -- "-! #' e:J..i.l ,:' J_,1,l ,;:i_. ii.;.,,,,,-~ o,J~i ,.:.,l),,i;;..J.~ ~I ..:.,\.ii_,;..·,~ ..l.lJ ,"-! ...:.,1.;)i1 ~ ·"'·-~' ..::.,1..,. A-1! ~ ,.:,~1 _......_...,,..)WI,.,,-.:;.....;...., .\~1 1, .:.,i 1..,: ,rLi ;;_,._;,; J..\Z' ;~,) :;_;, _1l r J~ • •.r-""' ._!) ""r ~ \ J ~ ~- ' .- , • Ir,,,'., ~, -- , r ,r- • J- •I.: ,L' • .1 \ ...;, 4 1.: J:;, ~ .di :,I.).\ ....,. ·~1....::JI .-1.ki ;.i.; .Ii. ~ ..I ~ •, .. r-· "'1r'"..,,, . , r ~ _,,. L '-' '· t.....· ./ ...., ABSTRACT From November 2001 to March 2002, the National Institute of Health, Islamabad, Pakistan, received 230 samples from 194 d1tterent sources for analysis ror anthrax spores. The5e 5e1mple5 were taken from letters/packages suspected of containing anthrax and from individuals exposed to them. When cultured on sheep blood agar, 141 samples yielded growth suggestive of Baell/us species. On the basis of growth characteristics, absence of beta-haemolysis, absent or doubtful motility and morphological charac- torc of tho iaolatm: on Gram stain, 62 isolatos wore considerod suspidou\l Anrl wArA inoculAted into guinea- pigs. Inoculated animals remained healthy well beyond the required observation period of 5 days. All the samples were therefore reported as negative for B. anthracis. Systems for handling and analysing suspected anthrax-contaminated materials are discussed. Experience d'une alerte au charbon llee au bioterrorisme au Pakistan RESUME De novembre 2001 a mars 2002, l'lnstitut national de la Santa d'lslamabad (Pakistan) a rec;u 230 echantmons de 194 sources differentes a analyser pour detecter la presence de spores du charbon. Ces echantillons provenaient de lettres/paquets suspectes de contenir le bacille du charbon, et d'individus exposes. Lorsqu'ils ont ete mis en culture sur gelose au sang de mouton, 141 echantillons ont produ1t une croissance faisant penser a des especes du bacille. Sur la base des caracteristiques de la croissance, de !'absence de beta-hemolyse, de !'absence de motilite ou de son aspect douteux et des caracteres mor- phologiques des isolats a la coloration de Gram, 62 isolats ont ete consideres comme suspects et ont ete inocuh:t5 a de5 ,;obaye5. Le5 animaux inoc;ule::, ::.ont restes :,ain:, bien au-dele. do In periode d'obeorvation requise de 5 jours. Taus les echantitlons onl done ete declares negatifs pour B. anthracis. Des systemes pour la manipulation et !'analyse des materials suspectes d'etre contamines par le bacille du charbon sent examines. 'Public Health Laboratories Division, National Institute of Health, Islamabad, Pakistan. Received: 11/06/02; accepted: 18108/03 20 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Introduction D1.:s1.:ribed as a disease ofamiquity, anthrax is primarily a zoonosis predominantly af- fecting sheep, goats, cattle and other herbi- vores from which man is secondarily i11fc:uc:u [/]. Caused by a Gram-positive, spore-forming bacillus called Bacillus an- thracis, the human disease occurs in 3 main clinical forms: cutaneous anthrax, inhala- Liu11 (ur pm:umunk) amhrax and gas- trointestinal anthrax. The cutaneous form is the most common and carries the least mortality while inhalation anthrax. is much less common buL is almost l 00% fatal if untreated [2]. Because of the long life of its spores and the fact that the spores can be prepared in bulk iu vuwder form and can be used as a dispersible aerosol, anthrax has long been considered an ideal weapon for biological warfare f 3]. Although no major deploy- meut of 11HLl11 a11. u~ a biological weapon has been recorded, the Japanese used it in the Manchurian War in the early l 940s [2] and there is evidence that during the Second Wo1hl War, lhc Allks came close to using anthrax. 'spore bombs' against the Ger- mans [4]. Recently. there have been widely publicized reports of letters containing an- thra"" :i.p01.:!!i \Jciug mailed lO individuals and organizations in an apparent spate of terror- ist attacks that arc analogous to explosive 'letter bombs' that are used to target indi- viduah, [1). Since the September 11 200 I terrorist attacks in the United States of America (USA), there have been a number of inci- <lc11Ls uf authrax-rdaLcd bioterrorism in rhc USA and other countries of the world. ln Pakistan, the first package suspected of containing anthrax was found in Islamabad in late October 2001. and was followed by similar incidents throughout the country during subsequent months. Soon aficr the first incident, the National Institute of Health in Islamabad was designated as the National Reference Centre for the diagnosis and management of anthrax. This paper documents the experience of the National Institute of_Health in handling and analysing samples of suspected anthrax from letters/ packages and from the individuals exposed to them. Methods Sample collection and transport Samples collected were of 2 types: non clinical/environmental samples and clinical samples. Three types of non-clinical and environ- mental samples were collcclcd: the sus pcctcd powder; the envelope, letter vr package in which the powder was re- ceived; and wipe swabs taken from inani- mate objects or i,:urfaccs thought to have been contaminated by the suspected pow- der. Universal precautions were followed according to the National Institutes of Health and World Health Organization (WHO) guidelines for the collection and transport of contaminated samples [5-7]. Clinical samples collected from exposed individuals con~isted of nasal swabs from anterior nares and skin swabs from areas of skin in contact with the suspect powder or the letter, envelope or package. Wherev- er po!,,;;iblc, swabs were collected in dupli- cate, 1 for culture and 1 for direct staining. Blood samples, rarely indicated, were taken directly into blood culture bottles using standard protocols for blood culture. Detailed instructions were issued to all rdcvant people about the proper transport of samples, preferably through a personal courier [SJ. The senderi; were ini.tructcd to ship the sample containers sealed in an out- er container made of non-porous material. Eastern Mediterranean Health Journal, Vol, 10, Nos i/2, 2004 21 This was enclosed in yet another container made of strong thick plastic or metal. Specimen handling in the laboratory Samples were processed according to the USA Centers for Disease Control (CDC) guidelines [7], All procedures, from the opening of sample containers to the issuing of the final report, were carried out inside a class II biological safety cabinet (BSL-11 ). in a separate room specified for this pur- pose. On!y designated members of labora- tory staff handled the samples using protective clothing, gloves, masks, etc. A!l items, including instruments and dispos- abks used in the test, were discarded into a container of ! Mr, sodium hypochlorite. Subsequently, reusable items were autll- claved and disposables were incinerated. After finishing work, all surfaces were wiped with hypochloritc solution. Non-c!inicallenvironmenta! samples For analysis of powders, a small amount was suspended in 1.0 mL sterile distilled water in a sterile universal container, then 0.1 ml of suspension \Vas inoculated onto sheep blood agar plate and incubated at 37 °C for 18-24 hours. For analysis of envelopes, the envelope was opened and any powder inside \vas cultured as abo,·e. The letter \vas pulled out and a piece 2.5 , 2.5 cm ·was cut out, pref- erably from an area free from \\.Ti ting. I he piece was transferred to 1.0 ml of sterile distilled water or saline and shaken for about 2 minuks. Then 0.1 mL of this fluid was inoculated on a sheep blood agar plate and incubated as above. For analysis of soil or dusts, about 2.0 g of material was suspended in sample pro- cessing solution (phosphate buffered saline with 0.3% polysorbatc-20 or normal sa- line), shaken vigorously and left for 2- 3 minutes. The supernatant was divided into 2 aliquots, l of which was heated at 65-70 °C fi.)r l O minutes and allowed to cool, then 0.1 mL from healed and unheat- ed aliquots ·was streaked on sheep blood agar and incubated as above. Environmental s,.vabs were placed in 3 mL of sample processing solution or nor- mal saline and shaken. The fluid was divid- ed into 2 aliquots, l of which was heated at 65-70 °C for 10 minutes, then 0.1 ml from both aliquots was streaked on sheep blood agar and incubated. Clinical samples Swabs from anterior narcs and skin \Vere streaked onto sheep blood agar plates and incubated for 18-24 hours. From the scc- und swab (or frum the same swab used for streaking), smears were made on slides and stained with Gram stain for direct micro- scopic examination. Rlood cultures were incubated for up to 7 days. From those showing growth, sub- cultures ,vere made on sheep blood agar. Analysis of cultures After incubation for 18-24 hours, inoculat- ed plates showing growths were examined for colony characters, haemo!ysis, mor- phology, spore frirmation, motility and cat- alase test. If these tests indicated growth of Bacillus species, the isolates \Vere then subjected to tests for species characteriza- tion. A 3-step strategy was adopted for identification of suspected isolates. Level A Cultures yielding large (3-5 mm) colonies especially those with ground-glass or me- dusa head appearance, which \Vere non- beta haemolytic and on Gram stain showing large spore-forming bacilli in chains, were non-motile and cataiase posi- tive, ,vere considered as suspicious and subjected to fu.1iher (level B) tests. 22 La Revue de Sante de la Mediterranee orientale. Vol. 10. N° 1/2, 2004 Level B Representative colonies from the above plates were subcultured on MacConkey agar, bicarbonate agar for capsule forma- tion (trypticase soy agar containing 0.8% NaHCO" incubated in a candle jar) and a gelatin stab culture. I\foeller-Hinton agar was inoculated in duplicate, 1 for penicillin susceptibility ( l O U) and 1 for the pearl- string test. For the pearl-string test, a heavy single streak was made on Mueller-Hinton agar. A l O U penicillin disc was applied over the streak, which was overlaid with a cover- slip. After incubation for 3-6 hours, growth from beneath the coverslip was ex- amined microscopically for the presence of strings of spherical cellular forms of the organism. Presence of such 'strings of pearls' is considered characteristic of B. anthracis [8], B. anthracis does not grow on Mac Conkey agar, forms mueoid colonies on bi- carbonate agar [9], gives an inverted fir- tree appearance in gelatin stab culture after a 2-3 day incubation, is susceptible to 10 U penicillin and may yield a positive pearl- string test. An india ink preparation was made from any mucoid colonies on bicar- bonate agar and examined microscopically for capsule formation. The capsule appears as a well-defined clear zone around the ba- cilli. Also a smear from mucoid colonies was stained with polychrome methylene blue (McFadyean reaction) and examined microscopically for capsule formation l7,JO}. A presumptive identification of B. anthracis could be made on the results of these tests, Level C For final confirmation, all presumptive pos- itive cultures were inoculated into guinea- pigs. Guinea-pig is highly susceptible to B. anthracis. Inoculation of 0.5 ml of a 24- hour broth subcutaneonsly ,viii usually kill the animal within 48 hours [ !!]. Bacilli can be seen in a direct ~mrnr Crom heart blood of the dead animal and can be isolated from blood and other organs [ / / ]. Cotonies were emulsified in 1.0 mL of sterile normal saline to give a slightly turbid suspension. Then 0.5 ml of this suspension (or 0.5 mL of an overnight broth culture) was injected sub- cutaneously over the thigh area of each of2 guinea-pigs. A third animal was injected with 0.5 ml of sterile saline as control. An- imals were observed for a minimum of 5 days, To speed up the results, all primary cultures giving suspicious growth (level A) ,vere also directly inoculated into guinea- pigs along with level B tests. Smears were made from swabs, pow- der suspensions and from suspicious growth on blood agar and stained with mal- achite green (5%, aqueous) for 45 minutes and counterstained with safranin for the demonstration of spores. Malachite green stains the spores green while the bacilli are stained red by safranin [7]. Results Over a 5-month period from November 2001 to March 2002, a total of230 samples from 194 sources were sent to the National Institute of Health for analysis. Samples \Vere sent from all parts ot the country. Ta- ble I lists the organization8 and individuals who were recipients ot parcels/letters sus- pected of containing anthrax. Details of the types of clinical and non- clinical samples proce~sed are given in Tu- ble 2. When cultured on sheep blood agar, 14 l samples yielded growth suggestive of Bacillus species (Table 3 ). On the basis of growth charaoteristice,, absence of beta haemolysis, absent or doubtful motility and morphological characters of the isolates on Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 23 Table 1 Recipients of parcels/letters suspected of containing anthrax Type of organization No. of samples Foreign missions 18 Foreign media organizations, banks and multinational corporations 17 Institutions/universities/hospitals 61 Government officials 48 Individuals/miscellaneous Total 50 194 Gram stain, 62 isolates were considered suspicious for 8_ anthracis and were there- fore inoculated into guinea-pigs. Inoculated animals remained healthy well beyond the required observation period of 5 days. All 1ao1e, rypes of samples collected for analysis of suspected anthrax Source No.of samples Site of clinical samples Anterior nares 42 Skin 26 Blood ? Culture for identification 1 Total 71 Source of non-clinical and ,mvirnnmenta/ samples Powders• 135 Swabs from inanimate objects/ surfaces 10 Papers, envelopes, packages, plastics 12 Miscellaneous 2 Total 159 Total 230 •Includes a few samples of wood shavings, hour or soil. the samples were therefore reported as negative for B. anthracis. None of the isolates yielded mucoid col- onies on bicarbonate agar, inverted fir-tree appearance in gelatin stab or a positive pearl-string test. However, for unexplained reasons a limited number of isolates wt:n:: found to be susceptible to penicillin. Discussion One of the most reliable criteria for the pre- liminary screening of Bacillus isolates for B. anthracis is non-motility of the isolate. Any Bacillus isolate exhibiting motility may be safely assumed to be a species other than B. anthracis. The reverse, however, is not always true as some strains of B. my- coides (B. cereus var mycoides) are also non-motile [12]. Susceptibility to gamma phage has been widely accepted as a reliable test of identifi- cation for B. anthracis [ 7]. However, a number of B. mycoides strains arc also re- ported to be susceptible to gamma phage r 13, I 4]. Experience at the Pakistan Nation- al Institute of Health during the present study has shown that, in the absence of supplies of gamma phage (which CDC has been unable to provide) or a polymerase chain reaction (PCR) facility, animal inocu- lation remains the mainstay of a definitive identification of B. anthracis. It is not un- common to isolate saprophytic members of the Bacillus group from the environment. In fact, they arc the commonest contami- nants in a clinical laboratory. But no other member of this group. except B. anthracis, will kill a guinea-pig within 48 hours when injected with a pure culture [II]. Our expe- rience also underlines the difficulties inher- ent in the definitive diagnosis ofanthrax by a routine microbiology laboratory. Without facilities for animal inoculation (or PCR or 24 Ll:t Awue cle Sante de la Mllditerranee orientale, Vol. 10, N" 1/2, 2004 Table 3 Results of cultures and animal inoculatlon with suspected samples ofanthrax Type of sample Type of Isolate Suggestive of Suggestive of Positive on guinea- Bacillus spp. B, anthraciB' pig inoculation (n=230) (n .. 230} (n=62) No. % No. % No. % Clinical samples 14 6 5 2 0 Powders 120 52 56 24 0 Environmental samples 7 3 1 <1 0 Total 141 61 62 'Zl 0 •Isolates with typical morphology on Gram stain, non-motile non-beta haemolytic, ,:-ata/as.,-po!llilivo. n "' total number of cultures tested. gamma phage), a presumptive diagnosis of B. anthracis based on inconclusive findings could have led to unforeseen complica- tions. It maybe no coincidence rhat since 11 September 2001, the USA has experienced a number of anthrax-related attacks with 5 deaths that were directly attributable to Lhesc: auacks. All died of inhalation anthrax; all but one received or had contact with let- ters containing anthrax spores [ / 5]. It has been speculated that Pakistan could also be a target for bimerrorism. Fortunately, in spite of a number of suspected incidents, this has proved to be mere speculation. It is well known that production of wcapons- grallt: anthrax is a highly sophisricaicd technology. Our experience underlines the fact that the capability to produce anthrax parcel/letter bombs is not easily available to a polcmial Lcrrorist; the only success of the perpetrators of these incidents has been to create an atmosphere of panic among the general public. Although the incidents described in this report proved to be hoaxes in every case, they nonetheless served to demonstrate the public ht:allh imphcauons of an actual or potential bioterrorism attack as well as the strengths and weaknesses of the systems in place to deal with it. The threats called for a prompt and coordinated response on the part of several government agencies, notably in health, law enforcement and in- fonnation. In spite of the fact that Pakistan has never faced a b10terronsm attack be- fore, its systems pcrtcmncd surprisingly well. Facilities for laboratory testing and prompt reporting were fully in place right after the first incident. In some cases, the law enforcement agencies not only investi- gated the incident but also collected and delivered the suspect letter or package to the testing laboratory from distant regions. Communication and coordination with the original recipients of the object and the gen- eral public on the one hand and the public health, the law enforcement and mass me- dia on the other, demonstrated the profes- sionalism and confidence with which the episodes were handled by the authorities concerned, particularly in the Mm1stry of Health and the National Institute of Health. Availability of a first-rate laboratory, Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2. 2004 25 backed by animal testmg facilities, made this task considerably easier. Conclusions It is concludod on the hasis oreetrong ,:cion- tific evidence that all the incidents of sus- pected anthrax parcel/letter bombs in Pakistan were hoaxes. Nevertheless, stan- durd operating procedures for Ji;;aslcr management in a bioterrorism setting should be formulated and their periodic re- view should be ensured. Isolates which are prnvi,ionally bbelled as B. anthracis on thc basis of presumptive tests should not be n:porlc<l unlc:c.s confirmed b:y a reference laboratory. It shou!d be noted that animal i11ocuk1tion. although no longer generally practised in clinical microbiology laborato- ries, still has a place in public health labora- tory practice in developing countries with Bearce resources. Acknowledgements The authors take this opportunity to grate- fully acknowledge the generous assistance and active participation of WHO Pakistan, during all phases of this study, both in the field as well as in the laboratory, particular- ly in tenm, of provision of cqwpment and supplies. A mobile laboratory provided by WHO under the Health Laboratory Support project played a pivotal role in hand.ling and transportation of suspected samples. Dr Khalif Bile Mohamud, WR Pakistan, and Dr Faizullah Kakar, WHO Epidemiologist, de- serve our special thanks for their valuable advice and guidance in this regard. The contribution of the following staff at the National Institute of Health is gratefully ac- knowledged: Mr Sohail Zaidi, l/C Immu- no!ogy and Virology Department, Ors A!taf Rosan and Zafar Toor, Epidemic Investiga- tion Cell, Dr Tvfohammad Hussain, 1/C Ani- mal House, and 't-.ir Mohammad Iqbal, 1/C Transport. \Ve are profoundly indebted to the following members of the laboratory staff for their invaluable technical help dur- ing this study: Mr Tariq Mahmood, Mr Mohammad Jamshed and Mr Abdul Basit. References 1. Bioterrorism alleging use of anthrax and interim guidelines for management- Urnted States, 1998. Morbidity and mor- t::?!ity WPPkfy TP[inrf 1 qqq, 4R·fiq_74 2. Terry C et al. Medical progress anthrax. New England Journal of medicine, 1999, 341:815-26. 3. Pile JC et al. Anthrax as a potential bio- logical warfare agent. Archives of inter- nal medicine, 1998, 158: 429-34. 4. Talaro K, Talaro A. Foundations in micro- biology. Boston, Massachusetts, WC Brown, 1996:582. 5. N1H/WHO. NIT/WHO guidelines for an- thrax. Disease control and surveillance, 2001 :3-5 b. Packaging prowcots ror morog1ca1 agents/diseases, Atlanta. Georgia. Cen- ters for Disease Control and Prevention, 2001 ( http://www. bt.cdc. gov.IL ab Issues/ Packaginglnfo.pdf: accGssed .29 August 2004). 7. Basic laboratory protocols for the pre- sumptive identification of Bacillus anthraci,5. Atlanta, Georgia, Centre3 for Disease Control and Prevention, 2001 26 La Hevue ae :;;ante ae 1a M801terranee orientale, Vol.10, NY 1/2, 2004 { http ://www.bt.cdc.gov/ Agent/ Anthrax/ Anthracis20010417.pdf: accessed 29 August 200-1). 8. Bailie WE, Stowe EG. A simplified test for identification of Bacillus anthracis. Ab- stract CBO. Abstracts of the general meet· Ing of the American Society fo,- Microbio/ogy, 1977:48. 12. Doyle RJ, Keller KF, Ezzelle JW, eds. Ba- cillus. In: Manual of clinical microbiology, 4th ed. W1whington DC, American Soci- ety for Microbiology, 1985:211-5. 13. Burdon KL. Useful criteria for the identifi- cation of Bacillus anthracis and related :::.pec;ie:::,. Jou111a.l of bae,/tuiuluyy, 1950, 71:25-42. 9. Meynell E, Meynell GG. The roles of se- rum and carbon dioxide in capsule for- rmition by Bacillus antflracls. Journal or general microbiology, 1964, 34: 153--64. 10. Parry JA, Turnbull PCB, Gibson JR. A colour atlas of Bacillus species. London, Wolfe Medical Publications, 1 983. 11. Wilson GS, Miles AA, eds. Tapley and Wilson's principles of bacteriology and immunity, 5th ed., volume 1. London, Arnold, 1964:1031. 14. Burdon KL, Wende RD. On the differen- tiation of anthrax bacilli from Bacillus cereus. Journal or mrectlous diseases, 1960, 107:224-34. 15. Update: investigation of bioterrorism- related anthrax. Morbidity and morlality weekly repol1, 2001, 50:1077-9. Public health response to biological and chemical weapons: WHO guidance This second edition of WHO's 1970 publication Health aspects of biological and chemical weapons includes information designed to guide preparedness for and response to the deliberate use of bio- logical and chemical agents that affect health. While noting that the probability of an attack with such weapons may be low, the guide underscores the magnitude of potential impacts on civilian populations and the corresponding need for publlc health authori- ties, in close cooperation with other parts of government, to de- velop contingency plans. For such plans to be effective, collaborative arrangements involving all partners have to be estab· lished and tested well before an incident or emergency occurs Recommendations and advice draw on the expertise of many spe- cialists around the world. The publication can be obtained from: Marketing and Dissemina- tion, World Hea Ith Organization, 20 Avenue Appia, 1211 Geneva 2 7, Switzerland (tel: +41 ZZ 791 2476; fax: +41 22 791 4857; email: bookorders@who.int). It is also available on line at: http:// www.who.int/csr/delibepldemics/biochemguide/en/lndex. html Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2, 2004 Anthrax: pathological aspects in autopsy cases in Shiraz, Islamic Republic of Iran, 1960-2001 S.Z. Tabei, 1 A Amin, A. Mow/a, 1 S.A Nabavizadeh 1 and A. Razmkon' 27 ~.:ii,,-!) ,;1~ _J (~~1 li....al1) cll e-! j" ..::.i'Jt:.- .j 6-?.'yyl.)1 .,...!Ji&.1.1 :~1 ;;~1 2001-1960 .:=, .ri-"'-1 L: ,....,L,a.) Ju.:.J1 ..J J..;..l.-,. .:.,"" ,._.,, /~'; :;., y ~ ~,-' j-J'• ..,.;.; ,~, ;: _,,...Jc1 jl :.a_..')IJ-1 ,.',,..;,,.'~-,~.a.!_; J·: • .,;, ..,,_.L,,- ..:;...L,....- ....,, _._...k]1 1.., .:-l-~ ,;,:,..icJ ,;,,J_i 1.u. J. ~W1 ,_JI 1_, .... ~ .. , ', .r- -- ..,/• ./ - s-- ~ ._, .r-y ....... .J ~ ' r- '----' ;J"...,._ 33 4-c:- ... J;S ,i...o ~· • ....., _\, ...:..,1 .,c...J\ 1')',.,;. (~~l ~ 1') .\.'J.;-1 ,..;;; ..;..,')'l,.. ._. 7-130 • - ' .I -- .... .I. -- L.r'~ • ..,, .... ..... ~ ""--· ........ ~ 1 ·~_,,->;,_,v- ~,J;, ~ ~,L..d..\ _ ~) ~~1L..l·1 oii ~~}.Y~,i ~ 1 ~ 1~"";-\J • ..'Jj _4-\ ;~1 ~\..;,_,.,\ 1. ;;_,1...,.,1 , _.., .-, '.JI jl.;;.YI ~ .,_!. ..;., Ji ,_,L.,.1 •<t JiS' Jj, . L, . ._.. '·, '.c ~ .. t:.\. , <" l ;;_, , --' · ~ ...... : 1 ....1- ...- • • r- ..., ....,.r.- , ..... l" -,-.;-- f'"''"' ~" 1 ~..,.,,..-- ~.:;;....;.~ ;_·~]_i ._,;;_,1_~--~--}·\ ~- .. _: ·-._;;-.._)~-~~~_;_'.;.,_:__,-A ~~ 1l.fa_: J..:~\ , ... : .. )~_, •• ,a.a1.JL- __..;;.,"µ1 '-5-.LJ..-1 ,-.--~~-fl :;_.1,). .. 1. ~I • ,.......,J.1 :;,,,. ",')'.;;,,. j L,._,,:, ,.._. .,_;;.;; ~ \11 .~. ' __.i:,;j1 J·I '.L, ;;_.L.:,1 ..:.,'1b- j Ww,, ~i ~ J> J .. i..,. 0 ~ .... ,..,;, ~OS .. M~ .. r . . .~-vJ.i. rte;!.-~ Jr'°' '-~u:- :- 7~_,~l ;;J-l.i ~Y- L: ~1 j~"'=" J ~~:-·1...; ~ 1~1 ~ 0~1 ~L~ J! ~~\ 1 ... ) 1, s..U ABSTRACT Anthrax, likti lutJtir i.;ulu,;i,;, :,;l ,uw:s d new epidem;c spre(ld in industrialized countricn, revealing some ambiguous aspects to the disease and providing new challenges to medicine. Shiraz University of Medical Sciences has records of 7130 autopsies performed in the past 40 years, 33 of which are anthrax cases. We reviewed all the pathology slides of these cases and classified the organs involved in a search for unr,;,cogni?Arl mir.m<::r.nr,ir. finrling!; The most common cause of death was sepsis, caused by organ in- volvement and direct cytotoxicity of Bacillus anthracis, in addition to its exotoxin production. Novel findings included hyaline membrane formation in respiratory system cases that is similar to acute (adult) respiratory distress syndrome and evidence of primary gastrointestinal involvement, showing the ability of the organism to pass the gastric barrier. Maladie du charbon : aspects pathologlques dans les cas d'autopsle a Chiraz (Republique islamique d'lran), 1960-2001 RE SLIME A l'instar de la tuberculose, la maladie du charbon connait une nouvelle poussee epidemique dans k,,;; pays ;ndustri::ili<:A<:, rAvP.l;rnt cP.rtRiM aspects ambious de la maladie et oosant de nouveaux delis a la medecine. L.:Universite des Sciences medicales de Chiraz a des dossiers de 7130 autopsies realisees au cours des 40 dernieres annees, dont 33 con cement des cas de maladie du charbon. Nous avons examine toutes les lames pathologiques de ces cas et avons classifie les organes atteints a la recherche de resultats de !'examen microscopique meconnus. La septicemia etait la cause la plus courante de daces, due a l'envahissement des organes et a la cytotoxicite directe de Bacillus anthrac1s. en plus oe sa production d'exotoxines. Les nouvelles decouvertes cornprenaient la formation de membrane hyaline dans les cas impliquant le systeme respiratoire qui est similaire au syndrome de detresse respiratoire aigue (adulte) et !'evidence d'une atteinte gastro-intestinale prirnaire, revelant la capacite du micro-organisme a passer la b<111 iere ga;<>trique. 'Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran. Received: 3010 7 /02; accepted: 09/01103 28 La Revue de Sante de la Mediterranee orientale, Vol. 1 O, N° 112, 2004 Introduction Anthrax, an m,:utc i11fi:i.;Liu11 caus1::li by Ba- cillus anthracis, is acquired through con- tact with anthrax-infected domestic animals, or anthrax-contaminated animal products [l,2], and ha:,; tl11:: puln1tial Lu bt: used in biological weapons [3,4]. While there is no clear evidence of direct human- to-human spread, the possibility has been dise-ussed [ 5, 6]. The disease is now extremely uncom- mon among humans but causes serious morbidity and mortality when encountered. The majority of desc1iptiu11:,; uf Lht: palhulu- gy of anthrax date from the end of the ninc- tee nth and beginning of the twentieth centuries. The preventive measures that were intcoduced at that Limt: l1<1vt: almusl eradicated the disease in some parts of the world and little attention has been paid to its epidemiology recently. Despite improved diagnostic and treatment Lt:dmiy_ut::,;, ,1.11- thrax, like other infections believed to have been eradicated, has emerged in a new epi- demic that has gained worldwide attention [7,8]. This ~crve:,; to remind w, ofou1 limit- ed knowledge about the disease and the need for better early recognition and diag- nosis that could result in more successful treatment of n:-~pirntory and gm,h i1: au- thrax. It is worth noting that in current practice complete autopsy of confirmed (and even suspicious) cases of anthrax is no longer rcco111mcndcd, in orde1 to J,;;- crease the risk of contagion [9]. As in other parts of the world, the num- ber of anthrax cases in the Islamic Republic of Iran markedly dccrcMcd in the laltc twentieth century, but individual cases are still occasionally reported [JO], especially among farmers and those who have direct contact with dome:,;tic dnimab or tht:ii products. The incidence of anthrax during 1996 was reported to be 0.54 per million population [ JI]. Shiraz University of Medical Sciences, founded in 1949, is ·a regional referral cen- tre for all disease~ and currently has an ar- chive of about 7130 autopsy records from the last 40 years. Many of the anthrax cas- es have been presented earlier in the litera- ture [12-14]. Our aim was to review the pathological findings in these autopsy records for unrecognized microscopic findings that could raise new concepts and to review the literature for theories about the pathogenesis of anthrax. We believe this would help improve diagnosis and treat- ment of the disease. Methods A review of records from the pathology ward of Shiraz University of Medical Sci- ences found 33 autopsies of anthrax cases performed between the years 1960-200 I. A 11 cases had been diagnosed by the clinico-pathological methods available at the time, such as Gram staininJ!: of fluids or tissues, different cultures and spore stain- ing of the isolated organisms. All of the di- agnoses had been confinned by a complete autopsy, either through bacterioloJ?:ical in- vestigations or the relevant organic histopa- thology findings. The haematoxylin-eosin stained slides and special stains including tissue Gram stain were reviewed again to confirm previ- ous findings and to look for new concepts. Cases were classified principally into cuta- neous, pulmonary and gastrointestinal cas- es, according to light microscopy histopathology findings. Related findings in other organs were also considered. Then the data was analysed and reported, fol- lowed by a brief review of the literature. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 29 Results There was no significant gender bias among lhc 33 autopsy records: 16 {48.5%) were from males and 17 (51.5~·6) females. All patients ·were aged between 1 year and 65 years, with a mean age of 28.4 years old. Most (63.6%) were between 20-40 years of age. Thirty out of 33 patients had been living in rural areas, and were thus likely to have been in dose contact with domestic animals. Under light microscopy, 28 cases out of 33 (84.9%) had respiratory manifestations of anthrax (Figure I). Most cases (26) had pulmonary congestion and haemorrhage with dilated interalveolar vessels and patchy parenchymal haemorrhage. Figures 2 and 3 show examples of marked exuda- tion of serosanguinous fluid in the alveolar spaces, accompanied by intra-alveolar haemorrhage and mild fibrin deposition. Typical hyaline membrane formation was noted in 5 cases indicative of acute (adult) respiratory distress syndrome (ARDS). Leukocyte infiltration consisted mostly of neutrophils; just l case had prominent lym- Congestion and haemorrhage Exudation Whrte blood cell infiltration Atelectasis Consoldation Hyaline membrane Necrosis Parenchymal oedema 0 phoplasmacytic infiltration. The inflamma- tion was intra-alveolar in IO cases and in- terstitial in 6 cases. Five patients showed parenchymal necrosis and 5 cases hyper- p 1 asia of the alveolar Viall and intra-alveolar haernosiderin-ladcn macrophages. Only 3 of those who had pulmonary in- fection showed evidence of pleural involve- ment, in the form of effusion and leukocyte infiltration. Well-formed acute lobar or patchy pneumonia was scarce. Eleven cases (one-third of all cases) had evidence of upper airway involvement and inflam- mation: l case in this group had cutaneous anthrax of the neck without any evidence of septicaemia or internal organ involve- ment, and died of asphyxia due to severe upper airways obstruction from oedema. Cutaneous anthrax was seen in 23 out of 33 cases (69.7%) but was the cause of death for only I patient (mentioned above). Several cases of cutaneous anthrax in our series had been treated for insect bites be- fore developing the characteristic skin le- sion of anthrax (a coal-black, scar-forming lesion). Ulceration and necrosis of the skin 26 rn 5 10 15 20 25 30 No. ot cases Figure 1 Histopathology findings in 28 autopsy cases with pulmonary anthrax 30 La Revue de Santa de la Medlterranee orientale, Vol. 10, N° 112, 2004 Figure 2 Low power view of acute ,~~pirn1nry rii'-!tl'f'~fo:" ~ynrirnnw in lung tissue. Note necrosis. congestion and inflammation with hyaline nwmorane formation in the alveolar tissue Figure 3 High power view of .tlveolar Li~sue, rcveuling the hyuline membranes (arrow) was the most common findin2 ( 17 cases). involving all layers of the skin (Figure 4). Other typical histological findings were: oedema ( 15 cases), va,cu lar congestion and haemorrhage (12) and white blood cell infiltration (8). Twenty-two out of 33 cases (66.7%) had gastrointestinal manifestations of an- commonly the small bowel (19 cases), the stomach (7 cases) and the large bowel ( 4 cases). The histopathology findings arc summarized in Figure 5. Only I case had asciles, while 6 of them had evidence of periloneal involvement. mostly in lite form of oedema and leukocyte infiltration. Gas- trointestinal involvement was the single cause of septicaemia and death in one- quarter of patients with gastrointestinal an- thrax (J 5% of all cases), all of whom showed peritoneal involvement and a de- gree of haemorrhagic oedema (causing ab- dominal protrusion in a few cases) and leukocyte infiltration. Lymphadcnopathy was detected in 13 of the 33 cases {39.4%). The lymph nodes affected were adjacent to the organs in- volved: the mesentric nodes in gastrointes- tinal cases and the cervical. axillary and parahilar nodes in pulmonary cases. Gener- alized lymphadenopathy was seen in a few cases. No specific histological changes were present in the slides. The most severe cases showed haemorrhagic Jymphadenitis and necrm,is. with extension to the adjacent mediastinum or mesentery. Congestion and neutrophil infiltration were more common. Bacilli were only rarely identified in the in- volved lymph nodes. Splenic congestion was a major finding. evident in 17 cases (51.5%). Five patients showed various degrees of congestion and infiltration of acute and chronic innamma- tory cells in areas of red pulps indicative of acute septic splenitis, and 3 patients (in- cluding the one with typhoid fever) showed splenic infarction. Significant splcnomcga- ly was noted in 5 cases on autopsy. Hepatic findings were noted in 17 cases (51.5%), mostly in the form of sinusoidal dilatation and congestion, mainly parenchy- mal and rarely subcapsular. producing hepatocellular necrosis in some areas. probably due lo a pressure effect. Fourteen Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 31 Ulceration and necrosis Oedema Congestion and haemorrhage Whrte blood cell infiltration 0 5 10 15 20 25 No. of cases Figure 4 Histopathology findings In 23 autopsy cases with cutaneous anthrax of these cases showed various degrees or parenchymal neutrophilic infiltration indi- cating hepatitis_ Abscess formation was noted in l case. Three out of 33 cases (9.1 %) had histo- pathological findings of meningeal involve- ment showing mainly leptomeningeal congestion and neutrophile infiltration. One patient had a haematoma in the subarach- noid space. Kidney findings consisted of congestion and intraparenchymal haemorrhage in 6 pa- Congestion and haemorrhage Uk:eration Inflammation Necrosis Oedema Perfoneal involvement tients (18.2%) with signs of tubular necro- sis in 3 of them. The adrenal glands showed fat depletion and cortical tubular formation in 5 cases (15.2%) indicating septicaemia, and 3 cas- es showed congestion and haemorrhage of the adrenal parenchyma. Bacillus anthracis was detected in 13 cases (39.4%) using haematoxylin-cosin or other special stains on the tissues. It is noteworthy that 1 of the cases was simul- taneously seropositive for typhoid fever 0 5 10 15 20 25 No. of cases Figure 5 Hlstopathology findings In 22 autopsy cases with gastrointestinal anthrax 32 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Figure 6 Anthrax bacllll Inside a skin lesion (Arrnw) Nntl!' th9 9por9-formlng baellll In a necrotic background (both O and H antigen titres were about I :320) with evidence of splenic haemor- rhagic infarction and liver congestion. This patient died of anthrax septicaemia not ty- phoid lever. Discussion The causative agent of' anthrax, Bacil/11s anthracis, is a large, non-motile, facultative and spore-forming Gram-positive rod (Fig- ure 6) A gh1t;imyl-pnlypeptide capsule is present that inhibits phugocytosis, and has a major role in the agent'<; pathogenic capa- bilities [15,16]. Anthrax toxin is well known as the major toxic component of the bacillus, but non-virulent toxin-producing strains have also been isolated [J 5]. These mutant strains fail to produce the poly- glutamic acid capsule. According lo the current classification of bacterial exotoxins, anthrax toxin has an AB pattern [J 7-20]. Two potent exotoxins, called 'oedema factor' and ' lethal factor' constitute the A domain which gains entry into the host cells by the B domain ('pro- tective antigen'). Antibodies against protec- tive antigen seem to confer immunity [16]. After entry, oedema factor produces tissue oedema through increasing adenylate cy- clase activity [ 18,/ 9]. It may also suppress neutrophil function [20,2 J], and hence leu- kocytes arc rarely encountered in anthrax lesions regardless of the organs involved and the severity. Lethal factor has recently been shown to possess an endoprotease activity, interrupting a vital cell-signalling pathway that brings about direct cell death and cytokine production (including tumour necrosis factor-a and interleukin- I~). It also inhibits mitogcn-activated protein ki- nase kinase (MAPK) and prevents cell pro- 1 iferation r22 24]. Both the organism and its spore can be infective. The most common route of entry fu1 i:111Ll11M is Ll1c skin (95% uf1.:ascs). Oth- er routes of entry are inhalation of airborne spores causing pulmonary anthrax (wool- sortcr's disease) or ingestion of the organ- i:sm or :spores in contaminated food leading to gastrointestinal anthrax. The former is the most lethal type, killing I 00% of the patients if untreated; the latter is the least common type but i3 ul:;o very dungcrou:s. Skin involvement in anthrax is charac- teristically painless but pruritic l25], which may be due to destruction of nerve endings in the affected areas of skin. Cutaneous manifestations are more prevalent in ex- posed areas of skin, most commonly on the head and neck [5]. Stings may play a rule in Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2, 2004 33 contagion, as some of the skin lesions be- gin as an insect bite [ ti,26], Several cases or cutaneous anthrax m our series had been treated for insect bites before developing anthrax skin lesions. The most common histological findings of cutaneous anthrax consist or intense prolonged oedema, vas- cular congestion. haemorrhage and necro- sis. Necrosis of the skin was the most common finding among our cases, involv- ing alt layers of the skin. Tht: necrosis i'.'l mainly due to direct cy1otoxicity of the or- ganism [27] rather than ischaemia due to vascular compression caused by severe u1:1.k:111i1. Culaneou:!> anthn,11 wa:5 n:;!;ordcd as the cause of death for only 1 patient, as death among cutaneous anthrax patients re- sults mamly from the systemic dissemina- tion of the disease [1,2,9,10]. In pulmonary anthrax, an acute alveolar or lobular pneumonia may develop, form- ing an extensive serofibrinous exudation throughout the parenchyma [28, 29]; the striking characlcristic of this pneumonia is the relative paucity of inflammatory cells. Haemorrhagic necrosis of the alvco lar sep- tum i.vith a large number of bacteria may be present. Mucosa! oedema may involve any level, from the oropharynx down to the al- veoli. Acute mcdiastinitis and mediastinal wirii>ning ri11i> to lymph~rii>niti<: rmrl h:iPmor- rhagic oedema in the mcdiastinurn may be present. Occasionally, intravascular throm- bosis may be a cause of death in respiratory anthrax [30]. In our series of patients, pulmonary congestion was the most common finding, Many of those with pulmonary involve- ment showed dilated interalveolar vessels and patchy parenchymal haemorrhage, Ex- udation of serosanguinous fluid in the alve- olar spaces accompanied by intra-alveolar haemorrhage and fibrin deposition ½as characteristic of the early stages of ARDS. leading to hya!ine membrane formation fol- lowed by respiratory failure. Typical hya- line membrane formation was noted in 5 cases: the other patients died before the hy- aline membrane could form (3-7 days). Short survival also explains the low fre- quency of parenchymal necrosis in these patients. since necrosis was found only in rhose who survived longer. Very fow 1.:c1scs showed hyperplasia of the alveolar wall and intra-alveolar haemosiderin-ladcn mac- rophages. Well-formed acute lobar or pald1y pm;uunmia. wa:,, scarce in our ca,1,cs. Oedema of the upper respiratory air- ways may be caused by primary mucosa! infection with bacilli [7], but there was ev- idence of $Ceondary spread of ocdemu from the skin surface to the deeper soft tis- sues in I of our patients. As previously mentioned, this patient had cutaneous an- thrax lesions on the neck und died from as- phyxia caused by severe oedema of the soft tissue and upper airways. No sign of sys- temic involvement was evident in this pa- tient. The alimentary canal may be involved in anthrax primarily from the mouth down to the large bowel. It seems that the symp- toms are caus:ed by bacilli in the tnm:i I<: :inn the gut-associated 1)1nphatic tissue [BJ, but light microscopy shows full thickness in- vol vemcnt of the gut. Although massive nPrii>m:i imd 11lcerntion with vascular con- gestion and haemorrhage is mentioned in the literature, other gastrointestinal findings are not much discussed. However, ascites and involvement of mesentery have also been reported. In our series, the most and least fre- quently involved gastrointestinal sites were the small and large bowel respectively; the most common was the duodenum, fol- lowed by the jejunum and the ileum. The rate of stomach involvement (7 /21 cases} was higher than previously reported [8,31,32], revealing that the bacillus can survive the usual gastric defence mecha- nisms such as gastric acid secretion. This 34 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 finding, and the large number of cases where stomach manifestations of anthrax were associared wi!h septicaemia and death, suggest primary gastrointestinal in- vol vernent in anthrax, which contradicts previous reports in the literature [7,8]. Ht:p11li1: invulverm:m was detected in half of our cases. showing some non- specific leukocyte infiltration in the liver parenchyma. Only l patient had significant abscess formation accu1111-1c:1.11icu by llu.: presence of many bacilli in the liver parcn- chyma. Hepatocetlular necrosis, if present, was focal and scant. Hiatopnthological findings in the spleen were mainly due to systemic infection in those patients with anthrax septicaemia; therefore, no definite conclusions can be drawn about splenic in-.•olvcmcnt. Vurioua degrees of congestion and infiltration of acute and chronic inflammatory cells in ar- eas of red pulps were indicative of acute septic splenitis. Five cases showed sple- nomegaly on autopsy but there was little correlation between spleen size and the pa- thology findings. I .ymph nodf' involve,m.,,n1 ;idjacent to the primary organ involved was present in nearly 40% of cases, with a few cases of generalized lymphadcnopathy. In its most severe form, haemorrhagic lymph:-11l1miti~ and necrosis were present, with extension to the adjacent mcdiastinum or mcsentery; hence the signs of mediastinal widening in chest X-rays [JJ]. Congestion and neutro- phil infiltration were more commonly found. Bacilli were rarely detectabJc in the involved lymph nodes (or other organs) and this might be due to antibiotic therapy before death. Besides, bacilli engulfed by inflammatory cells are more difficult to see. Some investigators recommend new im- munostaining techniques to reveal the ba- cilli, particularly the intracellular ones [34,35]. Meningeal involvement was found in a few cases in the form of non-specific con- gestion (mainly} and leukocyte mtiltrat10n. One case had subarachnoid haemorrhage. A case of anthrax accompanied by sub- arachnoid haemorrhage has been mcn- rioned in the literature [36]. The adrenal glands showed non-specif- ie signs of septicaemia, congestion and haemorrhage and were rarely infected di- rei.:lly by lhe organism. Involvemem of the kidneys was notably non-specific among our cases, showing congestion and haem- orrhage of the parenchyma. Nearly all ca:i.t::i. Ji,;;u :su111cli1rn;; arwr .tn- tibiotic treatment was started, so the rate of organism cultivation was low, since Bacil- lus anthracis was sensitive to most antibi- otics current at the time l/5,/6]. It ha.:s been reported that culturing. before 21 hours of antibiotic therapy yields the organ- ism in nearly all patients [8]. Conclusion Although there have been great advances in uu1 k11uwk<lge abuul Lhc palhogcnesis of anthrax in recent years, more research is still needed. Our review of autopsy findings was consistent with previous experimental ceport:s. I lowcve1, we uu:s,.a ~·1,;<l 111c:1.11ifl.:~la- tions of anthrax in some organs not previ- ous discussed, such as the spleen. The major findings were an ARDS-pattern of pulmonary involvement and a p.imary in- vol vcmcnt of gastrointestinal tissue includ- ing the stomach. Acknowledgements We would like to thank Mrs Shahmanesh, Mr Zebarjadi, Mr Jabedarbashi and all oth- ers who helped us in pcrfonning the above study. 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Carnes WH, Kaufmann AF In- halation anthrax in a home craftsman. Human pathology, 1978, 9(5):594-7. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 Cout des soins de sante de base dans une circonscription sanitaire en Tunisie A. Nouira, 1 A. Bchir,2 M Njah, 1 B. YazicP et S. Bou A/P 37 · • at..1.;.o ~~, j t....,L..,½1 ~1 ..:,i\..o.JJ..l ...,W\5::.; ~Y..:r ,_. - - ~ y tw, c-'-,:y. ~IA 'Cl.,;: .J~~ '~ "3ll -1/ ''.r-Y Jui J!,-)11 il~':}IJ ;;-l_,).,.i ;;);,'JIJ .b.J=:.:;lJ ..,_IJrP ~I ._:..,l_.....LJ._.I ~,_s::; Jr .;.,\..,. _,.L.11 ...uu :'-")\J.l ._,:.J.:-; ._) (1995) 11...o o.J.l ;;_,,l _/~11 ~I 1.;l.o _,l.l j5 .r' ~ ;;_,,llr.-'fl ._;,_,,!\.:(:JI y~ L..J .l.i J . _, )_r-Ll ___...li.s:'...JI L; _,....:; 1~ ;~ e:-'"'-'" JS'" ,.f· 1Wi :U,,1.- ,.__~; ""-'W'J\ L; _,.;; ~ •._r y c) ,•~\ ,._j ,._;.1-W.I ~ k,. <\..;.,,...=-I,...; .L...t.o.il ._,Jj._\ ..k...J U.., 'U pl...;.;:,') ,.;:_,\.,.::.....,, ~L....\ le_,.:,-....:, ,,,_:;...., t<I -.JL.":-'11 ~~ I .,I • I,.__ -__; L,T ~ I.,,,," -..:... ~ .. ,j i.Jt...-' 17.494 ., ; J5:_l i"wI Ji_i;)'I .:.,1.5"' J ,L,...-; _,; I).:.,;-' 1 219 099 ',?y-11 .Jlii)'l ~ ..J..i J .• ...1.,,- J y .._;,.,J\.S'..:JI if /.65.31 __,..;;i .ti) .(1995 ii.,:,~_,;~)--'.!-' 0.950 C:-'~ ~_,,.( J'JJ-' JS- .)lS-) ~y .:;f ~ <..$_r'-i ~Jlj .y ........,_)\Sd1 J! IJp 1->;J .~y/il ~ 4--'-- /.17.03 c:;-,vi l.,.-) ..:,;)_,.WI_}>- :i.)lr.-)'1 .:i..,tl>_,)I ,.;:_,l,..,l;,!..1 ~ -.:;...u.;i ..u 4--'-- /14.04 .:.,i_, ..._..,.)!..,Ji -=.,l.,..u,.\ ._fa- ..;;.....i.,i.;! ..u .......,_)~I if 1/.84.96 ,1_,l:.,;;; 2.764 ;;.:i',l}l; ~\ ;;_;u;J1 <.J 4.!u-JlJ ,i_,L:.,;.:i 6.847 ~)\,JI ~u-}J ,.;:,,1) .. c,;; .... ',/1 ._;,..,J\5j ..:..,\S' ...I.OJ ~.,.jl J _,kl1 ~ J _,.di .j ...... 1.J_J1 .JJOLs J . i}~-' 6.680 .... 0 u11 J ...:..,1)-e_}l J ,i.J1.:.,;., 3.680 ~ J . L _,_,.J.ll u.b.:11 J ~1.6"-' .,_,1_.,\.I /'Ll .. ,.:,.; .... I ;;~l.,.;.5"' 4-! ~ .:.,i ___._,J~I ---~ RESUME l..'.objectif de notre etude est de calculer le coot de fonctionnement des differentes structures de sante en premiere ligne et les coots moyens des services fournis dans ces structures durant un annee (1995). La region de retude est la circonscriptlon sanltaire d'Enfidha (Tunisie). Le coot global de fonct1onne- ment de la circonscription sanitaire s'eleve a 1 219 099 dinars tunisiens (TND) et les depenses publiques ·annuelles par habitant supportees par la circonscription sanitaire sont de TND 17,494 (un dollar US = l'.ND 0,950 en 1995). Les frais de personnel representent 65.37 % du coot global et ceux des medicaments , 17,03 %. Par ailleurs, 14,04 % sontdepenses pour le preventif et 84,96 % pour le curatif. Les coats unitaires sont de TND 6,847 pour la consultation curative, de TND 3,680 pour l'acte de vaccination, de TND 2,764 pour .@consultation perinatale et de TND 6,680 pour la consultation de medecine scolaire. Disposer d'informations -ii. propos des coats permet un meilleur usage des ressources, une meilleure equite et une prestation de '.aualite. "Costs of basic health services In a health district in Tunisia ;\BSTRACT Information on the cost of health services is essential for good planning and management and Jtia efficient use of resources. We calculated the total costs incurred in running primary health services for one year (1995) in the health district of Enfidha (Tunisia). The yearly operating expenditure for the health district was 1219099Tunisian dinars and the cost per inhabitant was 17.494dinars (US$1 = Tunisian dinar ~:950 in 1995); 65.37% of total costs went on staff and 17.03% on drugs. Looked at another way, 84,96% ~ent on curative services and 14.04% on preventive services. The cost of a consultation for curative care 'YaS 6.8_47dinars, for perinatal care was 2.764 dinars, for immunization was 3.680 and for school visit was §:l38o dimm,. The study helps to Identify ways In which cost analysis can be used to explore efficiency and resource adequacy in the district. :;,"1 -~ 11.epartement de Medecine communautaire. Facutte de Medecine de Sousse. Sousse (Tunisie). f}tipartement de Medecine communautaire, Faculte de Medecine de Monastir, Monastir (Tunisie). Pirection regionale de la Sante publique de Sousse. Sousse (Tunisie}. IE!~U : 28/08/01 ; accepte : 10/01 /02 38 Introduction La Revue de Sante de.la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Le progres des techniques medicates d'une part, l' evolution demographique et la transi- tion epidemiologique d'autre part ont induit une importante croissance de la demande et de l'offre de soins, particulierement dans les pays en developpement. I1 en a resulte une augmentation continue des depenses de soins, a l'origine d'une crise du finance- ment public de la sante dans la plupart de ces pays [JJ. Devant les limites des moyens, il est ainsi devenu imperatif d'optimiser l'utilisation des ressources mo- bilisees, d' operer des choix a differents niveaux d'intervention dans le systeme de sante et de decider des degres de priorite entre differentes alternatives (la prevention, les soins curatifs, et autres) [2]. Pour y parvenir, encore faut-il disposer d'un mini- mum d'informations apropos des couts in- duits. L'etude des coiits. l'un des outils essentiels de la gestion des ressources, nous pennet en effet de chiffrer les depen- ses, de determiner les grandes lignes de planification et de choisir entre differentes alternatives strategiques [3]. Ceci est d'autant plus vrai au niveau le plus peri- pherique du systeme, celui de la cir- conscription sanitaire. Celle qui est censee etre la porte d'entree et en meme temps l'unite fonctionnelle du systeme de sante se caracterise en effet par une certaine fai- blesse dans la gestion, entre autre traduite par une mauvaise utilisation des ressources allouees aux prestations de soins [2]. L'objectif de ce travail est ainsi de calculer le coftt de fonctionnement des differentes structures de sante composant la circonscription sanitaire (l 'hopital de cin.:omu.:riplion, ks i.;entres tle swlle) de meme que le cout moyen des services four- nis au niveau de ces structures. A travers cettc ctude, nous espcrnns cont.ribuer a fournir des informations sur les c01'.its en premiere ligne, ce qui permettra aux gcstionnaires du niveau central et du niveau local d'analyser le fonctionnement des structures et de prendre les decisions : appropriees. Methodes La region de l'etude est la circonscriptimi sanitaire (CS) d'Enfidha, une CS rurale ·. situee au centre-est de la Tunisie qui com- porte 69 688 habitants. Le secteur sanitaire prive y est tres peu developpe et le secteur public est represente par deux niveaux de structures operationnelles. Le premier niveau est constitue par 26 centres de sante de base (CSB) dont 46 % soot de petits centres, desservant chacun en moyenne. une population d'environ 2000 habitants et fonctionnant avec un personnel paramedi~ cal, u.ne sage-femme (1/6 du temps). Une consultation medicate y est assuree a raison de deux fois par semaine, lt:s aulrt:s joW'li etant consacres aux consultations de la sage-femme ou aux soins (dont la vaccina.~ lion). Le deuxicme oiveau ou nivcau de re- cours comporte l 'Mpital de circonscriptior avec des consultations specialisees, un sei:"· vice de medecinc intcmc (20 lits), une mo-· temite (15 lits), un service d'urgence, une unite de radiologie et un laboratoire d'analyscs biologiques. L'Etat contribue au fmancement de la. quasi-totalite des depenses (89 %) (salaires du personnel et une subvention de TND 288 000 par an). Le reste du budget de fonctionnement de la circonscription est fourni par les recettes propres des stnic~· tures sanitaires ( contribution directe des patients aux frais de consultations extemesJ d'hospitalisation et des examens complb- mentaires, remboursement par les caisS(!S d'assurance). Le personnel technique est compose de 10 medecins, d'un pharmacien, de deux chirurgiens dentaires, de neuf sages, Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 39 femmes et de 122 infirmiers et aides- soignants. Notre etude a considere !'ensemble des depenses induites durant une annee pour la totalite des structures de sante publique de la circonscription, soit 26 centres de sante de base, les consultations specialisees et les trois services hospitaliers de l'hopita1 de I.a circonscription. La demarche suivie lors du culcul du cout est inspiree de la methodolo- gie utilisee par I 'UNICEF et collaborateurs dans !'initiative de Bamako [J]. Elle con- siste a : a) identifier les ressources utilisees pour produire les services dont les co-0.ts sont a calculcr ; cctte categoric de re:ssout- ces (renouvelables ou de fonctionne- ment) englobe le personnel (admini- stratif ct technique), lcs fournitures (medicaments, vaccins, seringues, petit equipement), l'utilisation et l' entretien des vehicules, l'utilisution et l'entretien des batiments, la formation continue et la supervision ; b) estimer la quantite CUHSQlllillee· pour chaque ressource ou intrant durant l'annee 1995 ; c) anribuer des valeurs monetaires a chaque unite d'intrant et en calculer le cofit total ; d) repartir proportionnellement le coilt de chaque intrant entre les activites ou il intervient ; e J utiliser les mesures de la production de chaque activite pour le calcul des co-0.ts unitaires. Resultats f:• C>epenses totales Le co-0.t global de fonctionnement de la cir- conscription est de TND 1 219 099 (un pollar US = TND 0,950 en 1995), ce qui ,equivaut a une depense par habitant et par an au niveau des structures etatiques de la CS de TND 17,494 (Tableau 1). Repartition du cout selon le niveau de soins Les depenses ont ete reparties entre : • les CSB (70,40 %) avec un cout moyen par CSB de TND 32 793 ; • l'hopital (26,83 %) dont 46,94 % pour le service des urgences, 32, 16 % pour la matemite et 20,90 % pour le service de medecine inteme ; • et les consultations specialisees (2,77 %). On depense done par habitant TND 12,314 au niveau des CSB, TND 0,484 au niveau des consultations specialisees et TND 4,694 au niveau de l 'hopital (Tableau 1 ). Repartition du cout selon le type d'activite L'analyse du cofit par type d'activite mon~ tre que les soins curatifs correspondent a 84,96 % du total du cout au niveau de la circonscription, soit une depense de TND 14,862 par habitant et par an. Les soins preventifs forment le reste (15,04 %), soit une depense de TND 2,632 par habitant et par an (Tableau 2). La repar- tition du cofit des soins preventifs montre Tableau 1 Depenses pubUques par habltant et par type de structure (en dinars) Type de structure CSB{28CSB) Hopital Consultation specialisee Total Coutglob11l (TND) 858246 327084 33769 i 219099 Cout par o/o habitant (TNO) 12,314 70,40 0,484 26,83 - 4,694 2,77 17,494 100 40 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Tableau 2 Repartition du cout seton le type d'activite (en dinars) Activites coot global cout par "lo (TND) habitant (TND) Curatives 1 035 723 Preventives 183 376 Total 1 21 9 099 14,862 2,632 17,494 84,96 15,04 100 que 29,46 % du coilt est relatifa la vaccina- tion, 23,89 % a la medecine scolaire, 26,64 % a la consultation de perinatalite, 13,70 % a l'hygiene du milieu, 3,42 % a d'autres programmes nationaux (la tuber- culose, la rage, la lutte contre les envenima- tions. le paludisme) et 2,90 % a !'education pour la sante. Les composantes du coot Les frais du personnel ( des services generaux de soutien. technique, du labora- toire et du service de radiologie) represen- tent 65,37 % du cout global et les medicaments 17,03 % (Tableau 3). On depense ainsi par habitant et par an TND 11,961 pour le personnel et TND 2,979 pour Jes medicaments. Le cout fixe represente quanta lui 69,04 % du cout de fonctionnement. Selon le type de struc- ture, il varie de 67,09 % au niveau de l'h6pital a 88,05 % au niveau de la consul- tation de 2' degre et il est de 69,33 % au niveau des CSB. Le coOt unitaire par activite Les couts unitaires moyens des differentes prestations fournies au niveau des CSB sont de TND 6,847 pour la consultation curative, de TND 3,680 pour l'acte de vac- cination, de TND 2,764 pour la consulta- tion perinatale (avec TND 2,610 pour la consultation prenatale, TND 2,604 pour la consultation postnatale, TND 2,997 pour la consultation de planning familial et TND 2,656 pour la consultation de gyne- cologie), de TND 6,399 pour la consulta- tion en medecine scolaire et de TND 7,492 pour la consultation de stomatologie (Fi- gure 1). Au niveau de l'hopital, le emit d'une journee d'hospitalisation est de TND 15,426 en medecine interne et de TND 67,744 a la maternite. Si on considere Ies accouchements, le cout moyen d'un ac- couchement a la matemite s, eleve a TND 174,184 (environ le SMIG en Tu- nisie). Le cout moyen d'un malade hospi- talise au service de medecine est de TND 133,521. Le cout d'un lit budgetaire s'eleve a TND 2734,520 au service de me- decine et a TND 7013,800 a la maternite. Pour le service des urgences, le coilt d'une consultation est de TND 8,930. Les couts unitaires des consultations specialisees varient quant a eux de TND 6_,339 a 10,092. Discussion Sachant que les etudes relatives aux couts des services des soins de sante de base en Tunisie sont rares, nous avons eu pour ob- jectif d'analyser comment le budget de la Tableau 3 Composantes du cout Rubrlque Cout en dinars % Personnel 796964 65,37 Medicaments 207 555 17,03 Laboratoire 40834 3,35 Materiel medical 23186 1,90 Programmes nationaux 32323 2,65 Radiologie 22740 1,87 Autres 95487 7,83 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 41 8000 7000 6000 5000 <I) ~ 4000 C: o 3000 2000 1000 0 - C: C: <1) ~ 0 o- -~ ·- «l Em "' 0 C: - C: "/;:, :::) '<ll <I)~ 0 C: a. ~ 0 0 Figure 1 Coat unltaire par actlvite {en dinars) CS etait consomme. Pour ce faire, nous avons utilise une methodologie qui a fait ses preuves puisqu'elle a ete essayee dans plu- sieurs pays, en particulier a travers !'initiative de Bamako (Benin, Gambie, Ni- ger, Ouganda, Zai:re, Burnndi, etc.) [ 4). Par contre, notre etude presente des limites du fait qu'elle n'a conceme que le secteur public et qu 'elle a consjdt:\re uniquement le cout de fonctionnement supporte par la cir- conscription. De meme, dans le but <l'obtenir !es estimations les phis proches de la realite, nous avons choisi nos des de repartition en nous referant, d'une part, aux :donnees de la Iitterature et d'autre part, aux resultats des entretiens avec l'equipe de la circonscription a propos du deroulement des activites et de Ia gestion des ressources au sein de la circonscription. De ce fait, le choix de la repartition de certaines res- ·sources entre les stn1ctures ou entre. !es activites pourrait etre entache d'une cer- taine subjectivite. En l'absence d'autres al- ,ternatives, ce choix peut etre considere ;~onune justifie. C <I) <1) (I> <1) (I> C'>,ii :£~ .s = ·5, -~·ffi ·a, C: E 0 '-'- 0 .19"' - C: C: ell$ 15 ., 0 'O 0 £ ::::,- <I) <n a:: 0 -Q) <I) rn '<Il C 0 C :l: E 0 0. (.) >, 0 C!i ii5 Par rapport a l'annee de notre etude (1995), !es depenses totales de sante en Tunisie ont ete evaluees a 1072,9 millions de dinars, soit 5,9 % du PIB [5] et representent une depense annuelle moyenne de TND 120 par habitant [61. Depuis 1990, on a en effet depasse I'objectif fixe par !'OMS pour les depenses de sante (5 % du PIB) Par ailleurs, au niveau du ministere de la sante, la part du budget de fonctionnement (sans compter les salaires et les indemnites du personnel) des etablissements publics destinee aux etablissements de premiere ligne (hopitaux de circonscription et groupements de CSB) etait de 22,7 % [7]. En comparant les resultats de notre etude a ceux observes dans la circonscrip- tion de Medjez El Bab au nord-ouest de la Tunisie, nous constatons que les depenses par habitant et par an sont plus elevees a Medjez (TND 26,304 contre TND 17,494) [ 8]. Cette difference est due essentielle- ment a des depenses plus importantes au niveau de 1'hopital (Jes depenses par habj- 42 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 tant occasionnees par l 'hopital sont de TND 14,309 a Medjez et de TND 5,178 a Enfidha ). Ceci pourrait s' expliquer par la capacite et les activites relativement res- treintes a l'hopital d'Enfidha. Cette situa- tion serait a l'origine d'un taux d'orientation-recours eleve et d'une prise en charge plus cmlteuse par le troisieme niveau, d'ou l'inten~t de doter l'hopital de circonscription des ressources necessaires pour qu'il puisse, avec une bonne gestion, jouer son role d'orientation-recours et as- surer la continuite rles soins curatifs aux malades. En effet, lorsque les centres de sante et !es h6pitaux de premier recours fonctionnent de maniere satisfaisante, ils peuvent offrir la possibilite de repondre a plus de 90 % des demandes des soins de sante et de reduire ainsi jusqu'a 30 % la charge de morbidite [9]. La part des depenses de l 'hopital est a peu pres de 50 % en Zambie (cfo,trict de Monze) et de 73,53 % au Cameroun (district d'Obala) [10,11]. II est difficile neanmoins de porter tm jugement sur cette repartition qui depend de plusieurs facteurs. En ce qui concerne les composantes du cout, nos resultats concordent avec ceux retrouves clans la circonscription de Medjez El Bab ou le personnel represente 64,6 % et Jes medicaments 17,3 % du cout total [8]. Selon la litterature, on note en outre une variation de la part du cout du personnel qui est de 18 % en Zamhie [JO], de 83 % au Cameroun [JJ], de 54 % en Namibie [12] et de 43,3 % au Burundi [13]. Quant au cout fixe, il represente 70 % au Mali [14]. Il faut cependant noter qu'au Benin et en Guinee, la part du personnel qui etait de 80 % en 1986, soit avant la mise en oeuvre de l'initiative de Bamako, est passee ensuite a 49 % [15]. En fait, dans 1::i m::ijorite de.<: pays en developpement, la part des salaires dans le budget n'a cesse de croitre a la suite du developpement des systemes de sante et de l'augmentation des effectifs entre les an- nees 70 et 80, entrainant ainsi une diminu- tion des credits de fonctionnement courant. En Afrique, les couts de personnel sont ain- si le principal paste budgetaire du ministere de la sante. et plus de 60 % de la totalite des ressources publiques consacrees a la sante sont, dans l'ensemble, allouees aux salaires [16]. Les medicaments ont forme 1 7 ,03 % du cout de fonctionnement de la circonscrip- tion. soit une depense de TND 2,979 par habitant. 11 s'agit la uniquement du cout des medicaments delivres par les structures publiques. Si. en Afrique, les depenses con- sacrees aux produits pharmaceutiques representent generalement de 20 a 30 % du total des coiits de fonctionnement des eta- blissements sanitaires publics et prives et ne sont depassees que par les depenses de personnel [J 7], il apparait neanmoins im- portant d'observer qu'en Tunisie, par rap- port aux autres cot'.its de la sante, la part des medicaments dans le budget de l'Etat decroit regulierement. Elle est ainsi passee de 40,68 % en 1987 a 28,85 % en 1994 malgre !'augmentation de l'enveloppe des medicaments. Des !ors, un effort de re- flexion et de clarification a ete engage a plu- sieurs niveaux et ce, dans le cadre de la definition d'une nouvelle politique phanna- ceutique [ 18]. L'analyse de la repartition des couts par type d'activite apporte au gestionnaire des informations plus precises sur les desequili- bres constates. Ainsi, au niveau de la cir- conscription d'Enfidha, les soins preventifs ne representent que mains d'un cinquieme du cout global. faisant que la depense an- nuelle moyenne par habitant est sept fois plus elevee pour Jes soins curatifs com- pares aux soins preventifs. Sachant l'importance de la prevention, sur le plan national la politique de l 'Etat va dans le sens Eastern Mediterranean Health Journal, VoL 10, Nos 1/2, 2004 43 de l'augmentation des credits alloues a la medecine preventive, lesquels sont passes de 2,990 millions de dinars en 1992 a 7,990 millions de dinars en I 996, soit une augmentation annueJle de 33,4 % [19]. Dans cette perspective, l'Etat compte ainsi prendre en charge Jes actions sanitaires prioritaires entre autres, en renfor~ant les actions preventives en premiere ligne. En effet, ces actions constituent une com- posante essentielle pour ameliorer l'etat de sante de la population, et ceci par le deve- loppement des activites de depistage et d'education pour la sante. Conclusion Notre etude nous a pennis d'estimer les colits des structures et le coii.t moyen des services fournis en premiere ligne dans une circonscription sanitaire en Tunisie, une des informations essentielles pour la ges- tion des ressources, d'autant plus que la strategie de la circonscription sanitaire, pierre angulaire du systeme de sante tu- nisien, vise a rendre Jes circonscriptions sanitaires fonctionnelles, repondant aux criteres de gualite de service, de bonne ges- tion et d'efficience que les populations sont en droit d'attendre. Les etudes des coi'its permettent en effet, en assurant un meilleur usage des ressources, de garantir une meilleure equite et une prestation de qualite pour la population. Que cela soit au niveau national ou local, il est imperatif, pour ratio- naliser les choix budgetaires et oeuvrer pour une meiUeure allocation des ressour- ces humaines et financieres, de disposer de donnees de base et d'indicateurs pertinents relatifs a la securite. l' efficacite et les couts des techniques utrnsees et des services fournis a la population. RtJft5rences , OMS-UNICEF. Rapport de la confe- rence panafricaine sur le financement cdmmunautaire des services de sante. Volumo 1 : Rapport de la oonf6rcnco. Kinshasa (Zaire), 25-27 juin 1990. New York, UNICEF, 1991. 2 World Bank. A framework and Indicative cost analysis for better health in Africa. Washington DC, World Bank, Africa Technical Department, 1993 (Technioal Working Paper No. 8). 3 Analyse des couts pour les decisions de gestlon. Management rte fa pfamYic:ation familiale, 1993, 11(2}. 4 Hanson K, Gilson L. Coots, utilisation des ressources et financement des services de sante de base : Guide methodblogique. New York, UNICEF (!..:initiative de, Bami:lko, Rapport tech- nique N° 16). 5 ln<Jicateurs <Je sante. Sante Informa- tions, N" 25. Tunis, Ministere de la Sante publique, 1995:3. 6 Toumi A. La politique du medicament et le concept d'usage rationnel du medi- cament en Tunisie. (Table ronde : l'usage ratlonnel du medicament). MSP, DSSB, Les quatriemes journees nationales de sante publique, 19-21 septembre 1996 :1-2. 7 Prevision de budget du MSP pour l'annee 1997. Sante Informations, N" 29. Tunis, Ministere de la S1mte publique, 1996:4-5. 8 Mansouri F. Le coOt des soins de sante dans la circonscription de Medjez El Bab - Tunisie. [These de maitrise en sante publique]. Anvers (Belgique}, lnstitut de Mtidecine Truµicnle Pri11ce Leopold, 1995. 44 la Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 9 World Bank. World Development, Report 1993: Investing in health. New York, Ox- ford University Press, 1993. 1 o Hanson K, Chldele F. Cost, resource use and financing: a study of Monse District, Zambia. New York, UNICEF, 1992 (Bamako Initiative, Technical Report No. 12). 11 Couts, utilisation des ressources et flnancement des services de sante de district. Etude de cas : District d'Obala (Cameroun). New York, UN!CEF, 1993 (L:initiative de Bamako, Rapport tech- nique N° 20). 1 2 Cost, resource use and financing of uistrict health services.- A study of Otjiwarongo District, Namibia. New York, UNICEF, 1994 (Bamako Initiative, Tech- nical Report No. 22). 13 Hanson K, Nkunzimana F. Les coots et /'utilisation des ressources dans /es cen- tres de sanM de la province de Muyinga, Burundi. New York, UNICEF, 1992 (1.'.ini- tiative de Bamako, Rapport technique N° 13) 1 4 Diarna K, Robez-Masson D. Le finance- ment des couts recurrents de la sante dans le cercte de Djenne au Mali. New York, UNICEF, 1992 (L'.initiative de Bamako, Rapport technique N° 14). 15 Knippenberg R et al. Costs and effi- ciency: the Bamako Initiative, experi- ence in Benin and Guinea. New York, UNICEF, 1995. 1 6 Pour une Meilleure SaHtt:1 en Atrique. Washington DC, Banque mondiale, 1994. 17 World Bank. World development report 1992. New York, Oxford University Press, 1992. 18 Activites des commissions. Informa- tions pharmaceutiques, /II° 2. Tunis, Ministere de la Sante publique, 1996: 1- 6. 19. La demarche sanitaire nationale. Sante Informations, /II° 30. Tunis, Ministere de la Sante publique, 1997:4. Eastern Mediterranean Health Journal, Vol. 10, Nos 1 /2, 2004 45 Life expectancy and cause of death in the Kuwaiti population 1987-2000 M. E/-Shazly, r G. Makbou/2 and A. EI-Sayed3 •,?...J·, :;- ;.:,.-:;_.:,, _i..c,:. .1.,.cL1 _;_.,.L. .:; ..:.,,,~1 ,.,_, • .:.. ~· ..:,.,~1__. ,1.,_,,_;,11 ..:.,~ -~ f :u')l.;l-1 ~_;I _.;J -~".',"--'--,...;-> ~)-1 "';.;_j', .;.,I~_,]; .,:_,':j_J..,..o C::' ..!)J~ ~_,.'J ,.:_~.,sJ, ,.:15:., . .;,I ,_,;.J.: 2000-1987 .~\ ~ 4.5 1 "~I 2.2 '~~\.,:.~II t, JG.:- Jii ·f'\,,, ; ~; ~ ~ Afa 'L.,l,L.:- 75.5 . ~( 'l,4U:, 73,3 'tfi ;U-t :I ,ti..At,11 ....,/ -..,. C ......... ~ ,,I ._ ~· ...r" J J ..._ --J -._. - '-' J -..,,½-' \lj .,L.....Ji __;JJ 1..p ,__'.G,. )' ._-;.J fa' t-ll ~ _;.,} .L:.-.l, ._,.,L.. )'• ~ ~'y j', ..;..,'.,'...,.,. ~ fa J ~,1_'.-'jl_,, _J\ ~,e.& ~, 1, ·11\ ,.>::...' 1 . ..!1 .::.~I.~./ .. \I_; ,j~\\ . .,:.,_.._\.)'"-) y/--V.)!\ ~-L;_1,I ,,___:_..,,J.,. ~..., J1._""t-_,._\l J.=-: ;l._j,;-'L, :.__---})! ..J r~~I\ ..:__--.. -½ _ _,;l .:,~ .:_-L<~,1, t .. ~·~\ ~..ii'·_.~1. ~>~1 .J1 _ _.._u1 ~ _bJ1,-' s;;_,,1~';\ ~·1 __ ;,_r~., -~J-<.h ~~ ~~\ ~L..~: 'l .. )··~ ABSTRACT Census and health data were analysed to determine changes in life expectancy at birth during 1987~2000 in the Kuwaiti population and to correlate these with cause-specific annual mortality rates. Life expectancy at birth rose from 73.3 to 75.5 years with a gap between females and males, which increased from 2.2 to 4.5 years. For all causes of death except hypertension and ill-defined conditions, males had higher mortality than h::orr1dlto,;, Tl 1to lt:c1Lliriy 1,;c1u,;<;J,; vf ut1c1tt1i11111c1li:;,; wt1rt:1 i:;l.!1o11:m1k; l1tknl tli:;eiilStiS, lraflic accidents and cancer, while in females they were cancer, ischaemic heart diseases and hypertension. The problems of an ageing population will need to be considered in planning the health policies of Kuwait Esperance de vie et causes de deces dans la population kowe'itienne, 1987-2000 RESUME On a analyse les donnees de recensement et donnees sanitaires pour determiner les change- ments survenus dans l'esperance de vie a la naissance entre 1987 et 2000 dans la population koweTtienne et les com'.ller avec les taux annuels specifiques de mortalite par cause. L.:esperance de vie a la naissance est pa,.,.,;., de 70,0 a 75,5 an:i, l'ecart entre leis femme:. et le::. ilomme::. etant pa.:s:se de 2,2 a 4,5 ctr 1,;_ Let mortalite etait plus elevee chez les hommes que chez les femmes pourtoutes les causes de deces sauf pour !'hypertension. Les cardiopathies ischemiques, Jes accidents de la circutation et le cancer etaient les principales causes de deces chez les homrnes, tand1s que chez les femmes, c'etaient le cancer, les cardio- pathies ischemiques et l'hyoertension. Les oroblemes d'une population vieillissante devront etre pris en compte dans la planification des politiques de sante au Kowe'it. 'D,,:pa1tm,,:n/ of Me,i.li1.:1:1I S/1:1/i,_H,.-,;, M1:1tliu1! f'f&:s&;;trc:11 lnr:;(i/utt:1; "Deµanmem of Commum'fy Mer:llc/ne, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. 3Department of Health and Vital Statistics. Ministry of Health, Kuwait Received: 15109/02.· accepted.- 18108/03 46 La Revue de Sante de la Mediterraoee orientale, Vol. 1 o, N° 1 /2, 2004 Introduction The epidemiological transition is the most important historical change affecting the level and pattern of human mortality. The transition refers to the decline of acute in- fectious disease and the ri.:c of chronic de- generative disease over time [ l]. Conse- quently, lite expectancy has been increas- ing around the world. It is one of the key indic:1tors of pop11lfltinn hP,ilth nnn f'C'O- ~omic development. Farly and rapid gains m life expectancy in the early 20th century were due to improvement in living stan- rfarns ann organized efforts to control the spread of infectious disease [2]. The rise of life expectancy during the second half of the 20th century was slower because it de- pended on the reduction of death rates at older ages [J]. The most significant com- ponent of the mortality decline at older ages is the reduction of the rates of death from cardiovascular diseases, including heart disease and stroke, and from cance~ l 4]. The causes of change in li fc expectancy are many and varied. Epidemiological and public health factors such as lifcstvlcs and behaviours, along with the pattern of dis- eases, play ma:jor roles. The historical sta- bility of biological and other factors affecting mortality decline suggests that the most reliable method of predicting the fu- ture is merely to extrapolate past trends. Such methods suggest that life expectancy at birth in industrialized countries will be about 85-87 years at the middle of the 11 st century [ 5, 6]. In the Eastern tvfcditerranean Region, published studies about trends of Ii fe ex- pectancy at birth are scarce [7-J 2]. In a study carried in North Africa, it was found that life expectancy at birth was 50-52 years in I 970 and rose to 64-70 years in l 993, a change rhm was attributed to 1ht: decrease of infant and female mortality [7]. In the Arabian peninsula, due to the in- creased socioeconomic levels and gradual improvement in health status, life expectan- cy at birth has increased markedly [ H).J I]. The health of Kuwaitis has improved con- siderably in the past 20 years, owing to economic and social transformations that have ameliorared the problems of feeding, sanitation, hygiene, housing and social con- ditions in general, as well as health services [ 12]. It was postulated, in a study in l 984, that the pm~ntial gain in lift: t:A(Jt:ctarn;y vr the Kuwaiti population was due to elimina- tion of infectious diseases. Since this date, no study to determine trends in life cxpect- am;,y has been condm.:tcd. In this study, \.Ve aimed to define trends in lifo expectancy at birth in the Kuwaiti population during 1987 2000 and correlate the trends with cha.nging puttcrn:,; of cuuscG of death during the same period. Methods Study design This study was conducted in the Depart- ment of Health and Vital Statistics, Ministry ufHcallh, Kuw<til. Dtttu uu ull Jcatli:, in Ku- \Vait between 1987 and 2000 inclusively were collected retrospectively from copies of original Kuwaiti death notification forms and the computer databu:,c in the depart- ment. Data were analysed by sex and cause of death to examine trends in life expectan- cy at birth and cause-specific patterns of mortality among the Kuwaiti population over this period. Data coding Death notification forms in Kuu.c::iit are sent by health care facilities to 4 registration of.- fices distributed regionally to cover all gov- ernoratcs in the country. Copies of the nriginal death notification fonns 3re then sent to the Department of Health and Vi ta! Statistics for processing. First, the forms Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2.2004 47 are revised and corrected through feedback channel~ with the registmtirm offices and health care fa<.:i I itics, then the cause of death is coded, followed hy data entry, tab- ulation and reporting. Up lo 1994, causes of dea1h wf'n' r:orled according to the Inter- national c!assijicution of diseases, 9th re- vision (ICD-9! [I.n after which the cuding changed to /CD- IO l l 41. For the purpose of this study, to avoid incompatibility of the data. we recoded the underlying caust's of death from 1995 to 2000 according to !CD-9. There were no valid data for the year 1990 because it \vas the year uf the Iraqi invasion of Kuwait. Causes of death were aggregated into l 0 broad classes: ischaemic heart diseases; hy- pertension; diseases of the pulmonary cir- culation and other forms of heart diseases; lower respiratory diseases: cancer: conge- nital anomalies; perinatal conditions; endo- crine and metabolic diseases; traffic accidents; and ill-defined conditions (symp- toms, signs and abnormal clinical and labo- ratory findings not elsewhere classified). statistical anaIys1s Mortality rates \Vere computed for all caus- es of death combined and for the ! 0 leading cause groups, ranked according to the mean number of deaths during 1he srndy period. For the selected causes of death, we calculated the mortality rates over the 13 years, for each sex and ror both sexes combined, per 100 000 Kuwaiti pupulativu. Mid-year population estimates were ob- tained from the Ministry of Planning, Cen- tral Statistical Office. Li re [auk:. Wlvl C u~cd to determine the lifo expectancy at birth, i.e. hnw long the people live on average in a population [J 5]. It was calculated for each year using stan- dard lifo table techniques. Annual abridged Ii fe tables arc constructed using age- specific death rates derived from vitat reg- istration and census population data. Popu- lation data were aggregated into 5-year age intervals except for the first and last inter- vals. The first interval contained infants less than I year and the last those aged 85 years and over. As a result, the life table closed with the category 85 yi;ars and over. Calculation of the abridged life table was derived from the probability of death (q,), which depends on the number of deaths (DJ and the mid-year population (PJ for each age interval (x) observed during the calendar year of interest l 16]. The number or deaths in each age cate- gory was adjusted pn)portionally to ac- count for those whose age was not stated. An assumption was made that deaths with unreported agc were distributed among the various age groups in the same proportions as those for which age was reported. The numbers of deaths in this study represent complete counts of this event. As such, they were not subject to sampling er- ror, although they were subject to non- sampling error in the registration process. However, in the comparison of rates over time and among different groups, the re- sults were subjec1 rn random variutil111 ,111J were compared according to certain statis- tical assumptions. The difference between 2 rates was regarded as statistically signifi- cam at the 5% kvd if it .:Acecdcd 2x\/'({R! 1 N} + 'R" / N }) l I j ) :'. c wltcic R i~ the rate corre~ponding to N number of events. Detailed information un random variation may be found in the tech- nical appendix of Vital statistic.~ on the Uni ti:d Stute., [ / 7]. Correlation coefficients bct\veen life ex- pectancy at birth and cause specific mor- tality rates during the study period were determined using Pearson's correlation co- efficient (r). Manipulation and analysis of data were performed using Excel and SPSS, version 9 computer packages. 48 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Results During the period I 987-2000, Iii.: Lula] number of deaths per year in the Kmvaiti population rose from 1050 to -1448 among males and from 725 to 972 among females. Hmvcvcr, life ex.pectancy at birth incrcttscd from 73.34 years to 75.49 years for the to- tal Kuwaiti population (Table l ). The in- crease in life expectancy was higher among Kuwaiti females (3.33 years) than mule~ ( 1.05 years). The difference in life expect- ancy between males and females during each year was in favour of females and from 1987 to 2000 the difference in life ex- pectancy between females and males in- creased from 2.19 years to 4.47 years (Table I). During the study period. lifP PYpedancy in both sexes reached its lowest value in 1992. After 1992, however, a steady up- Table 1 Life expectancy at birth among males and females in the Kuwaiti populatlon 1987- 2000 Veer" Life expectancy 11l birth (years) 1987 1988 1989 1991 1992 1993 1994 1995 1996 1997 1998 1ggg 2000 Male Female Female-male Overall difference 72.22 74.41 2.19 73.34 72.14 73.80 1.66 73.00 72.32 73.10 0.78 73.27 71.38 75.14 3.76 73,10 70.47 72.-17 2.00 7168 73.94 75.25 1.31 74.67 74.10 75,91 1.81 74.99 72.69 7742 4.73 74.91 73.70 77.75 4.05 75.63 73.25 77.14 3.89 75.21 72.51 77.09 458 74.79 73.3:2 77.70 4.47 75.40 73.27 n.74 4.47 75.49 •No data available for the year 1990. ward trend in life expectancy at birth was recorded which was more marked in fe- males (Figure I). Life expectancy for males was 72.22 in 1987, decreased to 70.47 vcars in 1992 then increased lo reach 73.27 ·in 2000. The corresponding figures in females were 74.41, 72.47 and 77.74 years (Table l ). Table 2 shows the mean annual rate of · mortality for the study period, ranked by the cause of death in the IO groups of con- ditions. The mean annual mortality rates varied considerably for males and females. For all causes of death, males showed higher mortality rates lhan females except for hypertension and ill-defined conditions. The excess in mortality rates among males over females was statistically significant ror ischacm1c heart disi::ases (58.17 per I 00 000 males versus 3 1.20 per I 00 000 females; P < 0.05 ), traffic accidents (39.0 I per I 00 000 males versus 8 .18 per 100 ~00 females; f' < 0.0Y), pulmonary c1rculat10n and other hean diseases (22.60 per 100 000 males versus 15.89 per 100 000 females; P < 0.05). Although females sliowt'.d ;1 higher morrality rate from hyper- tension and ill-defined conditions than males, these differences were not statisti- cally significant. During tl,L, :.tut.!y ptTiuc.l, the leading causes of mortality among males were is- chacmic heart diseases (58.17 per 100 000 males), traffic accidents (39. 0 I per JOO 000 nrnlc.~) and c1111u:1 (37.75 per 100 000 males). Meanwhile, the leading causes of mortality among females were cancer (31.23 per 100 000 females), is- chacmic hvart di,,eusc:; (31.20 per l 00 000 females) and hypertension ( 30. 52 per 100 000 females). Table 3 shows the correlations bet\veen tifc expectancy at birth and cause specific mortality rates from the leading causes of death. Overall, there were significant nega- tive correlations between life expectancy at i • , ~ . ., -\ ·,, ,..w'' •' '1 _u;., . ~W'· ~I ......k;_. , .k... ._;.'.I J .. :.i ;,,.,..,,.,Ji ~I - ~, ._..1_. ~r,A. _, ~ ~ ., r- - Eastern Mediterranean Health Journal. Vol. 10. Nos 112, 2004 49 78 76 ..:: 74 t :.6 01 >- <> C: ~ a, Cl. >< (1) 72 - ~ _J D D D D n D 70 ~--~--~--~---~--~--~--~-----, .a. Females o Males 1986 1988 1990 1992 1994 1996 1998 2000 2002 Year Figure 1 Trends of life expectancy at birth among males and females in the Kuwaiti population 1987-2000 birth and the mortality rates from ischaem- ic heart diseases, lower respiratory diseas- es and ill-defined conditions. Among males, only traffic accidents and lower respiratory diseases were negatively correlated with life expectancy. On the other hand, life ex- pectancy among females was indirectly correlated with mortality rates from lower respiratory diseases, perinatal conditions and ill-defined conditions. However, mor- tality from pulmonary circulation and other heart diseases, ,vhich was ranked as the 7th leading cause of death in females, was positively correlated with female life ex- pectancy. figures 2 and 3 show the trends of these leading causes of death from 1987 to 2000. Mortality from these causes changed during the study years. In males, the mor- tality rate from traffic accidents was 40.93/ l 00 000 in 1987 and 41.13/100 000 in 2000, while the mortality rate from lo\ver respiratory diseases decreased from 29 .84/ 100 000 in 1987 to 16.55/100 000 in 2000. In females, the mortality rate from pulmo- nary circulation and other heart diseases was 9.01/100000 in 1987, increasing to 22.57/100 000 in 2000. Mortality from lower respiratory diseases and from perina- tal conditions during the study years fell from 20.76/100 000 and 29.77/100 000 to 14.50/IUU uuu and ':J.2// IUU uuu respec- tively (Tabk 4). 50 La Revue de Santa de la Meditenanee orientale, Vol. 10, N° 112, 2004 Table 2 Mean annual rates of mortality ranked by cause of death among males and females in the Kuwaiti population 1987-2000 Cause of death Mean annual mortality rate (per 100 000) Overall Male Female Female-male difference lschaemic heart diseases 44.70 58.17 31.20 -26.97* Cancer 34.49 37.75 31.23 -6.52 Hypertension 29.08 27.66 30.52 2.86 TrRffi,:, ,;,,rcidents 23.S.1 39.01 8.18 -30.82' Pulmonary circulation and other heart diseases 19.24 22.60 15.89 -6.72' Lower respiratory diseases 18.88 20.87 16.88 -3.99 congenna1 anomalies 11::\.bb 20.44 lti.66 -3.78 Perinatal conditions 18.87 21.11 16.63 -4.48 Endocrine diseases 16.27 17.28 15.28 -1.99 Ill-defined conditions• 16.39 16.27 16.54 0.27 Other causes 72.41 89.14 55.63 -33.82* All causes 312.50 370.30 254.64 -115.66* •Includes symptoms. signs and abnormal clinical and laboratory findmgs not eisewnere c1ass1fled. 'P < 0.05. Discussion One aim of this study was to examine the changes in life expectancy over time for both sexes of the Kuwaiti population. Our results indicate that life expectancy at hirth has increased from 73.34 years in 1987 to 75.49 years in 2000. This gain of life ex- pectancy (2.14 years) was mainly due to a decrease in crude death rates over the years of the study from 3.44/1000 to 2.91/1000 [18]. In spite of the 36.3~;, increase in the actual number of deaths from 1775 in the 1987 to 2420 in 2000, there was a progres- sive decrease in mortality rates per 100 000 Kuwaitis of both sexes during this period. This decrease can be mainly attributed to the considerable improvement of health status in the past 20 years. Economic and social transformations have led to the pro- gressive amelioration of health problems and improvements in health services. The reduction in rates of transmitted diseases and in infant, perinatal and maternal mortal- itv rates ha,e also contributed [12.I 8] ' According to the World Health Organi- zation report of 1i fo expectancy for 191 countries in 2000, Japan had the highest life expectancy for both males (77.5 years) and fcmak:s ( 84. 7 ycan;). Sic1 r<1 Lcunc hull lln; lowest male life expectancy (37.0 years) while Malawi had the lowest female life ex- pectancy (37.8 years) [19]. Kuwait was ranked a.) the 19th l<.n male und 45th for female life expectancy. Differences in life expectancy between countries can be at- tributed to many epidemiological and public health foctors [20, 21], including the rela- tionship between low life expectancy and poor income [22.23]. Eastern Mediterranean Health Journal, Vol, 1 o, Nos 1 /2, 2004 60 51 0 8 g -,-- --w "§ 50 40 30 20 - 1(] - ' 1986 ---------~- D 1988 1990 ----------- ----------~ 1992 1994 1996 1998 Year ----------~- 2000 2002 Acc,dents D Lower respiratory diseases Fioure 2Trends of cause-specific mortality rates among males In the Kuwaiti population 1987- 2000 Regarding 3Cx diffcrcncc5, our rc:mlt~ revealed that changes in lifo expectancy at birth were in favour of females. While the improvement of life expectancy was 3.33 years in females, it ,vas only 1.05 yeon, in males during the study years. The differ- ence in life expectancy bet\-.,,een males and females has doubted over the 13-ycar peri- od (from 2.19 to 4.4 7 year,;). Thi.: gender gap in life expectancy can be attributed to increasing male mortality from ischaemic heart disease and lung cancer, presumably due: the: early ::inrl wirlP,pre01d 01doption of cigarette smoking by men [24]. It has also been postulated that although women live longer than men in all areas the difference is most marked in poorer areas [25]. An additional goal of the study was to study the relationship between patterns of cause of death and life expectancy in Ku- wait. Cau5c-spccific annual mortality var- ied from males to females, Our study re- vealed that for all causes except hypertension and ill-defined conditions, males hod higher mortality than females, The leading causes of death in males were ischaemic heart diseases, traffic accidents and cancer. Meanwhile cancer, ischaem1c heart diseases and hypertension were n1ore common in females. This pattern of mor- tality mirrors the reported process of health transition in the developing world. The age- ing of the population, reductions in fertility. improved preventive and therapeutic con- trol of infectious diseases, and more afflu- ent lifestyle may all contribute to a decrease in communicable diseases and to an in- crease in degenerative and 'man-made' dis- eases and injuries [J,26, 27], 52 la Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Table 3 Correlations between life expectancy at birth and cause-specific mortality rates due to leading causes of death, among males and females in the Kuwaiti population 1987-2000 Cause of death Overall Male Female r P-vatue r .A-value r fl.value lschaemic heart diseases ---0.61 0.03 ---0.47 0.11 ---0.50 0.08 Cancer 0.40 0.18 0.27 0.38 0.30 0.32 Hypertension 0.27 0.37 0.08 0.80 0.01 0.98 Traffic accidents -0_4g O.OQ -0.6.2 002 -0.13 0.68 Pulmonary circulation and other heart diseases 0.57 0.04 0.19 0.53 0.73 0.005 lower respiratory diseases ---0.89 < 0.001 ---0.75 0.003 -0.72 0.005 congeni1aI anomalies U.l / U.!:>!:l U.14 0.65 0,14 0.65 Perintal conditions ---0.52 0.07 ---0.25 0.41 -0.64 0.02 Endocrine diseases 0.27 0.38 0.06 0.84 0.29 0.34 Ill-defined conditions" --0.78 0002 -0.51 0.08 ---0.71 0.006 Other causes -0.64 0.02 --0.49 009 ---0.84 < 0.001 All causes ---O.n 0.002 -o.n 0002 ---0.77 0.002 r = Pearson ·s correlation coefficient. •tncludes symptoms. signs and abnormal clinical and laboratory findings not elsewhere class/lied. Our data showed that male life expect- ancy was negatively correlated with death rates due to traffic accidents and lower res- piratory diseases. The increase in life ex- pectancy in males during the study years was associated with a decrease in mortality due to lmver respiratory disease from 29.84/100 000 in 1987 to 16.55/100 000 in 2000. However, the mortality rate trom traffic accidents did not change during the study years. This means that by lmvering the death rate from accidents, life expect- ancy for men could be improved. Female life expectancy was negatively correlated with mortality rates for perinatal conditions, lower respiratory diseases and ill-defined conditions and positively corre- lated with the death rate from pulmonary circulation and other heart diseases. All these causes of death showed decreased rates in females over the study period, ex- cept mortality from pulmonary circulation and other heart diseases, which showed an upward trend over time. Increasing death rate from pulmonary circulation and other heart diseases \Vas compensated by falling death rates from lower respiratory diseases and perinatal conditions. Overall, for both sexes combined, death rates due to ischaemic heart diseases and lower respiratory diseases were negatively correlated with life expectancy. The decline in mortality from these 2 causes was sig- nificantly associated with increasing life expectancy. This fits with the fact that 73''.'o of the decline in total death rates over this time period was due to a reduction in cardiovascular disease mortality. The cause Eastern Mediterranean Health Journal, Vol, 10, Nos 1/2, 2004 53 0 0 0 0 0 ,.... .§ ~ -~ 1ii t: 0 C 1ii ::I C C ro C ro G} :1: 40 30 20 10 ~ Perinatal causes ·-0-· Lower respiratory diseases - - - Pulmonary/other heart 0 r---,--------.------,--- -~----,----~---,-------,-- D di~Q~-.:.g.-.: 1986 1988 1990 1992 1994 1996 1998 2000 2002 Year l=ig11re .3 Trends of c1ms~speeifie mortality ram" among female" in the Kuwaiti population 1987-2000 of decline in cardiovascular disease mortal- ity is likely to be due to a combination of factors, including improvements in medical care in the form of better diagnosis and treatment or heart disease and stroke, de- velopment of effective medications for treatment of hypertension and hypercho- lesterolaemia and an increase in coronary care units and in emergency med1cal ser- vices for heart disease and stroke [ .-fl Increased life expectancies at birth lead to population grmvth and an increase in the proportion of the population who are elder- ly. When there arc more old people, per capita medical costs for a country will tend to be higher [ 2]. This raises the importance of dt:fiuia!:i ln;i:tll11 fJVlii.;i.;;s <1ml (JIUg,tam1m:s that will reduce the burden of ageing popu- lations on society and its economy. The de- vclopment of more long-term and geriatric care facilities should also be considered [28]. Conclusion Life expectancy at birth has increased in the total Kuwaiti population, more among females than males. Falling death rates from ischaemic heart diseases and lmvcr respiratory diseases \Vere correlated with rising life expectancy. With this continuing increase in life expectancy, survival to ad- vanced ages is much more likely, leading to problems of an ageing population that must be taken into consideration in planning the health services in Kuwait. 54 La Revue de Santa de la Mediterranee orientate, Vol. 10, W 1/2, 2004 Table 4 Mean annual rates of mortality from the leading causes of death among males and females In the Kuwaiti population 1987-2000 Year" Mean annual mortallty rate (per 100 000) Males Females Traffic Lower Pulmonary Lower Perinatal Rr.r.lrl~ntR nu1piratory circulation respirato,y conditions diseases and other diseases heart diseases 1987 40.93 29.84 9.01 20.76 20.n Hltl6 37.48 27.19 15.42 16.17 26.90 1989 34.29 18.74 10.85 17.72 19.53 1991 51.46 27.53 18.10 21.45 11.40 1992 43.91 26.22 12.28 24.55 16.47 1993 36.27 17.68 13.09 18.08 18.70 1994 32.14 19.17 14.75 13.24 18.66 1995 39.47 18.28 13.71 17.43 11.71 1996 32.77 1b.1;:! Hi.~ ,~.:.11:1 14.1:1!) 1997 42.80 18.69 16.67 16.93 15.35 1998 35.30 20.66 20.56 12.94 11.42 1999 39.11 15.64 21.10 13.25 10.06 2000 41.13 16.55 22.57 14.50 9.27 •No data available for the year 1990. References 1. Omran A. The epidemiological transition. Milbank memorial fund quarterly, 1971, 49:509-38. 2. Wilmoth JR. Demography of longevity: past, pr9sent, and futurl?. trenrl~ F1tpt:1ri- mental gerontology, 2000, 35: 1111-29. 3. Wilmoth JR. In search of limits. In: Wachter KW, Finch CE, eds. Between Zeus and the salmon: the biodemo- graphy of longevity. Washington DC, Na- tional Academy Press, 1997:38-64. 4. Achievements in public health, 1900- 1999: Decline in death from heart dii,• ease and stroke-United States, 1900-1999. Morbidity and mortality weekly report, 1999, 48:649-56. 5. Wilmoth JR. Mortality projections for Ja- pan: a comparison of four methods. In: CAsP.lli G, I. ni,P.7 A, P.ds_ HP.Rlth Rnrl mor- tality among elderly populations. Oxford, Oxford University Press, 1996:266-87. 6. Bell FC. Social security area population projections. Actuarial study no. 112. Washington DC, Office of the Chief Actu- ary, 1997 {SSA Pub. No. 11-11553). 7. Tabutin D. Evolution comparee de la mortalite en Afrique du Nord de 1960 a nos jours. [Comparative evolution in Eastern Mediterranean Health Journal. Vol. 10, Nos 112, 2004 55 mortality in North Africa from 1960 until today.] Social science and medicine. 1993, 36(10):1257-55. 8. Abyad A. Geriatrics in Lebanon: the be- ginning. International journal of aging and human development, 1995, 41 (2): 299-309. 9. Lambeth S. Health care in the Yemen Arab Republic. International journal of nursing studies, 1 988, 25(3): 171-7. 10. Bener A, Abdullah S, Murdoch JC. Pri- mary heath care in the United Arab Emir- ates. Famify practice, 1993, 10(4):444-8. 11, Hamacieh RR. Bahraini women's health: a background paper. Eastern Mediterra- nean health ;ournal. 2000, 6(1 ): 159---67. 12. AI-Bustan MA, el-Zein FM. Kohli BR. Po- tential gains In IIre expectancy or Kuwaiti nationals through partial and complete elimination of infectious and parasitic disease mortality. APMIS: acta patholo- gica, microbiologica, Qf immunologica scandinavica Suppl, 1988, 3:88-90. 13. International Classification of Diseases, Version 9 (ICD-9). Geneva, World Health Orguni.:o.tion, 1078. 14. International Statistical Classification of Diseases and Related Health Problems, 1989 Revision. ICD-10. Geneva, World Ht:ii:!llt1 01yi:111iLi:1liu11, 1992. 15. World population data sheet 1999. Washington DC, Population Reference Bureau, 1999. 16. Hertz E, Hebert JR. Landon J. Social and environmental factors and life expect- ancy, infant mortality, and maternal mor- tality rates: results of cross-sectional comparison. Social science and medi- cine, 1994, 39(1):105-14. 17, Vital statistics of the United States, 1991. Volume II, mortality. Part A. Hyattsvi lie, Maryland. National Center for Health Statistics, 1994. 18. Kuwait annual statistics reports. Kuwait, Ministry of Health Department of Statis- tics and Medical Records, 1987-2000. 1 q Wnr!rl hA;;ilfh rApnrl ?(}nt MAnfRI hARlfh: new understanding. new hope. Geneva, World Health Organization, 2001. 20. Wilkinson RG. Income distribution and life oxpoctuncy, British medical journal, 1992, 304:165-8, 21. Chenet Let al. Changing life expectancy in central Europe: is there a single rea- son" Journal of public health medicine, 1996. 18:329-36. 22. World Bank. World development report 1996.· from plan to market. Oxford, Oxford unIversI1y Press. 1 sso. 23. Mackenbach JP. Income inequality and population health. British medical jour- nal, 2002, 324:1-2. 24. Waldron I. Recent trends in sex mortality ratios for adults in developed countries, Social science and medicine, 1993, 36:451-62. 25. Abbasi K. Difference in life expectancy between rich and poor is widening. Brit- ish medical Journal, 1997, 315: 1559-64. 26. Gwalkiri DR, H~uv~lir1t:i P. lrnµruviny ll1t:i health of the world's poor. British medical journal, 1 997, 315497 ~8 27. Mosley WH, Bobadilla J-L, Jamison DT I he health transItIon: IrnpIIcatIons tor health policy in developing countries. In: Jamison DT et al., eds. Disease control priorities in developing countries, New York, World Bank, 1993:673-99 28. Santana P. Ageing in Portugal: regional iniquities in health care. Social science and medicine, 2000, 50:1036-52. La Rt:Wut:i dt:i San le dt:i la M8dlrnrrnnee orlentale, Vol. 1 o, N° 112, 2004 Capture-recapture methods for estimation of fertility and mortality In a rural district of Turkey D. Adan, 1 H. Ozoobc, 1 M. Bcrtan2 and E. Karaaoooolu 3 \.$' .J.) ¼At)! ~l:11 .J ~\.:t jlJ ~~I .,r..J.i,:) .l,ti.l';/1 a, y J J,JJ..l';/1 J), _,Jj._~1_)15" .:>y-) ,JL;_, Jr-',~} J')\_,,, ,,:.,')l_,1 ~., 01,':(,.Ji J _,,... 0L. .,..w., ._:_;IS ,~: w ... ,,.-1 .kU:J')11 • ., r _., .1>li:.l:1• J _,1, .__1J.u1 • ..L,, ...::...-<~1 :A...4"~1 ..::-v_,J..v )i 4->I~ -.:.,\..,},JI 1.ua -.:.,lJu.J) j,J.L,,_' J' o~I) o_,-,\11 ,~ jJL..) \l~I) oy_;llj ,"-!.,ill J~ : ..,r iia J.,L.a.,, -......,,i-. (.,,"' ..:;.,I_. _,k.ll ..:;.,.~I J..i _.: . ..i.;..I) .J..L.,.,, :_,,.- )ly y, Lt ; 1l.....;S"t ;5'i ,jW..~IJ ~4-\11 ":'.l..,oJ ~I-'-; ,'-J,,;\JI ½-----II "-,_i..,o)1 ?If ,._r--l1 ._r~'JI j-...u .:>f_,_ld.' ..:_,,_, .,:...Ji ..;, 1.$'; J ~J ~ J .~ ,,s_;. r 0 <~-1 -.;.,l.-J~1 ,.L. JJ> ~, ~J'.>)'1 -.:.,IJ.,-}IJ • / • • " \ I • ,;;t .!}L,, ,:__~ ,,_Li ,;;_,_,,:.Loi; ._:_;IS , .. ::.h~_.JiJ ...::..,l_._.,il .,',..ucl JI ~J') .1999 f}:.5.\iJ-•,'I .:,.-'?~ J.,l.i)-/ tUi,.; ._j 0~1 1."-~ t) ~j\~I '-~ ;_._..\_)..J'1 J.~_;;_.., +~LJ-.'1 ~~ ~}L _. . ~-._fl~ J\~I ~~ fu.i..;i; ,,j}_i) J_., ;JI i\.b_j "'!.J~ ~-,;-~ ~) ,..} .J.....c,_,,_11 ABSTRACT The study used capture-recapture methods to determine if information on births, deaths and f;:,rnily rl;:,nnino 11<::A nht;:,jn,:,c! frnm twn rl;:,f;:, <;:n,Jrr:A<: [irf'lVirlP<: fh,> c;;:im,:, nr rnnrp r:nmplpf,:, information than ttiat available from a single source. Five different data sources used were: village heads l[nukhtars), commu- nity heatth volunteers, primary health care centres, maternal and child care units and local administrative units (health group presidencies} in 1 O selected villages in a rural area of Turkey from May to October 1999. Although the numbers of deaths and births were estimated, no estimation of the number of women using any family planning method could be made. The study highlights some data collection problems of the surveil- lance system in Turkey and recommends that the routine surveillance systems be strengthened. Methodes de capture-recapture pour !'estimation de la fecondite et de ta mortalite dans un district rural enl\Jrqule RESUME L.:etude a utilise des methodes de capture-recapture pour determiner si las informations concer- nant les naissances, les deces et le recours a la planification familiale obtenues aupres de deux sources de donnees fournissent les ml!mes informations.au des informations plus completes que celles provenant d'urn, '""ul<> source. Cinq diff@r<>nt,a,;; ,;;.ourc,a,;; d" donn,;,,a,;; ont ,;,t,;, utili,;;,;,,a,;; : l,a,;; ch"fs d" villag" (mukhfars-), les volontaires de sante communautaires, les centres de soins de sante primaires, les services de soins de sante maternelle et infantile et les administrations sanitaires locales dans 10 villages selectionnes dans une zone rurale de la Turquie de mai a octobre 1999. Bien que le nombre de deces et de naissances ait ete estime, aucune estimation n'avail pu etre faite concernant le nombre de femmes utilisant des methodes de planification familiale. t.:etude met en evidence certains problemes lies au recueil de donnees du systeme de surveillance en Turquie et recommande que le systeme de surveillance systematique soit renforce. 1D,.p:arlm,.nt of Public 1-/Q;,/th;'O..p;,rtm,.nt of Bi'oist:;atistics, F;,cwlty of MQdicima, J../.ac<alt<ap<a Univ<ars:ity, Ankara, Turkay. 2/ntemational Children's Centre, Ankara, Turkay. Received: 14111/02; accepted: 22106/03 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 57 Introduction Capture-recapture methods (dual enumer- ation) were first developed by ecologists for estimating total animal populations and are now used in many fields of science. Al- though use of the methodology in human populations was first documented in the lit- erature in 1949 by Chandra-Sekar and Deming[/], it was used in population cen- suses in 18th century France. Since then. capture-recapture has been used in the es- timation of the numbers of births and deaths in India and in the population census hdd in the United States in 1990 [2,JJ. The methodology can be used for estimating unknown populations in epidemiological studies; some examples include estimating prcvale111::i;;~ uf ~pim.1 1.Jifo.hl, 1:u11gc11ital ru- bella syndrome, cancer and intravenous drug use [4-6]. In Turkey, factors such as migration from rural to urban areas and financial and technical inadequacies in health care provi- sion may have a negative influence on the efficiency of the surveil1ance systems in the health service [7,8]. It is a common problem in developing countries that health care ,staff are unaware of how and why records are completed. These factors af- fect the reliability of the record systems, especially in rural areas. Therefore, another practical method such as capture-recap- ture can be m,cd to estimate an unknown pop11lRt1on The first objective of our study was to use capture recapture methods to estimate births, deaths and the frequency of family planning use in a small mral ar~R nfTnrln~y from May to October 1999. A second ob- jective was to determine to what extent col- lection of information on vital events and family planning acceptance from two sources of data provides the same or more complete infonnation than is available from a single source. Methods Background Ilea/th services in Turkey The organization of health care services in Turkey is relatively complex. Health servic- es arc provided by both the public and pri- vate sectors. In the public sector, the Ministry of Health (MOH) is the leading health care provider at primary, secondary and tertiary levels. Health care at primary level is mainly provided by the MOH through primary health care centres, which provide outpatient health care and primary prevention activities, and collect routme data on maternal and child care, infectious diseases and vital events [9]. A number of primary health care centres report to anoth· er office under the MOH, the health group presidency (HGP), which facilitates admin- istrative activities at the district level and collects data from the health centres. Pub- Ji1,; hu:;pilab p1uviue :se1:umfa.ry iind tertiary health care activities. Other public institu- tions and private institutions also have im- portant roles in providing health care .~crviccs in Turkey. Rewrding births and deaths in Turkey In Turkey, the General Directorate of Pop- ulation and Citizenship Affairs (GDPCA) of the Ministry of Interior is a centralized structure, responsible for keeping popula- tion registers such as births, deaths and other vital events. It branches into the country through the office of the district directorate of population (DDP). The DDPs keep population registers and record vitR I ev,:,,nts at the district level then transfer them to the provincial offices of GDPCA. All the data arc gathered in the capital office based in Ankara. There are some difference<: hetween the birth and death registration systems in ur- ban and rural areas in Turkey. In urban ar- eas, as soon as a birth occurs, the birth 58 La Revue de Sante de la Mediterranee onentale, VOi. 1 u, W 11<', <'UU4 certificate of the newborn should be regis- tered by the DOP at the district level. In ru- ral areas, if the delivery L)CCurs in hospiral, the hospital ,hould issue the birth certifi- cate. But for a home delivery the certificate might be issued either by t.he nurse from the primary health can: cenm:: ur by Liu.: mukhtar who is the village head. The mukhtar is also responsible for issuing death certificates when a death occurs in the village. Ht: ~huuld then uffiLCiully inform the DDP at the district level. In urban areas, municipalities issue the burial pennits and report deaths to the State Tnslitute of Sta- LisLiLCs (SIS) l/0). Maternal and child health care services in Turkev fvi,'ltcrnal and child health care :-crvicc:'I nrc usually provided by primary health care centres and by maternal and child health care and family planning units (l\1CHUl, ah~, v.·ithin the lv10H. Nursee1, mid~YiYes and physicians are service providers in all of these units. Midwives and nurses are the staff responsible for detennining and fol- lowing up women of reproductive age liv- ing in their \vorking area, improving the use of family planning methods, identifying and follo·wing up pregnant and postpartum women and infants a;: \veil as follo,,.,cing up nc\.vboms for the first 6 years and carrying out immunizations. Studv ,1ru,1 ,,nd population Polatl)' is a district of Ankara province lo- cated about 76 km west of the capital An~ kara. The rural part of Polatly includes 90 vilbgcs. In re,,,.nt ye;ir,, mir,rntinn from rural to urban areas of Polatly has in- creased. Therefore, some vital statistics (crude birth rate, crude death rate, the numhf'r nf women uc;ing: family planning. etc.) have been underestimated in the re- corded health service data [11]. Haccttcpc Public Health Foundation has set up a project entitled "Community based reproductive health services for adoles- cents and adults in Po lad) district, Ankara" in 26 villages of Polatl). The aim of the project is to increase the health status of the target population by using i;unm1w1ity participation methods. Within the project, community health volunteers \Vho have the potential to be leaders in their own commu- nity are determined and sekcLed from women and men in the study villages. Fe- male health volunteers arc responsible for registration of births, identification of v,,'omcn aged 15-49 years, regislraliun ur womens gynaecological complaints, follow-up of pregnant/postpartum women, identification of newborns, distribution of condoms, oral cuntran:pli vec; aml fulil: acid iron deficiency pilJ:... for anaemia, and education of women about reproductive health. Male community health volunteers an: respuusibli; Cur i 11 Cui rJJing uH.:u abuul reproductive health, especially about sexu- ally transmitted diseases, distributing con- doms, recording deaths and supporting the V.'OIIICII hcaltlt vulur1lcc1s. Currrn1u11ily health volunteers use data fonns to record their activities in the field, including follow~ up of women aged 15-49 years; follow-up of pregnam.:y, pu~lp<11lurn ;iuu 11cwuu111 care; and birth and death records [11]. Data estimations The current study was conducted in the region of the community participation project. Ten out of 26 villages were select- ed proportionally according to the popula- tion sizes of the villa5c3. A;,; it w11~ p\11nncd as a method trial, the most important issue was not the representation power of the to- tal 26 villages but obtaining the greatest ..:overage of the population. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 59 l-./umber of births Two independent data sources \Vere used to estimate births: the records of the HGPs and the birth records (infant determination fonns) from the community health volun- teers. The formula used for estimation of births for the capture-recapture method ,vas: (Jvf+ I) (n + I) iV= (m + l) -1 where N= thi.: unknown total number of births M =number of births in community heahh volunteer records n - number ofbirths in HGP records m= number of births identified in both captures (matches L The formulas shown be!m:v were used to calculate the variance (Var) and 95~o confidence interval (CI) for the estimate of lV: Var(]{)= }vi x n (M - m) (n - m) / mJ N = ± 1.96 '11Var (N) For estimation of births, 5 matching cri- teria specific enough to define the case ,:vcrc recorded in each data source. The degree of matching was defined based on 5 different standards (A-E). For standard A, all the criteria should be exactly the same in both data sources. For standards B-E. the criteria were progressively reduced so that each subsequent standard required one less criterion for matching. J\lumber of deaths In this study, the deaths occurring in the previous 6 months were evaluated using 2 independent data sources: death certificates registered by the mukhtar and death records (death detem1ination forms) from the community health volunteers, If all the criteria in both records matched exactly, then the matching standard 'NUS accepted as standard A For standards 8-E, the crite- ria were progressively reduced. so that each subsequent standard required one less criterion for matching, as was done for es- timating births. Numher <f \ll'Otnen using fami(v planning Data on the forms of community health volunteers, primary health care centres and MCHUs were used to calculate the number of women using family planning methods. The name and surname of the women \Vere used as matching criteria. N' = --- where n k nu i=l E) l\1 = total number of women using family planning methods. k = number of data sources used. £1 = the probability that the event occurs in the 'i'th source. ( 1 - E) "" the probability that the event does not occur in the 'i'th source, n = (nl U n2 U n3) .,., nl + n2 + n3 - (n I n n2 ) - (n I n n3) - ( n2 n n3) + (nl n n2 n n3) n I number of women using family plan ning methods in community health volunteer fonns. n2 = number of women using family plan ning methods in primary health care unit fr1m1s. n3 = number of women usmg family plan ning methods in MCHU fonns. Results In this study, 5 different data sources were used for c~timating the unknown number5 of births, deaths and women using any family planning method (Table l ): mukhtar, 60 La Revue de Sante de la Mediterrnnee orientale, Vol. 10, N° 1/2, 2004 Table 1 Data sources and sample sizes in the first capture for each data source (Polatly, May-October, 1999) Variable Data source CHVs PHCs HGPs Mukhtar MCHUs No. of births No, of deaths No. of women using 10 24 family planning 382 23 C..'HV = community nea/tn volunteer. PHC = primary health care centre. HGP = health group presidency Mukhtar = village head. 17 21 5 MCHU = matemal and child health care and family p/anmng unit. indloatc3 nat toao,..ded. community health volunteers, primary hcolth cure centres, mutcmal ond child care units and health group presidencies. Births According to the record,; of the community health volunteers, IO births occurred be- t\Veen May and October in the study villag- es. During the same time period, there were 17 births according to the record,; of the HGP. The estimated number of births was 65 ± 3 ! if all the matching criteria were the ;;ame in both data sources. This number was found to be 32 ± 18 when 4 of 5 matching criteria were the same in both data sources. If only 1 criterion of 5 was the same, the estimated number was 21 ± 5. It was assumed that at least 3 of the cri- teria would define a birth in each data source. From this perspective, standard 'C' was the lea,;t accepted category (Table 2). Deaths There \vere 21 deaths recorded in the com- munity health volunteers' forms. This number was 24 according to the registries of the Public Registration Office based on information from the village mukhtar be- tween May and October 1999. The estimated number of deaths was I 09 ± IO I .4 if a 11 the matching criteria were the same in both data sources (Table 3). This number was 49 ..L 16 if 5 of 6 match- ing criteria were matched and 27 ± I if I of 6 matching criteria was matched. The least accepted category for death numbers was the stundurd 'C'. However, in each catego- ry 'C', 'D' and ·E' the estimated number Table 2 Estimated number of births by the capture-recapture method (Polatly, May- October 1999) Standard No. of No. of Estimated no. A B C D E matchoa pooplo (out of 5) 5 2 4 5 3 5 2 5 8 of births :1: 95%CI 65± 31 32 :t 18 32 ± 18 32 ± 18 2i :t 5 Matching enter/a: name, surname, name of husband, date of birth. sex of baby. Cl = confidence interval. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 61 Table 3 Estimated number of deaths by the capture-recapture method (Polatly, May- October 1999) Standard No.of No.of Estimated no. matches people of deaths :t (out of 6) QS%,CI A 6 4 109± 101 B 5 10 49 ± 16 C 4 19 27+ 1 D 3 19 27± 1 E 2 19 27 ± 1 Matching criteria: name, surname, sex, place of death. date of death, age of death. Cl = confidence interval. ,vas 19. In other words, there wn:.. 110 llif- frrenee between the standards in which ei- ther 4 or 2 <.:riteria matched. The criteria that did not differ from each other were: name, surname, sex and name of the vil- lage. The mukhtar reported more deaths than community health volunteers did. ffomcn using_famiZv planning According to the community volunteers' records, 382 women ,verc using any meth- od of family planning between May and October 199') in the study village;;. Thi:s number was only 23 in primary health care unit records and 5 in the records of the MCHU. The number of vmmen using any family planning method could not be esti- mated. Discussion Only 10 vi II ages were included in this study, thus the study population was too small to generalize the results. The study was designed as a trial for assessing the applicability of the capture-recapture methodology in the field, which has not been commonly used before 110\v in Tur- key. The capture-recapture method is very sensitive to the matching procedure. Tht: matching criteria developed for estimation should be specific enough to define the cases. The cut-off point for the matching criteria might change the results of the study. lf the matching criteria are less strict, the estimated total number of cases is lower. For this reason, matching criteria ·were selected very carefully in this study. The criteria for births-women's name, surname, husband's name, date of birth and sex of baby-v.·erc descriptive enough to define a binh in Turkey. In Turkey, there are some legal obliga- tions in recording births and deaths. ln this study, there were some problems about de- tcrmini ng and ~ccording these 2 vital events. Both traditionally and culturally, people give more imprntance to deaths than to births. As soon as a person dies, tradi- tional ceremonic~ arc performed in the community. This means that community health volunteers arc sensitive to the occur- rence of a death and therefore their death records might be more accurate than their birth records. Furthern.orc, the mukhtar is legally required to report deaths within a specified time. This is one or the most im- portant reasons why es1imation 1)f deHths arc more accurate than the estimates of bi11hs and family planning. Although there arc legal regulations about registration of births by primary health care centres, no births \Vere regis- tered by these centres. This is \vhy \Ve used the HGP records for estimation of birth numbers. One of the basic assumptions of the capture-recapture method is that the study population should be closed [5]. In our study, the study region is very close to the capital and the migration rate is very high in the area. In addition, a number or people live in the district centre in winter and re- 62 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 turn to their villages for the agricultural ac- tivities in summer. These factors might have weakened the propeny or· being a dosed population and affected our estima- tions. Another key assumption for applying capturc-n:capture is that the data :murces should be independent of one another [ I 2]. In this project, we should take into consid- eration that community health volunteers might n:fcr people who arc pregnant or have health problems to the health centres. In this situation, a positive dependence might have caused a lower estimate of 'N' than the expected values. Nevertheless, the prevalence of referring people to health centres was 4.3% among community health volunteers [JJ]. Therefore, the esti- mation of birth nurnhi:-:n: might h~ lowF.r than the expected number. The number of women using any family planning method could not be estimated. The capture-recapture method has usually been used for estimating rare and diagnos- able diseases such as birth defects and spi- na bifida [2, 13]. In the case of family p]anninJ;!;, however, there is the problem that couples may change their family plan- ning method over time. For example, a woman using an intrauterine device at the beginning of the study might have changed this method and begun to use oral contra- ceptives at the end of the study period. There was also the problem that data sources for family planning method use are widely dispersed and not coordinated with- in the area. The private sector plays an im- portant role in providing family planning services and it was impossible to match the records of the public and the private insti- tutions. For this reason, estimating the number of women using any family plan- ning method was not possible. The capture-recapture me1hod has been used extensively for estimating the size of animal populations where marking of animals after capture lessens the possi- bility of errors. for epidemiological studies with humans, the estimation is more com- plicated. In conclusion, it can be said that the method of vcrificution of the number of vi tal events as used in this project has been pre-tested. We hope that this study high- lights some data collection problems of the surveillance system in Turkey. By uging capture-recapture, some health measures, especially births and deaths, could be esti- mated in a rural area in Turkey, but the matrhine; rritF.ria, cli~trih11tion of the health institutions and other limitations might af- fect the estimates of the real numbers of deaths and births. It should be remembered that the cap- ture-recapture method is an alternative method for the estimation of unknown events. The major approach should be to strengthen the routine surveillance systems in developing countries. Acknowledgements We are grateful to Associate Professors Lev- ent Akyn and Bahar Gii~iz Do~an for support that they gave throughout the study. We are grateful to United Nations Family Planning Association for financial support and ac- knowledge the 'Safe Motherhood Project Team' for data collection. We are also grate- ful to the health staff working in Polat1y dis- trict for their cooperation. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 63 References 1, Chandra-Sokar C, Deming WI:, On a method of estimating birth and death rates and the extent of registration. Jour- nal of the American Statistical Assoc,a· tion, 1949, 44:101-15. 2, McCarty JD et al, Ascertainment cor- rected rates: applications of capture-re- capture methods. International journal of epidemiology, 1993. 22(3):559-65. 3. Sudman S, Sirken MG, Cowan CD. Sam- pling rare and elusive populations. Sci- ence, 1988, 240:991-6. 4. Hook EB, Albright SG, Cross PH. Use of Bernoulli census and log-linear meth- ods for estimating the prevalence of spina bifida in livebirths and the com- plctcnc::is of vitul record reporta in New York State. American Journal of epidemi- ology, 1980, 112:750-8. 5. Sutter RW et al, Assessment of vital sta- ti:-.tic:-. and :-,urveilla.nce dalct fu1 111u11ilur- ing tetanus mortality, United States, 1974-84. American journal of epidemi- ology, 1990, 131: 132-42. 6. Egeland MG, Perham-Hester KA, HOOK EB. Use of capture-recapture analyses in fetal alcohol syndrome surveillance in Alaska. American journal of epidemiol- ogy, i 995, 1'11:335---'11. 7. Sumbulo~lu V, SOmbOloOlu K. Data col- lection skills for health staff. Health infor- mation system training series, 1st ed. Ankara, Mini;itry of I lea.Ith, 199G:14-G. 8. Tezcan S. Epidemiologic data sources- medical research epidemiology Ankara, Haocttopc Publ10 Hoalth Foundation Press, 1992:161-71. 9. Tezcan S. Information on morbidity and causes of death in Turkey. In: Wunsch G, Ha.ncyoOlu A, ed::,. Ma1bidity and ma1ta.l- ity data: problems of comparability. Insti- tute of Population Studies publication no. IPS-HU.97-01. Ankara, Hacettepe Uni- versity Institute of Population Studies Publications, 1997: 191-208. 10. Hancyo~lu A. A demographic assess- ment and causes of data and information on Turkish mortality. In: Wunsch G, HancyoOlu A, eds. Morbidity and mot1al- ity data· problems of comparability. Insti- tute of Population Studies Publication No:IPS-HU97-01. Ankara, Hacettepe University, 1997:209-34. 11. Asian D. Estimation of the number of us- ers of family planning methods, births and deaths in villages selected in rural areas of Po/ally district, Ankara by capture-re-capture method [thesis]. An- kara, Department of Public Health, Hacettepe University, 2000:29. 12. Ackman OM, Birkhead G, Flynn M. As- sessment of surveillance for meningo- coccal disease in New York State. American journal of epidemiology, 1986, 144:78-81. 13. Honein MA. Paulozzi LJ. Birth defects surveillance: 'assessing the gold stan- dard'. American journal of public health, 1999, 8:1238-40. 64 La Revue de Sante de la Mediterranee orientale, VoL 1 0, N° 1/2, 2004 Adolescents' use of health services in Alexandria, Egypt: association with mental health problems M. Afifl' a...-,i:JI ~1 ..:..,~ .u,.~JIJ ,~ "-!.y,L.:.S:....'jl ~~\..:.,Lo~ ~1)1 ~\~\ ~~ ~· ~L).5-....:,.._,;_ • ..:.Jj::, .k\.:,.-)\) .._,.~1_).11 i_..P. ~I~ ~I ._J\..,i,....d,...l t'1~'1 cjL.i,; ~ 1_)....J\ __..;;, ~~~~ ,.:_,,:..i.!I J;U.il ..,..,;)~, ,j· 1577 ,:....a, _;:_.i..i,h;, 1 0.0-~ ;;,,,;,-1_,..!...-- J~ ;;,,_1_;..i.!I .,:...le'- ·..,..a-" ,",Cj-1.;..C't c) ~I ' ii,;. ._rJ.)I, ,.._.,J1 .,._;, ,JI ', ~ l,..;I_:, ~ ...:.,i)l..;;...,1 • I., 1,.:_.._C,,1 ,L.l; 19. 14 ',c, ...,. ,~; - ,1 "-' ~ - .J'""'- ... i y~ L _,. ._, _,. M .... , .._, ...;' .. ,i '-'~· I - i..... ...I ...I j'L_..i. _, JLl.k\l c.,;...U ..,.,1.6'':.'\.: ..._,l_,.;. ; r"" Wu ~I.=,- J) ,~'J.1 ~I _j ~I _;:_,L,.J..il._i \1~\) ~I ..;.,bl,,,,;,I ,,,.._1_.-.:..::.-1 ,~: ..,.,)1~1 if /.97.1 t,~i -UJ -~t).1 F .:r L;L, ,._w;:..'---c: .,_.;.ill ~l:...wl L~I ;;_.~ i.1 .<I, ... _!,j .-.L..J '/93. 7 JI,. ~ ~: ... , ... J1 -~ ; '""" ..... .11\ ::.-,.,. - ~ J"' r' ,I 1~,;:-. j , ½ J .._, .,... .., .:;~\ ..,:....iL_:.._:.L1 ('_Gc__:_____,,."1 .i.:. ~ "/.13.6 .ji_:. ~I ~ 1, .__::_,L,.J..,_~ t--L-~ 1, ....Li~ "/.16_8 .)t_,.. _::'i~·_/·~jl 'e°'1~·1 ,·.~ :;•L;1~1., (1 8 ~-::--~)\·1 ~) ¼1_11 ~· . .j -.,$~ ,_~_.,.,. ,- ...... ;t.;W1 .._:....k..:·1; _.lj~ ~_r\11 .._. "o :i.c:.,; l.k_,1) (5.53 - .__,,..._,- _; ',:', '-') '.i.Jl_,_1.,c- _-",'/'i .:_c" owL..:.1_. (2 93 - ~-,,c-----c J \'I ~-,--·) -.,.,'ci~\11 '--- ABSTRACT The study assessed patterns of health service use by adolescents and the association with mental health problems in Alexandria, Egypt. A systematic stratified random sample ol 1577 school students aged 14-19 years completed a self-report questionnaire about demographic and health status, use of health services in the previous year, and the Children's Depression Inventory and the Adolescent Sell-Report Aggression Scale. Overall, 97. 1% of students reported using school health clinics once or more in the year l>efore lire :;tuuy, 93.7% µrir1rc1ry tri:,c11U1 <,;i:,11lIe:s, HL6o/o r11i:,11lal l1t>c1ll11 ,;t,1vi,;t,::; c111u 13.6'l'i:, vtt1e1 l1t,<1tl!1 services. A history of organic illness in the previous year (OR= t .80), having depressive symptoms (OR= 2.93) and having aggressive symptoms (OR= 5.53) were significantly associated with frequent use of health services (?: 4 visits/year). L.:utilisation des services de sante par les adolescents a Alexandria (Egypte) : association avec les problemes de sante mentale RESUME L'etude a analyse les schemas d'utilisation des services de sante par les adolescents et l'association avec les problemes de sante mentale a Alexandria (Egypte). Un echantillon alealoire systema- tIque s1ra1me oe t 577 tyceens ages de t 4 a 19 ans a remptl uri quesuurma1re u·au10eva1uauor1 sur la situc1lior1 demographique et l'etat de sante, !'utilisation des services de sante au cours de l'annee precedente, ainsi que l'inventaire de depression chez l'enfant" Children's Depression Inventory "et l'echelle d'evaluation " Adolescent Self-Report Aggression Scale ". De maniere generale. 97, 1 % des lyceens signalaient avoir utiti,;:g I,;,,; c,;,ntr,;,s medic;,uv scolairs>s unp fni, no, ph,co :a, I1Y,, 1r<: rlP t':annt>P rrA~Prl:anl t'o:\trirl+>, q:17 % IA.c; centres de sante primaires. 16,8 % les services de sante mentale et 13,6 '%, d'autres services de sante. Des antecedents de maladies organiques au cours de l'annee precMente (OR = 1,80), le fait d'avoir des sympt6mes depressifs {OR= 2,93) et des sympt6mes agressifs (OR= 5,53) etaient associes de maniere significative avec !'utilisation frequente des services de sante (e: 4 visites/an). 'Directorate of Research and Studies, Ministry of Health, Muscat, Oman. Received: 29/04/03; accepted: 20/08/03 Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2, 2004 65 Introduction Many teenagers depend on multipk: sourv es of health care, and school personnel arc important sources of health-related infor- mation [J]. The expansion of school-based health services since rile early I 970:s is a specific response to meet the medical needs of youth [2]. Adolescents are often vulnerable to particular health risks and face multiple barriers to al.:ct:s:sing l11;<1.IU1 care. School-based clinics represent an al- ternative model of health care that responds to the unique health issues of adolescents by offering preventive, cumpn:ht:11:sivc sc1- vices, including mental health and other sensitive services [3]. According to Parker and Roy, the chances of becoming depn:sst:d in c1uuks- cence increased in the latter part of the 20th century and the onset of depression is observed at a younger age than before [ 4]. They added rhat adolesl.:em depn::issiuu b manifested either as melancholic symp- toms or as irritability and anger. The association between adolescents' use of' health servin:s antl Lht::i1 1111::utal health status is controversial. Pastore et al. found that the average users, frequent us- ers and non-users of a school-based health cemre did nol differ in tht:: u11,;11ltil h1::altb problems measured in their study [51, whereas others have found that depressive symptoms were associated with increased service uti1izaliuu [6]. The aim of this smdy was to assess the patterns of use of different health services by secondary school adolescents aged 14- 19 yt:ars in Alt:!i.andria, Egypt, <1.wJ to exam- ine the association between utilization and adolescents' most common mental health problems, namely depressive and aggres- sivt: :sy1nplt1111). Methods Subjects ln a cross-sectional school-based study in 1996, 1577 students of both sexes were selected by systematic stratified random ~ampling from 12 secondary schools rep- resenting the 6 districts of Alexandria, Egypt. Research instruments A self-report questionnaire was designed by the researcher to be completed by sec- ondary school students. Jt included derno- gruphic and personal data such as age, sex, birth order, number of friends, number of family members, degree of family coher- ence, satisfaction with schoul, history of dropping u class and history of organic ill- ness in the year prior to the study. Respon- dents were asked how many times they had visited primary care centres, school health clinics, mental health services or other health services (e.g. private clinics, general or military hospitals) in the previous year. The questionnaire also included a question on cigurcttc smoking (never-, ever-, ex- or current smoker). The Arabic Social Class Scale [ 7] was applied to participants' re- sponses. This uses the degree of parents' education, occupation and crowding index (number of family members divided by number of closed rooms in the accommo- dation). To obtuin a history of emotional distur- bance in the previous year, students were asked if they had had any emotional or psy- chological problems that made them con- sult a doctor in the year before the survey. Two further tools were used to assess ado- lescent depression, which usually mani- fests either as melancholic symptoms or as irritability and hostility [ 4]: la Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 • The Arabic version of the 27-item Chil- dren's Depression Inventory [8] covers an array of depressive symptoms. t.ach of the 27 items of the inventory assess- es I symptom by presenting 3 choices arranged from O to 2 in the direction of incn:asing psychopathology and total score ranges from Oto 54, The invento- ry's test-retest reliability was 0.9 and the cut-off score was 24, which means that adolescenrs having this score or above were considered to have depres- sive symptoms. • The Arabic version of the 14-item Ado- lescent Self-Report Aggression Scale (9], covers an array of aggressive symptoms. Each of the 14 items of the inventory assesses I symptom by pre- sentmg J choices arranged from O to 2 in the direction of increasing psychopa- thology and total score ranged from O to 28. The scale's split-half reliability was U./o tor boys and 0.65 for girls and the cut-off score was 18 for both sexes, which means that adolescents having this score or above were considered to have aggressive symptoms. It took around 40 minutes for the stu- dents to complete the questionnaire and other scales during a class session. Data processing and statistical analysis Uata coding, entry and management i.vas made using the Epi-lnfo statistical program [ I 0]. followed by data analysis using SPSS, version 6 for Windows [Jl]. Ethical issues To preserve confidentiality. no direct or in- direct identification of respondents was used. The adolescent respondents gave their verbal consent to participate in the study. Pre-testing of the questionnaire was conducted on I 00 students of both sexes before running the study. Results From the 12 secondary schools in Alexan- dria, 1577 adolescent students (49.8% male} competed the questionnaires and se 1 f-report ~r::1 le~ Th,.:-ir ages rangc.,d from 14 to 19 years with a mean of 15.8 years (SD 1.3). Table l shows the different utilization patterns of hra 1th services. by adolescents. School health clinics had the highest rate of utilization; 97. l ¾ of students used this fa- cility once or more in the year before the Table 1 Utilization of different health services by 1577 adolescents in the year before the study No.of Respondents visiting: visits.lyear Primary care School health Mental health Other health centres clinics services services No. % No. % No. % No. % 0 100 6.3 45 2.9 1312 8.3.2 1362 86.4 1 920 58.3 842 53.4 265 16.8 215 13.6 2 511 ~~4 fi06 38.4 0 0 0 0 3 28 1.8 50 3.2 0 0 0 0 4 18 1.1 34 2.2 0 0 0 0 ···----·-------· Eastern Med11erranean Health Journal, Vol. 1 o, Nos t/2, 2004 67 study. compared with 93.7% for primary health centres, 16.8°/o for mental health services and 13 R!'i, for other health servic- es. Only 17.0% of the sample used every type of health service studied at least once in the year before the study. About 57% of the sample reported having used more than 1 source or care in the year. The median number of visits to any of the cate.gories of health services was 3 and the range was 0-10 visits. Adolescents were grouped into frequent users (4 or more visits/year) and infrequent users (0-3 visits/year). Overall, 46 7 (29 .6%,) of the samp!c were frequent users of health ser- vices. The percentage of adolescents fre- quently usmg health services distributed according to their age is shown in Fi).'.ure 1. No significant difkrencc in frequent utili- zation \Vas noticed betv,·een different age groups. The respondents' scores on the depres- sion scale ranged from 1 to 43, ,vith a mean of I J .2 (SD 6.17). After applying the cut- off score of 24, 69 ( 4.4{1/~) of the sample were considered to have depressive symp- toms. The adolescents' scores on the ag- gression scale ranged from O to 26, with a 35 326 29.4 30.2 30 ~ 25 <I) <II 20 ::, c 15 0 10 0 5 0 f<f\ '1, t,,'o'o" P.,0, '1, 1.f"' .,t. ~'\ .,<:> ,;, ,s,'' .,io "" ,$' mean of 11 (SD 4.4). Applying the cut-off score of 18, 78 (4.9%)) of the sample were considered to have aggressive symptoms. Overall, 190 (12.0~·o) students reported a history of emotional disturbance. There were significant associations between hav- ing a history of emotional disturbance and having (kpn:ssive symptoms and aggres- sive symptoms (Table 2). Such association was examined before entering the history of emotional disturbance in the logistic re- gression model as a confounder to depres- sive or aggressive symptoms. Adolescents \Vho reported frequent use of primary health centres or school health clinics were more likely to have aggressive and depressive symptoms than infrequent users. The correlation coefficient bct'1vcen number ot visits to health tac1ht1cs and de- pression and aggression scores respective- ly were 0.14 and 0. I 39 (P < 0.00 I). The coefficient correlation between depression and aggression scores was 0.428 (I' < 0.001) (data not shown in tables). Table 3 shows the variables that were significantly positively associated with fre- qucm use of health facilities in a multiple logistic regression model. These were: a 28.3 296 ~ ,_'l,0 ';,,r:-::,, '.\'\' 0 ""' ,;, ,:, '-S:,, '5.' ,,, .,__'o "() ~'5.' ~o''l> Age (years) Figure 1 Distribution of frequent users ot health services by age (n"' total number of respondents in each age group) 68 La Revue de Sante de la Mediterranee orientale. VoL 1 o, N° 1/2, 2004 Table 2 Association of depressive and aggressive symptoms with adolescents' history of emotional disturbance in the year before the study Symptoms History of emotional disturbance Total Depression No Ve,,;. No. % 158 10.5 Nn No. % No. % 1350 89.5 1508 100.0 Ye:, 02 40.4 :J7 5:J.0 00 100.0 Mantel-Haenszel X2= 3.99, P= 0.046 Aggression No 175 11.7 1324 88.3 1499 100.0 Yes l!J 1\:1 . .:: 53 80.8 713 100.0 2 Mantel-Haenszel X = 80.19, P<0.001 Total 190 12.0 history of organic illness in the year before the study (odds ratio tOR} = 1.80), having (lepre,co,;i,,c -.:ympl,.Hii¼ 1nR = 1 Q;) ,1n,i having aggressive symptoms (OR 5.53 ). Birth order (oldest child), history of drop- ping a class at school and history· of emo- 1 ion al <listurhance were significant negafrvely associated variables. Age, sex, social class score. satisfaction with school, number or Criends, and family coherence \Vere not significantly associated with fre- quent usage. Discussion The association between adolescents' psy- chiatric symptoms and the pattern of utili- zation of health services has to our knowledg,.:, never been sl~1died before in Al- exandria. However, the study relied only on self-report questionnaires that, despite be- ing easy to apply, might yield inaccurate re- sponses. The study should therefore be viewed as preliminary. The results or the current study noted under-utilization of mental hcallh services 1387 88.0 1577 100,0 by adolescents. Cohen and Hesselbait men- t10ned that the under-use of services of middle income :inti mrnl chil.iren might rea- sonably be ascribed to access problems [ 12]. Kulka l'.l al. indicated that people of lower socioeconomic status have a lower rate of mental health service utilization [/ 3]. This is inconsistent with our findings, which showed no significant association between utili/ation of all types of health fa- cility and the social class of the study sam- ple. We also showed that there was no significant association between frequency of utilization of health facilities and the ado- lescents' sex. ,vhich is similar to what Th- ompson et al. found in their study [ 14]. Adolescents' age also had no association with utilization. Ryan ct al. mentioned that age and sex were more important in pre- dicting use of illness-related care than rou- tine use of medical care [ 15]. The under-utilization of mental health services could be a resort to avoid the stig- ma ofhcing mentally ill, lack ofcontidentl- ality on visiting the crowded general hospitals or because health insurance for Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 69 Table 3 Independent variables associated with frequent use of health services (4+ visits/year) by 467 adolescents In stepwise logistic regression analysis Variable OR Aggressive symptoms 5.53 Depressive symptoms 2.94 History of organic disease 1.80 Higher birth order 0.92 History of dropping a class 0.70 History of emotional disturbance 0.60 OR = odds raNo. Ci = confidence interval. adolescents is not extended to private: rlin- ics. Ziv et al. found that adolescents under- utilized physician offices and they were more likely to be uninsured than other age groups r/61. Ryan et al. concluded that having a regular source of care and health insurance were strong predictors of using medical care (/ 5]. School health clinics were the most highly utilized facility in the current study. Only 2.9% of the sample did not use this facility in the year before the study because all school students in Alexandria, Egypt, are medically insured within the school health clinics, school health polyclinics and school health hospitals. That was in com- parison with 6.3% who had not used pri- mary health centres, 83.2% not using mental health services, or 86.4% not using other health services. School-based clinics staffed by an interdisciplinary team of health care professionals are among the pi- oneering efforts that address both health and education of adolescents ll7]. School 95%CI P-value 3.33-9.19 < 0.001 1.71-5.06 <: 0.001 1.18--2.77 <0.001 0.85-{).99 0.02 0.51-0.97 0.03 0.41-0.89 < 0.001 herilth clinic~ can also increase students' health know ledge and access to health- related services [18]. Adolescents \vho reported more fre- quent use of prim:iry ht'."Alth t'."entre~ or school health clinics were more likely to have aggressive and depressive symptoms than others. Consistent evidence has shown that a substantial proportion of peo- ple with emotional problems and mental disorders are treated in the physical health sectors [ 19, 20]. Alegria et al. found that subjects with high scores for psychiatric symptoms were also found to make more use of general health services [ 2 l]. Johnson ct al. found that major depression and dc- pressi ve symptoms were associated with increased service utilization [ 6]. Hansson et al. also concluded that patients in contact with psychiatric services were more fre- quent users of other medical services [ 22]. In contrast, Katerndahl and Realini con- cluded that subjects \vith panic symptoms reported higher rates of health care utiliza- 70 La Revue de Sante de la Mediterranee orientale, VoL 10, N° 1/2, 2004 tion despite having less insurance coverage and experiencing barriers to access [ 2 3]. The high utilization pattern of general health facilities by adolescents with depres- sive or aggressive symptoms in the current study could be explained if adolescents in- creased their utilization of general heath services when psychiatric services utiliza- tion was reduced. It could also be assumed that somatization occurs in response to stress for the predisposed personality, which in turn would increase utilization of the general health services. Conclusion and recommendations Depressive or aggressive symptoms were associated with increased utilization of school health clinics and primary health centre facilities. To achieve the goal of mental health care for all Africans, psychia- try should be included m the pnmary health care programme. Physicians actually pro- vide services to more patients with depres- sive symptoms than to patients with tormally defined conditions of depressive disorders. For those working with adoles- cents, it is important to take into account all aspects of the individual's world. Cumula- tive life stress, friendship networks auJ self-esteem should be considered when working with non-clinical as well as clinical populations. We n:1,;ummcml fu1 Lhc:1 1;tudy ui,ing standardized personal interviews to estab- 1 ish a psychiatric diagnosis for adolescents in addition to reviewing utilization patterns l1u1J1 11ca.lth facility records in~tcad of 9clf- reported use of health services. References 1. Klein JD, McNully M, Flatau CN. Adoles- cents' access to care: teenagers' self-re- ported use of services and perceived 1:1i.;1,;t1i:;::; lu 1.onfidential care. Archives of pediatrics and adolescent medicine, 1998, 152(7):676-82. 2. Ryan S, Jones M, Weitzman M. School- based nea11n services. Currem opinion ;n pediatrics, 1996, 8(5):453-8. 3. Brindis CD, Sanghvi RV. School based health clinics: remaining viable in a changing health care delivery system. Annual review of public health. 1997, 18:567-87. 4. Parker G, Roy K. Adolescent depression: a review. Australian and New Zealand journal of psychiatry, 2001, 35:572-80. 5. Pastore DR et al. School based center tllili7ation: a survey of users and nonus- ers. Archives of pediatrics and adoles- cent medicine, 1998, 152(8):763-7. 6. Johnson J, Weissman MM, Klarman GL. Service utilization and social morbidity associated with depressive symptoms in the community, Journal of the American Medical Association, 1992, 267(11 ): 1478-83. 7. Fahmy Sl, EI-Sherbini AF, Determining :;i1111-.1lt1 parameters for social cla:iaific;a- tion for health research. Bufletin of the High of Institute of Public Health, 1983, 8(5):95-9. tl. AOu-Nazel MW. A sruay ot cfepresslofl among Alexandria preparatory school students [DrPH thesis]. Egypt, Alexan- dria University, High of Institute of Public Haalth, 1990. 9. Afifi M. A mental health component in pri- mary health care for prevention afld management of adolescent suicidal be~ havior [DrPH theaia], Cgypt, Alexandria Eastern Mediterranean Health Journal, Vol. Io, Nm; 1/2, 2004 71 University, High of Institute of Public Health, 1996. 10. uean AG et al. EPl-fnfo, version ti. Stone Mountain, Georgia, USO Inc., 1990: 469-98. 11. SPSS Advanced statistics 6. 1. Upper Saddle River, New Jersey, Prentice Hall, 1994.12. Cohen P, Hesselbart CS. De- mographic factors in the use of children mental health services. American Journal of public h<'uilth, 1998, 02:49-52. 13. Kulka RA, Veroff J, Douvan E. Social class and the use of professional help for personal problems: 1957 and 1976. Journal of neaftfl and socia.f tJ&l1t1viur, 1979, 202-17. 14. Thompson JW et al. The use of ambula- tory services by persons with and with- out phobia. Medical care, 1988, 26(2): 183-98. 15. Ryan SA et al. Utilization of health ser- vices by urban adolescents. Journal of adolescent health, 1996, 18(3}: 192- 202. 16. Ziv A, Boulet JR, Slap GB. Utilization of physician offices by adolescents in the United States. Pediatrics, 1999, 104(1 pt 1 ):35-42. 17. Harold RD, Harold NB. School-based clinics: a response to the physical and mental health needs of adolescents. Health and social work. 1993, 18(1 ):65. 18. Kisker EE. Brown RS. Do school based health centers improve adolescents' ac- cess to health care, health status, and risk-taking behavior. Journal of adoles- c9nt h9a/t, HIQ6, 18(5):335--43, 19. Leaf PJ et al. Factors affecting the utiliza- tion of specialty and general medical mental health services. Medical care, 1908, 26:9-26. 20. Wells KB et al, Sociodemographic fac- tors and the use of outpatient mental health services. Medical care, 1986, 24;75-85. 21. Alegria M, Robles RR, Vera M. Psychiat- ric symptomatology and health care utili- zation. Puerto Rico health sciences 1ourna1, 1988, /(1) 1tr-~. 22. Hansson L, Persson KB, Bergquist L. Pa- tients with mental illness in primary health care. A long-term follow-up of health care utilization and contact pat- terns with psychiatric care. Scandina- vian journal of primary health care, 1997, 15(3):129-33. 23. Katerndahl DA, Realini JP. Use of health care services by persons with panic symptoms. Psychiatric services, 1997, 48(8): 1027-32. 72 La Revue de Santo de lo. M6dltorro.n6o orionto.1e, Vol. 10, N° 1/~, 2004 Practice and awareness of health risk behaviour among Egyptian university students A. Refaat1 _,rAA .} ~~ y~ '->~ ~ ;ll J _),~4 J pl ~I .!J _,1-ly ~ yl .:...Jo) jL-i -=-~., .... i •• .., . .,;.1~, . .!:.,_,ii ;j .-,1, • .,11 ;J ,::-~1_: JC.t., ).i...:.ll, Jp; ~' ~µ, i-"L...,i :L.o~I s.i.J ),WI.; Jfah1 ~' ~;-u ..:..,t.....JW1_, .:.r-1)1 .;..; _ ,11.:, -./Y' 1, _ _:;-i ;;..p~ ~J t...1J.:. a.i")\AJI .;.,~_, ,(/.18) L)~ 121 <.SJ..I ~l l-.JI.: _}.:1.-t, J_#I .:.J.,UI ,:_,5., f j ·.r-- _j ~t,,,. ..,..~ RI ..l.i _., . _).l:..14 _i.. _,.u¼.1 ~\ .::.-\.$ ~..l-.11 ..:,1 _;.il _, ..;.,1J..l:o..l.1 _, J ~\ ,.;oi.w:, &JI ~x t!' ~lf-! , ..,.,...JI J ('~IJ , _,/' ..ill ,_,J.-1 ../' ,.kW\.; .J _,..;.,l,l ~ _,!-ll ~ )I .;:.;\.:,~I ,:ii .:..J....dl ._j _,.-:l~ ~I .:.r- /.30 ,s.u ;;.:, yU,, _;~'fl J_,,.. .;:.;L. _,w.·, ~IS":, . ),,WI.; .!.alp':i/t ("..u- _, ,:; ..r.,S ~L- ..:.,~. ~-,_, y i.,,li _,lJ "-½- _, ,;i _ ,i_...,~I ~ly I~ t ~ ..;.,t.... ).t l_,.i, _;..ii ;,):!..i.!I -,.,~I ~ ,) W' ,~')\,bll -(1/.30) ~"-/--;1, (1/.30) ('i..,,.'J1 y1...,, _, y J Jt......!.l ~ )1 J.....,..J.\ .:.,IC" J . '-o----. ;.! _,...J.1 ..s ,.....ii ABSTRACT Health risk behaviour contributes markerlly to today's major killers. A descriptive cross- sectional study was conducted to assess current awareness and practice of health risk behaviour among Cgyptian university studcnl3. Only 121 otudcnto ( 18%) were pro.oticing ricky behaviour. Tobaooo uco, alcohol and drugs use and risky sexual behaviour were positively correlated. Multiple regression analysis revealed that the main determinants of risky behaviour were being a male, of older age, having a high allowance and having no attention to danger. About 30% of students tacked adequate knowledge on AIDS. Most of those who had sexual relationships did not use contraceptives or anv method of protection from sexually transmitted infection. Main sources of knowledge were the media (38%) then peers (30%). Pratique et connaluance des comportements ii risque pour la sante chez les etudiants egyptiens RESUME Les comportements a risque pour la sante contribuent sensiblement aux causes principales de daces actuelles. Une etude transversale descriptive a eta realisee pour evaluer la connaissance et la pratique actual/es des comportements a risque pour la sante chez las etudiants egypliens. Sauls 121 etudiants ( 18 %) avaient un comportement a risque. La consommation de tabac, d'alcool et de drogues et le comportement sexuet a risque etaient correles positivement. L!anatyse de regression multiple a revele qua Ies pr1ncIpaux determlnanis des componernerm, a ril:Kjue eti:iie111 le l1:liI1.J'eue u11 y1:1.ri,;u11, 1.J'eIn:1 µlu~ aye, d'avoir une allocation d'etudes elevea et de ne porter aucune attention au danger. Environ 30 % des etudiants n'avaient pas les connaissances suffisantes sur le SIDA. La plupart de ceux qui avaient des relations sexuelles n'utilisaient pas de contraceptifs ou d'autres moyens de protection contre les infections sexuelle- m9nt transmissibh;u; I gs, m~rfoas, (~A%) Al IA.<: l"Jl'lir.c {~n %) rnnstitwiiAnt IP.s ririndriAIP.s sourl'.AJ:; de r:nn- naissances. 1Department of Community Medicine, Suez Canal University, lsmailia, Egypt. Received· 07/11/02; accepted 22104/03 Eastern Mediterranean Health Journal, Vol. 10. Nos 1/2, 2004 73 Introduction Today, the health of young people-and the adults they will become-is critically linked to the health-related behaviour they choose to adopt. Young adulb ai:;cd 15-24 con1;tituted about 20% of the Egyptian population in 2000 [/], and university students, whose health and productivity are determined by their current behaviour, an.: the future high- ly educated work force. This study aims to evaluate the awareness and practice of health risk behaviour among Egyptian uni- vcr:;ity 1;tudcnts, focusing on the use of to- bacco, alcohol and drngs and unsafe sexual practices. Surveys among youth and young adults ( I 0-24 y·car:;) in the United States of Amer- ica during 1991-1999 shmv the trends for health risk behaviour. The improved behav- iour types included sexual practices. On the other hand, tobacco, alcohol and drug uc;c worsened [2]. Kann et al. showed that 35%, of high school students in the United States of America had smoked cigarette~ during the 30 days preceding the survey [3]. ~ In the :r-..1iddle East region, however, studies have given a different picture. In Egypt, a study done on students at Suez Canal University found that prevalence of current smoking was much lower. 12.7% in general, and commoner in males and tho3c of older age. tvfo"t smokers livi.:d in urban areas, lived with smokers, and used their pocket money to buy cigarettes [ 4]. About one third smoked the waler pipe too. A ,,tudy done in Syria reported the prcva- len ce of current smoking among high school adolescents to be 16% for boys and 7% for girls. Smoking was strongly associ- ated with parcntul und sibling smoking; high school students from families with parents and1or siblings who smoked were 4.4 times more likely to be current smokers than those from non-smoking families [5]. In a Turkish study there ,vas evidence for the effects of school type, a smoking- related attitude, presence of a stepmother, father's use of alcohol, sister and brother who smoke, student's alcohol use, and par- ticipation in art activities as determinants of smoking among middle and high school students in Ankara [6]. Methods A descriptive cross-sectional study was carried out on students at Suez Canal Uni- versity main campus in lsmailia. The schools were stratified according to type of sh1dy: health. mathematical. scientific and human studies. One school was randomly selected from each study type. For the pu;- poses of future intervention, students were randomly allocated from student lists of the first and second years of the 4 selected schools: medicine, computer and informat- ics, agriculture and education. A questionnaire was designed, adapted from the questionnaire of the Centers for Disease Control and Prevention 1999 risk behaviour survey [7] with cultural modifi- cations. Questions were added regarding source of knowledge and awareness of the danger of any of the types of risky behav- iour. Awareness of the dangers of each practice was indicated on a 5-point scale ( 0-4), \vhere 0 indicated not at all and 4 indicated strongly aware. The questionnaire was tested on 87 vol- unteer students to check its validity and to estimate the sample size. Necessary chang- es were made after testing. There were 30 063 students enrolled for the academic year. The sample size at 95%, CI, was estimated using £pi-Info (version 6.4d) to be 655 students (721 stu- /4 La Rtwuti! dti! Sc:111l~ U\/ la, M,!,o.Jilt:11a,11,!,to v1itor1ltde, Vot. 10, N" 112, 2004 dents adjusting for drop-out of l 0%). Questionnaires were printed, enveloped and uistiiliutc:d vii1 the junior faculty and students' affairs staff of the selected schools according to their weighting: 180 for medicine, 240 for agriculture, 250 for t::Uui.;aliuu and 51 for computer:, ~md infor- matics. Epi-lnfo was used primarily for data entry. Data was analysed using SPSS, ver- siu11 9.0. Sui.;iodcmographic charactcri:stics were described. Risky behaviour in each domain was identified as the following: • Tobacco use: current smokers of ciga- n.::Llc:s 01 wal-.;1 pipes or othcr5, • Alcohol and substance use: current us- ers of alcohol or other substances, • Unsafe sexual behaviour: having multi- ple partners, or sex without contracep- tives or protection from sexually transmitted infection (STI). The different types of behaviour were analysed in relation to the students' socio- demographic characteristics, attention to risky behaviour and source of information using test of significance and odds ratio. A new variable was computed from practice of risky behaviour and examined by multi- ple regression analysis to identify its deter- minants. As the study deals with young adults, certain ethical steps were implemented: • Fonnal approval was obtained from lhe vice president of the university for edu- cation and student affairs. • Approval and support from deans and vice deans of the selected schools were also obtained. • Junior faculty and students' affairs em- ployees who shared in distributing the questionnaires were introduced to the aim of the study and the importance of confidentiality for students who re- sponded to the questionnaire. • All the questionnaires were enveloped to preserve the confidentiality of the re- spondent:! • The questionnaire began with a descrip- tion of the study and a clear explanation of its purpose. Results Of the 72 I questionnaires sent out. fii;i7 were returned (95% response rate), 172 (25.0%) from the school of medicine, 48 (7.0%) from informatics, 237 (34.5%) from education and 230 (33.9%) from ::ig- riculture. Sociodemographic characteristics The mf'rli im aee of the students was 18 years; 59.0% were female, 71.0% urban residents and 98.8% never married. There were 3 fonnally married female students, while 5 male students stated that they were orfi married (not officially registered). Many of the students' parents were educat- ed up to university degree level (50.6 % of fathers and 34.5% of mothers) while only 12.1% of fathers and 25.7% of mothers were uneducated. The median monthly al- lowance was 90 Egyptian pounds (mode l 00 Egyptian pounds) and 121 students (17. 7%) were working in addition to their study (Table I). The majority (58.0%) of students had a moderate awareness of the dangers of risky health behaviour while 25.9% had no awareness at all. The main source of infor- mation was the media (37.5%) followed by friends (29.8%). Tobacco use . One third of the students in the study had ever smoked cigarettes with a median age of starting smoking of 15 years. Current smokers constituted 12.2% of the stu- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 75 Table 1 Sociodemographic characteristics 01 students practising different types of behaviour Characteristic Tobacco use Alcohol and Sexual behaviour Total (n= 108) drugs ( n = 36) (n=27) (N::687) 04 OR % OR % OR % Age(years) '.>18 27.8 1.0 28.9 1.0 25.9 1.0 54.7 ~19 12.2·· 3.9 71.1" 3.5 74_1• 3.6 45.3 Sex Female 11.1 1.0 18.8 1.0 18.5 1.0 59.0 Male 88.9** 17.0 81.2* 6.5 81.5*' 6.8 41.0 Residence Rural 25.9 NA 22.3 NA 15.4 NA 29.0 Urban 74.1 NA n.1 NA 84.6 NA 71.0 Marital status Single 99.1 NA 98.9 NA 92.6 1.0 98.8 Married 0.9 NA 1.1 NA 7.4' 8.7 1.2 Work No 62.9 1.0 57.6 1.0 48.2 1.0 82.3 Yes 37.1*' 3.6 42.4*' 3.7 53.a·· 6.0 17.7 Allowance (Egyptian pounds/month) ::. 100 50.0 1.0 52.8 1.0 59.3 NA 73.1 >100 50.0 .. 3.4 47.2' 2.6 40.7 NA 26.9 Father's education Uneducated 8.6 NA 12.5 NA 11.1 NA 12.l Primary 9.5 NA 5.7 NA 7.4 NA 13.4 Preparatory 8.6 NA 6.8 NA 7.4 NA 6.1 Secondary 16.2 NA 14.8 NA 18.5 NA 17.9 Univeroity 67.1 NJ\ 60.2 NA 55.6 NA 50.6 Mother's education Uneducated 23.6 NA 22.0 NA 11.1 NA 25.7 Primary 8.5 NA 7.7 NA 22.2 NA 10.3 Preparatory 6.6 NA 77 NA ::!.7 NA !'i.6 Secondary 26.4 NA 24.2 NA 33.3 NA 23.9 University 34.9 NA 38.5 NA 29.6 NA 34.5 School of study Medicine 20.4 1.0 22.2 1.0 7.4 1.0 25.0 Informatics 4.6 0.8 5.6 0.9 3.7 1.8 7.0 Education 13.9 0.5 5.6 0.2 7.4 0.7 34.5 Agriculture 61.1·· 2.7 66.7** 2.4 81.5 .. 9.0 33.5 Attention to risk Nona(O) 35.s· 1.5 36.1 NA 37.0 NA 25.9 Moderate (1-2) 48.6 1.0 55.6 NA 48.1 NA 58.0 High (3-4) 15.9 1.0 8.3 NA 14.8 NA 16.1 ------------------------ Y••t , Y-, ,:.,b.i..Jl < __,.;,'..JI .I.IP.', ,,JWI ~\ ..Ji.:,.. da .... J.:l,I J _,.:J ~I ..l.P.,1 76 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Table 1 Sociodemographic characteristics of students practising different types of behaviour (concluded) Characteristic Alcohol and Sexual behaviour Total Tobacco use (n:: 108) % OR drugs(n=36) (n=27) (N=687) source 011mow1eage Family 6.3 1.0 Study 12.5 3.1 Friends 48.a·· 6.2 Modia 32.6 3.0 Total 100.0 15.7 ·Significant at P < 0.05 . .. Significant at P < 0.001. (JR = r,(i(.fg. ratio. NA = not available. dents, with those smoking daily consuming 600 cigarettes per month (mode). The ma- jority of smokers had tried to quit. About one fifth (20.4%) had ever tried smoking water pipes while only 10.9% were cur- rently smoking, mode 1 time in the previ- ous month. Water pipe use in cigarette smokers was 72%. About 3% had tried other tobacco products, mainly the pipe, mode I time in the previous month. The students had high awareness of the dangers of smoking both cigarettes and water pipes (Table 2). Alcohol and substance use Alcohol was ever tried by 14.4% of stu- dents questioned, median age 17 years for first use. Currently only 4.1 % were drink- ing alcohol, mode I time in the previous month. Awareness of the dangers was very high. Marijuana was ever tried by 6.8% of subjects, with median age 18 years for first use. At the time of the study, only 2.5% were using it, mode I time in the previous month. Seven students ( 1.0%) ever tried heroin at median age for first use of 13 % OR % OR % 0.0 NA 8.7 NA 19.1 10.0 NA 0.0 NA 13.6 46.7 NA 47.8 NA 29.8 43.3 NA 43.5 NA 37.5 36.0 5.2 100.0 3.9 100.0 years. Only 4 were still using it, mode 2 times in the previous month. Only 8 stu- dents ever used intravenous drug injection at median age of 13 years for first use and only 3 students were sti1l using it daily. Ever using stimulating drugs was reported by 9.3%, while I 8.2% ever sniffed sub- stances such as benzene, paints and sprays. There was very high awareness re- garding the danger of all drugs among stu- dents (Table 3). Unsafe sexual practices About 10% of the subjects ever had sex, median age for starting sex 16 years. Only 4.8% had sex in the previous 3 months, mode l partner. One third of them did not use any contraception and 61.5% did noth- ing to protect themselves from STI. A quarter of the students who had sex in the previous 3 months used coitus interruptus as a method of contraception. About one third did not have enough knowledge on AIDS. Attention to the danger of having multiple partners or unprotected sex was very high (Table 4). Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 77 Table 2 Health risk behaviour in regard to Table 3 Health risk behaviour In regard to tobacco use, N= 687 alcohol and substances use, N= 681 Practice No. "lo Practice No. "lo Ever smoked cigarettes 209 30.4 Ever tried alcohol 99 14.4 r.11rr .. nt ,:,mnkl"lr>< 84 12.2 Current alcohol consumer 28 4.1 Ever smoked water pipe 140 20.4 Ever tried marijuana 47 6.8 Current smokers of water pipe 75 10.9 Current user of marijuana 17 2.5 Current smokers of both cigarettes Ever tried heroin 7 1.0 ano water pipes 54 7.9 Current heroin user 4 0.6 Tried to quit smoking (n= 84) 59 70.2 Ever use of intravenous drug Where cigarettes were obtained injection 8 1.2 (n., BO) Current use of intravenous Bought them 54 !:>/.!> drug injection 3 0.4 Another person gave them to me 21 26.3 Ever used stimulating drugs 63 9.2 Another person bought them for me 1.3 Ever sniffed spray, benzene or Took them from a pcroon without oaint 125 18.2 his notice 4 5.0 Ever driven a car or motorcycle Other tobacco-related practices under alcohol or substance Snuff 9 1.3 influence (n= 450) 16 3.6 Pip@' 1n 1 !, Cigar 1 0.1 Median Mode Median Mode Age of first drinking alcohol (years) 17 18 Smoking prevalence Days of alcohol consumption• 2 1 Age of starting smoking (years) 15 17 Age of first marijuana use (years) 18 18 Days cigarettes smoked Davs of mariiuana use' 3 1 {i111111:j 1,111:jviuu:; 111u11U1) :'lO 30 Number of cigarettes smoked Age of first heroin use (years) 13 13 (in the previous month) 90 600 Days of heroin use• 2 2 Days water pipe smoked Age of first use of intravenous (in thR JlrRViOLIR month) 4 drugs (ye~n,} 13 1S Days of other tobacco use Days of intravenous drugs use• 30 30 (in the previous month) 2 Awareness of the dangers of: Awareness of the dangers of: Smoking 4 4 Alcohol 4 4 Water pipe 4 4 Marijuana 4 4 Heroin 4 4 Intravenous drug injection 4 4 Stimulants 4 4 N = 687. • in previous month 78 La Revue de ::.ante de la Med1terranee oriemale, Vol. 10. N° 112, 2004 Table 4 Health risk behaviour in regard to sexual practices, N= 687 Practice No. % Ever had sex 68 9.9 Had sexual relations in the previous 3 months 33 4.8 Had alcohol or drugs before sex the last time (n = 33) 10 30.3 i--lf!" knnwlMQIUln AlnS 4.-"">4 AA.1 Used contraceptive in the last sexual encounter (n = 32) Nothing 12 37.5 Pills 3 9.4 Condom 5 15.6 Cream/gel 2 6.3 Coitus interruptus 8 25.0 Others 3.1 Not sure j 1 Used protection against sexually t ransmitted infection in the last sexual relationship (n = 26) Nothing 16 61.5 Condom 5 19.2 Other 4 15.4 Not sure 3.8 Median Mode Age of starting sex (years) 1,6 17 Number of sexual partners in previous 3 months 2 Awareness of the dangers of. Having multiple sex partners 4 4 Having sex without protection 4 4 __ ,., ___ Risky behaviour The risky behaviour is summarized in Table 1, which shows that: • Tobacco current users constituted 16% of the students. Tobacco use was high- er among older students (OR: 3.9, 95% CI: 2.5-6.0); males (OR: 17.0, 95%, Cl: 9.0-31.5); those with higher monthly allowance (OR: 3.4, 95%, Cl 2.2-5.2): those who were working (OR: 3.6, 95%, CT: 2.3-5.6); slu<ll:lllS ur ag1 il'ul- turc (OR: 2.7, 95% Ci: 1.6-4.8); those paying no attention to risky health be- haviour (OR: 1.8, 95% CI: 1.1-3.0) and those gl:ltiug their i11ru1111ation from friends (OR: 6.3, 95% CI: 2.3-18.9). • Current users of alcohol and other drugs comprised 5% of the students, more among the older students (OR: 3.5, 95% C:I: l.6-7.9); males (OR: 6.5, 95% Cl: 2.7-16.6); those having higher allowance (OR: 6.2, 95% CI: 1.7--23.1 ); those who were working {OK: 3.7, 95% CT: I. 7-8. l ): and students of agri- culture (OR: 2.4, 95% CI: 1.1-6.0). • Sexual risky behaviour was reported by only 4()/o of the students. Tt was more prevalent in older students (OR: 3.6, 95% Cl: 1.5-8.7); male students (OR: 6.8, 95% Cl: 2,5-!8.I); orfi married lOR: 8.7, 95'Yo Cl: 1.7-45.4); and stu- dents of agriculture (OR: 9.0, 95% Cl: 2.0-56.0). As shown in Table 5, there is a statisti- cally significant correlation between the 3 types of risky behaviour. Only 121 subjects ( 17.6%) were practising risky behaviour. Multiple regression analysis (Table 6) re- vealed that the main <lctcm1inan1s of risky behaviour were being male ( OR: 9. 7), older in age (OR: 2.3), having a high allowance (OR: I. 7) and paying no attention to danger (OR: 1.5). Discussion Health risk behaviour, which can be a con- tributing factor in the leading causes of mor1ality and morbidity among youth and adults [3], is often established during youth and extends into adulthood. The different types or behaviour are interrelated and are Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 79 Table 5 Correlatlon between the three types of risky behaviour, Pearson correlation Risk behaviour Tobacco Alcohol Sexual use and behaviour drug use Sexual behaviour 0.345 .. 0.457 .. 1,000 Alcohol and drug use 0.419 .. 1.000 Tobacco use 1.000 "S1gniffcanl al P < 0.001. preventable. These include tobacco use, al- cohol and other dmg use, and risky sexual behaviour that can result in unintended prcgnuncy and STI, including IIIV Two thirds of all deaths among persons aged > 25 years result from only 2 caw,· es-cardiovascular disease and cancer. Th,: commonest type of risk behaviour a5- sociated with these 2 causes of death is linked to tobacco use, which is initiated during adolescence [3]. The results of the present study confinn the result:'\ of a pre- vious study [ 4] and show that tobacco us- ers were mostly male, older in age, working or with high allowance, paying no Table 6 Determinants of risky behaviour, multiple rcgrcaaion analyais Variable B p OR 95%CI Makel 2.2743 <0.0001 9.7 5.5-17.0 Older age 0.8324 0.0009 2.3 1.4-3,8 High allowance 0.5494 0.0248 1.7 1.1-2.8 No attention to risk 03941 0.0346 1.5 1.1-2.1 Model significant at P < 0.001. OR = odds ratio. Cl= confidence interval. attention to risks and highly influenced by peers and the media. The cigarette smoking rate has been stable since that study over all years, however, prevalence of smoking of water pipes increased dramatically (72°-o of smokers in the current study compared with 30~-o in the previous one). This is probably a reflection of the new trend among the youth in Egypt for smoking wa- ter pipes in cafes. Despite the banning _of cigarette advertising in the Egyptian media, the depiction of water pipe smokers is widespread in TV serials and movies and is associated with pleasure. In addition, ad- vertisements for water pipe tobacco prod- ucts are common on Arab satellite channels. The effect of this habit on pul- monary function in comparison to cigarette smokers and non-smokers was investigat- ed [ 8] and the results showed that the detri- mental effects of water pipe smoking are not as great as those of cigarette smoking; Jung function parameters were higher in water pipe smokers, especia!ly the parame- ters for small airways. \Vatcr pipe smoking, however, has adverse effects on general health; it may predispose to oral cancer and is associated with a statistically increased incidence of squamous cell carcinoma and keratoacanthoma of the lips. [ 9] Intensive and sustained efforts to counter-market tobacco among youth are necessary to negate the "friendly familiari- ty" created by tobacco advertising and to communicate the true health and social costs of tobacco use [IO]. Although the main risky behaviour of the students in this study ,vas tobacco use, 4'% or them practise unsafe sex. risky be- haviour and 5% practise substance use. As they get their knmvledge mainly from me- dia that project drug use and extra-marital sex as not culturally accepted, they were highly aware of their risks and minimally practising them. 80 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 112, 2004 In addition, 18.2% ofthe sn1dents in the study had ever sniffed substances such as petrol products, paints and sprays. Petrol sniffing as a specific fonn of substance abuse is associated with dysfunctions that range in severity from subtle cognitive im· pairment to encephalopathy and death. Petrol sniffing causes a progressive decline of cognitive function that eventually leads to permanent neurological changes 11]. Only 70% of the subjects had enough knowledge on AIDS. Most of those who had sexual relationships did not use any method for protection from S TI nor did they use contraceptives. friends, the social culrnre at university, and the interaction of the two with the developmental character- istics of the period between adolescence and adulthood arc more imponant influenc- es on sexual relationships than parents or high-school sex education classes. How and whether friends talked about sex and practised sate sex were strong nonnative influences in predicting safer sex among individuals [12]. Adolescents have not changed their behaviour in response to the pandemic, despite being ,veil informed about HIV/AIDS and having positive atti- tudes toward HIV/ AIDS prevention [ f 3]. Those AIDS-prevention programmes which, rather than merely providing infor- mation, focus on helping youths perceive HIV as a problem, motivating them to act safely and implement safe acts have suc- cessfully reduced actolescems' risk acts. The majority of the students in this study got their information on AIDS and sex from friends and the media. The mass media in Egypt does not offer enough in- formation on AIDS. In a previous study it was found that only 7% of female and 62% of male medical students approved doing tests for the detection of AIDS, reflecting cultural sensitivity (A. Refaat. Knowledge and attitude of' medical students towards premarital examination program. Paper presented at the 1st international confer- ence of behavioural medicine, Cairo, Egypt, November 1994). The present study shmved the 3 types of risky behaviour were correlated and that ~ludent:s :mnleu them l.J1;fu1e uuiver:sity ai,e and in sequence: smoking at age 15, sex at 16 then alcohol and drugs at age 17. In the United States of America also, it was found II1c1.l ctdule:sc.ent~ engage in multiple health- risk behaviour according to age and that many adolescents engage in these kinds of behaviour serially rather than at the same time [14]. Conclusions and recommendations Less than one fifth of the students in this study practise risky behaviour, mainly as toh:u~r:n 11sc Thf'y pai<l moderate attention to risky behaviour, and got their informa- tion from the media and peers. The study revealed certain types of risky health be- haviour that are not usually stressed in health communication programmes, such as smoking of water pipes, sniffing of pe- troleum products and lack of infonnation on AIDS. Based on the results of this study, it is recommended that a health Cl1mmunication programme be designed targeting Egyptian youth and adolescents that addresses all the types of risky behaviour identified. Counter-marketing campaigns should high- light a tobacco-free lifestyle as the majority lifestyle of diverse and interesting individu- als. Acknowledgements 1 ·would like to thank Suez Canal University Vice President for Education and the deans Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 81 and vice deans of the faculties included in this studv for their kind suppmi. I appreci- ate the h~lp of the Jtmior faculty, employees of students' affairs and all the students who shared in the study. References 1. International data base. US Census Bu- reau, 2003 (http://www.census.gov/ip~/ www/idbprint.html, accessed 13 April 2004). 2. Adolescent and School Health Informa- tion Service. Fact sheet: youth risk be- havior trends, 1991-1999. Silver Spring, Maryland, Centers for Disease Control ana l-'revent1on, National Center for Chronic Disease Prevention and Health Promotion. (http://www.talkorg.com/ nccdphp/dash/yrbs/trend. htm. accessed 8 April 2004). 3. Kann L et al. Youth risk behavior surveil- lance-United States, 1999. Journal of school health, 2000, 70(7):271-85. 4. Hassan F, EI-Defrawi MH. Smoking among students of Suez Canal Univer- sity. Egyptian journal of psychiatry, 1996, 19:49-60. s. Maziak W. Smoking in Syria: profile of a developing Arab country. International journal of tuberculosis and lung dis- ease, 2002, 6(3):183-91. 6. Ozcan YZ, Ozcan KM. Determinants of youth smoking-evidence from Turkey. Substance use and misuse. 2002, 37(3):313-36. 7. Youth risk behaviour survey, 1999 ques- tionnaire. National Centre for Chronic Disease Prevention and Health Promo- tion Division of Adolescent and School He~lth, Centers for Disease Control and Prevention, Atlanta, USA, (http:// 8. 9. www.cdc.gov, accessed 7 September 2001). Kiter G el al. Water pipe smoking and pulmonary function. Respiratory medi- cine, 2000, 94(9):891-4. El-Hakim IE, Uthman MA. Squamous cell carcinoma and keratoacanthoma of the lnwAr liri ::issoci::ited with "Goza" and "Shisha" smoking. International journal of dermatology, 1999, 38(2):108-10. 1 o. McKenna J, Gutierrez K. McCall K. Strat- egies for an gffoctive youth cou~h;r- marketing program: recommendations from commercial marketing experts. Journal of public health management and practice, 2000, 6(3):7-13. 11. Cairney S et al. The neurobehavioura! consequences of petrol (gasoline) sniff- ing. Neuroscience and biobehavioral re- views. 2002. 26(1):81-9. 12. Lear D. Sexual communication in the age of AIDS: the construction of risk and trust among young adults. Social science and medicine, HlQ5, 41(9)·1311-?3 13. Rotheram-Borus MJ, Mahler KA, Ro- sario M. AIDS prevention with adoles- cents. AIDS education and prevention, 1095, 7(4):320 36. 14. Brener ND. Collins JL Co-occurrence of health-risk behaviour among adoles- cents in the United States. Journal of adolt:1::,cc1nt health, 1998, 22(3);209"----13, 82 Ld Revue de Sdnte de la Medlterranee orlentale, VOL 10, 1\1° 1/2, 2004 Opioid use in patients presenting with pain in Zahedan, Islamic Republic of Iran V. Rahimi Movaghar, 1 F Aakhshani, 2 M. MohammadP and A. Rs.himi-Mo.,-e.ghar" <.ll_;.!J ,.:,i1.u,1.) _j ~611 .rP _}.I _j Jy,-ill ~.)-)~1 j,,,.J.)~1 ('\~1 )-~'cioy ~> .,:_,-,_.,~ '""'..,_,. <.f-4-- '-.!"\..,:,,_,;,i_., ;;,,...,.;,,1.o 'J\.j,u,.,. --- ~i 1.ou -.::...,_,,.,., ,.J .._-w, ._\--1_.,J1_. / '-11 .__..,.t..1 J...,._.;l.1 ""-""':.'1 ,,y½, ,~•-1,.-.:...::...1 J'~·' L,, ......... "-"'_., .. ,..1 :a.....,,~1 ,_,L.....:....,I J~li ,!JJ.:,J ,~.1,;, ~)1 ,s_p-;jl )"" r-'JI ,jc5'" .,:_ .. j_\1 .,:_,,_,;'.di ~_). 1 y 480 ~.;. ;(..,I;;, _},-L..,,j ~"-'-= ,..u, j_,-,-.:J, _. t )'.,,:,,c.1_: (':<.J" • ..,-"' -.:..r" y, t~·'J . .:.,u.,.,_; ~~ ..:..,b~ -~ ...,, ..i,w, ~Gi r'..L.~'1 )~1 J.;_,._... .)\.S"" _uJ _ ~1 w1;1 J, .. l_yJ\ ~-.,.a 1 a ~ ~ }.i.l½ ._j.,,~1, ~;_..,,-~_/:J1 ~...,~\11 t1--~1 -..')I.<, !Ji..,. .,:_~ f J .. f '/I / ½------,) )1 ,->I~ ...:___;\S" :,cj,J1 ~ J' j,e :_..-, /28.5 j_....,J., :;..,_; _,._,.'):, :..,y'i'I -..:,.._;,S ._5JJ '(A-"-i '-.;;... if J,J,,i ,__µ) "J"!- __,; .. UI) y~.l' ,f "i',_, ~'_....,J.1 ..;,_..,;':i' '½_,~':;, t', .. 1,.--._:...,.1 ,j,-, '½,-, ~jlil~ Z72.9) ~\..i .. J.,,._.,~I\ e:,· J"'~l ~_.0)11 ~.,,~~\11 -~L_l_~-1 '-~·\..,"'",.,.. :~\l~L L---:L\ ___:L ... \..,q..,J\ e=· ;.;_;"')'~ .:JLI (.Jr ....:..,.I_~ 0-U './.·174 ,j-/~ .. ~-I~~~ ~- 11--:>:-_; s...5-\~ :/.58.5) .:;_~~-ti __ ~ (,: 1, .. "LL.........,~1\ c .. \+-,-U-~-·1 ~· ...... -l; '/204 (-:"" T/_38.3t ~; ~-';iS°........:-.- ~--~- ~_,.,~:.i1 ~(-_ .. ~_L..'1 _;:~ __:__~" ~/.21.8 ,__l.!L.i. ... ~-'.'~....L .. './60,8) _r~~----J'I -..:_ .. ~~~; -(,:___. .. ...,~\ ....::...., ... ,_., ~--'"-~-1...,i '26_1 ,, _ _\.-•Li-• './60) ~-~-)1 --=--"_f-·"'_; ~(_;_,11,_-~~-~'J.·1 ...:,_:_C ,:_1_:,-L· ~1:_2_1.J , _ __h,Li_. ABSTRACT To study the prevalence and factors associated with opioid use in pain. 480 consecutive patients with a chief complaint of pain were interviewed at 1 O clinics in Zahedan The data were analysed in relation to 18 possible associated factors. The prevalence of opioid use was 28.5% in patients presentino with pain. There was no signil1cant relation between opioid use and chronic pain (2 6 months), but there was a relationship with the following 5 !actors: previous opioid use by friends (72.9% versus 20.4%, without friends using). occupation {58.5% private sector employees/self-employed versus 17.4% housewives}, cigarette smoking (60.8% versus 21.8% not smoking!, consultation for a psychological problem (38.3% versus 23.3% without), and death of a spouse (60.0% versus 26.1°;, without). L'utHlsatton des opio"ides chez les patients souffrant de douleurs a Zahedan (Republique islamique d'lran) RESUME Alin d'EltudIer Ia prevarence et Ies Tacteurs assocIes a I u111Isa1Ion d op101des pour 1es douIeurs, 480 patients consecutits qui se plaignaient principalement de douleurs ont ete interroges dans dix centres de sante a Zahedan. Les donnees on! ete analysees en relation avec 18 facteurs associes possibles. La prevalence de l'utilisation des opioides etait de 28,5 % chez les patients souffrant de douleurs. II n'y avail ~ucun-,,;:, re,l.abon slgnific-ative. G-ntn~ I\Jtili~ation do-&: opio'i·dQ~ Qf lQ~ doulQun:; chroniquc;:.~ (~ 8 moi~} 1 ma;~ ii y avail une relation avec les cinq facteurs suivants . l'utilisation d'opioides precedemment par des amis (72,9 % contra 20.4 % sans utilisation par des amis), la profession (58.5 % employes du secteur prive/ travailleurs independanis contre 17.4 % femmes au foyer). le tabagisme (60.8 % contre 21,8 % non- fumeurs). la consultation pour un probleme psychologique (38,3 % contre 23,3 ~'o), et le deces du conJoint (60,0 % contra 26, 1 %,). 'Department of Neurosurgery; 'Department of Health; 3Department of Epidemiology and B1ostatrstlcs, Zahedan University of Medical Sciences, Zahedan, Sistan va Baluchestan, Islamic Republic of Iran. 'Iranian N;ation;,I c.,ntr<> .for .IJ.ddiclion StudiPll, Tr,hr:,n Uniwrsity ol Mr,dic .. ,:,/ Scir,nc,;,., and D.,p,;,rfmQnf of Mental Health Research, National Research Centre for Medical Sciences, Tehran, Islamic Republic of Iran. Received: 22/10/02; accepted: 01/06/03 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 83 Introduction Opium is une ur many drugs lhal decrease pain [I]. Little is kno,v about whether chronic pain leads to opioid misuse; studies have shown that from 3% to 23% of pa- li1::11ls wilh chrunic paiu an: a,li..liclt:li lo upi- oids [2J]. Some believe chronic pain leads to opioid use, more hospitalization, reduced physical efficiency and more psychiatric symplllms (4). Others argue thaL il is lbe biopsychosocial nature of humans, rather than the pain itself, that predisposes certain individuals to opioid use [5]. Bclwccu 9~ii anu 27% uf wiliLc malc opioid addicts reported that their addiction started with a prescription from a doctor for an opioid analgesic to tr,:,at a painful \.'umlitiu11 (2.J]. 111 a similar IClTJll stuuy of 58 patients, the authors warn physicians that severe oral opi01d dependency occurs more frequently than previously recognized [6]. lu d !Mliumd ~LUU)" uCvJJiUl!l ,tuui\.'l~ io the Islamic Republic of Iran, pain was mentioned by 17.5% as a trigger to opioid use [ 7]. Tln:u;; are 111ultiµk Ca;.;tuis that lwn: been documented as associated ,.vith opioid use, including demographic characteris- tics. personality, genetics and environment. Some of lhe~e iudU1.k. yuu11ge1 <1ge, iJei11g divorced/widowed/separated, having a family member who uses drugs, encour- agement to use by friends or others [8-10], failure in cdm::atiun, st:vert" e1.:'-->11u111i1.: LlqJ- rivation, social isolation (separation from family) [10], illiterate or poorly literate fa- ther or mother [9, II], unemployment [11,12], cheap price or opioiJ:, [13], uul knowing the harmful effects of opioids or believing they are useful l9,JU,12j, ciga- rette smoking [ R], alcohol use [!/,I 4.15], hi5tory of drug use [16], p1;ychnsocidl problems such as depression [9, 10, 17, JR], HIV positive, history of sexual abuse [JY], past history of rnnsultation in opioid clinic andm treatment during l 2 months before bemg 111 pnson i llll As far as we knmv, there has been no evaluation of the prevalence ofopioid use in patients suffering from pain in the Islamic Kcpubl1c or lran. Our study was done in the south-east of the Islamic Republic of Iran, an area which is the main gateway of opium transit from Afghanistan and Paki- stan to Europe and where opioids may be easily accessible. Sistan va Baluchcstan province is also socioeconomically a very deprived province. \Ve studied opioid use in patients with pain attending clinics in Z:a- hedan, the main city of the province. The aims ofth.:: study were to ascertain: v..-heth- er chronic pain causes opioid use; the prev- alence of opioid use in patients presenting with pain; and the predisposing factors for opioid misuse (i.e. why one patient con- sumes opioids and another does not). Methods A cross-sectional study was conducted on 480 consecutive patients who presented ,vith pain at the study clinics in Zahedan, There is no pain clinic in Zahedan, so pa- tients with pain are refen-ed to various clin- ics within the city. The 10 clinics selected were those where specialists agrei:d to par- ticipate in the study: 3 neurosurgery, 3 psy- chiatry, l preoperative anaesthesia, I physiotherapy, I emergency and l neurolo- gy clinic, Around one-third of consecutive p~tients attended the neurosurgery clinic, one-third the psychiatry clinic and one- third the other clinics. The study ,vas con- ducted over 2 months in March and April 2001. The inclusion criteria were all pa- tients aged over 16 years old with a chief complaint of pain. 84 La Revue de same de la ME!dlterranee orientale, Vol. 10, N° 1r2, 2004 A questionnaire was devised to collect data on sociodemographic variables, char- aun istii.::; ur pai11 arnl upiuiu use (lypes ur opioids taken, amounts taken and routes of administration). In our study, chronic pain was defined as frequent or constant pain fu1 a i.lumliu11 uf 6 muulhs 01 111u1e. A.;uk: pain was defined as pain frequently (al- ways/often) for 1 month or less. Opioid use was defined as occasional or regular use ufupium, upiurn n;sit.lu.: (.\hin:h), heiu- in, morphine or codeine in the previous year. The questions covered 18 factors that have been associated with opioid use: age, mah: st:x, u11t:mpluym.:11t, illit1.:rn.;y, urban residency, divorce, death of spouse, loca- tion of pain, duration of pain, frequency of pain, opioid use recommended by friends 01 pl1ysh.:1au, dga1 elle s111uki11g, alcuhul drinking, history of opioid use in family, history of opioid use in friends. decreased economic situation, death of friend or fam- ily 111e111\Je1 au,J puu1 p::<)'C:hulu!,aiiLOa! health. Our practical definition of poor psycholog- ical health was the patient's report of opioid use for relief of psychological stress, histo- 1y uf .;u11~ullaliu11 fu1 a psyd1ulugi.;al prnb- lem or history of psychological treatment. The questiomiaire was prepared at the pain clinic of the Medical University of Iran fol- luwiug a lit1:rnlurt: rev it:w mn.l wa~ 111uuifieu in Zahedan University of Medical Sciences. Four other psychiatrists reviewed the ques- tionnaire for face and content validity. The spe!.:io.li:,l:, di the diui.;s udive1ed the questionnaire to patients by interview to minimize bias between literate or illiterate patients. The specialist and assistant in t::ad1 diuiLO we1e liai11eu i11 l1uw lu ddi vc1 the questionnaire. Comparisons of patients with and with- out opioid use and associated factors were 1mH.k: willi d1i-:;4ua1et.!, Slw.kut t-le~l und logistic regression analysis. SPSS, version 6 was used for the statistical calculations. Results Of the -·180 patients ,,.,ith pain, 57.5%, were female. The mean age of pain patients was 36.0 ± SD 13.9 years. A total of 81.0~:o \Vere married and 6.0~io had experienced the death of a spolise. Only 7.0<!,::, of pa- tients were unemployed; 77.0% of female pain patients were housekeepers. There were 46.7% illiterate patients (62.0%, of the women and 25.1%, of the men) and 32.1% had attended only guidance school. The pain was said to be located in the head, lower back or the whole body by 75 .6% of patients. The duration of pain was chronic (;::a: 6 months) in 64.4% of pa- tients. The frequency of pain was de- scribed as ·always' or "often' by 71.5';.:~. The ovorall prevalenoe of opioid use was 28.5°-<l (137/480) in patients present- ing ,;vith pain. Opium and opium residue {shireh) was used by 65.9~•~ and 15.9ll,;-. of users respectively. 1'1ost users (02, n.:~) had consumed for more than 2 months dura- tion. Consumption \vas 1 or more times per day for 70.1 % of users. The most common method of consumption wa8 inhalation, used in 59.1 % of cases. There were 5 pa- tients using cannabis (hashish). Opioid users claimed pain as an origin of their opioid U8e in 79.6~/4, of case,:. Al- though opioid use was more prevalent in chronic pain than acute pain (26J%1 versus 15.9%>), the result was not statistically sig- nificant {P -~ 0.05,1. On the other hand, sta- tistical analysis did not show that pain preceded opioid use (P = 0.074). In the first stage of analysis, 11 of the IR factorn included were a,::,;ociated ,,.,ith opioid use: age, sex, occupation, education, death of spouse, consultation for a psycho- logical problem, cigarette smoking, alco- hol, opioid use in the family, opioid u~e in friends, and worsened economic situation. The number of alcohol drinkers was low. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 85 In the second step, a logistic regression test was performed to eliminate confound- ing factors, leaving 5 factors that remained significant (Table I): previous opioid use by friends, type of occupation, cigarette smoking, neuropsychiatric consultation and death of spouse. Among those whose friends were opioid users, 72. 9% were us- ers compared with 20.4% without friends using. People working in the private sector or self-employed were the highest opioid users (58.5%) and housewives the lowest (17.4%); unemployed people were 29.4%. Among cigarette smokers, 60.8% were opioid users compared with 21.8% among non-smokers. Among patients needing neu- ropsychiatric consultation, opioid use was 38.3% compared with 23.3% among those who did not. Opioid use in those who had experienced the death of a spouse was 60.0% compared with 26.1 % for those who had not. Table 1 Factors associated with opioid use among 480 patients presenting with pain Variable Total Opioid users Non-users fl.value No. No. '¼ No. •1. Op;oid use in friends <0.001 Yes 70 51 72.9 19 27.1 No 333 68 20.4 265 79.6 Tulotl 403 119 29.5 264 70.5 Occupation 0.023 Manual/semiskilled worker/farmer 56 18 32.1 38 67.9 Government employee 79 23 29.1 00 70.9 Private sector employee/ self-employed 65 38 58.5 27 41.5 Housewife 213 ':fl 17.4 176 82.6 Unemployed 34 10 29.4 24 70.6 Total 447 126 28.2 321 71.8 Cigarette smoking 0.005 Yes 102 62 60.8 40 39.2 No 312 68 21.8 244 78.2 Total 414 130 31.4 284 68.6 Neuropsychiatric consultation 0.013 Yes 175 51 38.3 108 61.7 No 29'2 68 23.3 224 76.7 Total 467 135 28.9 332 71.1 Death of spouse 0.034 Yes 30 18 60.0 12 40.0 No 426 111 26.1 315 73,9 Total 456 129 28.3 327 71.7 - ------·-·- ...... 86 La Revue de Sante de la Mediterranee oriantale, Vol. 1 0, N° 1/2, 2004 Discussion Opioid use wM 28.5'}~ among puticnl3 pre- senting with pain to clinics in this city in the Islamic Republic of Iran. Availability of drugs is a potent predisposing factor to opi- oid use [ 2 I]. The nearby countries of Af ghanistan and Pakistan are 2 of the major production areas in the world, named the • golden crescent'. When op! oids ~re ~ore readily available, the stigma m society 1:. re- duced· and if they are cheap, the vicious cy- cle of dependen~y and crime is less [2]. Our study found no significant associa- tion between opioid use and chronic dura- tion of pain. Millions of patients worldwide are regularly exposed to opioid analgesics for the treatment of pain. The documented in,;;iJi.;ncc of ia.trogcnic uddiction from the treatment of acute pain or cancer pain is extremely low [22]. A prospective study in a community family practice clinic com- paring a group of patients with chronic se vere lov,' back pain with a contrnl group attending for other reasons found no signif- icant difference in the prevalence of sub- stance u5c disorder between thcoe 2 groups [23]. Patients with chronic pain are simply representative of the general population rather than having a higher prevalence rate of ~ub:,tancc use disorder [ 5). Current use of opioids in the Islamic Republic of Iran has been reported to be 5.85% in males and fem ales ;;:: 15 years [ 2 4]. The study of opi- oid addiction in Victnom \Var veteran,~ showed that the overall prevalence of opio- id addiction in the study group had dropped to that of the general United States popula- tion a Iler veteran:, had been buck home for 3 years [25]. It seems that opioid use for the treatment of pain is no different from opioid misuse in the stressful environment of war. In a previous study, 81 % of codeine- dependent patients said that their codeine use started with a chronic pain problem [/4]. In our study, a similar proportion of opioid users (79.7%) told us the same. However, we found no statistically signifi- cant relationship between the presence of chronic pain and opioid use in pain patients. The identification of an add1ct1ve disor- der in a patient with chronic pain does not necessarily preclude the use of opioids as a component of pain management, unless maladaptive patterns of behaviour develop which define addiction. These are adverse con seq ucnccs such as persistent over- sedation, loss of control over use and pre- occupation with using opioids despite ade- quate analgesia [26]. Diagnosing addiction and drug-seeking behaviour is important in chronic pa in patients [ 2 7l It should be emphasized that pam 1s not the main culprit in opioid misuse; biopsy- chosocial risk factors are especially impor- tant for addiction disorder. The Screening Instrument tor Substance Abuse Potential (SISAP) [ 2H] helps the clinician categorize patients into lower or higher risk of abusing prescribed opioids. Patients who are at higher nsk tor substance abuse. mcl_ude those whose exceed 3--4 alcoholic drmks per day, those who admit to marijua~a or cannabis use in the past year and patients under 40 years old who smoke cigarettes [15]. We found 5 risk factors associated with opioi<l use in pain patients: previous opioid use by tr1ends, occupation, cigarette smok- ing, neuropsychiatric consultation and death of a spouse. A cross-sectional non- concurrent cohort study among young males m south~west Chum using multivari- ate analysis identified the folloi,ing signifi- cant risk factors for drug use: being dh'orced/widowed/separated, having been encouraged by friends/others to try drugs, smoking cigarettes, and having a family Eastern Mediterranean Health Journal. Vol 10, Nos i/2, 2004 87 member who used drugs [8]. In our study, smoking cigarettes and/or being widow\:d were also significantly associated \Vith opi- oid use, but being divorced/separated, hav- ing been encouraged by friends/others to try drugs, and having a family member who used drugs were not significantly as- sociated with opioid use. In a European multicentre study of drug injecting in pris- on, friends injecting opioid substances were identified as a risk factor [20]. The role nf friends was the most impottant as- sociated factor in our study. It seems friends have more influence than families in this particular situation. There was a higher level of consultation for a psychological problem among opioid users than non-users in our study. Another study has shown a 23~-~ depression rate and 21 % anxiety disorder rate among codeine-dependent patients [ 14]. Predisposing factors for illicit drug use have been shown to be unemployment and poor education [ 12]. In our study, howev- er, people working in business were the most likely to use opioids. Greater spending power for luxury goods and increased lei- sure time over recent decades have been linked to increased drug abuse in society [21]. In an anaiysis comparing addicts and non-addicts in the Islamic Republic of Iran, cigarette smoking and alcohol were associ- ated with opioid use [J J]. Opium is the most commonly misused substance in our country [7.11]. These agree \Vith our study showing an association between cigarette smoking and opioid use particularly opium. In other studies [ 7, 1 l], there were more men than women using opioids, but in our study sex was excluded by the logistic re- gression analysis. Historical anecdotes sug- gest that more addicts \Vere women 200 years ago L 29 J, but it seems that nowadays men have more opportunities to misuse opioids [30]. There is a high prevalence of opioid use in patients who complain of pain in Za- hedan. Opioid use in friends was the most important associated factor for opioid use in pain and further research into this would help parents, teachers, trainers and leaders of society to know how to deal with this. Cliniciai1s with pain patients should be aware of the other factors associated with opioid use, such as cigarette smoking and asking for psychiatric support from neuro- consu \tants. More support for widows and widov..ers, whu arc a small but , .. ulncrablc group, may be needed. Pain provides a guilt-free reason for opioid use and more research is needed into opioid use in society generally, not just small groups such as stu- dents, and the biopsychosocial factors in- volved. Acknowledgements This work was fmppnrted m part by a grant-in-aid for scientific research from the Zahedan University of Medical Sciences. We thank our partners in the pain clinic of Medical University oflran for taking part in preparing the research proposal, and in UPtvlC and Zahedan University of Medical Sciences for technical support and prepar- ing and editing the manuscript. The follow- ing investigators collaborated in the study: Ors Seyyed Alireza Sadjadi, lv1ohammed Safdari, Mehran Scdagat-kish, Bahram Ke,;hmirian. Seyyed Mostafa Alavi, Nou- tizehi-Shahbakhsh, Ali Moghtaderi, Tahereh Zohravi, Eemani Vahhashi, and Ivfr Abbas Arab. 88 La Revue de Santa de la Mediterranee orientale, VoL 10, N" 1/2, 2004 References Pappagallo M. Heinbero LJ. Ethical is- 11. Davoudi F. Rafeyee S. Comparing self sues in the management of chronic non- introduced addicts and non-addicts in malignant pain. Seminars in neurology, cultural indicators in Tehran. Pain, 2000, 1997, 17(3):203-11. 2:56-60 [In Persian]. 2. Fishb.aln DA, Rosomoff I-IL, Rosomoff 12. Kassay M et al. Knowledge of 'drug' use RS. 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Chronic pain and the dis- eaee of addiction: The interfacing role,:,; of pain medicine and addiction medicine. 90 La Revue de Sante de la Med1terranae orientale, vo1, 1u. N° 1r2, 2004 Right heart haemodynamic values and respiratory function test parameters in chronic smokers M. Gutbaran,' T Gagatay, 2 T Gwrm:r1' and P. Cagatay " ;:fo." )1 ~..U.1 ~J.J ~1 J_y y1 .;.,1}-r-'"'1 .::.il:.;Ltwo J _;f.:':il ~I _j ~_t'.U1 ~~.I.JI ~1 ,,;':,\i.lS"" -.;,~ ,.:,--.. J:. __ -..,._,:; ,...,i.::\i.15 ,.,-.)_,; ,J\J, J .. J.. .:-1Jy ~ ).'i J.,;.,:..u', ,y 24 ..;.JJ ~)11 ~ ..,'11 J!~ ., rl .Gi ~1 u.i,; _,)1 .:.-" ..... I.,_, .:-.i. ... f :u"J\.:l,,,1 .:-L, _;,,J,1 .,.. 14 G.i..l JlS' J..i, -~'- <.;i.b 11 .:-1,'...;:...:-1 I'-" ..::...)..::c,J .,_;-, 11<)1', -....li]1 ,;.,:,~_ -,-~\...ii.I ... ~ T -- __. .. - y .,,. . L • I ~ ' ,,_ • .r ...... W" ,o,, ~1,, lu - 1-1 :;~, ,,._., ,lu •. .i.1 u__j1 ,,._. ..!,I_, .l,,L,' ,1 ;....I.A}I ,- lz.l ,:.,1,5' • , ... ·•• ..5.:,l_i_.;1 ,S ~) ,;.,:, _,. 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J: ~ _,.,,JJ1 J J..l./ ,;;LS:.: ,:,-.,.;,.:.J.il ._;..u c:_,..-}1 cf"l_,__;\I', -,:; f} , ... ,·" _,JJ ABSTRACT During coronary angiography in 24 chronic smokers with coronary heart disease, cardiac function measurements were taken and correlated with respiratory function tests. Fourteen patients had evidence of chronic obstructive pulmonary disease. Garo1ac output nao a direct corre1a11on w1tn vital capac· ity, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV ,), and velocity at 25% of FVC (Vmax25). Pulmonary artery resistance was inversely correlated with FEV/FVC, while pulmonary artery oxygen saturation weakly correlated with FEY, and Vmax25. The pulmonary artery pressure had a weak correla.tion with the pulmonary artery rcoiotanoo and an intem,ediate corralation with thQ right atrium and lht,;1 right ventricular pressures. Early diagnosis and therapy of chronic obstructive pulmonary disease in smok- ers may be possible without using invasive methods. Valeurs hemodynamlques du coeur droit et parametres du test de la fonction respiratoire chez des fumeurs chroniques RESUME Lars d'une angiographie coronaire realisee chez 24 fumeurs chroniques atteints de coronaro- pathie, des mesures de la lonction cardiaque ont eta effectuees et correlees aux tests de la fonction respiratoire, Ouatorze patients presentaient des signes de maladie pulmonaire obstructivechronique. Le debit card1aque avail une correlation dlrecte ave-c Iii =µd<Jil~ viidli;,, la capacite vitale forcee (CV,), le volume expiratoire maximum/seconde (VEMS) et le debit expiratoire maximum a 25 % de la capacite vitale forcee (Vmax25). La resistance arterielle pulmonaire etait inversement correlee au rapport de Tiffeneau (VEMS/ CVF), tandis que la saturation en oxygene du sang arterial au niveau de l'artere putmonaire etait faiblement correlaa au VEMS at au Vmax25. La pres9.ion i:irtAriAIIA f")lllmnnaire eta it faiblement correlee a la resistance arterielle pulmonaire et ii y avait une correlation moyenne avec les pressions de l'oreillette droite et du ventricule droit. Le diagnostic precoce et le traitement rapide de la maladie pulmonaire obstructive chronique chez les fumeurs peuvent etre possibles sans avoir recours a des methodes invasives. 'Institute of Cardiology; 2Chest Department; 3Department of Biostatistics, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey. Received: 21 /11102; accepted: 03108103 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 91 Introduction Chnmic ubstructiv·c pulmunary disease (COPD) is characterized by chrome im- pediment of air circulation in the lungs, which usually has a slmv progression and is mostly irreversible. COPD is a complex condition, inlluenced by multiple genetic and environmental risk factors [1,2]. Smoking is one of the most common environmental causes ot CUPlJ; 1t mcrcas- es I 0-fold the risk for the disease com- pared with non-smokers. The dose- response relationship between cigarette smoking and pulmonary function is wcl!- cstablishcd [/]. Respiratory function tests rapidly worsen over time in smokers. The adverse effect of smoking primarily works by aum;king Lhe larger airways and then rhe small arterioles. The diagnosis of COPD is then easily made atter these changes have become irreversible and airways obstrnc- tion Im~ rn.:nu n;d [ l], COPD is a major cause of morbidity and mortality worldwide. Thus, early diag- nosis and cure of the disease is very impor- tant. The gradual increase of airways resistance causes some changes in pulmo- nary hacrnodynamics, such as pulmonary hypertension and pathological changes in the right heart. The pulmonary vm;ocon striction and hypertension that occurs through alveolar hypoxia leads to deteriora- tion of right heart function. Alveolar hy- pc,xia does not need to be continuous; right ventricular hypertrophy develops with as little as 2 hours a day of hypoxia and abnor- mal pulmonary hacmodynamics have been rPpnrtPd in r:.tif'nt\: \:vith only nocturn~,l oxyhaemoglobin desaturation secondary to sleep apnoea [3]. COPD is defined by a reduction of the maximal expiratory flO\v rate that is pro- gressive and irreversible. Intermediate or high level COPD is detennined through the forced expiratory volume in the first sec- ond (FE\1). Dividing FE\\ by the forced vital capacity (FVC) is a sensitive test for mild-degree COPD [/]. Pulmonary hypertension is the most im- portant factor in determining the prognosis of patients with COPD and the measure- ment is most accurately made during right- heart cathctcrization [ 4]. In COPD patients, the right ventricular ejection fraction (RVEF) is often reduced [5]. COPD, com- bined with deterioration ofright ventricular function and pulmonary hypertension, lim- its peripheral oxygen utilization, reduces exercise capability and increases mortality [ 6]. Thus, it is necessary to recognize and control pulmonary hypertension as early as possible. The structural and functional ad- aptations of the right ventricle to the in- creases 111 atterload posed by disorders ot the rcspiratory system are commonly re- ferred to as cor pulmonale. Detailed history taking, physical and X- ray examinations and electrocardiography may be helpful in diagnosing pulmonary hypertension and cor pulmonalc, but due to anatomical differences of the thoracic strnCLur..: it is noL always possible to obrnin accurate results. In addition, specific ex- aminations such as arterial blood gas mea- surements, echocardiography, angiography and right-hc,ut ,;atheteriLativu ~huulu ue undertaken [ 1, 71- The aim of the study was to investigate whether pulmonary function tests can pre- dict right hcmi prc:-;:mrc without the need to perform catheterization. It is hoped this will lead to better early diagnosis of deterio- ration in pulmonary funct10n as \veil as hae- 1nodynamic functions cuuscd by chronic smoking. Methods The study was carried out in the Institute of Cardiology of the Cerrahpasa Medical 92 La Revue de Santa de la Mediterranee onentaie, vo1. ,u, N° 11~. :.!UU4 Faculty at the University of Istanbul. The participants were 24 patients (3 women and 21 men) with known coronary heart disease who were referred for coronary angiography between February and May of 2002. Considering the risk and the cost of the cathetcrization procedure, we only in- tervened in patients who were chronic smokers and in need of cardiac catheteriza- tion for their coronary problems. The evaluation of COPD was made by the Department of Bronchopneumology. COPD was evaluated in the patients through detailed history, clinical examina- tions, chest X-ray and pulmonary runction tests. Pulmonary function tests were un- dertaken with a computerized spiromcter (Vitalograph). The following were calculat- ed: peak ex:piratory flow rate (PEF), vital capacity (VC), FVC, FEVP and flow rates at 25%, 50% and 75% lung of FVC (Vmax25, Vmax50 and Vmax75). After obtaining informed consent from the patients, right-heart catheterization was performed with a 6 F (French) multipur- pose catheter via the vena femoralis using the vacuum puncture method. The pres- sure was measured via liquid filled pressure monitoring sets with an external pressure transducer. Left heart as well as right heart pressures were taken. The following were measured: pulmonary artery pressure (PAP), pulmonary artery resistance (PAR), pulmonary capillary wedge pressure {PCWP), right atrium pressure (RAP) and right ventricle pressure (RVP). For measurement of arterial partial oxy- gen pressure (PaO2) and haemoglobin lev- els, blood samples (2 mL) were taken from the main pulmonary artery and the aorta using heparinized syringes. PaO2 was mea- sured through a gas analyser, which calcu- lates oxygen saturation using the Severinghaus equation. The procedure was terminated after removal of the arterial and venous sheaths and after control of bleed- ing. The respiratory fum:liun data wc1:s linked to the data obtained through cathe- terization. Cardiac output (CO) was calcu- lated with the direct Fick method [8J and then placed in thr: PAR formula [9]. The normal range for PAR was taken as 0.9 ± 0.3 8 mmHg min/L for the 30-49 years age group and 1.0 ± 0.5 mmHg min/L for those aged over 49 years [10]. Statistical evaluation of the data was perfonned using Pearson correlation and regression analysis. Results The mean± SD age of the participants was 52.1 ± t0.7 years. All the patients were chronic smokers; 21 had smoked a packet of cigarettes (20 singles) daily for more than 15 years and 3 had smoked a packet daily for about 11- l 4 years. Of the 24 pa- tients, 14 were diagnosed with mild COPD; none were in the acute exacerbation phase of their disease and none had any cardiac valve disease. The remaining 10 patients did not meet the COPD criteria. Haemoglo- bin values for the group were 13-16 g/dL (mean 14. l g/dL). Cardiac output showed significant (P < 0.05) direct correlations with VC (r = 0.50), FVC (r = 0.50). FEV1, (r = 0.47), Vmax:25 (r = 0.45). Vmax50 ( r = 0.48} and PEF (r - 0.47). A weak and direct correlation was found between PAP and PAR (r-= 0.44, P < 0.05). A strong and direct correlation was found between PAP and PCWP (r = 0.84, P < 0.05), and a medium and direct correla- tion between PAP and RAP (r = 0.68, P < 0.05) and RVP (r == 0.65, P < 0.05) (Table 1). Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 93 Table 1 Correlations of cardiac and respiratory function parameters In 24 patients with chronic obstructive pulmonary disease Parameters Correlation r ft.value compared COandFEV1 0.48 <0.05 COandPEF 0.47 <0.05 COandVC 0.50 <0.05 COandFVC 0.50 -<0.06 CO and Vmax25 0.45 <0.05 CO and Vmax50 0.48 <0-05 CO and PAR -0.46 <0.05 PAP and PAR 0.44 <0.05 PAPandPCWP 0.84 <0.05 PAP and RAP 0.68 <0.05 PAPandAVP 0.65 --;;Q.05 CO = cardiac output; FEV, = forced expiratory volume in 1 second; PEF = peak expiratory flow rate; Vmax25 = 25% of forced vital capacity; Vmax50 "" 50% of forced vital capacity. PAP = pulmonary artery pressure; PAR = pulmonary artery resistance,- PCWP = pulmonary capillary wedge pressure; RAPPP = right atrium pressure; RVP = nght ventricle pressure_ There was a very weak and direct cor- relation between PaO, and Vmax25 (r = 0.40, P < 0.05) and 1--·tv 1 (r = U.J7, P < 0.05). A very weak and inverse correlation was found in all patients between PAR and rhe F.EV/FVC ratio (r = --0.J.:,, ~ < U.UJ). In the COPD group of 14 patients, there was a medium strong inverse corrdation between PAR and FEV/FVC (r"" --0.54, P ~ 0.0'.'l). Discussion The pulmonary circulation is a dynamic system that is affected by mechanical, neu- ral and biochemica] factors. Beginning from the response of the pulmonary circu- lation to these stimuli, researchers arc at- tempting to reverse pulmonary hyper- tension. Oxygen inhalation, acetylcholine and tolazoiine infusions have been tested for their ability to overcome the reflex pul- monary vasoconstriction. A serious pulmo- nary vasoconstriction may develop in elderly COPD patients with left heart insuf- ficiency due to alveolar hypoventilation and the resultant hypoxia. Inhalation of I 00% oxygen in these patients causes PAP and vascular resistance to drop [/]. In this study, we determined oxygen salumtion of the aorta and the pulmonary artery as well as PCWP, PAP, RVP and RAP, cardiac output and especially PAR. PAR gives the resistance pressures of the main pulmonary artery, the arterioles and the precapillary and pulmonary capillary beds. In comparison with PAP, PAR is a better way to determine the presence and the severity of pulmonary vascular disease ll JJ. We therefore investigated the relation between PAR and the pulmonary function test parameters, and revealed that there was an inverse correlation between PAR and FEV 1/FVC. In the study of Wolf et al. with krypton- 8Im perfusion, the RVEF was investigated in COPD patients and in healthy individuals [12]. The RVEF was distinctly low in COPD patients and there was a linear in- verse correlation between PAP and RVEF. In COPD patients with pulmonary hyper- tension, RVEF was clearly lower than in COPD patients without pulmonary hyper- tension. Concerning RVEF. they again found a weak positive correlation with the PaO2 and .FEV1, but no correlation with par- tial CO2 pressure, pulmonary hypertension orFEV/FVC. The data of Wright et al. show that PAP and pulmonary artery wedge pressures and cardiac output were normal at rest [13]. 94 La Revue de Sante de la Mediterranee orientale, vo1. 10, N" 112, 2uu4 However, patients ,vith more severe dis- ease showed greater increases in PAP and pulmonary artery wedge pressures with exercise than did patients with minimal or no disease. Oxygen breathing had no effect at rest but it lowered PAP and PCWP during exercise in the patients with more severe disease. Histological studies showed that patients with moderate obstructive lung disease have strnctural changes in the pul- monary arteries consistent with pulmonary hypertension when compared with patients with minimal or no disease. Zhang ct al. showed that exercise testing can identify the early phase ot latent pulmonary hyper- tension and that in cor pulmonale patients PAP rises after exercise [ 14]. The criteria for pulmonary hypertension are a mean l'Al' greater than 20 mmttg rest- ing and greater 1han 30 mm Hg on exercise. The RVP increase cannot be determined for these criteria. PAR is more sensitive in showmg the nght ventricular load in con- junction with PAP [9]. In 14 of our pa- tients, PAP was greater than 20 mmHg. There was a direct correlation between P/\Kand l'AP. According to the Fick formula, cardiac output is equal to the right ventricular flow, assuming that there are no intracardiac shunts lil'J. lt is thus useful to note that we found a direct correlation between cardiac output and FEV 1, PEF, VC, FVC and the Vmax25. As COPD develops, the parame- ters above and the right ventricular ourpm deteriorate. Furthermore, it seems consis- tent that there is an inverse correlation be- tween the cardiac output and PAR an<l a direct correlation between the PAP and the PCWP and the RAP as well. PEF is a useful measure of pulmonary health status. In a study of van Heiden et al., a trend towards reduced peak flow was already evidcm in teenagers who smoked and whose parents were smoking [ / 5]. ln a similar study, the results showed that, even for younger peo- ple, cigarette smoking is associated with signi!lcam cte1rtmemal effects oH cardiop- ulmonary function and exercise tolerance. Objective evidence of an effect of smoking on cardiopulmonary function and exercise tolerance in this agt: group may d~~i~L edu- cators and health care professionals in con- vincing teenagers to quit smoking [ 16]. Pulmonary function testing, at least the measurcmem or rev 1, in ,tll mi1.h.lk:-ttgcu smokers has be...:n recommended. The smokers with abnormal FEV 1 should be ad- vised to quit smoking f 17]. Further investi- gations are needed to um.icrsLai11J Lin: relationship of oxygen saturation to Vmax25 and FEV 1 values, although we found a correlation between these paramc- rers aml PaO 0 • Finally, w-e could have obtained results that are more reliable ifwe had focused on COPD patients and compared their right hean prt:ssures m.:1.:unli11g tu Lli:;ca:.e :;cvcr- ity. Our study evaluated right heart function for patients who primarily came for coro- nary angiography an<l then we looked for COPD. Since wi.: had llll :;cvc1c COPD pa- tients, right heart function did not show deterioration. Invasive diagnostic proce- dures are usually unnecessary if non-inva- sive smdies im.li1.:.:11c 111i!u tu modcra.tc pulmonary hypertension in chronically hy- poxaemic patients with severe airways ob- struction. V/e should keep in mind that then: is ctn i11v1;r~e coudatiun between th,; FEV /FVC ratio and PAR, and a direct cor- relation between the Vmax25 and FEV 1, which arc indicators of a mild to moderate dq,rree of COPD. Wt: L,clit:vc that this ilp- proach may he useful for estimating deteri- oration of right heart parameters without using invasive methods and thus improving the t:arly t.li11gr1osi:; and thernpy of chronic obstructive pulmonary disease in smokers. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 95 References 1. Fi::;lumm AP. Fulmon<Jry diseases and disorders. New York, McGraw-Hill, 1998, 2:1159-70. 2. Silverman E et al. Genetic epidemiology of severe early-onset chronic obstructive pulmonary disease. American Journal of respiratory and critical care medicine, 1998, 157: 1770--8. 3. Klinger JR, Hill NS. Right ventricular dys- function in chronic obstructive pulmo- nary disease. Chest, 1991, 99:715-23. 4. Oswald M, Weitzenblum E. L'hyperten- sion arterielle pulmonaire des affections respiratoires chroniques. {Pulmonary ar- tery hypertension in chronic respiratory diseases.] Revue du praticien, 1991, 41: 1548-53. 5. Matthay RA et al. Right ventricular func- tion at rest and during exercise in chronic obstructive pulmonary disease. Chest, 1 992, 101 (suppl.) :255-62. 6. Weitzenbaum E et al. Course of pulmo- nary haemodynamics in patients with chronic obstructive pulmonary disease. Chest, 1979, 75:656-61. 7. Vandiviere HM. Pulmonary hypertension and cor pulmonale. Southern medical iournal. 1993, 86:7-10. 8. Grossman W. Clinical measurement of vascular resistance and assessment of vasodilator drugs. In: Grossman W, Baim D~. Arb:. CarrliRr. r.athP.tP.rin1fion. an- giography and intervention, 4th ed. Philadelphia, Lea and Febiger, 1991. 9. Yang SS et al. From cardiac catheteriza- tion data to hemodynamia parameters. New York, FA Davis Company, 1972. 10. Lemher C, eel. Getgy sctenrmc raoles. Basel, Ciba Geigy Limited, 1990, Vol. 5. 11. Wang C, Zhang HY, Weng XZ. Pulmo- nary vascular resistance index as pa- rameter for detecting right ventricular afterload. Zhonghua nei ke za zh1; 1991, 30:502-5 [in Chinese]. 12. Wolf JE et al. Measurement of right ven- tricular ejection fraction with krypton- 81 m in chronic obstructive pulmonary disease. Bulletin europeen de physiopa- tho/ogie respiratoire, 1986, 22:539-44. 13. Wright JL et al. The structure and function of the pulmonary vasculature in mild chronic obstructive pulmonary disease. The effect of oxygen and exercise. Ameflcan rev,ew or resp,ratory disease, 1983, 128(4):702-7. 14. Zhang ZX. The clinical investigation of the pulmonary arteriaf pressure in stable-stage chronic obstructive pulmo- nary disease with cor pulmonale. Zhonghua fie he he hu xi za zhi, 1991, 14:353-5 [in Chinese]. 15. van Heiden SN, Hoal-van Heiden EG, van Heiden PD. Factors influencing peak expiratory flow in teenage boys. South African medical Journal, 2001 , 91 ( 11 ) : 996-1000. 16. Louie D. The effects of cigarette smoking on cardiopulmonary function and exer- cise tolerance in teenagers. Canadian respiratory Journal, 2001, 8(4):289-91. 17. Kurosawa H. Clinical examinations for COPD. Rinsho byori, 2000, 48(12): 1118-24 [in Japanese]. 96 La Revue de Sanle de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Detection of cotinine in neonate meconium as a marker for nicotine exposure in utero N.A. Sherif, 1 S.M. Kamel,' O.S. AI-Ashkar, ~ O.A. Sharaki, 0 E.A. Seif' and E.A. Hegazy' ~ )1 J:"-1~ .:.t?M .. .o ..,-.:.U ~1~ 01.JJ _,i, ~ .; ~ fa1 ..;..;.s Jl.,::J ,......,_._., J.:,u ,)' ... J ,~,.r- _;,,b\.;:. ")lu:. ,__,.i.!.\'1 ~ ... Li ,J.,15" _lJ. r'""" '---"i.r i..,.1.__.i. .. , -½? :i......,,.; -$ jL,,,...,,- ..u--i J' :.,~ .r(.,cJJ ~.:, ") J J,i ~ _?-J ~ J..1/. :>-" I~ .)l .. u _,]1 ~ _J :.,~ _pjl ..; .r-' __,..y { : L,p"jj..\ .;.,;,I~' Jl ..,...a-- ,•-1;.LC)'' J -~"J)i fa~ Jl .:;,--.:,i _Jl_,lll ,,:.A.\ll~JI ~ _u) -~ ,+-<l-'4-·i j_ .. ,'-.Jj ,GI t:,u :.,,40.,,.,-.,. f 10 •J.-.f"-"il ~.J..1 1 Jl.,:- .. u __ ,.;,_,,,d4 .,;:.,i.:.,,:.J..., 10 ,.,;:.,~lo ..:.,\.:.,,;...v 10 :.,;:.,le-~ c.5_,.:-J, :.:i ...G:-J .,,.} .J/1, u), ,J _:, .. ~ .. ;1..u) • ...::.:i+-\11 J_,.,J ._,...w :.f' ..::..,'"""' ~ .i.:.J -c:.~ 'W .~l..t...::.)'1 ~Ll.1 ~Lll~- ~1._; ,.s_J ...:_.,"'y~'1 ,.::....,lJ;...,,~1 0...J ~ -..:_.:- 1'-t!-'"\11 ~---~ -.j ~1~_,.S:.U ~--~I, , . .>~- ,:""I~ ._pl?! _bl'---,-7/'1 ~I~ ."J~J ~IJ s_...11Jt_1H ~-.,,_ .:_,.,,.;.,._;-_ _s-...,~ ~) 1 ,_.;;::rl\ ..::~ J··,..J~\") 1.:-l,::. LJ-~-" J.>-_j ~1} ~I, -'~ \_·~ ~ ,._::..,¼,..~\11, J}-'._~ --;--'1,.,J ~~ ~ .. ;__:.;_...s:JI .,:.._,½,.~4 ~~ i,..,ls_,,-_~ ~µi .J .:..,ad J-;(j\ ~-~_,,_:..-. .. . -~_}1,..,(1_.,.l-'Lj ;l._?--- ~-j,-l 0 ~1\ ~)G,:-_\j ~ .. ~u _)·j,L..l.l .._.~ _ r't;jl .)~ )I 1._~)1~ '~ _.,J ~ ABSTRACT Noonoto mooonium cotinine level was evaluated as a marker of prenatal exposure to nicotine from tobacco smoking by mothers. Mothers admitted to a maternity hospital in Alexandria, Egypt, were divided into 3 groups: 10 active smokers, 10 passive smokers and 10 with no tobacco exposure during pregnancy. Urine and saliva samples were collected from mothers and first·day meconiurn samples from their neonates. Mean maternal urinary cotinine levels, measured using radioimmunoassay, differed signifi- cantly betiNeen the 3 groups, as did mean salivary cotinine and mean cotinine levels in meconium. There was a significant positive correlation between cotinine levels in meconium and both maternal urinary and salivary cotinine levels, Meconium is an ideal biological marker for testing direct fetal exposure to tobacco smoke in the neonatal period. Detection de la cotinine dans le meconlum du nouveau-ne comme marqueur de !'exposition a la nicotine in utero RESUME Le taux de cotinine dans le meconium du nouveau-ne a ete evalue en tan! que marqueur de rexposition prenatale a la nicotine du fait du tabagisrne de la mere. Les meres ad mises dans une matemite a Alexandria (Egypte) ont ate reparties en trois groupes : 10 fumeuses actives, 10 tumeuses passives et 10 femmes qui n·avaient pas ete exposoos au tabac pendant la grossesse. Des echantillons d'urine et de sative ont ete recueillis chez les meres et des prelevements de meconium du premier jour ont ete effectues chez leurs nouveau-nes. Le taux moyen de cotinine urinaire de la mere, mesure par radio-immunodosage, differatt signilicativement entre les trois groupes, tout comme le taux moyen de cotinine sallva1re, ains1 que le taux moyen de cotinine dans le meconium. II y avail une correlation posttive significative entre le taux de cotinine dans le meconium et le taux de cotinine salivaire et urinaire chez la mere. Le meconium est un marqueur biologique ideal pour deceler !'exposition directe du fcetus au tabac dans la periode neonatale. 1 Department of Forensic Medicine and Toxico/ogy;2Department of Obstetrics and Gynaecology; 'Department of Clinical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. Received: 01/09102; accepted: 20/07/03 Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 97 Introduction There is no doubt that smokmg durmg pregnancy is hazardou, to both the mother and baby. The harmful effects of maternal smoking have been well documented, The relation between maternal cigarette smok- ing and adverse pregnancy outcomes in- clude abruptio placenta, bleeding during pregnancy, premature rupture of mem- branes, fetal death, neonatal mortality, and deficits in growth, intellectual and emotion- al development and in behaviour [1]. The majority of epidemiological studies have found no association between cigarette smoking and congenital malformations [2], However, one study suggested that moth- ers agc<l 35 years and older who smoke may have a higher nsk of dellvering infants with minor malformations [J]. The risk of passive smoking or environ- mental exposure to tobacco smoke has been a major concern in the past nvo de- cades. It has been suggested that passive maternal smoking may be associated with lower score on tests of neurodevelopment as a result of long-term neurotoxicity [4], This could be explained by the fact that fe- tal and neonatal levels of carboxyhaemo- globin are generally higher than maternal concentrations because or a higher affinity of fetal haemoglobin for carbon monoxide [ 4]. Cotinine is a more specific indicator for rhe inhalation or tobacco smoke, i.e. nico- tine, compared with other indicators such as carboxyhaemoglobin. Carboxvhaemo- globin is a non-specific indicato; as it is formed on exposure to carbon monoxide, which is widely distributed as an air pollu- tant and is also endogenously produced. Cotinine is the major metabolite of nicotine [J]. It is considered a better marker of long-term exposure to tobacco smoke than the parent alkaloid, since it is endogenously produced only through an oxidative meta- bolism of nicotine in the body [ 6]. It is also more easily identified, since its concentra- tions are higher in both blood and urine. This is due to its longer plasma half-life (30 hours) as well as a more protracted excre- tion rate [ 7. 8]. The aims of the study were to: evaluate the use of neonate meeonium as a marker of prenatal exposure to nicotine from to- bacco smoking by the mother; to study the correlation between maternal urinary and salivary cotinine levels and the levels found in the neonate meconium; and to study the effect of nicotine on birth weight. Methods The study ,vas carried out from I July 1999 to 31 January 2000 on 30 consecutive mothers and their neonates admitted to El- Shatby Maternity University Hospital. All mothers \vere interviewed and a full history was taken with emphasis on history of smoking during the last pregnancy. Neo- nates were weighed and clinically examined for any congenital anomalies. The mothers were subdivided into 3 subgroups accor- ding to smoking habits: 10 mothers with a history of active smoking during the preg- nancy; 10 mothers with a history of pas- sive smoking during the pregnancy; and lO mothers \.vith no exposure to smoking du- ring the pregnancy. Urine and saliva were collected fron1 mothers as well as first dav meconium from their neonates, Consent -;,._,as obtained from mothers before urine collection. Urine was collected from mothers at the time of delivery by a catheter to avoid contamina- tion of urine with blood. A 10-20 mL sam- ple of urine was placed in a plastic container and frozen at -15 °C to -20 °C until the time of assay. A saliva sample of 2-3 mL was collected (unstimulated) from mothers shortly after labour an<l placed in 98 La Revue ae same ae Ia Medllerranee onema1e, VoL 10, N° 112, 2004 plastic test-tubes and deep frozen until the time of assay, First-day meconium was collected straight from the diaper of tht: nt:- onates using a spatula and deep frozen in plastic tubes until the time of extraction. Cotinine extraction and assay The urine and saliva samples of the mo- thers were centrifuged and the supema- tants were assayed directly by radioim- munoassay (RIA) using a double antibody nicotine metabolite procedure (Diagnostic Products Corporation, Los Angeles, USA) [9]. The procedure is a liquid-phase RIA in which cotinine labelled with iodine 125 competes for antibody sites for a fixed time with cotinine (and other nicotine metabo- lites I in the patient's sample. After incuba- tion for a fixed time, separation of bound from free parts is achieved by the polye- thvlcnc glycol (PEG)-accelerated double an"tibody method. Fina1\y, the antibody- bound fraction is r1rt>cipit:1teci :mci counted The patient sample concentration is read from a calibration curve. The reproducibility of this method was examined on urinary samples selected to represent a range of 3 different cotinine levels. Results revealed a coefficient of variation of 5.3%-9.4% for intra-assay (within-run) and 4.3%---6.8% for inter-as- say (run-to-run) results. After thawing. meconium samples of 0.5 to 1.0 g were ,vcighcd and vortexed rigorously in 5 mL of methanol. After cen- trifugation at 1500 x g, the supernatant was dried in a 40 °C water bath using a stream of nitrogen [I OJ, The sample was then re- constituted with 1.0 mL of methanol and 50 uL was taken off and assayed using the same RIA method [9]. Statistical analysis · Statistical analysis was made using SPSS, version 8 [11], Statistical tests used were the mean and standard deviation (SD), F-test (ANO VA), Pearson correlation coef. ficient, Spearman correlation coefficient am! Sd1t:fft: tesl. A P-v<1l ut: of 5% w.is used as the level of significance. Results Maternal data The age of the active smoker group ranged from 20 to 32 years with a mean of 27,8 ± J.7 years. The age of passive smokers group was lower, ranging from 18 to 35 years with a mean of 26.3 ±. 5.4 years. In the non-exposed group, the age ranged from 20 to 29 years and the mean was 25.0 ± 2.9 years. There was no significant dif- ference bet\veen the mean ages of the 3 groups (F = l.l 5). The number of cigarettes smoked per day by the mothers of the active smokers group ranged from 2-18 cigarettes with a mean of 11.7 ± 5.3 cigarettes. Neonatal data Using the Scheffe test, neonates whose mothers were active smokers had a lower IIIC:<111 I.Jirt]1 wcighl lh11.11 lhu:,;c whm,e mo- thers were passively exposed to smoke (mean difference 200.0 ± 82.5 g), This dif- ference was not significant, however. Neo- uat,;;;:,; whu:,;c mullic1:,; :,;,m:,kcd had a significantly lower weight than those with non-smoking mothers (mean difference 490.0 ± 82.5 g) (P < 0,001) (Table l ). The mc<1.n birth weight of neonates in the pas- sive smoking group was less than those in the non-smoking group (mean difference 290.0 ± 82.5 g), and this was also signifi- cant (P < 0.05). Laboratory data The present study revealed an overlap be- nveen the levels of maternal urinary coti- n ine in active and passive smokers. The highest level was detected in the active Eastern Mediterranean Health Journal, Vol. 10. Nos 1/2, 2004 99 Table 1 Mean difference in birth weight In relatlon to maternal smoking habit Groups compared Active (n= 10) versus passive (n = 10) smokers Active (n = 1 O) versus non- smokers (n= 10) Passive (n = 1 O) versus non-smokers (n = 10) SE = standard error. smoking group, ranging from 1390 to 22 300 ng/mL, with a mean of 16 l l O ± 10 851 ng/mL (Table 2). In passive smo- king mothers, the cotinine level ranged from 79.3 to 14 385 ng/mL, with a mean level of 3096 ± 5783 ng/mL. The lowest level was detected in the urine of non- smoking mothers where it ranged from 0 ng/mL (non-detectable) to 122.5 ng/mL with a mean of 75.1 ± 42.2 ng/mL. There \-Vas a significant difference in the urinary cotinine levels across the 3 groups (F = 14.41, P < 0.01). There was a significant difference in the mean cotininc levels in mothers' saliva among the 3 groups (91.8 ± 101.6 ng/mL, Difference in birth weight (g) Mean SE -200.0 82.5 -490.0 82.5 -290.0 82.5 P-value 0.07 ,:Q,001 0.006 13.7 ± 19.2 ng/mL and 1.1 ± 2.0 ng/mL in active, passive and non-smokers respec- tively) (F = 6.79. P = 0.01) (Table 3). There was a significant difference be- tween the mean cotinine levels in the saliva of active smokers and passive smokers us- ing the Scheffe test (mean difference 78.2 ± 26.7 ng/mL). There was also a signifi- cant mean difference between the salivary cotinine levels of active smokers and non- smokers (mean difference 90.7 ± 26.7 ng/ mL) (Table 4). The Pearson correlation test showed a positive correlation between the cotinine levels in mothers' saliva and mothers' urine (r= 0.582, where P = 0.01) (Figure!). Table 2 Maternal urinary cotinine levels in relation to maternal smoking habit Smoking Urinary cotinine level (ng/ml) group Range Moan SD Aclivesmokers(n=10) 1390-22300 16110.0 10851.3 Passive smokers (n= 10) 79.3-14 385 3095.9 5782.8 Non-smok?.rs (n= 1 Cl) F-test SD = standard deviation. 751 4::>? F=14.41, P.::0.01 100 L<t Revua da S<tnte de l<t Medite,r<1nee orie11tale, Vol. 10, N~ 1/2, 2004 Table 3 Maternal salivary cotinine levels in relation to maternal smoking habit Smoking group Salivary cotinine level (ng/ml) Range Mean SD Active smokers (n= 10) 1.7-250.0 91.8 !01.6 Passive smokers (n= 10) 0-65.0 13.7 19.2 Non-smokers (n= 10) Q----6.5 1.1 2.0 F-test F=6.79, P<0.01 SD = standard deviation. Table 5 shows that in the active smoker group, the cotinine level in meconium ranged from 232 to 700 ng/mL with a mean of 367.2 ± 143.7 ng/mL In the passive smokers group, it ranged from 148 to 350 ng/mL ,vith a mean of263.4 ± 52.5 ng/mL, while in the non-smokers group it ranged from l 53 to 213 ng/rnL with a mean of 185.0 ± 24.2 ng/mL. Within the 3 groups, there was a significant difference in the co- tinine levels in meconium (F = IOAS, P = 0.01). There was a positive correlation be- tween the cotinine levels in meconium and in mothers' urine (r 0.688, P 0.01) (Figure 2). There was also a ~ignificant positive correlation between the cotinine levels in meconium and in mothers' saliva (r = 0.784. P = 0.01) (figure 3). The Pearson correlation test showed a :significant negative correlation bctv,rccn the cotinine levds in maternal urine and the neonatal birth weight {r = 0.546, P = 0.01) (Figure 4). The study also showed a signif- icant negative correlation between the coti- nine level in meconium and hirth weight (r = 0.497, P = 0.0 I) (Figure 5). Discussion Cigarettes are the most common non- medicinal dmgs used by pregnant women llZJ. The present study was carried out to evaluate mcconium as an altcmalive hiolog- ical marker for the detection of the nicotine metabolite cotinine. Thirty mothers and their neonates were chosen for this study. The small sample size is due to the small number of mothers who confessed that they smoke, as smok- ing by women is culturally unacceptable in Egypt. The babies were all full term, as gestationally premature babies were ex- Table 4 Mean difference ln maternal salivary cotinine levels in relation to maternal smoking habit Groups compared Active (n = 10) versus Difference in salivary P.value cotinlne level (ng/ml) Mean SE passive {n = 10) smokers 78.15 26.7 0.024 Active (n = 10) versus non-smokers (n= 1 O) 90.74 26.7 0.008 Passive (n - 10) versus non·smokers (n= 1 O) 12.59 26.7 0.895 SE "' standard error. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 101 • r1 ••c • • • C:.J CJ 61 % 0.1 10 100 1000 Maternal salivary cotinine levels {ng/ml) + Active smol<ers D Passive smokers A Non-smokers Figure 1 Correlation between cotinlne levels in maternal saliva and maternal urine eluded from the study. This was to limit any confusion bctv,,-ccn the effcctll of to- bacco smoking by the mother during preg- nancy and the effects of prematurity. The maternal data showed tnat there wa:s no significant difference betwcet1 the mean age of active smokers, passive smok- ers and non-smokers. That both smoking and exposure to passive smoking arc not Table 5 Cotinlne levels in neonate meconlum in relation to maternal smoking habit Smoking group Active smokers (n= 10) Passive smokers (n= 10) Non-smokers {n= 10) F-test Meconlum cotinine level (ng/mL) Range Mean SD 232-700 367.2 143.7 148-350 263.4 52.5 153-213 185.0 24.2 F= 10.45, P=0.01 6D - atandard deviation. confined to a specific age group highlights the general lack of awareness regarding the effect of smoking during pregnancy. The mean number of cigarettes smoked by the active smoker group was 11. 7 per day. This is almost idcnticaJ to the study of Eliopoulos et al. who found the mean num- ber of cigarettes smoked per day by preg~ nant smokers was 11.8 [I 3]. In the present stu.dy using the Sc-heffo test, the lowest birth weight was recorded in neonates of active smoking mothers. This is to be expected, as it has been re- ported that for every IO cigare.ttes smoked by mothers, the risk of delivering a low birth weight for gestational age infant in- creases by a factor of 1.51. The effect is do.:e dependent, and is not the result of a shortened gestation period, but is due to fe- tal hypoxia arising from decreased utcroplacental perfusion [/4]. Neonates of pas~ive stnokins motben al!!o had 11 1,ignit:. icantly lower birth weight than babies of non-smokers in our study, indicating the dangers of passive smoking to neonates. 102 500 450 400 200 150 La RtWue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 • • • [] • 'U • _, . ~ . ~ .Qi 100 -+---~--~--------- 10 100 1000 10000 100000 Maternal l)rinary cotinine levels (ng/ml) • Active smo\.:.ers a Passille smokers A Non-smokers Figt,ira 2 Corrol•tion hl!lt,,vAP,n ct1tlnine levels In maternal urine and neonate meconium .3 500 I 450 . § 400 C: 360 0 0 <I) 300 E . !. 250 'I!. <I) >" 200 .lll :: ~ -~ .Iii 15 0 0.1 + •• D • Dcil+.:J At> 10 100 • 1000 Maternal salivary cotrnme levels \ng/mL) + Active smokers D Passive smokers t,, Non-smokers flg1Jre;, Correl•tl11n bt1lweo11 iw,;;illnlne levela In neonate m,:,.:onlum 11nd maternalsanv .. Cotininc was chosen for detection of smoking as it is the main metabolite of nic- otine (70%) [15,16]. Its long plasma half- life (30 hours) and protracted excretion rate mcun thut concentration~ in both blood anrl urine are hieh [ 7.8]. The present study showed that cotinine was detected in the urine and saliva of active, passive and non- smoking groups, ranging from a mean of 16 110 ng/m I . in active smokin~ mothers to Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 .!!2 100000 ., > .m 10000 m . 5 C ,.., 1000 o-0 -' --... E .... a, -~ E- 100 :5 ~ ~ 10 ,., ~ • • • ~ • • D • • D Cl 0 El /:;. D /:;. 2500 2600 2700 2800 2900 3000 31JO 3200 3300 3400 3500 3600 '.l700 3800 3900 4000 Birth weight (g) • Auti-.-e :,rnokers Cl l"'a<1oivo omokar" A Non-f:mok,;,r,; Figure 4 Correlation between cotinine levels In maternal urine.and birth weight 500 • :::; 450 t • -S 400 • E :, c= 350 D 0 • ill E 300 • 0 • Cl _.; • § D gj 250 0 > • .9l D • A <I> 200 /:;. A _s;: I::,, ·= t! I::,, 0 150 D I::,, () 100 +----.---,------""""T"-~-----.--..--~~~-.--~----~-..--------. 2500 2600 2700 2800 2900 3000 3'00 3200 3300 3400 3500 360Q 3700 JEOO 3900 4000 Birth weight (g) • Active smokers D Passive smokers t:,. Non-smokers Figure 5 Correl11liu11 bt1lwe11m cotinh1e levels in neont11te mcoonlum and birth w•lght 103 3096 ng/mL <'.1-nd 75. l ng/mL in pas5iw und non-smoking mothers respectively. There was an overlap ben-vccn the range of ma- ternal urinary cotinine levels in active and pa5sive smokers, which agrees with the study of Wald et al. [ 17]. This may be at- tributed to variations in exposure, as an ac. tive smoking mother may be a light smoker 104 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 while a -passive smoking mother may be lu::11v.ily CAJ-'V.'ICU to smoking. The- study also revealed a slight overlap between urinary cotinine levels of passive and non-smokers. This is expected if the exposure is slight in t!itc" pa:s1;ive group. The presence of cotininc in the urine of non-smokers is not surpris- ing as complete avoidance of cigarette smoke in the environment is almost impos- sible. Al~o, there arc 1>mall amounts of nico- tine in common foods such as potatoes, eggplant and tea [18]. There were significant differences be- twc1;n the 3 group~ in both the mean coti- nine levels in mothers' urine and the mean cotinine levels in mothers' saliva. Using the Pearson correlation test, we found a signif- ici:lnt pu:-;itive correlation between cotininc levels in urine and saliva (r = 0,582, P = 0.01). So mother's saliva could serve as an alternative to urine a~ a ma1'ker for <letec- tiuu of tobacco smoking, It i.o1 ca:iicr to ob- tain and difficult to adulterate, The presence of cotinine in meconium was used as a direct indicator of fetal expo- :;urc to toba.cco .:1m,1king in the neonatal peiiod as cotinine is mainly deposited in meconium through bile secretion and to a lesser extent by fetal swallowing of amniot- ic fluid containing fetal t1rinc [!5,16). The study revealed a significant difference in the cotinine levels of meconium between the 3 groups (F""' 10.45, P"'" 0.01). The mc:nn -.:onccutrntion of cotininc in the meconium of neonates of active smok- ers was significantly higher than in neo- nates of passive and of non-smokers. But the mc:an concentration of cotinine in the meconium of neonates of passive smokers was not significantly higher than that of neonates of non-smokers. Ostrca ct al. used lUA to measure nico tine metabolites in the meconium which was extracted by vortex-mixing (0.5-0.6 g) meconium with 10 mL distilled water a11d 1 mL concentrated HCI, then filtering the homogenate through glass wool and using the centrifuged (9770 x g for l 0 min- utes) supernatant for the assay. They re- ported much lower cotini11e levels ranging from 10.9 ng/mL in neonates of non-smok- ers to 54.6 ng/mL in neonates of heavy smokers [19], whereas the range of meco- nium cotinine levels in the present study were from \ 53 ng/mL in neonates of non- smokers to 700 ng/m L in neonates of active smokers. These differences in the levels could be ~ttributed to either the difference in the extraction method used, as the ex.~ traction procedure substantially affects the outcome of the analysis {20], or to environ- mental tobacco smoke eKpoi.ure in the present study. As regards babies' birth weight, the Pearson correlation test showed a signifi- cant negative correlation between both ma- ternal urinary cotinine levels and neonatal meconium cotini.ne levels and babies' birth weight. This confirms other studies show- ing the.t tobacco smoking leads to low birth weight and that fetal hypoxia increases with increasing exposure of the mother to tobacco smoke [/4]. Conclusion Cotinine was detected in maternal urine and saliva and these two biological tlmds are good markers for tobacco smoking. Simi- larly, its presence in meconium proved that meconium is an ideal biological marker for testing direct fetal exposure to tobacco smoking in the neonatal period. This is im- portant as it may throw light on the cause of a neonate with low birth weight. Added to this, collection ot meconi.um 1s ~asy and non-invasive. Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2, 2004 105 References L F\ore MC. Cigarette smoking. 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Clinical chenm,tiy, 1995, 41 : 1614-6. 106 La Revue de Sante de la Mediterranee onentale, VoL 10, N° 1/2, 2.004 Growth charts of Egyptian children with Down syndrome (0-36 months) N.A Meguid,1 A.I.S. EI-Kotoury,2 G.M.H. Abdef-Salam,2 M.O. EI-Ruby2 and H.H. Afifr .AA1..,_.:JIJ .,;,,'j~ d..,11\J.) : iJ JI' .lo j~ ~l..Al,1 ~_r'UI Jl..il,~I ~ ..:..,l,i~ ,? JL- 'i,,1-J)I ~ •t')LJI .,w, •-''~ '(,S~I .u-,i ,,V ,.S~ 350 J _....(_JI .h..: .! J_.jJI_, _....,JI ....,_,....._, _,,..JJ ...:.,~. ,.J.J>I ~I! ..:;..,)'l..J.J Uy.UI ~.i,. ~ ;L..,~1 0':: r-1',,w.f c.h,; J.-> (..:.>1_;)11 ,:_,.-• 162) )_,.s'.UI J"' 188) .JJb Vj)1~ • ..:.,;.iWI .Y-:!r"'-11 JW..\11 ..:.:" ~~_.!-'"'½·, J\.ik½I IS..i.\ v- _jl y: ...;;.,l_iA;,, :.J)\-' ".vj'J.::.J: . .,::;1W\ _s:.u .ii,.._~ .i,) ,\~ 36J • .,-y;1 ,.;:.I..., ,,$'1 ._..,..a.; y j ~,., ;_,, j'Y.::t . .) ,-:WI Juk'i!I J\.aiJ -~t,,,.- y J../:11 ..;;')'Ji ..;.,l_,.;-.]1 J":J,,- .u.l_,..!.il ,.;J\.4ll, .:.IJ.)) (.,_I!,- 90 sJJ) ~ ,.:P ,._,-"_f' . .:.IJ.) ,_;..ii} bj ~ ~1_;~1 0 ..u t...;,..':JJ Jj_,JI J (.r"Y. ~,:., .:., ; .JJ ~-L ~I 4-'- _. ..,:;..,; 1S' ·,..J .\1: .:,;:.-JI j')I,_,,:., .. ,1.L,.:. . J; _;, ~- ,:, ... L.all ~ ._. __,;I .iL - ...i ....,...,. , • - ..J ._..,i~ ./ ... - ~- "":i' i..,;.,:. V ..T ... )Z- V 1.....,,.. ..T - ._;J.; 1..1 ,J,.tA, ~i J _,w1 J ~ r .J _:b :\..-j;i,...{. ~y,w!.1 ).,$ J.ll iSJ.l .:.,IS ..u! . J.,S JJ1 __,;--ll -c..~i c/"1)1 .,,,..._II 0" ._',)';J\ .,!.,')'.:Ji, -=-'(_.,.;-l, J~ ..i>,\p\ ABSTRACT A study established growth and growth velocity curves for weight, length and head circumfer- aencc i" SSO E9yptian Down cyndro= chi\dran (1 SS m:.1.\es and "\S2 le.ml'lles) f1r,rn 0-'.'.\f\ mnnth!l !)awn syndrome children t1ad poorer growth variables than normal heatthy children through the first 3 years of life. Down syndrome ch'1\dren with associated oongenital heart disease (90 cases) had signilicantly lower weight, especially in girls, compared with those without heart disease. In the first 2 years, growth velocity for weight and hear;! circumference were higher in Down syndrome females than males, while growth velocity for length was higher in males. Down syndrome boys had slightly higher velocity of length than normal children in the first 3 years of life. Les courbes de croissance des entants egyptlens attelnts du syndrome de Down (ages de o ii 6 moia) RESUME Une elude a perm is d'etablir les courbes de croissance et de vitesse de, croissance pour le poids, la tallle et !e perimetre cranien chez 350 enfants egyptief\s, ages de o l':. '36 mois, qu\ e\a\ent atteints du syndrome de Down (188 gar~ns et 162 filles). Ces enfants avaientdes variables de croissance inferieures a celles des en1ants normaux en bonne sante pendant les tro·1s premieres annees de la v·1e. Les enfa.nts atteints du syndrome de Down qui presenlaient une cardiopathie congenitale associee (90 cas) avaient un poids signiticativement plus faible, particulierement les filles, que ceux ne presentant pas de cardiopathie. Au cours des deux premieres annees, la vitesse de croissance pour le po1ds et le perimetre cranien etait plus elevee chez las filles atteintes du syndrome de Down que chez les gan;:ons, tandis que la vnesse de croissance s1a1uraIe e1a11 plus 81evee chez It!::, y<lr i,;t.111:s. L~i:, gar~on:s atteinu. du ~yndrome d~ Down avaient une vitesse de croissance staturale legerement plus elevee que les en enfants norrnaux au cours des trois premieres annees de la vle. 'Department of Research on Children with Special Needs; "Department of Human Genetics, National Research Centre, Cairo, Egypt. Received: 12/03102; accepted: 26106/03 Eastern Mediterranean Health Journal, Vol. 10, Nos i/2, 2004 107 Introduction Down syndrome (trisomy 2 J) is the most prevalent unbalanced chromosomal aberra- tion seen in live births, with an incidence of I pt;:1 600 Ii Vt;: 1.J11 tk, 01 1 p1:1 I 50 com.:cp- tions [Jl It results in moderate to severe mental retardation, high risk of congenital heart disease and other multiple malfonna- tiu11,c >Hnl/01 variuus 1ucdiu'll ploblcms. These congenital malformations have a consistent effect on physical development [2]. Growth retardation is one of the cardi- mil fca1.urc5 uf Duwn 11yndromc, chara.ctcr- ized by deficient prenatal growth, i.e. reduced by (L5- l .5 standard deviations (SD) from normal control mean values, and c;,.tcndi1Jg po:.tnat,1lly th.rough the end of growing at 3--5 years of age [3]. Pro- gressive de-institutionalization of DowJJ syndrome children and their integration into the community, with improved medical and psychological follow-up, have greatly changed their lives and lengthened their life span {4,5]. Alth,;mgh growth is influenced by bio- logical and environmental factors, 'racial variations certainly have a major role. The publication of growth charts specifically for children ·with Down syndrome in vuri- ous populations, e.g. American, Sicilian, Dutch and French [3.6-8], has drawn at- tention to the importance of constmcting growth charts for Egyptinn Down syn- drome children. The potential benefits of growth charts include: growth monitoring to detecl any deviation in growth patterns. evaluating the efficacy of measures aimed at promotjng growth, providing reassur- ance to parents, evaluating the results of clinical research or intervention for individ- ual patient:, and, finally, comparing their growth with thal of the normal population. This study aimed to establish grmvth curves for Egyptian children with Down syndrome aged 0-36 months to investigate anct characterize their size, monitor tht:ir growth and evaluate the effect of congeni- tal heart disease on their growth pattern. The present study provides reference data (growth charts) for weight, length and head circumference for Egyptian children ,vith Dovm syndrome covering the age range 0-36 months based on cross- sectional and longinidinal data. Methods The study ,,vas carried out between Janu- ary 1999 and July 2001. The data for this study were based on 1700 observations of 350 Down syndrome children: 188 bovs (53.7%) and I 62 girls (46.3~·;;) aged 0-36 months with free trisomy 21. All were cas- es referred to the Human Genetics Clinic at the National Research Centre for diagnosis, genetic counselling and/or attendance at early intervention and stimulation pro- 1:,'Tammes. The data represent an unselect- ed. therefore presumably unbiased, sample of children with Dmvn syndrome in Egypt. The DO\vn syndrome children v,1ere divided into 2 groups: group 1 was 260 children without congenital heart disease ( 143 males and 117 females) and group 2 was 90 chil- dren with congenital heart disease ! 45 males and 45 females). Each patient underwent pedi_gree analy- sis, meticulous clinical examination and ba- sic anthropometric measurements. Chro- mosomal analysis by G~ba.nding technique, complete thyroid orofile and electtocardio- graphic (ECG) examination were done in all patients. Patients v.·ith mosaic 2 J or trans- location and those with malabsorption, hy- pothyroidism or severe congenital he~rt disease were excluded. Down syndrome patients with associated mild and moderate congenital heart disease were included in 108 La Revue de Sante de la Mediterranee orientate, Vol. 10, N° 1/2, 2004 the study. Children with mild congenital heart disease had a single cardiac defect withuut pulmonary vascular involvement and did not require medication or surgery. Those with moderate congenital heart dis- ease had more complex cardiac defects, u fi,;;;11 rt:4uiring digitalis, while severe con- genital heart disease consisted of serious anatomic heart lesions, e.g. tetralogy of Fallot. All studied Down syndrome children lived with their family members. Growth measurements (weight, length, head circumference) were taken at 3- monthly intervals. Measurements were tak- c11 by trained physicians and a second per- son assisted in alignment and immo- bilization of the child during the measure- ments. Length was measured to the nearest 111illimt:trc using a recwnbent length board infant measuring table. The weight was as- sessed by a sensitive balance scale to the nearest gram. Head circumference was mi;;a::>urt:<l w rhe nearest millimetre by a non-stretchable plastic tape taking the max- imum occipitofrontal diameter. The record- ed measurements for weight, length and hcaJ cin:umference represent a combma- tion of cross-sectional and longitudinal data. The dala for Down syndrome children wi;;1,;;; cumpared with data obtamed from measurements on normal healthy Egyptian children (2735 girls and 3315 boys) from birth to 36 months visiting Cairo hospitals ovc1 1996-2000 (Egyptian growth charts, published by the Faculty of Medicine, Cairo University and the National Research Cen- tre, Cairo, Egypt). Giuwth curves tor weight, length and head circumference comparing male and female Down syndrome cases (group I) with normal children were plotted using polymm1ial curves. Baker and hts co-work- ers found that polynomial curves adequate- ly represent the growth pattern [9]. Growth velocities for weight, length and head circumference were calculated for 6-monthly intervals for group 1. The mean value for each age interval was sub- tracted from that for the subsequent age interval. Growth velocities for Down syn- drome cases were compared with the growth velocities of normal children. Statistical analysis of data was carried out, using SPSS software, version 6. Based on age and sex, the data were divided into monthly intervals since birth until 36 months. Descriptive statistics and percen- tiles (3rd, 50th, 97th) were estimated for weight, length and head circumference for each sex for group I . Means and standard deviations were calculated for group 2. Student t-test was used to compare the mean of weight, length and head circum- ference at all age intervals between the 2 sexes, and between the 2 groups and the normal population. P values < 0.05 were considered significant. Results At birth, all Down syndrome children in the study showed tower mean anthropometric va1ues than that of the nonnal children. For weight, length and head circumference thf' values were: -1.6 SD, 2.2 SD and -1.8 SD for boys, and -1.7 SD, -2.8 SD and .3.5 SD for girls respectively (Table 1 ). Of the 90 Down syndrome patients with associated congenital heart disease (group 2), common atriovcntricular canal was the most common congenital heart disease seen in 34.4% of our sample (31 cases), followed by ventricular septal de- fect in 26.7% (24 cases) and multiple car- diac anomalies in 13. 3 % ( 12 cases). These Down syndrome patients with congenital heart disease had significantly lower weight, especially in girls, than those with- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 109 Table 1 Mean anthropometric measurements for Down syndrome children at Dirth compared with normal children Variable Males Down syndrome Mean so Weight(kg) 2.97 -1.6 Length (cm) 49.3 -2.2 Head circumference (cm) 34.f! -1.6 n = total number of children. out congenital heart disease (P === 0.02) (Ta- ble 2). In comparison with the normal popula- tion, patients with Down syndrome in group 1 and group 2 showed lower values of weight, length and head circumference. In boys of group I, the mean weight, length and head circumference were re- duced by 1.5 SD, I .6 SD and 1.8 SD below the mean of the normal boys respectively. The girls showed a reduction of l .6 SD, 1.7 SD and 1.8 SD below the mean of nor- mal girls for weight, length and head cir- cumference. Down syndrome boys of Females Normal Down syndrome Normal Mean Mean so Mean 3.90 2.86 -1.7 3.80 54.0 48.1 -2.8 53_3 06.8 32.7 -'3.5 36.5 group 2 showed mean values reduced by 2.8 SD, 2.2 SD and 1.8 SD for weight, length and head circumference respective- ly; the girls had redul:Liuu:s of 2.8 SD, 2.9 SD and I. 9 SD respectively. Males and females of group 2 had sig- nificantly lower mean weight versus group J patients (P = 0.03 am.I P ~ 0.02 rcspec lively). They also had lower values for mean length and head circumference but these were not statistically significant com- pared with group I (Talilc 2). In all age stages, Down syndrome boys of group I and group 2 showed higher val- Table 2 Mean anthropometric measurements for male and female Down !!l.yndrome children with and without congenital heart disease Variable Weight(kg) Length (cm) Head cir~umference (cm) Down syndrome males No heart Heart P. disease disease value (n"" 14$) (n=45) 9.3 7.8 0.03• 73.8 71.9 0.50 43.7 42.0 0.06 n = total number of children. 'P < 0.05. Down syndrome females No heart Heart P. disease disease value {n= 117) (n=45) 8.6 7.1 0.02· 70.8 68.5 0.30 42.1 41.3 0.40 110 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 ues for weight, length and head circumfer- ence when compared with girls (Table 2). Huwcvi.::r, these values did not reach statis- tical significance. 0 0 0 9 12 H!I 18 21 24 U ;:10 33 36 Age (monttis) Figure 1 Weight growth charts (0-36 months) for males with Down svndrom@ {ianlid llnes) compared with 50th percentile of normal Egyptian males (dotted line) 0 3 6 9 12 15 18 21 24 27 30 33 36 Age (months) Figure 2Weight growth charts (0-36 months) for females with Down synarome (solid lines) compared with 50th percentile of normal Egyptian females (dotted line) Growth charts at the 3rd, 50th, and 97th percentiles from 0-36 months for male and female Down syndrome patients (group I) were constructed and compared 0 3 6 9 12 15 18 21 24 27 30 33 36 Age (months) Figure 3 Length growth charts (0-36 monthe) for male• with Down syndrome (solid lines) compared with 50th percentile of normal Egyptian males (dotted Une) 100 I 95-: so I 85 -' E 80 I 0 75 . ;;- 70 - a as I ~60· /./. _. 55 \·:·::,, / .. / 50 , // 45 j/ 40 . 35 - -,-- ' ,--·, - r -· .-- --- 0 3 6 9 12 15 18 21 24 27 30 33 36 Age (months) Figure 4 Length growth chart.11 (D--36 months) for females with Down syndrome (solld lines) compared with 50th percentile of normal Egyptian females (dotted line) Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 111 55 ·, 52 ~ E 49 -J ---"·-~--! ::; /~ _EID 40 _:~./r _,,, ___ ,,..--.,., i/" / i3: 37 r,:, ,,, .!!:: ' ,I" u 34 . ./ m: 31 Y :J. 281 25 ' ... ,.. r-, -·· ' ·-r ,--- -,- I 0 3 6 9 12 15 18 21 24 27 30 33 36 Age (monthc) Figure 5 Head circumference growth charts (0-36 months} for males with Down syndrome (solid lines) compared with 50th percentile or norma11:gyptlan mal1111a (1Jott1111d line) with the 50th percenlih: fu1 the normal group (Figures 1--o). Growth velocity for Down syndrome girls (calculated for 6 monthly intervals) showed higher values of w~ight and hca.d circumference versus Down syndrome boys. However, both sexes reached the same values by the end of the third year. Urowth velocity of wt:ighL fur Down syn- drome cases was higher than the normal children until the 12 and 18 months of life in girls and boys respectively. Then it be- came lower until 24 awJ 33 month:; for girls and boys respectively (Figures 7 and 8). Velocity of length for Down syndrome girls was lower than the normal group; however, the gr1:c1ti;;isl deficiency was be tween 15 and 33 months (Figure 10). On the other hand, Down syndrome boys showed velocity of length slightly higher than the nonnal population at all age inter- vals (Figure 9). Velocity of head circumference for Down syndrome girls showed higher val- 55 s2 -1 E 49 .J .!!, ~ 46 55 43 $ 40 § /> / . ?_ 37 ~ .. --·/ ,,.. ~ 34 I//,/ "D / / &! 31 / / ::c: 28 ··. 25 ~ ·7···· ~, --.---- I -··r-- --i--1- I 0 3 6 9 121518 21 24 27 30 33 36 Age (months} Figure 6 Head circumference charts (0-36 months) for females with Down syndrome (aolid lincc) cbmparod with snth percentile of normal Egyptian females (dotted line) ucs than the normal group until age 12 months. Then it was lower until 24 months and, after that it showed higher values than the nonnal population. A similar trend was :.een in Down syndrome hnys (Figures 11 and 12). Discussion We have produced the first growth charts relevant to children with Down syndrome in Egypt from birth until 3 years old in both sex.es. Current data indicate that growth patterns of children with Down syndrome differ from those of normal children during the first 3 years of life. At birth, the growth pattern ofEgypliim children with Down syndrome ranged from -1.6 to -3.S below the mean of the normal population. The same tendency wa.., reported in French babies with Down syn- drome at birth [8]. On the other hand, growth reduction by 0.5-LS SD from nor- 112 La Revue de San!e de la Mediterranee orientale, Vol. 10. N° 1/2, 2004 4 35 3 -a 2.5 ~ E 2 er, ·a, :5, 1.:, 0.5 0 - 0 3 6 9 12 15 18 21 24 27 30 33 36 Age {months) figure 7 Weight velocity curves for males with Down syndrome (solid line) compared with normal Egyptian males (dotted line) 3.5 l 3 _, 2.!J -I Ol -"' ~ 2 1 £, ~ 1.5 - I 0.5 , I 0 I ·- r--r- 1·- I 1·- -r-1-, O .J e 9 12 l !J Hl 21 24 27 30 33 36 Age (months) Figure 8 Weight velocity curve for females with Down syndrome (solid llne) compared with normal Egyptian females (dotted line) ma? control means was reported in Ameri- can children [3]. This could be due to racial variations. However, our results confirm that the growth retardation started prenatal- ly and was more severe in cases with K 12 i i 9 ~ ~ 6 J 3 I ,--, ' 0 3 6 9 12 15 18 21 24 27 30 33 36 Age (months) Figure 9 Length velocity curve for males with Down syndrome (solid line) compared with normal Egyptian males (dotted line} E .!:. .c -en § 18 - 15 1 12 l g 6 I 3 ~ I 0 ' 0 ,-~"'T-'' -,-r··-·1 3 6 9 121518212427303336 Age (months) Figure 1 o Length velocity curve for females with Down syndrome (solid line) compared with normal Egyptian females (dotted line) Dovm syndrome with congenital heart dis- ease, which was the same observation of Wessels et al. []OJ. All through the firs! 3 years of life, growth charts showed that male and fe- Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 113 'f ~ .., ~ .!!! E :::, <.> ,!,, <.> -,:0 <G Q) :t 6 5 4 3 2 0 f ~~-! -, 0 3 6 9 12 1$ 1S 21 24 27 30 33 36 Age (months) Figure 11 Head circumference velocity curve for males with Down !Jyndrome {sl'.llld llnel comoared with normal Egyptian males {dotted line) male patients with Down syndrome had lower gn,wth µammeters compared with normal children. Similar results have been documented by other researchers [Jh 8,ll], which demonstrate the growth retar- <lalion effect of trisomy 21. Further analysis of the current growth charts re- vealed that growth impainnent in Down syndrome is not severe and that children with Down syndrome are less likely than nomial children to remain at a iiven ner- cemile level. The growth retardation ranged from -1.5 to -l.8 SD in Down syndrome chil- dren without congenital h.eart disease and - LS to -2. 9 SD in Down syndrome chil- dren with congenital heart disease com- pared with a group of nonnal children from l to 36 months. These results demonstrate a trend toward better growth in Down syn~ drome children without cardiac anomaly and add weight to the effect of mild to moderate congenital heart disease on the growtlt retardation seen in Dl)wn syn- s 6 s. 5 4) (.) C 4 4) a, E s ~ 0 ,f;;: 2 0 .,,, jg X 0 ·> - - 0 !~ r-- 3 6 9 12 15 18 21 24 .27 30 33 36 Ag8 (months) Figure 12 Head c1rcum1erence velocity curve for f0maler; with Oowtt ityndMm@ ~aoliA Jina) compared with normal Egypttan females (dQ«e<f Une} · drnme patients having cardiac anomalies. Both boys and girls with congenital heart disease showed significant weight reduc- tion compared with Down syndrome chil- dren without cardiac anomalies (P = 0.03 and P = 0,02 respectively). Howevex, val~ ues Df lengili and head circumference did not reach the statistii:;al significance, It seems !ikdy, rhercfore, that the influence of congen\ta\ beart disease in our sarrip!e affected weieht more than the other param- eters. These results arc in concordance with those reported before ( 3, l 21. At all age stages, Down syndrome boys. elther with or without congenital heart disease, showed higher growth pa~ rameters than girls. However, no statistical significance between the 2 sexes was not~ ed. This is in agreement with the American. Sicilian, Swedish and English Down syn~ drome growth charts showing significantly higher length and head circumference 1n boys versus girJs l3A,6./3./4L 114 La Revue de Sante de la MeditefraMe mientale, Vol. 10, N° ~/2, 2004 Most pub\ished data showed deficient gro,vrh velocity ail through the firsl 3 year~ of life but these authors did not comment on sex differences in growth velocity (J,8,/2], Interestingly, our results demon- strated higher growlh velocity in children ,vith Down syndrome versus nonna! chil- dren during the first 12-18 month of life, showing higher values in girls than boys \except for length). While during the 2nd year of life reduced growth velocity was equal in both sexes, by the 36th month of life growth velocity of Down syndrome pa~ tiems reached values slightly lov..-er than the normal population. The increased growth velocity, especially during the I st year of life, could be due to the great care that our pa.l{ems were receiving from meir families, and the proper nutritional and medical con- sultations applied to their lifestyle. All our patienis lived with their families and most of them wc:rc breastfed during the flrsI 12-- 18 months of their life. This finding high- lights tl\C imponam role of home care tmd breastfeeding and their effect on grmvth. Leonard and his co-workers attributed a similar observation to emotional support of rhe family and i.!1creascd nutritional adequa- cy [15]. In conclusion, growth charts at all per- centiles showed reduced patterns of growth in Dmvn syndrome compared wirh nomrnl children. The correct use of growth charts spedfic for Down syndrome can help highlight a physical developmental de- lay and suggest rhe ne1;;d rn look for con- comitant diseases affecting growth. In addition, comparing our growth velocity with other results emphasizes the impor- tance of breastfeeaing aJH.I (le-inslitutional- ization during the early years of life. Our data also confirm the negative influence of congenital heart disease on growth pat- terns, especially on weighl gain. References 1. James S el al. Abnormal folate met8.bo- lism and mutation in the rnethyl- tetrahydro1o\ate reductase gene may be maternal risk factor for Down syndrome. Am~,i,:;an journal of r;linir;al nutti(ion, 1999, 70:495-501. 2. Clementi M et al Neonatal growth pat- terns in a population of consecutively born Down synorome cnndren. Ameri- can Journal of medical genetics, 1990, 7:71-4. 3. Cronk CE et al. Growth charts for chil- dren with Down syndrome: 1 month to 18 years of age, Pediatrics, 1988, 81 : 1 02- 10. 4. Palmer CGS et al. Head circumference of children with Down syndrome {0-36 months). American Journal of medical genetics, 1992, 42:61-7 5. American Academy of Pediatri.cs, Com- mittee on Genetics. Health supervision for children with Down syndrome. Pedi- atrics, 2001, 107(2):442-9. 6. Piro E et al, Growth charts of Down syn- drome in Sicily: evaluation of 382 chil- dren 0~14 years c,l age. American journal of medical genetics supplement, 199U, 7:615-/0. 7. Cremers MJ et al. Growth curves of Dutch children with Down's syndrome. Journal of intellectual disability re- search, 1996, 40:412-20. 8. Toledo C et aL Growth curves of children with Down syndrome. Anna/es de genetique, 1999, 42(2):81-90. 9. Baker LA, Reynolds C, Phelps E. Bio- me\rical analysis of individual growth Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 115 curves. Behavior genetics, 1992, 22(2): 2!:>3-64. 10. Wessels MW et al. Poor outcome in Down syndrome fetuses with cardiac anomalies or growth retardation. Ameri- can journal of medical genetics, 2U03, 116:147-51. 11. Fernandes A et al. Characterisation of the somatic evolution of Portuguese chil- · dren with Trisomy 21-preliminary re- sults. Down's syndrome, research and practice, 2001, 6(3):134-8. '\2 Cronk CE. Growth of children with Down's syndrome: birth to age 3 years. Pediatrics, 1978, 6i :564-8. 13. Styles M E et al. New cross sectional stat- ure, weight, ond head oircumfQrenee ref. erences for Down's syndrome in the UK and Republic of Ireland. Archives of dis- ease in childhood, 2002, 87:104-8. 14. Myrnl\d A et rt!. Growth 1:,hart:s for Down'o syndrome from birth 10 18 years of age. Archives of disease in childhood, 2002, 87:97-103. 15. Leonard ~ et al. survival of Infants llu111 with Down syndrome: 1980-1996. Pae- diatric and perinatal epidemiology, 2000, 14(2):163-71. The Work of WHO In the Eastern Mediterranean Region: Annual Report of the Regional Director l January--31 December 2003 This report (published In both Arabic and English) describes the ar- eas of work earned by the WHO Regional Office for the Eastern Medi- terranean for the year 2003. It can be obtained from: Distribution and Sales, World Health Organization Regional Office For the Eastern Mediterranean, Abdul Razzak Al Sanhourt Street, PO Box 7608, Nasr City, Cairo 11371, Egypt. Telephone (202) 670 ZS 35; Fax: (202) 670 24 92/4. Both the English and Arabic 1Jerslons are avaUable free on line at http://www.emro.who lnt/rd/annualreports/2003/lndex. htm and http://www.emro.who.int/rd/annualreports/2003/arabic/ lndex.htm 116 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Fragile X syndrome: a clinico-genetic study of mentally retarded patients in Kuwait L.A. Bastt1ki, 1 F Hegazy, 1 M.M. AI-Heneidi, 1 N. Turki, 1 A.S. Azad' and KK Neguib1 ~_,$JI _J ~ ~ ~ /' Js- ~\)) ~J!..r" J,.,...IJ~ :~l X ~I J.., j'*-4 ~ JL.5' ,y _.,, y.1 ,_;; _; 4.,u ,-.,,-~1 4-- •(_,;JG,,,.- w.1.o ,...,,<.,,_,_ J.,) J.jjl c}WI _;..:-61., cJ:-!L,.,,11 J_,5"' ill y 182 ..::...J...t, '-.S~ ._,,.;L,:;.-,,1 '-'IJ~ ~;;:.ii c) ~_rl ;L.,.,")!j..l ~WI .JL,:,,:,-1 rl..b....:....,,l, c'll~_, ,~\ X µ1 ;..)"'>b --~ ;.,_.,,,_,..JI _fl,,IWI ..:.,,- p'\ _,i ~ l~~I ;;,,. j~ . .:, y.L.a.. ~L ~I y ;;,,,li..c ;;,_,.,. )~ ,fa (/.11) ~..,.. J.~ .)I J.>.e J ..u J . jl~ y.-iJ J--.-Lll .FRAXE t' _,ii _j ;; .,..._b _:,,;-- _vlll y -,st ($.i.l er<.. t) ,FRAXE t' y _j ;; .,._b y ~UI ~\ X µ1 y f---i y JS. ~ JJ,I X µ1 ;;_. j';,\.:.:,, '½.l.l _:if .J.Sl; ,y (/55) r-r' 11 _:ilS· J.µ1 ~ y J ~ I j)--i : C.,s:.. "-l ..r-r-l I C" ';11 I ~ i .,:..; \.5' -l, J . ,)'J "~\ .,,; __,J.j-1 --,-' _,.L}~ I J j1 ~ r,lJ ~ I js,l...81 ~ ~ J,~1 ~'::,\11 L.( .(/.85) 45 _).-1 ..b) l (1/.90) '-,µ_JI ~WI j}-,i, (/.90) ~~\11 -...~, (/.100) if /55 .j ..:.~ 01.;,,...d--l ..:,_;IS""_, ,(/30) -=.,l.,.")l> ':JIJ (/45) :l.,j"l.lll ,(/.45) ~\., j..,,l_pl ~ -~ hl>L/ l,.J t___,J.,.11 _p. l,. ;;_,;--:,-) :l.;_.,,:.,,.....JI p,1WI ..:.,..;\,S"J ,-:,.,':JlJ.-1 ABSTRACT In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction (PCR) testing. Twenty patients (11 %) were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus: none had mutation at the FRAXE locus. Of these, 11 (55%) were confirmed fragile-X-positive by both cytogenetic and PCA techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactiv- ity. Less common were avoidance of eye contact (45%), autism (45%) and seizures (30%). Large testes were found in 55%, of cases. Pre-pubertal and post-pubertal clinical criteria were different. Syndrome du chromosome X fragile: etude cllnicc,.genetlque chez des patients presentant un retard mental au Kowe"it RESUME Dans une etude prospective au Kowe'ft, 182 patients de sexe masculin presentant un retard mental qui remplissaient 5 ou plus des criteres cliniques du syndrome de l'X fragile ont fait l'objet d'un examen PCR (amplification en chaIne par polymerase). Vingt patients (11 °/o) etaient fortement suspectes d'etre atteints de ce syndrome du fait d'une mutation au niveau du locus FRAXA ; aucun patient n'avait de mutation au niveau du locus FRAXE. Les techniques de cytogenetique et de PCR ont permis de confirmer que 11 (55 %) de ces patients etaient X-fragiles. Les caracteristiques cliniques res p!us courantes etaient un front proeminent, un palais ogival, un relachement des articulations, de grandes oreilles, une machoire proemi- nente, une taille superiente a cilli correspondant au 10" contile et une hyperactivite avec troubles de l'altention. Le falt o·eviter le contact v1suel (4::i %), l'autisme (45 "lo) et 1es convulsions (::30 %) etaient moins courants. On a observe dans 55 % des cas une macro-orchidie. Les criteres ctiniques prepubertaires et postpubertaires etaient differents. 'Kuwait Medical Genetics Centre, Kuwait. 2Neonatal Unit, Department of Paediatrics, Adan Hospital, Kuwait. Received: 09110/02; accepted: 06/05/03 Eastern Mediterranean Health Journal, Vol. 1 O, Nos 1 /2, 2004 117 Introduction Fragile X syndrome is the second most common cause of inherited mental retarda- tion with an estimated prevalence of 0.4- 0.8 per 1000 males and 0.2-0.6 per 1000 females [ J]. More recent studies using mo- lecular genetic testing of the gene for frag- ile X have estimated a prevalence of 16:100 000 to 25:100 000 males affected with the syndrome [ 2-4]. The syndrome is mainly characterized by a variable degree of mental retardation, typical long and nar- row facial appearance, large ears and large testes [5,6]. It is inherited as an X-linked dominant trait with reduced penetrance, i.e. only 80% of carrier males and 30% of car- rier females are affected [7]. The responsi- ble gene was identified in 1991 and was designated as 'fragile X mental retardation gene I' (FMR-1) [8]. The fragile site was located at Xq27 .3 and designated as FRAXA, which can be observed in the metaphase chromosome following selec- ti.ve culture c.onditions. Three other fragile sites, 1 proximal and 2 distal to FRAXA. have been cloned and termed FRAXD' FRAXE and FRAXF respectively. ' Chromosome analysis using modified culture technique to induce fragile sites is ?o longer used due to its low sensitivity and mcreased costs compared with DNA- · based techniques. Direct analysis of the ~GG expansion mutation by Southern blot- tmg has begun to replace cytogenetic anal- . ysis for the laboratory diagnosis of fragile X SJ'!1drome as it detects all the repeat ex- pansion mutations including both full and premutation. However, blotting is a rela- tively expensive and labour-intensive pro- cedure, particularly in the context of screening routine referrals. The non-radioactive polymerase chain reaction (PCR) method specific for FMRJ gene mutation detection is a very rapid test and has high sensitivity for normal and lower premutation repeat size. However, potential misdiagnosis from false negatives is rare due to cellular mosaicism. - The aim of the present study was to ap- ply PCR testing for the first time in Kuwait and use it as a screening tool for detection of fragile X syndrome among a group of mentally retarded male patients who had clinical signs of the syndrome. Methods This prospective study in the Kuwait Med- ical Genetics Centre, Kuwait, started in January 2000 and lasted for 30 months. Clinical study The participants were 182 male patients re- ferred with mental retardation of unknown etiology for clinico-genetic evaluation and diagnosis. A prcconstructed sheet was used to record the following: nationality, age, pa- rental age at patient's birth, consanguinity, birth weight height, occipto-frontal cir- cumferance, craniofacial features, derma- tological findings, skeletal findings, neurological and psychological features, speech, hyperactivity and the external gen- italia. Associated anomalies and pedigree study were included too. Neurological and psychometric evaluations were conducted on each patient. Cognitive ability was as- sessed m,ing the Wechsler Intelligence Scales (for Children or Adults). The sever- ity of mental retardation was categorized into one of 3 groups according to the intel- ligence quotient [IQ] score: mild (50-70), moderate (35-50) and severe (20-35). Patients were selected for the study if they fulfilled 5 or more criteria out of the most common 10 criteria associated with fragile X syndrome: mental retardation of unknown cause, family history of mental 118 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 112, 2004 retardation, large ears ( ear length > 7 .0 cm), large testes (testicular volume > 25 mL), long narrow face (inner canthal dis- tance < 3.5 cm), prominent ears/jaws, high arched palate, calluses on hand, hyperac- tivity, avoidance of eye contact. After informing the parents about the purpose of the study, peripheral vein blood samples (5 mL) were taken from each pa- tient and stored in tubes with EDTA antico- agulant. Cytogenetic analysis was performed on blood samples ci,dtured for 96 hours in folate-deficient tissue culture medium 199 with 5% fetal bovine serum. Laboratory testing Blood samples were obtained from healthy individuals for calibration of the·test. The deoxyribonucleic acid (DNA) of the pa- tients and control subjects was extracted from blood samples. The concentration and purity of DNA were measured in a PCR reaction before use. Two sets of primers were used for mutation detection of the FRAXA (FXDI and FXP,) and FRAXE (598 and 603) loci. The primers were syn- thesized locally in our laboratory using 391 DNA synthesi'1'ers. For amplification of the triplet repeat sequences at the FRAXA and FRAXE loci, the total volume of PCR mix was 25 µ,L, containing 100 mg of DNA mixed with 20 pmol of FXDI and FXE and 35 pmol of :ciQR and 60J primers to amplify FRAXA CCG and FRAXE CCG repeats respective- ly. It also contained: 2.5 µL of lOX poly- mera.,;:e hnffer (Taq, RioCarta, San Diego, California, USA); 2.5 µL dimethyl sulfox- ide; 200 µmol/L from each of dATP (deoxyadenosfoe 5'-triphosphate), dCTP (deoxycytidine 51-triphosphate), dTTP (deoxythymidine 5'-triphosphate), 100 pmol of dGTP (deoxygnanosine 5'-triphos- phate ), 100 µmol 7-deaza-2-dGTP; and 0.25 µL (1.25 unit) of DNA polymerase en- zyme (AmpliTaq Gold, RinCarta, San Di- ego, California, USA). The amplification was carried out using the ,Gene Amp PCR System 9700 (Applied Riosystems, Foster City, California, USA). The PCR was start- ed by DNA denaturation for 10 min at 95 °C followed by 40 cycles of 91 °C for 1 min, 65 °C for 1.30 min and 72 °C for 2 min with a final extension for 7 min at 72 °C. A total of 15 µL of PCR product were analysed by electrophoresis using 2% agar- ose gel, l % agarose iind 1 % low melting agarose gel (Nusieve GTG, Cambrex, East Rutherford, New Jersey, USA) containing 0.5 µg/mL ethidium bromide. Results Out of 182 mentally retarded patients, 20 patients proved to be positive for fragile X syndrome by the PCR technique, giving an incidence of 11 %. Figure 1 shows the am- plification products of FRAXA and FRAXE. Table 1 shows the clinical features of the fragile-X-positive patients. The fre- quency of siblings (85%) and relatives (70%) affected with fragile X syndrome was high. The most frequent clinical fea- tures among our patients were: mental re- tardation (100%), prominent forehead (100%), hyperextensible joints (100%), high arched palate (100%), large ears (90%), prominent jaw (90%), height> 10th centile (90%), attention-deficit hyper- activity (85%), stereotyped speech (85%) and biting hand movements (85%). Large testes (55%), avoidance of eye contact (45%), autistic-like behaviour (45%) and seizures (30%) were recorded less fre- quently (Table 1 ). There were some differences between pre- or post-pubertal patients. All post-pu- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 119 - 111 ---- ----- ..... ' ... ••• Lanes 1,4,6 and 7 are negative DNA samples of PCR products within normal range of repeat size (up to 224 bp) Lanes 2,3,5 and 8 are suspected to be positive DNA samples With FRAXA mutation showing fall· ure of amplification due to high repeat expansion. Lanes 1 o to 17 are ampll!lcatton products of FRAXE locus of the same DNA samples showing that all cases are negative tor FRAXE mutation l.anes 19 to 22 are PCR amplification products of FRAXA locus using C7d GTP·For more confirma· lion 01 positive DNA samples Lanes 9 and 18 are negative controls without DNA figure 1 AmpHflcation products of FRAXA andFRAXE bertal patients had macro-orchidism (100% tif 11). The most prominent features )among the 9 pre-pubertal fragile-X-posi- tlye patients were: prominent forehead, JOO%), hyperactivity (100%), hyperex- ~nsible joints (89%), large ears (89%), Tablo 1 Characteristic features of mentally retarded patients positive for fragile X syndrome by PCR Features No.of $/o patients Stage of puberty Post-pubertal 11 55 Pre-pubertal -9 45 Family Siblings with fragile X 17 85 Relatives with fragile X 14 70 Behavioural characteristics Mental retardation 20 100 Attention-deficit hyperactivity 17 85 Stereotyped speech 17 70 Biting hand movements 17 70 Autistic behaviour 9 45 Avoidance at eye contact g 45 Seii:ures a 30 Physical characteristics Prominent forehead 20 100 High arched palate 20 -100 Hyperextensible Joints 20 100 Ear length > 75th centile 18 90 Prominent jaw 18 90 Height> 10th centile 18 90 Birth weight> 3 kg 17 85 Dry skin 15 75 Head circumference> 50th centile 13 65 Large testes 11 55 Flatfeet 6 30 Gynaecomastia 5 25 No cases were found of abnormal heart, peatus excavatum or kyphosis. n = number of patients. high arched palate (89%), prominent jaw (78%), avoidance of eye contact (56%), stereotype speech (56%), autistic behav- iour (33%) and seizures (22%). There was no difference in the severity of mental re- tardation among pre-pubertal and post-pu- bertal groups. Mild and severe mental retardation were equally found (around 120 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 45% In both groups), while moderate men- tal retardation was found in 1 patient in each group ( around 10% ). There were major differences between the percentage frequency of the criteria among the positive fragile X patients and mentally retarded patients negative for fragile X (Table 2). Cytogenetic analysis detected only 11 cases of fragile X syndrome (55% of the cases positive by PCR), an incidence of 6% among mentally retarded patients. Discussion Fragile X syndrome is the second most common cause of inherited mental retarda- tion and is characterized by relative macro- cephaly or nonnocephaly, variable degree of mental retardation, typical long and nar- row facial appearance, large ears and large testes [1,5,6]. The dysmorphic features are seldom severe and many males in the past were referred purely with mental retarda- tion_ The population prevalence of fragile X syndrome has been reported to vary from 0.4-0.8 per 1000 in males and 0.2-0.6 per 1000 in females [3,9,101. More recent studies using molecular genetic testing of FMR-1 have estimated a prevalence of 16: 100 000 to 25: 100 000 males affected with fragile X syndrome [2-4]. The preva- lence of females affected with fragile X syndrome is presumed to be approximately one-half of the male prevalence. A popula- tion based prevalence study of affected African-American males revealed a higher estimate, 39: 100 000 to 78: 100 000 at 95% confidence interval [ JJ]. Among mentally retarded patients. the incidence of fragile X syndrome varies from 3.5% to 8% [12,/3], an incidence lower than that reported here (11 ¾). Our higher incidence may b~0due to selection of the patients based on the most prominent criteria of fragile X syndrome, which in- creases the likelihood of finding fragile X positives. Alternatively, the PCR technique might increase the detection rate: we found 11 % of mentally retarded patients were Table 2 Frequency of fragile X traits In fraglle-X- positive and -negative mentally retarded patients Clinical sign Fraglle-X- Fragile-X- flvalue positive negative (n = 20) (n= 162) % "lo Long narrowface 100 38 < 0.0001 High erchen pi:1late 100 21 -< 0.0001 Large ears 90 29 <0.0001 Hyperactivity 85 18 <0.0001 Large testes 5.5 10 <0.0001 Avoidance of eye contact 45 7 < 0.0001 n "" number of patients. Eastem Mediterranean Health Joumal, Vol. 10, Nos 1/2, 2004 121 positive using PCR compared with 6% us- ing cytogenetic analysis. The symptoms and signs of mental retardation are variable, anrl hyperactivity and seizures are common features. The degree of mental retardation varies from mild to severe, depending on the age group of the selected cases [14- 16]. Brain scans in fragile X syndrome are usually normal. However, Mostofosky et al. studied 32 males with magnetic reso- nance imaging (MRI) and found the size of the cerebral posterior vermis was de- creased, the hippocampus enlarged and the fourth ventricle increased [17]. A low fre- quency of fragile X cases (0.5%) was found among males with unexplained learn- ing difficulties and language delay [2, 18, 19]. There are some specific features asso- ciated with fragile X syndrome. These are not necessarily found in all patients at dif- ferent age groups and the frequency of each feature is age dependent. The most suggestive criteria for the diagnosis. of fragile X syndrome found in this and other studies were: mental retardation, a family history of mental retardation, large or prominent ears, an enlarged face, attention deficit hyperactivity disorder and antis-. tic-like behaviour. Tf a patient had 5 of these features then no case of fragile X would have been missed. The frequency of macrocephaly (cir- cumference > 50th centile) in our study was low (65%) compared with other re- ports [20] that the single most useful clini- cal criterion is head circumference above the 90th centile. Macro-orchidism is difficult to identify early in life and it is frequently absent in the pre-pubertal period. The frequency of en- larged testes in our study wa.~ 55% overall, 100% in post-pubertal patients. This find- ing is consistent with other studies [1,5,6,13]. Accordingly, the presence of macro-orchidism is not necessary for the diagnosis of fragile X syndrome in the pre- pubertal child. The frequency of macro- orchidism in fragile X syndrome varies from 11% to 20% [1.21]. Other studies have suggested a relation- ship between autism and fragile X syn- drome. However, a molecular study of 141 patients showed no association of autism with fragile X syndrome and the Xq27 re- gion is not a candidate gene for autism [22]. Nevertheless, the present study showed a high incidence ( 45%) of patients who had autistic-like behaviour and most of them were in the post-pubertal stage. Other authors have reported a lower inci- dence of autism in fragile X syndrome (10.7%) [J]. Familial cases of fragile X have been re- ported before [23] but were not as high as reported in our study (85% and·70% of pa- tients had affected siblings and relatives re- spectively). This incidence represents the frequency of fragile X syndrome among the siblings and relatives of fragile X pa- tients themselves and not among the men- tally retarded patients. Genetically, all mothers of isolated male cases of fragile X must be assumed to be carriers of a permu- tation or full mutation and ahout one-third of carrier females are retarded [24]. How- ever, around 70% of females with a full mutation have below average IQ (less than 85%) [25]. Premutation was found to be behind the phenomenon of phenotypically normal transmitting males with no fragile sites [21.26]. This was confirmed by the discovery of an unstable CCG trinucleotide repeat sequence in the gene (FMR-1) [27,28]. Repeat length appears to be an im- portant but not sufficient condition leading t.o instability of the FMRw/ gene [29,3f1]. Tt has been suggested that expansion of the CCG trinucleotide repeat occurs during 122 La Revue de Sante de la Mediterranee orientate, Vol. 10, N° 1/2, 2004 early development and not during meiosis [31,32]. In males carrying full mutation, only sperm carried the premutation. How- ever Malter et al. looked at the gonads of the fetuses carrying the full mutation and showed that full expansion alleles were de- tected in oocytes and in the testes of 13- week-old males [33]. Screening of fragile X syndrome can be carried out by different techniques: cytoge- netics, molecu1ar or antibody testing for FMR.-1 protein (using blood, chorionic vil- lus or hair root samples) [34-38]. DNA testing is a cost-effective alternative to cy- togenetic analysis, while antibody testing for FMR.-1 protein is rapid but of limited use (false positive results are high) and needs to be used in conjunction with DNA methods. In conclusion, the criteria needed for diagnosis of fragile X syndrome will de- pend on the age of the patient The labora- tory diagnosis should depend on molecular studies rather than cytogenetic ones. PCR is the most suitable screening tool and should be confirmed by Southern blotting. Relerencss 1. Iqbal MA et al. Cytogenetlc diagnosis of fragile X syndrome: study of 305 sus- pected cases in Saudi Arabia. Annals of Saudi medicine, 2000, 20:214-7. 2. Murray A et al. Population screening at the FRAXA and FRAXE loci: Molecular analyses ot boys with learning oifficuI- ties and their mothers. Human molecular genetics, 1996, 5:727-35. 3. Turner G et al. Prevalence of fragile X syndrome. American journal of medical genetics, 1996, 64:196-7. 4. De Vries BB et al. Screening and diagno- sis for the fragile X syndrome among the mentally retarded: an epidemiological and psychological survey. Collaborative Fragile X study group. American journal of human genetics, 1997, 61:660-7. 5. Fryns JP. X-linked mental retardation and the fragile X syndrome: a clinical approach In: Davies KE, ad. The tragUe X syndrome. Oxford, Oxford University Press, 1989. 6. Hagerman RJ. Physical and behavioral phenotype. In: Hagerman AJ, Cronister A, eds. Fragile X syndrome: diagnosis, treatment and research. Baltimore, Johns Hopkins University Press, 1996. 7. McKusick VA, Francomano CA, Antona- rakis SE. Mendelian inheritance in man: catalogs of autosomal dominant, auto- somal recessive and X-linked pheno- types, 9th ed. Baltimore, Johns Hopkins University Press, 1990. 8. Verkerk AJ et al. Identification of a gene ( FMR- t) containing a CGG repeat coinci- dent with a breakpoint cluster region ex- hibiting length variation in fragile X syndrome. Cell, 1991, 65:905-14. 9. Morton JE et al. Fragile X syndrome is less common than previously estimated. Journal of medical genetics, 1997, 34: 1-5. 1 o. Crawford DC et al. Prevalence and phe- notype consequence of FRAXA and FRAXE alleles in a large, ethnically di- verse, speclal education-needs popula- tion. American journal of human genetics, 1999, 64:495-507. 11. Crawford DC et al. Prevalence of · the fragile X syndrome in African- Americans. American joumal of medical genetics, 2002, 110:226-33. 12. Jacobs PA, Mayer M, Abruzzo MA. Stud- ies of the fragile (X) syndrome in men- tally retarded populations in Hawaii. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 123 American journal of medical genetics, 1986, 23:567-72. 13. Tayel Set al. Two step fragile X screening programme in mentally retarded males. Kuwait medical journal, 1999, Sept.: 257-62. 14. Kluger G et al. Epilepsy and fragile X gene mutations. Pediatric neurology, 1996, 15:358-60. 15. Curts LM, Wiegers AM, Fryns JP. Intelli- gence and the fra(X) syndrome: a review. Genetic counseling, 1991, 2:55-62. 16. De Vries BB et al. Clinical and molecular studies in fragile X patients with Prader- Willi like phenotype. Joumal of medical genetics, 1993, 30:761-6. 17. Mostofsky Set al. Decreased cerebellar posterior vermis size in fragile X syn- drome: correlation with neurocognitive performance. Neurology, 1998, 50:121- 30. 18. Mazzocco MM et al. The prevalence of the FMR1 and FMR2 mutations among preschool children with language delay. Journal of pediatrics, 1998, 132:795- 801. 19. Teague Jet al. FRAXA and FRAXE: evi- dence against segregation distortion and for an effect of intermediate alleles on learning disability. Proceedings of the National Academy of Sciences of the United States of America, 1998, 95:719- 24. ·20. Mila M et al. Screening for FMR1 and FMR2 mutations in 222 individuals from Spanish special schools: identification of a case of FRAXE-associated mental re- tardation. Human genetics, 1997, 100: 503-8. 21. Sherman S. Epidemiology. In: Hagerman RJ, Silverman AD, eds. Fragile X syn- drome. Baltimore, Johns Hopkins Uni- versity Press, 1991 :69-97. 22. De Vries BB et al. Variable FMR1 gene methylation of large expansions leads to variable phenotype in three males from one fragile X family. Journal of medical genetics, 1996, 33:1007-10, 23. Smeets H et al. Normal phenotype in two brothers with full FMR1 mutation. Human molecular genetics,, 995, 4:2i 03--8. 24. Sutherland G, Mulley J. Fragile-X syn- drome and other causes of X-linked mental handicap. In: Rimoin D, Conner M, Pyeritz R, eds. Principles and practice of medical genetics, 3rd ed. New York, Churchill Livingstone, 1997:1745-55. 25. Klauck SM et al. Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients. Human ge- netics, 1997, 100:224-9. 26. Pembrey M, Winter R, Davies K. A per- mutation that generates a defect at crossing over explains the inheritance of fragile X mental retardation. American journal of medical genetics, 1985, 21 : 709-17. 27. Richards RI. Sutherland GR. Dynamic mutations: A new class of mutations causing human disease. Cell, 1992, 70:709-12. 28. Reiss AL et al. Frequency and stability of the fragile X premutation. Human mo- lecular genetics, 1994, 3:393--8. 29. Rousseau F et al. Prevalence of carriers of permutation-size alleles of the FMR1 gene-and implications for the popula- tion genetics of the fragile X syndrome. American journal of human genetics, 1995, 57:1006-18. 30. Zhong N et al. Fragile X founder effects and new mutations in Finland. American journal of msdfca! genetics., 1996, 64: 226-33. 31. Wehrle D et al. Mitotic stability of fragile X mutations in differentiated cells indi- 124 La Revue de Sante de la Mediterranee orientale, Vol. 1 o, N° 1/2, 2004 cates early post-conceptional trinucle- otide repeat expansion. Nature genetics, 1993, 4:140-2. 36. Willemsen R et al. Rapid antibody test for fragile X syndrome. Lancet, 1995, 345: 1147-8. 32. Reynters E et al. The full mutation In the FMR-1 gene of male fragile X patients is absent in their sperm. Nature genetics, 1993, 4:143-6. 37. Willemsen R et al. Rapid antibody teat for prenatal diagnosis of fragile X syndrome on amniotic fluid cells: a new appraisal. Journal of medical genetic.<:, 1997, 34: 250-1. 33. Malter HE et al. Characterization of the full fragile X syndrome mutation in fetal gametes. Nature genetics, 1997, 15; 165-9. 34. Oostra BA et al. Guidelines for the diag- nosis of fragile X syndrome. Fragile X Foundation. Journal of medical genetics, 1993, 30:410-3. 35. Wang Q et al. Cytogenetic versus DNA diagnosis in routine referrals for fragile X syndrome. lancet, 1993, 342: 1025-6. Some facts on genetics 38. De Vries BB et al. Screening for the frag- ile, X syndrome among the mentally re tarded: a clinical study. The Collaborative Fragile X Study Group. Journal of medi- cal genetic.s, 1 QQQ, 36:467-70. • 7 mllllon children around the world are born annually with severe genetic disorders or birth defects. • 90% of Infants born with genetic disorders are found In develop- Ing countries, contributing slgnlflcantly to global chlld mortality. • Mutations have been characterized for most major single-gene disorders, and there Is a growing understanding of the role of genes In complex diseases such as cancer, cardiovascular dis- ease, diabetes and asthma. • The final version of the entire Human Genome sequence was un- veiled In April, 2003. • r'reventlon and management of genetic disorders are µublbtied health priorities in some developing countries, for which the WHO Human Genetics Programme (HGN) Is developing significant ca- pacity Dullding Initiatives and normative and regulatory gulddnLe. • The top ten biotechnologies for improving health in developing countries have been Identified by a WHO Human Genetics Col- laborating Centre. Source: WHO Fact sheets: Genomic Resource Centre; genetics and health (http:/! www. who. tnrlgenomtcslabout/en/E_grc .Jlnal.pdj) und (http://www. who. int/g,:nomics/ en/E _ hgn-Jinal.pdj) Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 125 Apolipoprotein B gene polymorphisms in people in the East Mediterranean area of Turkey L. Tamer,' K. Tanriverdi, ~ B. Ercan, 1 A. Un/u, 1 N. Sucu, 3 H. Pekdemir4 and U. Atik1 .l;..... _r\.l J r' ~ ~\ 4ib.:.l1 .j !l1.;'l!1 .s.iJ ...,.. - ,;Ji J..r-_r-i _y.'it Ji": J~f ,.w ,..~ j~:I ,,,,...l..." ,:_,.----- -~ j""--* ._,i._;)I Js' ,,,)I.!;} ,,,.,u,,•_, ,-,s.s_,Ai._,;L ,_:L,_AS ,y>l..i _}o_,'.·_i-1 -.::.,\,:".;.......o ..:.,,,. ._;l;5j, -~,, ,:.,:,j°J.,i,~1 .j -.;.,":,!~~- b')' Jt.!;1 cJ :...,k...JI ..::.,t_,.;.;,J1 -'-!) J.i :L.,.,":JJ-l µ 1 ._J,S- .:.,_,/, .j ---.r Jl 100 - '-c' S:,~Jjy,)_y.i .J ,.:.,Ip,!./':}_: .. : .. ,;\ ..UJ ·t-d• ,_) JJJ-,.l~11 LiJ-" ..u: -(~~ ..,.-. 35.'IJ .:.,:,-:,,,,-/,·•_, .Jl;_,-.,,_;;-<-- 3500 ~} ,c:,~ -<- 3500 :,•,!-Ye }'1'•) :)lc.lt (Jljr,!} +- 3500 :..,--,.;-r_;½I) C9774T (3500 •/')I)._,., - .:,,.;Jj.,i,.,,)y'jJ ~I 0 1,_pl )_?-, J-1.,..,, ~w.i' J'"' 145J .,s.i.,....,J1 ~l, ._: . .,;WI ..:.r' '179 ,,,t ._:.ll~: ,(_:~ 4- 3500 ~)'./1) G9775AJ ..:.>I;,~· , _,.-L,> / ..ti: , ~ P.' j r- _).<.- a:l, .$ ;..Ji y.,,U1 :.j ct.-....,\·, .:..."' 272) ,~..01 -.::.,~ .l, A ..,_.- _:.1~ • .i'JJ'rdY")fi •,..Jo~ { t._. "'r<c-.,.~,,,_;., _.,,.,kll ._,-L,.W ,.p~I _/~ ;;_,..._,,.....r -.:.,l,;.iJ,.:Ji) ~)·"•-•;Ji .o.,..;kJ\ _;....:.~-~I o..i.,, j" <,,>~ .),,;:.,Jt fa l J ,~I ..j") ;.J~ _jl.,-.,.\ y.iJ ~I y-lo;:)I \°''~4 ~~ ..b) _,.,L,.,,i o _.,._; ) 1 _,j _! 100 - c..,-.> 0',> _, f _,J _,/,tJ ~1 ~1_,...w1 4-< J-w ~I o.U )1,i UJ • ._;..,'1~\ .,!J..!..:J ._;;, ... \~ .. A •• ••_1 11 ~ ... ....::'I..J\ J ; \ \\ ABSTRACT POim mutatJons in the receptor binding domain at low density lipoprotein may increase choles- terol \eve ls in blood. Three mutations of Apo B-100 protein result in defective binding (Arg 3500 Gin, Arg 3500 Trp and Arg 3531 Cys). We estimated the frequency of Apo B point mutations (codon 3500) C9774T (Arg 3500 Trp) and G9775A (Arg 3500 Gin) in 179 atherosclerotic, 145 hyperlipidaemic individuals and 272 healthy individuals in the east Mediterranean regkln of Turkey. Lipid and lipoprotein levels were measured with routine biochemical analyser and Apo B mutation was detected using real-time PCR. Neither mutation was found. In this region, Apo B-100 protein mutations are rare ancl causes of hyper!ipidaemia and athero- sclerosis may there lure ue urm:1li:lled tv l!it:,11 ,. Les polymorphismes di.I gt.ne de I apolipoprot01ne B dans la population de la r0gion est- m0dlterran0enne en Turquie RESUME Le5 mutatiOn5 ponctuelles sur le site de lloison du r0ooptour doo lipoprot0ines d& ba,;;,;:9 d1insi«zl peuventfaire augmenter le taux de cholest0rol sanguin. Trois mutations de \a prot0ine apo B-100 entra nent une liaison d0fectueuse (Arg 3500 Gin, Arg 3500 Trp and Arg 3531 Cys). Nous avons estim0 /a fr0quence des mutations ponctue\lesde I apo B (codon 3500) C9774T (Arg 3500 Trp) et G9775A (Arg 3500 Gin) chez, 79 patients ath0roscl0rotlciues, 145 sujets hypertipid0miques et 272 sujals en bonna sant0 de la r0gion est-m0diterran0enne en Tutquie. Le taux de lipides et de lipoprot0ines a 010 mesur0 I aide d un analyseur biochimique el la mutation de! apo Ba 0t0 recherc110e en utilisant la PCR en tsmps r0el. Aucune mutation n a 010 trouv0e. Dans cette t0gion, les mutations de la prot0ine apo B-100 sont rares et les causes de I hyper\ipid0mie et de I ath0roscl0rose peuvent done ne pas CEtre li0es ces mutations. 'Department of Biochemistry; "Department of Cardiovascufar Siirgery; 'Department of Cllrdiology, Faculty of Medicine, Mersin University, Mers/n, Turkey. 2Department ot Biochemistry, Faculty of MBd/dne, Cukurova University, Adana, Turkey. Received: 09110/02; accepted.' 19/03/03 126 La P,eNue de San\t, de \a Med\terranee orientale, Vol. 10, N" 1/2, 2004 Introduction Nearly two-thirds of all circulating choles- terol is transported by low density lipo- prolein (LDL) particles. The plasma con- centration of chok:,tero! i,j regulntcd by which circulating LDL is taken primarily into the hcpatocytes. Apolipoprotein 8-100 (Apo B-100) is the major protein associated \Yith the LDL po.rtick and cont-ain:.. the ligand that binds LDL to its receptor [I]. Human Apo B-100 is a large, hydrophobic protein of 4536 amino acids and a molecu- lar weight ofupproximutcly 540.000 Du. It is synthesized in the liver I 2J. Gene muta- tions in the LDL receptor or in the receptor- binding zone of the Apo B-100 can disrupt binding ,md impair removal of circu1uting LDL. More than 150 mutntions have been identified in the LDL receptor gene, associ- ated with familial hypercholesterolaemia (FH), un outosomo.l domimmt inherited dis order characterized by severe hypcrcholes- tero\aemia, frequent presence of tendon xanthomas, and premature coronary heart disease [3]. To date, several point mulations of the putative rc~eptor binding domain of Apo B- 100 have been identified [4,5J. Only 3 of thc,c m.uto.tion,, lw.,'c been nhown to pro duce binding-defective Apo B- l 00 by appropriate genetic and functional investi- gations [ 6, ?]_ The first substi.tutkm to be di:,covcrcd, and apparently the most fre quent one, is Apo B-100 (Arg 3500--i-Gln). The other 2 substitutions are Apo 8-100 (Arg 35004Trp) and Apo B-100 (Arg 3531 >Cys) and occur less frequently [l, 5, 61- l:ompared with Apo B-100 _(Arg 3500~Gln), B- ! 00 (Arg 353 l ~c:ys) is as- sociated with a smaller increase in LDL. Consi:,tcntly, LDL that contained /\po B l 00 (Arg 3531 ~Cys) exhibits less reduc- tion of LDL receptor binding in vitro than did LDL cndo'.ved with Apo 8-100 (Arg 3500--->G\11) [6,8]. In the present study, we aimed to esti- mate the frequency of Apo B point mutations (codon 3500) C9774T (Arg 3500-----.;Trµ) ,mu 09775A (A.lg .3500-----,.0111) in 179 patients ,.,.,.ith atherosclerosis and compare this with 272 healthy subject!s and 185 hypercholesterolaemic patients in the pt:upk liv iug VII Lht: c;<.tsl Jvti..:Jilc:Ua11t:a11 coast of Turkey. Methods Participants A total of 596 people were included in the study from. the people living on the East Mediterranean coast ot Turkey. The study sample included 272 healthy controls ( I 33 female, I 39 male), 145 controls with hy- percholesterolacm,ia (117 female, 28 male) and 179 patients with atherosclerotic coro- nary artery di seasc (69 female and 110 male). All participants were randomly re- cruited from 2 hospitals in Turkey; uni ver- sity hospitals m Mersm and Adana. The participants were aged between 40 and 60 years. Patients with coronary artery dis- ~ase were classified according to their cor- onary ang10graph1c evidence ot 2 ·10% stcnosis of a major coronary a1tery. They were attending the cardiology clinic and scheduled to undergo coronary by-pass. In all, 124 patients with atl1eroscteros1s (6Y~/o) had a history of myocardial infarction and 90 patients (50%>) had smoking history. Pa- tients with diabetes were ex.cludo,;;d from the study. The control group was selected from clinically healthy individuals whose lipid parameters were in the normal refer- ence range. They had no history of coro- nary heart dts.:ase, diabetes or hyperten- sion; 115 ir1dividuals (4:! %,) had a smoking Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 127 history in the control group. People who had .:huk~tcrol levels of 200 239 mg/dL \Vere considered as having borderline high blood cholesterol and those ;:o: 240 mg/dL cholesterol levels were considered as ha- v iug high blood i.;hok.stcrol [9]. Since both levels are undesirable for blood cholesterol, we considered that individuals with choles- terol levels 2: 200 mg/dL had hypercholes· lernlacmia; 75 (52'}(,) c1ubjects had a smoking history in the l::,'l'OUp with hyperc- holesterolacmia. Whole blood (EDTA-anti- coagulated) and scrum were collected after an uvcmight fa5t. DNA isolation DNA samples were isolated from blood .sampk.s, collected by ~·enepuncture in ster- ile siliconized ~DTA2-mL Vacutainertubes, using High Pure PCR Template Preparation Kit and MagNA Pure LC DNA Isolation Kit I by MagNa Pure LC automated DNA isola- tion instrument (Roche Molecular Bio- chemicals, Mannheim, Germany). Detection of Apo B mutation The determination of Apo B mutation was done using Real-time PCR and the Apo B mutation detection kit (Roche Diagnostics, GmbH, Mannheim, Germany). Real Time PCR Principle: a 207 bp frag- ment of the apolipoprotein B gene was am- plified with specific primers from human genomic DNA. The amplicon was dP:tPPlcrl. by fluorescence using a specific pair of hy- bridization probes. The hybridization probes consist of 2 different short oligo- nucleotides that hybridize to an intPmal '-e- quencc of the amplified fragment during the annealing phase of the PCR cycle. If a mutation is present, the mismatches of the mutation probe with the tnrget dest/\bi lize the hybrid. With a wild type genotype, mis- matches do not occur, and the hybrid has a higher T 1,1· The temperature is slowly in- creased and when the mutation probe melts off and the 2 flnorPscent dyes are no longer in elose proximity, the fluorescence de- creases. For mutated genotypes, this occurs at lower temperatures than for the wild type genotypP In addition, we performed DNA se- quencing of 5 randomly selected patients, 5 controls and 5 individuals with hypcrcho- lcsterolaemia. Measurement of lipids and lipoproteins Apolipnpmtein A (Apo A) and Apolipopro- tein B (Apo B) were dctennined by immu- noturbidometric methods. Triglyceride (TG), total cholesterol tTC) and high den- sity lipopmtein (HDL) were analysed by GPO/PAP enzymatic colorimetric, CHOO/ PAP enzymatic colorimetric and direct COHD/PAP enzymatic colorimetric me- thods, re~rectively. LDL content was cal- rnlated from the primary measurements using the empirical equation of Friedewald et al. f 1 O}. All these parameters were dcter- mincrl hy ( 'ohas lntegrn 700 biochemical analyser (Roche Diagnostics, GmbH, Man- nheim, Germany). The results were ex- pressed in terms of arithmetic means ± standimi rlcviation. Results The lcvcb of TC, HDL, LDL, VLDL, TG, Apo A and Apo B are given in Table 1 . Our results shmv that there was an increase in the levels of TC, LDL, VLDL, TG and Apo D and u decrease in Apo A levels in individu- als with hypcrcholcsterolaemia and patients with atherosclerosis compared to normo- lipidaemic controls. On the other hand, nei- ther C9774T (Arg 3500~Trp) nor G9775A (Arg 3500-')Gln) mutations for Apo B codon 3500 was detected in the indi- viduals by Real-Time PCR. 128 L() -- .J CD .J CA~ :c: 't Cl -:. E (\J ci +r co <".i "'" 0 r,,.: (\J tl (') .,.; '° (\J C\I "'" tl rn I,!) 0 ~ C\I ti I{) N N 0 (Q C\/ ti cc <".i La Revue de Sante de la Mediterranee orientale, Vol 10, N° 1/2, 2004 (I} r.ii 0 0 (\J ci (\J ti 0) ...,. ... ... in "'" ti m 0 1.11 ~ (Q C") +I 0 o:i C0 ci +r I() r,,.: C") <ii cr, 0 l'- V),... e II ~ C: .c . -~ < Discussion The Apo B arginine-to-glutamme change at codon 3500 by been established as a cause of the failure of the LDL particle to bind to its receptor and the consequent hypercho- lt:sterolaemia of familial detective Apo B- l 00 [5]. The Apo B (Arg 3500~Gln) muta- tion has been identified in the USA, Den- mark, Germany, Italy, France, Austria, Australia, the Netherlands, South Africa, Switzerland and indirectly in Notway and Sweden since some of the probands from the Oregan study were of Norwegian and Swedish descent [ 2]. However, the muta- 1 ion has not been detected in either Finland or former Soviet Union republics. The Apo B-100 (Arg 3500~Gln) mutation has been observed with an approximate trequency of I in 500 to 1 in 700 in populations of European (Caucasian) origin [2,8]. Several point mutations of the putative n::1:epmr binding domain of Apo tl- l UU have been identified. Only 3 of these mutations have been shown to produce defective binding Apo 8-100 by appropriate genetic a.ml functional investigations [J-(). /0, 12 J. The first substitution to be discovered, and apparently the most frequent one. was Apo B-100 (Arg 3500__:;Gin). The other 2 sub- ~lilutiuns,Apo B-100 (Arg 3500~Trp) and Apo B-100 (Arg 353l~Cys), occur less frequently [ 8, 13]. Teng et al. showed that the prevalence uf helcrozygorc in 373 Cllmesc md1v1duals with hyperlipidaemia was 0.3% for the Arg 3500~Gln mutation and 2.4 %) for the Arg 3500--~ffrp mutation [13]. When 373 unrc- lateLI irn.lividuals with hyperlipidacmia were screened for the presence of Apo B-100 mutations, Tai ct al. found 9 Arg 3500---,.Trp index cases, 7 classified as having type Ila and 2 as having type lib hyperlipidaemia [ 14]. The authors reported that one of them was of Scottish descent Eastern Mediterranean Health Journal, Vol. 1 O, Nos 112, 2004 129 and the others were of Asian descent. They suggested that Arg 1,;;oo~Trp alleles were inherited from a common ancestor in Asian populations. Fisher et al. investigated 297 consecu- tive individual., with I nL concentrations> 155 mgldL and triglycerides < 200 mg/<lL for Apo B mutation. Apo B-100 (Arg 3500-----)Trp) was described in just I family of European origin in 2 families with a mixed Chinese and Malayan descent, in I family of Asian descent living in the Glas- gow region and in another 9 unrelated indi- vidual!;: from T:ciiw;m [ /5]. In our study ,vc investigated the fre- quency of Apo B point mutations (codon 3500) C9774T (Arg 3500------tTrp) and G9775A (Arg 3500-4Gln) in 596 individu- als (272 healthy controls, 185 controls with hyphercholesterolaemia and 179 patients with atherosclerosis). Neither C9774T (Arg 3500~Trp) nor G9775A (Arg 3500--tGln) mutation was found in the oeople living on the Easl Mediterranean coast of Turkey. As can be seen in our study, the mutations of Apo B-100 protein are very rare. As regards this population, they were not observed in our sample. References 1. l::lrown MS, Go1asteln JL A rtli;t:1J.Jlu1 me- diated pathway for cholesterol homeo· stasis. Science, 1986, 232:34-47. 2. Gingsberg HN, Dixon JL, Goldberg \J_ VLDL/LDL cascade system: assembly, secretion and intravascular metabolism of apoprotein 8-containing lipoproteins. In: Betteridge DJ, Illingworth DR, Sheperd J, eds. Lipoproteins in health and disease. London, Arnold, 1999:55- 70. 3. Cheong ML et al. Denaturing gradient- gel elet:l!Uf.Jllu1 e,:,i;:; ;:;i:;reening of familial defective apolipoprotein B-100 in a mixed Asian cohort: two cases of argi- nine 3500-c>tryptophan mutation associ- at,;:,d with :ci unique haplotype. Clinical chemistry, 1997, 43:916-23. 4. Soria LF et al. Association between a specific Apolipoprotein B mutation and familial dofectivo Apolipoprotgin R-1 r)(I Proceedings of the National Academy of Science, 1989, 86:587-91. 5. Gaffney D et al. Independent mutations at i:;odon 3500 ot the Apolipoprotein B gene are associated with hyperlipi- dernia. Arteriosclerosis and thrombosis, 1995, 15:1025-9. O. rullingcr CR ot al. Familial ligand-rlAfP.r.- tive Apolipoprotein B: Identification of a new mutation that decreases LDL recep- tor binding affinity. Journal of clinical in- vestigation, 1995, 95:1225-34. 7. Pullinger CR et al. The apo\ipoprotein B R3531 C mutation: Characteristics of 24 subjects from 9 kindreds. Journal of lipid rP.<U#lfr:h, i9Q9. 40:318-27. 8. Fisher E et al. Mutations in the Apolipoprotein (apo) B-100 receptor- binding region: Detection of apo B-100 {Arg 3,oo - Trg) assor.i;:it,=,,fl with two new haplotypes and evidence that apo B-1 00 (G\u 3• 01 - Gin) diminishes receptor- mediated uptake of LDL. Clinical chem- istry, 1999. 45:1026-38. 9. Bachorlk PS et al. Lipids and dyslipoproteinemia. In: Henry BJ, ed. Clinical diagnosis and laboratory meth- ods. 20th ed. Pennsylvania, WB Saunders Company, 2001 :224-49. 10. Friedewald WO, levy RI, Fredrickson DS. Estimation of the concentration of low- dirnsity liporirotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry, 1972, 18:499-502. 130 La Hevue de Sante de la Mediterranee orientale, Vol. 1 O, N° 1/2, 2004 11. llmonen M et al. Screening of the 3 - two- thirds of the coding area of the apo B o,=,.n,;, in Finnish hypercholcotcrolemic patients. Report of six new genetic vari- ants. Atherosclerosis, 1997, 128:191-9. the Apo/ipoprotein B gene on LDL re- ceptor binding. Atherosclerosis, 1998, 137.167-74. 14. Teng YN et al. Familial defective Apolipoprotein 8-100: detection and haplotype analysis of the Arg (3500) --t Gin mutation in hyperlipidemic Chinese_ Atherosclerosis, 2000, 152:385-90. 12. Ludwing EH et al. Association of genetic variationa in Apolipoprotein B will1 t1y- percholeslerolemia, coronary artery dis- ease, and receptor binding of low density lipoproteins. Journal of lipid re- search, 1997. 38:1361-73. 13. Gaffney D et aL Influence of polymor- phism Q3405E and mutation A3371V in 15. Tai DY, Pan JP, Lee-Chen GJ. Identifica- tion and haplotype analysis of Apo-lipo- protei n B-100 Arg 3500 - Trp mutation in hyperlipidemic Chinese. Clinical che- mistry, 1998, 44: 1659-65. A practical guide for health researchers A practical guide for health researcher5, by Mahmoud F Fathalla and Mohamed M.F. Fathalla, Is Intended for health researchers, who are not limited to scientists pursuing a research career, They include health professionals, administrators, poli,y-mr1kNs and nongovernmental organizations, among others, who can and should use the scientific method to guide their work for improving the health of Individuals and communities. This comprehensive guide covers , amonQ others. the areas of ethic,;; in rPsearch, choice of research, preparing for research, conducting research, analysing and Interpreting results, disseminating research and writ- ing a scientific paper It is highly readable and easy to understand. The guide can be obtained from: Distribution r1nrl O::,;:;iP"'>, World Health Organization Regional Office for the Eastern Mediterranean, Abdul Razzak Al Sanhourl Street, PO Box 7608, Nasr City, Cairo 11371, Egypt Telephone: (202) 670 ZS 35; Fax: (202) 670 24 92/4. It Is also available free on line at: http://www emm 1,11hn intfpubllca- tl o ns/pdf/h eal th researchers _guide. pdf ~-------------------------------./ Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 Improved serum HDL cholesterol profile among Bangladeshi male students during Ramadan fasting M. Rahman, 1 M. Rashid,2 S. Basher,3 S. Sultana4 and MZ.A. Nomanf 131 ,,) )_,£°.JJ! ~"Jf.WI ,.s.JJ .j..Alf .j .u~J ~),l ~\ ~~J.,,.U J_.,.J-,!J>,ll ~ 1 -,A .:.,,--.i. ~~) (lo\,,...<> ~L:ji ~;)~ -,,.s'L...o.; ~ _;w ,.;.;u..L,. o.J...t<- -~-i ~ .~)', .:i_,..i.... ,,:_,.a"-)',~- r'J . ..J-.!.o".lw. .; ~~".,11 ..,J, jj1 .:.·· .:.r-~ J .J--4-1.1 ~~ ~ .)'.....-_, r1__, _,.:, ~ i' :t....."jJ..1 >L..A, JrW~J L.,-r-J;;.U 11 r .... ~1 JJ 2:~; ~f"' ~b---1-., 1;_,~ y r-..u1 ~~,., ~~1 ...:,.,\_._.,y.JJ ~~1cii ,._,oH·y .:;L..., ~ ~l:,;i w~t- t..;,Ll..:1.___,,l.1 U:..< --~· .,._.,.J,-1 .:..,·., ,..;,...;.;c1 ..... , _._:;.t..;~-, ,\.,.;,,..;', . .,. ~ _._,._,, .J~- 7 - ' . ..... \ ...-~- ..__ ,I - :l.,I ~ ~~J ~ ~~~ p( ~~JJ1 . .!J'")\~l .)i_S ..LlJ :~ ~"yj~_, _,,_J ~1__J1 ;µJ, . ._;_JL-t} ~ A.i_)1ui.,L1~ ,·r ... --- ; (.,jl~.., ~ ,;..L7i ~~ ~~.~ '. .:Ul:-'_C_ii ~)J -~·•r ... ,.~,;.,_1.1 ,-,,.~_ • ..JI 11.,-;.......,.J$ ~1~-,1 .ti-'! .~.J..iu l~-~)I_._,. -· ~ -· ,.._., L ...,. ..,.. .._,. ,,.1, ........ _,_,,. - _. - _, • _)-y:; J 1 ..;\::S'.JI . ~' -.~I ,,;,:,, _, _.,.] 1• J J ;--J ;;- ) , ___ µ, J .! ~ _,_s::3, '-J _:,; ~ _,_.,;.; ~l:A .:.,$..,_ (' .)~ _; ._j ;;_,1.!.,<_jl t:<' _)I -,..~I ~'\', _,,-!I J) j<....J _,5- -:.,4~ ,.-<...-..;JI o.o-'..L11 ..;..,')'.,.L-:J1 ~) ,..:.,1...1.,,_r--ol;J1 . .:.,_;__..!1 • / .. ->'-: ,,,:,i.,...;':i\ t-JJ1 ~ :::-~ u'.>\.$. C:" i---·0' .!l".i4'---'J .... A,.C.)1 ~ .r- :::- ..,,_,~1 -.;·;,1,.,. , ~..,,,. J .~1\......c...._) r~ ~Gl 0 1~~ ,~)-" ~~·1 ~_,.,:)1 J.;J-,J_r-- ~1-.,.._;"Y' ~ J! ... ;;.,d..IJ>-"" ... J.l r---:.,,, ABSTRACT Effects Of Hamadan rastmg on serum lip/ds 0120 hEmJmy rn;;les i118c111yla.d.,:,l1 w .. ,e a:s:sea,.ed. Anthropometric parameters and blood lipids were measured 1 day before Ramadan, day 26 of Ramadan and i mon1h after Ramadan. Body weight and body mass index decreased significantly during Ramadan corn- pared With before and after Ramadan. Fat intake was significantly higher during Ramadan than after. High- rlen,:,ity /ipnf1rniPin (HDL) r.nolesterol increased significantly clurinQ Ramadan, Other lipids were not significant~ different. Regression analysis of Ramadan HDL cholesterol levels indicated positive association with pulse rate and fat intake and negative association with systolic blood pressure and weight loss. The findings indicate improved HDL cholesterol profiles during Ramadan. Amelioration du profif d1.1 eholoeterQ I HDL eerkp,10- ch&z uos 4tudi;onts hang.ladl!.ls pendant le jeune du mois de ramadan RESUME las effets du jeiine du mois de rama.d.an sur Jes l(oides seriques chez 20 sujets de sexe masculin en bonne sante au Banglaoesh ont ete evalues. Les parametres anthropometnques et les lipides sanguins 011t &te mesures tm jour avant le ramadan. au 2& jour du ramadan et un mois apres le ramadan. Le poids corporel et \'indice de masse corporelle ont consideran1emem a1rnmue pendant le rl:lrnad11r I p!:11 '"'JJ!X'rt au.a: mesures avant et apres le ramadan. L'.apport lipidique etait significativement plus eleve pendant le ramadan qu'apres. Le cholesterol des lipoproteines de haute densite (HDL) augmen1ait de maniere significative pendant le ramadan. Les autres lipides n'etaient pas significalivement differents. L:analyse de regression pour li:!<i tau.v d-., chnfA~f4rnl Hnf flAndant f e ramadan indiquait une associahbn oositive avec la frequence du pouts et l'apport lipidique et une assoc'iation negative avec la pression arterie\le systolique et la perte de poids_ Ces resultats montrent une amelioration des profils du cholesterol HDL duram le ramadan. 'Department ot Comm1..1nity Medicine, Rangpur Medical College, Rangpur, Bangladesh. 2/n<:tit!Jt" ,c,f Pvblir HPRith :;,nrl Nutritinn. MnhRkhBli. Dhaka. Banoladesh. 'Department of Community Medicine. Sylhet Osmani Medical College, Sylhet, Bangladesh. 4 Gynaecotogy Outpatieat Department, Rangpu, ,tfe,:m7al Colki'ge h0sp.itaJ, .Ra.ngpv.~ Bar,g.ladeslt 'Division of Family and Consumer Sciences, College of Agriculture, Forestry anr:1 Consumer Sciences. West Virginia Unive.rsily, Morgantown, West Virginia, United States of America. R,u:eiv1>rl· ?Rtn3/0?: accepted: 23/12102 132 Introduction La Revue de sante de la Mediterranee orientale, VoL 10, N° 1/2, 2004 Ramadan fasting is one of the 5 pillars of Islam and one of the most significant iba- dat (worships) of Islam [JJ. Throughout the world, millions of Muslims fast during Ramadan to fulfil this religious obligation. Because the lunar calendar dctennines the month of Ramadan and is about 11 days shorter than the solar year, Ramadan is not fixed to any season. The timing of daily fasting varies from country to country and with the season in which the month of Ra- madan falls. Thus, depending upon the sea- son and the geographical position of the country, the length of the fast varies from 12 to I 9 hours per day (2]. During Ramadan, Muslims abstain from food and drink from dawn until sunset. Traditionally the practice is to eat 2 meals. l before dawn, sahri, and I just after sun- set, ijtar. Often Muslims eat a greater vari- ety of foods in theirmeah during Ramadan than in other months. As a result, the Ra- madan fast provides an excellent opportu- nity to study the effects of various diets on the human body and can serve a~ an excel- lent research model for metabolic and be- havioural studies [3]. Ramadan fasting and starvation are not synonymous. Many physiological and psy- chological changes take place during Ra- madan, most probably due to tl1c changes in eating patterns, eating frequency and sleep patterns [4]. Some studies in the east- ern Mediterranean area bave indicated im- proved high-density Hpoprotein (HDL) cholesterol during Ramadan fasting /'5,61. The objective of our study was to in- vestigate the serum lipid profile as influ- enced by diet patterns and other parameters during Ramadan. Methods The study was conducted in Dhaka, Bang- ladesh, with 20 healthy male volunteers re- siding in the hostel of the National Institute of Preventive and Social Medicine (NIP- SOM}. Prior to selection, written consent was obtained from each. Clearance was obtained from the Ethical Committee of NIPSOM. Data were collected at 3 inter- vals: before Ramadan (l day before the start of Ramadan). during Ramadan (day 26 of Ramadan) and after Ramadan (I month after Ramadan). Data collection started in December l 998 and ended in March 1999. During the month of Ra- madan the average duration of fasting was approximately l2 hours and the maximum ambient temperature ranged from 11 "C to 29 °C [7]. The mean age± standard devia- tion of the volunteers was 38.27 ± 4.07 years. All volunteers were in good health and none were using any medication. All were engaged in light physical activities and the nature of their work was more or less similar. Body weight and mid-arm circum~ fercncc were recorded before, during and after Ramadan. Diet infonnation was obtained during Ramadan and after Ramadan using 24-hour recall method for 3 consecutive days. No dietary intervention was provided to the volunteers and they were allowed to eat anything they wanted. Food intake was analysed for energy, protein, carbohydrate and fat. Diet composition was calculated with published and u11publi!1hed composi- tion tables of the foods of Bangladesh (A. Haque, unpublished data) [ 8]. Blood was tested in the Department of Nutrition and Biochemistry of NJPSOM. Before and after Ramadan. blood was col- Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2, 2004 133 lcctcd in the morning after overnight fast- ing; during Ramadan it was taken JUSt after breaking the fast with a glass of water. To- tal cholei.terol, HDL cholesterol and triglyc- erides were determined by enzymatic methods. Low-density lipoprotein (LDL) cholesterol was obtained by the fomrn1a: LDL cholesterol = total cholesterol - HDL cholc5tcrol · lriglytE-ridcs/5 Determination ofa!! biochemical param- eters was done with a photoelectric colo- rimeter and reagent kits (manufactured by Human Gcse!lschaft fur Bjochcmica und Diagnostica GmbH, Weisbaden, Germanv) f9l. . Data were analysed by ANOVA for model-period (fixed effect) and subjects (rando1n eftecl) using StatSofi Statislico, version 5. The mean values of the 3 test periods were compared for significant dif- ferences using Duncan's multiple range t- test at P < 0.05. Results Anthropometric measurements The mean values of anthropometric mea- surements significantly changed before, uutillgiludu1krRmnad,ut(T<1bl~ I). i\.llpa ramcters at day 26 of Ramadan, i.e. body weight. body mass index (BMI), mid-ann circumference, pulse rate and systolic and uic1sLulic blood prcs:mrc, were 3ignificantly lower than pre-Ramadan values (P < 0.05 ). One month after Ramadan fasting, body weight and other parameters had a trend to 1c...:uup lo pre-Ramadan ,'ltatu:;; however, they were still significantly lower than the pre-Ramadan values (P < 0.05). When the post-Ramadan values were compared with ll1<:: uay 26 Ramadan values, body weight, BMT, mid-arm circumference and 3ystolic blood pressure were significantly higher (P < OJ)S ). Pulse rate and diastolic blood pres- :.1.11 c; w1;;1 c not significantly different. This indicates longer lasting lowering effect of Table 1 Anthropometric and other measurements (mean :1: standard deviation) of the 20 healthy male volunteers Measurements Weight(kg) Body mass index (kg/rn2) Mid-arm circumference (cm) Pulse rate (per minute) Sy:;toli,,. blood pre:,:,urr_, (mm Hg) Diastolic blood pressure (mmHg) ---· 'One day before Ramadan. 0 One month after Ramadan Pre-Ramadan• 64.05 ± 7.78" 24.20 ±2.48' 27. 75 ± 1.88' 82.5 ± 8,9" 124.3 ~ 13.9' 82.3 ± 11 .4' Day26of Ramadan 62.07 ± 8.08" 23.44 ± 2.52" 27.20 :i 1.88· 75.2 ±7.8" 111.8*10,B• 77.3:z.10.6d Post-Ramadan1> F P.value 63.05 :1: 7.75° 14.1 < 0.001 23.81 ~ 2.37'' 13.4 < 0.001 27.42 .:t 1.91 d 13.1 <0.001 77.0±8.0d 21.0 <0.001 1180t g Qd ?f,~ <0001 78.8:t: 10.6° 9.04 <0.001 V1ss1m11ar superscnprys ma)t;are ~rgmlf,,arrl dt/fe,rc,;,e,., o,,-/w~c,r1 .t' m~..:ins; Duncan'a multiplo rango t.ta.;t P<O~ ' 134 La Revue de Santa de la Mediterranee orientals, Vol. 10 .. N° 1/2, 2004 Ramadan fasting on _pulse rate and diastolic blood pre.s:surc. Energy intake Total daily energy, carbohydrate and pro- tein intake ,vcrc not 3ignificuntly different between during and post-Ramadan periods (Table 2}. However .. there was a significant increase in fat intake (P <: 0.0 I). Energy fron1 fat a.,; a p.:rccnt •Jf die l\._1tal ._:n,.;igy intake ,vas I 0.6% during Ramadan versus 7.6% after Ramadan. Significant decreases in blood glucose levels during Ramadan :1uggcst energy intake a..:, the limiting factor in our study (Table 3). Table 2 Mean energy intake {:I: standard deviation) of the 20 male volunteers during and after Ramadan Energy intake During Percent of Post- Percent of Ramadan total energy Ramadan total energy intake Intake Energy (k.ca\/clay) 2113.8 ± 168.5 2134.1 ± 132.6 Cd.r bol i'{d( ctl.e (g(day) 406.3'.!:49.9 TT.1 ;1;5.2 433.3 :t: 42.f) B1,l:!:5.0 Protein (g/day) 64.6 ± 20.5 12,3 ±4 1 60 1 :t 21.5 11.3±4.1 Fat (g/day) 24.7 ±3" 10.6 ± 1.4 17.9 ± 3.6i 7.6±1.5 -;-;,,SJgnific~nt diff~.rtJnc~ ,bg/wP@n 2 .m_,,.qns: al P r~ 0.01. Table 3 Serum lipids and glucose measurements {mean± standard deviation) o1 th~ 20 healthy male volunteer:1 Measurement Pre-Ramadan Day26of Post-Ramadan F P.value Ramadan Tula/ cllo/e:;terol (my/dLJ 108.4 ± ,30.32 IM.I5± 24.24 17<1 ± 29.06 I. I NS HDL cholesterol jmgldL) 38.14±7.40 46.71 ± 14.33" 41.72 ± 7 70 4.1 <0.05 LDL cholesterol (mg/dL) 103.92 :t 34.57 92.33 ± 23.40 99.68 ± 27.54 1.2 NS Triglycerides (mg/dL) 146.66 ± 72. 78 131.04±41.47 152 71±5759 1.7 NS Total cholesterol/LDL cholesterol 4.6± 1.3 3.7±0,9' 4.3 :1: 1.1 5.2 < 0.01 LDUHDL cholesterol 2.9:i: 1.2 2.1 :I: o.s• 2.5 :t 0.8 4.3 <0.05 Cluoono (mg/dL) 05.3 .1. 14.F 85.G.1.10.4 01.0 ;_ 11 .6 4.8 ...c{l.0$ Dissimilar superscripvs indicate significant difference between 2 means; Ounc1u1's mul!iple range !-test at P < 0.05. lDL = !ow-density lipopro!ein, HDL = hioh-density 1/ooDrotein. NS = not significant al P < 0.05. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 135 Serum lipids Significant improvement in the HOL cho- lesterol profile (H DL cholesterol, total cho- lesterol/HDL cholesterol, LDL cholesterol/ HDL cholesterol) wa& observed during the Ramadan fasting period compared w1tll th..:: pre-Ramadan p..::riod (P < 0,05) (Table 3). There were no significant diff crence& in t~- ta~ cholesterol, LDL cholesterol and triglyc- cndcs between the 3 periods" Discussion Anthropometric and other measurements The mean difference between pre- Rn~nadan • .md during Ramadan hrn-\y weights was 1.97 kg. Significant reduc- tions in body weight, BMI and mid-ann cir- cumference during Ramadan suggest that the subjects in our study had a nC'g>1tivt> en- ergy balance (P < 0.05). Similarly, many studies have reported \vcight foss during the month of Ramadan fasting [3, 10-16]. in contrast to this, onic• Swidi /\rahi;m .~n1dv reported weight gain during Ramadan [ / 7] and stili others did nut find any significant change in body weight [2, 18]. Tn one study among healthy mal1c",, :l .;;ignificant reduc- tion in skin fold thickness was reported during Ramadan fasting r 3J, A study of Tu- nisian women suggested that increased fat oxidation during Rrm1~1d:,n fa,r1ne, results in an _adaptive mechanism for body weight maintenann: [l 8]. Our observation of de~ creases in systolic and diastolic blood pres~ sure is supportr;:d by the finrlings of Athar and Habib [/ 6). Energy intake The mean ellPtgy intake during Ramadan (2113.8 ± 168.5 kcal/day) was somewhat below the average energy consumption of Bangladeshi people, which has been esti- mated a1 '.2244 kc.al/nay [7]. Among tropical Asiatic maks energy intake has been re- potted to be 25~7 kcal/u<1y uu uunnal days with a reduction of 20%1-25% during Ra- madan fasting [ 1 O]. In contrast, Frost et al. reported increased energy intake dming Ramadan ( 3680 kcal/day) 1,;uu1µarcd with energy intake after Ramadan (2425 kcal/ day) [17]. There were no significant differences in carbohy(1raie and prntt:in i11l,1.k.c during and after Ramadan in our study. The Bureau of Statistics of Bang1adcsh reports avl.'.rage protein consumption to be 65 g/day (7J. This is approximau~Iy iu ag1 i:cwent with the reported protein intake of our subjects. Protein intake has been reported to increase during the month of Ramadan fasting among both Ttmhian wumt:u and Jvforoc':: cans [ 4.18]. Fat inti:ike was significantly higher among our subjects during Ramadan (P < 0.(101). This wa.-; :;imilar Lu inL=rcMc~ in fot intake during Ramadan among Tunisian women and among Moroccans [ 4, J 8], Bangladeshi people prefer fried food items during ({tar. Thi:; habit i11L'rcn~c1J the intake of unsaturated fat (mainly soybean oil) that ultimate[y results in an increase in fat con- sumption during Ramadan. It may be noted lhat fa[ intak1: calui ic:. a:. a pcrccntag<.: of total energy intake during and after Ra- madan in our study were far lO\ver than is consumed in the affluent societies of some industriaHzcu ualium,. Bei;;.au:;c low intake of fat rather than excess fat is a concern in the general population in developing coun- tri cs like Bangladesh, it seems that during R.amactan nn int.:1ke :.lightly improved. Serum lipids It is wel1 established that a high level of HDL diukstcrol has an inverse rclo.tion with coronary heart disease [ 19). The im- proved HDL cholesterol profile in our study is supported by many studies [ 4c -6, 20, 21]. 136 la Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Streja •tt al, and Murphy et al. nGted sirnilar incrca:,cs in IIDL chok:,tcrol profile:, in 2 non-Ramadan studies [22.23 ! . Nonethe- less, some studies have reported decreases [3,2./]. In multiple regression analysis (r' = 0. 74, P -< 0.00 l, n - 20), IfDL chok~tcrol was positively associated with pulse rate and fat intake and negatively with weight loss and higher systolic blood pressure. The prediction equation i:;: HDL cholesterol "" 1.4024 + 1.4032 pulse raw+ L5642 fat intake - 0.9608 systolic blood p«:,Mnc - 4 }295 wc:ight change where HDL cholesterol was measured in mgidL, fat intake ,vas measured in g/day and -weight change was calculated as ,,,-eight on Ramadan day 2(, -i,veight bcf1._1\s: Ramadan measured in kg. Improvement in H DL cholesterol profile with higher fat intake agree1s with the find- ings of Nonw.ni ct al. [1]. In conclusion, Ramadan fasting con- tributed t0 better hlood lipid profiles under the prevailmg limited energy intake condi- tions of the 5tudy. One of the co11tributiug factors may be higher fat intake. The find- ings may have an application in improving HDL cholesterol levels among subjects irre- spective of religion under rc:-.trictcd cnci gy intake conditions. References 1, f'Jomani MZ/\. Dietary lat. blood cholco teroi and uric acid levels during Ramadanfasting. International journal of Ramadan fasting research, 1997, 1: 1-6. 2. Muazzarn Ct Aamdda11 lastiug d111/ 111t1di- caJ science. l\fracombe, Devon, Arthur H. Stockwell Limited, 1991 :5-32. 3. Hal/ak MH, Nomani MZA. Body weight loss and change$ 1n blood IIpid levels m normal rnen on hypoca\oric diets during Ramadan lasting. American journal of clinical nutrition, 1988, 48: 1197-21 o. 4. Adlouni A et al. Fasting during Ramadan induces a marked increase if'1 h,gh- density lipoprotein cholesterol and de- crease in low-density lipoproteln choles- terol. Ann~/.:, of nutrition c:md m<"ta.boli.:;m .. 1997, 41 :242-9. 5. Maislos M et al. Marked increases in plasma high-density lipopro1ein choles- terol arrer prolongeo rasung during Ra- madan. Americt.n joumal of clinical nutrition, 1993. 57·.640-2. 6. Maislos M et ol. Gorging and pla5me. HDL cholesterol~the Ramadan model. European journal of clinical nutrition, 1998, 52: 127-30. 7. Stali!:;;ti(,·al µoc:IH;1t /Juo/i of Baflgladesh 1998. Dhaka, Bangladesh Bureau of Statistics, Statistics rnvisiof'1, Ministry of Planning, 1999:1-432. e. HashId M. i--ood and nutrition. In: Rashid KM, Khabirudd'1n M, Hyder S, eds. Text- book of community medicine and public health. Dhaka, RKH publishers, 1995: 112-2€. 9. Al!ain CC et al. Enzymatic determination of total serum cholesterol. Clinical chem- istry, 1974, 20:470--5. 10. Husain R, Duncan MT, Chang SL. Effects of fasting in Ramadan on tropical Asiatic Moslems. British journal of nutrition, 1987, 58:41-8. 11. Prentice AM et al. Metabolic conse- quences of fasting during Ramadan in Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 137 pregnant and lactating women. Human nutrition: Clinh::al nutrition, 1083, 37C: 283-94. 12. Nomani MZA, Hallak MH, Siddiqui IP. Ef- fect of Ramadan fasting on plasma uric i:I.Gil.l c1.11d !Jm.Jy weighl in healthy men. Journal of the American Dietetic Associa- tion, 1990, 90:1435-6. 13. Sliman NA, Al-Khatib FA. Effect of fasting Hamaaan on ooay weigm ana some blood constituents of healthy Muslims. Nutrition reports international, 1988, 38: 1299-306. 14. Takruri HR. Effect of fasting in Ramadan on body weight. Saudi medical journal, 1es9, rn:491-4. 15. Nomani MZA, Baloch SK, Siddiqui 1P. Changes in serum cholesterol levels and dietary vegetable-tat at restricted energy intake condition during Ramadan fasting. International journal of food science and tectmology, 1992, 4: 30--tl. 16. Athar S, Habib M. Management of stable type 2 diabetes mellitus NIDDM during Is- lamic fasting in Ramadan. Paper pre- sented at tile rirst mrernat1ona1 congress on Health and Ramadan, 19-22 January 1994, Casablanca, Morocco. 17. Frost G, Pirani S. Meal frequency and nu- tritional intake during Ramadan: A pilot study. Human nutrition: Applied nutrition, 1997, 41 (A):47-50. 18. EI-Ati J, Beji C, Danguir J. Increased fat oxidation during Ramadan fasting in healthy women: an adaptive mecha- nism for body-weight maintenance American journal of clinical nutrition, 1995, 62: 302-7. 19. Gordon OJ, Rifkind BM. High-density li- poprotein-the clinical implication of ro- cent studies. New England journal of medicine, 1989, 321 :929-34. 20. Rashid HU, Ahmed S, Chhetri PK. Ra- mad;;m fasling: Study uf llilh,ner1l bio- chemical parameters. Journal of inter- national postgraduate medical re- search, 1996, 11(1):14--6 (abstract). 21. Akan11 AU, Mo1ImmIyI OA, Ab0ella N. Beneficial changes in serum apo A-1 and its ratio to apo Band HDL in stable hyper-Jipida0mic subjects after Rama- dan fnoting in Kuwait. European journal of clinical nutrition, 2000, 54: 508-13. 22. Streja DA et al. Changes in plasma high- density lipoprotein cholesterol concen- tration a.fler weight reduction in gro~sly obese subjects. British medical journal, 1980, 281 :770-2, 23. Murphy MC et al. Meal frequency: does ii aetermJne postprancllal llpaemia? Eu· ropean journal of clinical nutrition, 1996, 50:491-7. 24. Larosa JC et al. Effects of hlgh-protein, low-carbohydrate dieting on plasma II- poproteins and body weight. Journal of the American Dietetic Association, 1980, 77:264-70. 138 La Revue de Sante de la Med1.terranee onentale, \/01,. 10, N° 112, 2004 lschaemic stroke in Jordan: a 2-year hospital-based study of subtypes and risk factors Y. Bahou1, H. Hamid2 and A. HadidF 1,1-'~1 J_,. .... .:.,-:?-- a..i.J. ..;.,~1 ~ ofa.r ;;....1J:, :.:.i:i/~1 _J :1,ul.oii)'l l,,&-\..o..ui ~1 ..,lk,.;,:-')'1 j,oly J ,Y,, __,.ill ,~L-· '-cl Of' ~')'-..J ul,o ~<-.,, c:,.· 1-,_;·...- s.--i\...o.,, ~.;.,,,_,,.. 200 c:.J.f-· "c-'1.,,::,...,1 :.,,, •. 1.1' ~~_,-i :<l.,,p~I ~~ ~-->-_,\_r-4) ~'!..>- 61.2 -=,-~_;/, ,~\ .JW- ~\j_!' .~_r'J~~ .. ;_r-,J J)1-..:--=. ½~_;)11, ~~I__:~~~ 1,_~~f~ s.::.,Lc:_(_JI } ::.~ _;_,<" '.'! (i:51 .5) , ., ,), I ~·~- ':,'1 ,,.. l.o ,,,..C:. ;;,,,,,a. ,...;JI _1.li\, .$1 .:,ts·, ,(L.,\.,c. 95 - 29 ~ ,;-- Li:i ,1 ~ ~ Ji.k.,_,.;. '.,I \.'I.,:: ,cS-i 2l5 , ,('f.8.0) ;,:...._...:.._;_.. ..:,,lS"" L...J1 .,__;;, "'-',c:_,, ,.s,. ,.,,:--WI "--"'l.o .. Lil ._ ..., - ...... .,,. ... ,,. ' ~- .... ~ . ~I L.J.i ~,1-~ y· s_.-~) ~-·~J·, ~~l ~.,P ~~lJt ¥~-01 ,.:...,~.l1 ..j ~-~1 _, ~ ~\-' t....Ui .l:.-----1 1, ~ ,._:;..., 1'--~ -~ ~-... -LJ-1 ::;,____i:-i...,._Lll .._,:_~l--.:...-<: ___ J1 ~ ~- ~. _)l__b__::__~ '-'II ~Al~ ~·:(\ ._ .. -~I 0:::.\1·1 .;_,.l_,il_.._._ jl ~;~ ~ ,._ ........ - ~ .,,., ..__ ~ ~ i.,.....- J "i<-½" .,, -· _\.,.i_',-r ,_~-;) L_>-~il .Jl-,1:_~ 1. L) ~41 ._Ji_.,,.__;i_\! ·=-,l,,_:,,..'.- -F-;-L.......__\1 ~Jl.1_, .... :..J1 ,J _l_j_L_c;_, --~' -~)1 ~·~ ..__,;-I .._; . J~, ~-----<... -~ ~ 67 __;.,U_) ~-.~ ~ .... -~ ~~l_.~ ~ '-~ ~-~ ..... ~) ~~~ ~-,_-d-;-1 ~L.. ... d~ ~L£....J1 ~J ,(/50 L..-~ 103 ,:,:~ ..:,-- ~;-" 34 ,.PJ) .._,i.:.UJI ~I c.,I ~.I _L<..::., ,,;..,jS' J' ..U_j (~/ '103 C:.'oe J W.,,.,. ~ r""' 4,-.k,v ~ ,._:1y.l1 J! ~;,.....11 j ~ ?" _;.':,'i..,L., .>' i,85) ...:,-.:., ;~, c,1L.::J1 i.,i (LS"", ... . ~ i~_.A-p _,'L~~ ._j l..._....~j..J.r ..._..j_:r;..: -.?°\1. L1_.._.L1 ...;..,·i....,.~'-{1 ,.:..~ d.~l~ -~\.-5°~ (~ ~ ABSTRACT A retrospective study was made of 200 consecutive patients with first-ever 1schaernic stroke, admitted ~o Jordan University 1-\ospltal over a 2-year per'1od. The mean age was 61.2 years (range 29-95). The most common stroke subtype was lacunar infarct (51 .5%), but frequency of cardioembolic stroke was low (8.0%). Hypertension. diabetes mellitus and smokinq were the most common risK lactors 1or atheroscle- rot1c non-cardioembolic stroke. Chronic atrial fibrillation was the most common risk factor !or cardioembolic stroke. No patient had severe extracranial carotid or vertebral artery stenos1s (> 50% narrowing). Lacunar strokes presented predominantly as pure motor stroke (67/103) and were mainly in the internal capsule (34/ 103). The favourable outcome (85% discharged home) may be due to the relatively young age and the pr,..dornin;in,;,;, oi lacun.;r ·,nlarct,;:. L'accldent lschemique cerebral en Jordanle : etude hospitaliere sur deux ans des sous-types et des facteurs de risque RESUME Une elude retrospective a ete realisee sur une periods de deux ans chez 200 patients consecu- f,v,,m,;,nt :<dmt<: A l'Hi\r,it:<l 11nivpr<:it;:,i,e rlP .lnr11;:,niP rrnir un r,mmi.::ir inmrr.tus dm•hr~I I 'AgA mny,cm At:<jt rlA 61,2 ans (fourchette . 29-95 ans). Le sous-type d'accident cerebral le plus courant etait l'infarctus lacunaire (5"1,5 %1, mais la lrequerice des emboties cerebrales a·or1gine card'1aque etan taible (8,0 %). l'hypertension, le diabete sucre et le tabagisme etaient les facteurs de risque les plus courants pour les Infarctus cerebraux non cardio-ernboliques d'onglne atheroscleroti.que. La fibrillation auricu!a',re chron\que eta\\ le fac,eur de risque le plu" cour(l.rtl pour lea embolieo c6rebrolea d'origino card1oquc. Auccm pationt n'ovoit do ot6nooc severe de l'artere vertebrale ou de la carotide extracranienne (:>so% de retrecissement). Les m!arctus lacunaires se presentaient principalement con1me une hemiplegie motrice pure (67/103) et etaient localises surtout dans la capsule interne (34/103). L'issue favorable (85 % des patients sont rentres a leur domicile a la sortie de l'hopital) peut etre due a l'age relativement jeune et a la predominance des infarctus lacunaires. ---------------- 'Department of Internal Medicine, Dw1sion of Neurology Jordao University, Amman, Jordan. 2Departments of Neurology and Psychiatry New York University New 11:>rk, United States of America. Received: 26/01/03; accepted: 03/08103 Eastern Mediterranean Health Joumal, Vol. 10, Nos i/2, 2004 139 Introduction Stroke is the thi.rd ka,fo1g cause of d~alh and among !he leading causes of disability in the United States, Europe and m,wy de- veloping countries i /}. Mme recent studies demonstrate that different ethnic/racial populations may have different incidence rates and may be predisposed to different stroke :c;ubtypes. For instance, African Americans have a si6'11ificantly higher inci- dence and mortality rate cornpan:.d with white peo-p!e Ul. Elderly Hispanic patients have a lower mortality rate secondary t-1 stroke compared with white people. Afo- can-,1\mtric:1rr, and Nafr.;e Americans a!so present more frequently with lacunar inf- arcts and intracranial haemorrhage [.Jl, Meamvhile, the difference in cardioembolic stroke rates between African-Americans ,1.nd whites js not statistically significant However, these rates are lower 'in His-panic Amedcans [31- Few studies have explored the risk fac- tors and prevalence of stroke in the Arab popu\ation and n.o \i.tudy could be found re- garding stroke in Jord<\[) [4~SJ A hospital- based studv in Sudan demonstrated an earlier incidence of stroke but a similar risk factor profile to other populations [ 7J. l n a hospital-based study in Qatar, patients also had 0ar\ier peak stroke rates as well <1s high-er rn.tes of hyper!ension anJ diabetes [ 8J. The largest Arab registry is in Saudi Arabia, which also demonstra1eo an earlier on'iiet 1)f strnkc (4]. In Saudi Arabia, large infarcts (56%--67%, of all strokes) were the most common stroke type; there was also a large proportion of lan1nar infarets (33~-o- 46%} [4l This case review of 200 Jordanian pa- tients with ischacmic stroke was <:onduct- ed to explore the age and sex distributi<m, stroke subtypes, risk factors, cl111ica! and imaging findings, treatment and outcome. Methods The Jordan University Hospital is a 530-bed tertiary care teaching hospital provi.dittg health <'a.n: to a large section of the middle- class Jordanian population. As the major university hospital in Jordan, it serves as a principal reform.! centre for the entire Jor- d,mian population. The case notes of 200 consecutive patients with first-e,'er i.s- chaemic stroke adrnitted to the hospital through the emergency department be- tween January 2000 and December 2001 were rcvie,ved. We applied the definition of stroke given by the \Vorld Health Organization f 9]: rap- idly developing clinical si~ns of fo<:al or global disturbance of cerebral fonction, with symptoms la:;dng 24 hours or longer or leading to deatli, \VJUJ no appaTent cause othcl' than , 1ascu{a,; mi.gin. All patients had an initial computed to~ mography (CT) brain scan to exclude -in- truccrebral haemorrhage fo\lowed afler a fe\\' days by a second CT and/or magnetic n:sonm1ce imaging tMRI) scan to confinn the infarct location and size. When clinical- ly in{iicated and tcchnicaHy feasible, some patients had carotid Doppler ultrasnund and/or magnetic resonance ang1ography ( MRA} of the neck and brain ~'essels to rule out aI1criDl steno.sis or occlusion. Most pa- tients had 2 D-tran:-tliorncic echoc~rd10- graphy to n1\e out a ,,atvulopathy or left atrial/ventricular clot. Tests for hypercoag- ulable slate or vasculitis were done when clinically indicated, Each patie11t was assessed for risk fac- tors for stroke. Hypt-'rtension, di,1betes me)- litus, and hyperliptdaemia were defin-ed by standard guidelirtes [10-12J. Ischaemic heart disease, myocardial infarction and atrial fibrillation v,cre confinm:d by a 11- )ead e)ectnY..:ardiogram (ECG) and wid1 a cardiology consultation. History of prior 140 la Revue de Sante de la Mediterranea orientale, Vol. 10, N° 1/2, 2004 transient ischaemi,;: attacks and smoking wcro nlso noted. An assessment was made of the cause(s) of the stroke and these were clas- sified into subtypes using the TOAST c1ite- ri u [ 13] and uocordi ng to ,vhether tho cau,;e was determined or undetermined {2 or more possible causes or negative evalua- tion). Ma.nag~ment ir1cluded treatment with antip!atelct drugs (aspirtn 325 mg/day, ticlnpidine 250 mg twice daily), anticoagu- lants (,:varfarin, maintaining an international nonna\i,,-cd ratio of 2 3), r,hysiothcrnpy, antiocdcma agents (mannitol), reduction of risk factors or supportive measures, each when indicaled. None of the patients re- ceived thrombolytic drugs o,ving to the lack of supportive facilities at this hospital and late presentation to the emergency de- partment (the mean time between onset of ;;troke and Hrrival at the emergency depart- ment was 21 hours, range 6-120 hours). Outcome was dassifkd broadly into: ambulatory with mild neurological deficit, moderate neurological deficit compromis- ing activities of daily living (aphasia, hemi- paresis, assistance in ambulation), arid severe neurological deficit (hemiplegia) or -., cgetative state and death, Results There were 200 patients with ischacmic stroke, accounting for 3.5';-;, of admissions to the medical ward/intensive care unit dur- ing the study period. The mean age was M.2 years, range 29-95 years, comprising I l 2 males and 88 fi.!males (male to female ratio of l .3 ), The age and sex distribution is shown in Tab\e 1, Most of the patients ( l 59/200) were between 5 l and 80 years; however, there was a high proportion of patients ,vith stroke aged under 55 years (41/200) Table 1 Age and sex distribution of 200 pati<:;,nta with firat--cvcr IGchacmio atroko A.ge(years) Male Female Total No. No. No. 21-30 0 31-40 3 2 5 41-50 14 8 22 51---60 37 22 59 61-70 38 31 69 71--80 12 19 31 81-90 7 4 11 91-100 0 2 2 Total 112 88 200 ~--- ----- The cause of stroke could he deter- mined for 161 patients ( 80.5%); the major- ity of cases (51.5%) \'i'ere lacunar infarcts (Table 2), Most of the ctiologically undeter- mined cases, 30/39 (76.9%), had athero- sclerotic and/or lacunar infarcts. The risk factors for each stroke sub- type are shovm in Table 3. The most common risk overall was hypertension {76.0%,) followed by di.abetcs mellitus (44.0?-~), smoking (35.0%), hypcrlipi- daemia (33.0"-/o) and ischaemic heart dis- ease (20.S')io), Hypertension was also a major risk factor for lacunar infarcts in 87 out of 103 patients (84.5%) followed by diabetes mellitus in 49/103 (47.6%) and smoking in 30/103 (29.1%). Among the l 52 patients with hyperten- sion, 100 had known hypertension, 23 were nev.r!y diagnosed and 29 had uncon- trolled hypertension at the time of stroke. Among the 88 diabetic patients, 59 had known diabcte~ mel\itus, 14 were newly di- agnosed and l 5 had uncontrolled diabetes mellitus at the time of stroke. Among the 66 Eastern Mediterranean Health Journal, Vol. 1 o, Nos 1/2, 2004 141 Table 2 Subtypes of ischaemic strokes among ioo patients With tlrst-ever lschaemic stroke, classified using the TOAST criteria [13) --~-~-- ---- Category No. of % patients (n = 200) Gause determmed Large artery ;ithero»r.lero,;;is 4D ?O {) Lacunes 103 51.5 Cardioembolism 16 8.0 Hypercoagulabfe state 2 1.0 Total 161 80.5 Cause undetermined Atherosclerosis and/or 1acunes 30 15.0 Embolism with 2+ possible causes J ,:'..U Negative evaluation 6 3.0 Total 39 19.5 Total 200 100.0 - - n = total number of patients. patients with hyperlipidacrnia, 35 had known and 3 l ne,.1.,.Jy diagno.s:ed hypcrlipi- daemia. Among the 70 smokers, 62 ,vere males and 8 females. No risk factors ex- cept elderly age could be detennined in 12 patients. Two patients had hypercoagu!ab!e state (primary antiphospholipid syndrome). There were 16 patients (8.0%) with cardioembolic strokes. The majority ( 14/ ! 6) ,vere female pa(iems above the age nf SO years (7 above 70 years) \Nith 12 out of I 6 ha,·ing chronic atrial fibrillation and at least 1 other risk factor (mainty hypertcn- s ion and left ventricular hypertrophy). None of the patients with atrial fibrillation had therapeutic levels of warfarin before the stroke (2 patients discontinued war- farin, 4 "''ere taking ,varfarin but were sub- therapcutic, the remainder w·crc not taking the medication). ~ Large artery atherosclcrntic strokes (2O.O''.1o uf cases) were preduminantly in the carotid territory (22/37) as opposed to the vertebrobasilar region ( 15/37) and pre- sented mainly with hemiparesis/hemiplegia wi1h or wirlwut aphasia and lateral homon .. ymous hcmianClpsia. MRI and/or CT brain scans showed infarcts located predomi- nantly in branch vessels ( 13/22 in a branch of middlt' cerebral anery and 8/15 in the posterior cerebral artery). Strikingly, none of these patients had haemodynamically significant extracranial carotid or vertebral ane1)' atbnosclerosis (i' 30';·;) luminal nar- rowing) on carotid Dopp\er ultrasound and/ or MRA of neck vessels. The most com- mon clinical presentation of lacunar inf- an:ti; wa~ pure motor suoke (07/103) follo\ved by mixed scnsorimotor stroke (26/ l OJ). The most common lacunar inf- arct location on CT and/or MRI brain was in t!te iu(i;:rmd rnpsuk (J4/J 03) fulluwcd by multiple locations (25/ I 03) and the periven- tricu!ar area (J 7/103). Lacuncs v."ere shO\vn on CT scan in 73 out of 103 patients (70.9'% ), bul in t 7./103 ( U\,5°1ii) they were seen only on MRI and in 13/103 were shown on both scans. Of the etiological\y undetermined stroke subtypes, 30 pa1irnts ha(t atherma.:Jerosis and/or lacuncs. Three patients had embo- lisms with 2 or more possible causes: 2 had atrial fibrillation and hypertension and the Lliiu.l o.;aJtliuiuyupathy aml liypeILt.:nsiun, There were 6 patients with a negative eval- uation who had multiple risk factors (hy- pertension. diabetes mcllitus. smoking)_ A f1:w Ln:atmc:nt l'omplicaliun: 01.> curred. Four patients had bleeding duode- nal ulcers due to aspirin and 2 had warfarin toxicity. With regard to outcome, most pa- tirnts uid wtcll. AC\1.:r a mean follow-up of 18 months (range J to 24 months), J 7O pa- tients (85.0%) were discharged home. Among those discharged, J 07 had mild - ,. ~ Table 3 Risk factors for stroke among the 2D0 patients with first-ever ischaemic stroke according to subtype (most patients had more than one risk factor) Risk factor Cause determined Cause undetermined Total (n = 200) Large Lacunes Cardio- HC AS/ Embolism Negative artery (n= 103) embolism state lacunes plus" evaluation .-( AS (n=16) (n=2) (n::::30) (n=3) (n:6) . [n== 40) N>- No, No. No. No. No. No. No. No. 'le, :c: Hypertension 32 87 28 5 152 76.0 r-I - - - Ill - ::c (.· DiabetEs mellitus 26 49 - - 10 3 88 44.0 t .; C: t Smokirg 16 '31 - - 14 - 3 70 35.0 II) C. II) ~,- Hyperlipidaemia 18 30 - - 14 - 4 66 33.0 CD Ill (. lschaemic heart disease 10 22 - - 9 - - 41 00.5 :::I ii}; t. Previol.'s transient ischaemic a. (I) attac< 8 6 - - 3 - - 17 8.5 iii"" ~t~ 6 3.0 s: Obesity 3 3 - - - - - (I), ~ C. ;= [ Chronic atrial fibrillationb - - 12 - - 3 15 7.5 ; Prosthetic val\!e - - 3 - - - 3 1.5 :::, (I). - tt, f. Myocardial infarct - - 1 - - - - 1 0.5 Q Antiphc:spholipid syn~rome 2 2 ·,.O ii)' - - - - - - J ~- Nothin{; identified - 5 - - 6 - 1 12 6.0 ~ AS = alherosclerosis. ~ c •• -): HC = hypercoagulab/e. .o n = tot6.I number of patients. z t •Embofi;;m with 2+ possible causes. 0 _._ bAssociated with hypflrtension anclor dil!betes Tiellitus. t3 N t 0 0 ,., Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2, 2004 143 neurological deficit an<l 63 required assis- tance with ambul:ition Tht" l::itter group of patients had a prolonged stay in the hospital due to lack of a rehabilitation centre at Jor- dan University Hospital. Thirty patients (15.0%) died, 10 rlne to large infarcts in middle cerebral artery territory with hernia- tion, 7 due to brainstem infarcts and 13 secondary to medical comorbidities (such as aspiration pnP11monil'l, cleep vein throm- bosis with pulmonary embolism, sepsis, re- nal failure). Discussion Several points emerge from this retrospec- tive study of 200 patients with first-ever is- chacmic stroke admitted tu Jun.Ian University Hospital over a 2-year period. The stroke admission rate of 3.5% was similar to that from other Arab countries [4-(),14]. The mean age of uur palit:ub (61.2 years) was younger than in industri- alized countries. For instance, in the Framingham study the mean age of stroke pa,ients was 65.4 yt:ars fur 1111;;11 aud (,6, l years for \V0men [15]. In the Northern Manhattan Stroke Study (NO-MASS) the mean age at ischaemic stroke was 70 years [16]. Concerning stroke subtypes, 161/200 (80.5'~/o) of our patients had a stroke of de- terrnined cause, similar to the determined 1;l!uk.1:: 1atcs 9(,/IJG (70.5%) found by Con- ti ( / 7]. The majority of determined strokes were !acunar infarcts (51.5%), which were more frequent compared with other Middle Eastern and Western studies [2 R, 14 Ni]; the frequencies of lacunes in most popula- tions ranged from l l % to 42%. Our higher percentage of lacunar infarcts may be due to the higher rule of hypertension in our patients compared with most populations. In addition, the proportion of large artery atherosclcrotic strokes (20.0%) was simi- Jar to some studies [ l 7, 19] but less than in others (30% and 39.5%) f ltU/l. Cardi- oembolic strokes in our series (8.0%) were less frequent in comparison \vith other studies (17.5% to 31 %) f 17-19,27,3 I]. The number of patients (3.()%) with a neg- ative evaluation was less than that found by others [ 1 7, 31] and furthermore these pa- tients did not receive transesophageal echocardiography to rule out cardiogenic or aortic arch cmbolic sources. As demon- strated by AmarL'nco, as many as 38% of patients with no discernible cause for em- bol ic strokes rnav have atherosclcrotic plaques > 4 mm in diameter in the aortic arch l20l The most frequent risk factor in our pa- tients with non-cardioembolic strokes was hypertension (76.0%). followed by diabe- tes me!litus (44.0%). Hypertension was also a major risk factor for lacunar infarcts, as was diabetes mellitus and smoking. Sim- ilarly, in a population-based ,tudy in Minne- sota, Sacco noted that hypertension was found in 81 % of patients with lacunar inf- arcts [211. Smokin.g and hyr,erlipidaemia were also important risk factors in our study, as in other Middle and Far Eastern studies [J 4,26]. Concerning cardiocmbolic strokes, the most common risk factor was chronic atri- al fibrillation ( 12/16 patients) associated with other risk factors (diabetes mellitus, hypertension with left ventricular hypertro- phy) occurring in women above the agl' of 50 years, which is in agreement with other studies [2.?-25]. Interestingly, we had few men with atrial fibrillation in this study. With regard to clinical and imaging find- ings in non-cardioembolic strokes, there was a striking absence of severe extracra- nial carotid and/or vertebral atherosclerosis (> 50°,'o naiTOwing) in all of our patients. This is similar to Qari's study, in which only 4 out of7l Saudi Arabian patients had 144 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 severe carotid stenosis l 14], Other Middle Eastern reports [./J found a higher frequen- cy of lacunar infarcts and a less trequent prevalence of extracranial large artery dis- ease. On the other hand, pure motor stroke was the most common sign of lacunar inf- arcr (67 of I 03 patients, 6J.U%), which is m accordance with other studies. [16,26,27]. The most frequent location was in the internal capsule (34/103). With respec1 to cardioembolic strokes, the most common clinical sign was hcmiparesis/ hemiplegia with or without aphasia and all patients had cortical infarcts in accordance with Dulli et al. where the odds rat10 tor cortical stroke was highest for atrial fibril- lation on ECG (OR= 4 77; Cl: 2.08 l0.94) [18]. In carctioembolic strokes, only 6 out of 16 of our patients were on warfarin prior to their stroke (2 had stopped recently prior to the stroke and 4 had sub-therapeutic lev- cl s). Thus 12 out of 16 patients (D%) were not properly treated with warfarin prior to stroke. The problem of undcrtreat- ing patients with atrial flbril!ation has been (h;:monsrrared by Ibrahim and Kwoh who found in a cohort of 2093 patients with heart failure and atrial fibrillation that only 414 patients (20~'o) rccdved oral anticoag- ulams [29]. Old age was negatively associ- ated with their use. Deplanque ct al. also noted that among 13 7 patients with atrial fibrillation eligible for oral anticoagulation, 108 (78.8%)) dili not receive treatment [30]. With regard to outcome, after a mean follow-up of 18 months, 85% of patients were discharged home (two-thirds inde- pendent, one-third dependent) and 15% died. The mortality rate was in the lower range, similar to Vilalta and Arboix's Barce- lona registry at 14% [ 3 I]. lkebe et al. found among 315 stroke patients followed up for I year that 33% died, 13~'(, were dependent and 54% independent in activities of daily living [32]. The relatively good outcome in our patients may be due to their relatively low mean age and the predominance of la- cunar infarcts. In conclusion, this study has shown, first, a younger age of stroke prevalence compared with developed countries~ sec· ond, a distinctive predominance of lacunar infarcts with absence of severe cxtracranial atherosclerotic disease and a lower fre- quency of car<lioembolic strokes; and, third, that the major risk factors for non- cardiocmbolic and cardiocmbolic strokes were hypertension and chronic atrial fibril- lation respectively. Although this study has the limitations associated with being a small, rctrospecti vc, hospital-based study, our results suggest the morbidity and mor- tality of stroke would be greatly reduced by appropriate management of hypertension. The lacunar stroke and hypertension rate is higher than most regions, and should be a focus of public health in Jordan and the Arab world. Furthermore, more nursing homes and rehabilitation centres in Jordan may reduce the length of hospital stay. Fu- ture community-based stroke registry and clinical trials in the region would further elucidate the health needs of the population. References 1. Bonita R, Stewart AW, Beaglehole R. In- ternational trends in stroke mortality: 1970-1985. Stroke, 1990, 21:989-92. 2. lynch GF. Gorelick. Stroke in Afrir.;:in Americans. Neurologic clinics, 2000, 18(2) :273-90. Eastern Mediterranean Health Journal. Vol. 10, Nos 112, 2004 145 3. Staub L, Morgenstern L. Stroke in His- panic Americans. Neuro!ogic clinics, 2000, 18(2):291-307. 4. Al Rajeh S, Awada A. Stroke in Saudi Arabia. Cerebrovascular diseases, 2002, 13(1):3-8 5. Al Jishi A, Pochiaratu K, Malian J. Profile of stroke in Bahrain. Saudi medical jour- nal, 1999, 20:958~62. 6. 1:::1 Lunrn S, Ahmed M, Prakc1sl1 P. SL1vk.e. Incidence and pattern in Benghazi, Libya. Annals of Saudi medicine, 1995, 5:367-9 7. Sokrab TE, Sid-Ahmed FM, Idris MNA. Acute stroke type, risk factors, and early outcome in a developing country: a view from Sudan using a hospital-based sample. Jourm:il of ::;troko ;1nd c0r9bro- vascular diseases, 2002, 11: 63-5. 8. Hamad A et al. Stroke in Qatar: a one- year, hospital-based study. Journal of stroke anU C!;;!r1:1lJ1uva.scular diseases, 2001, i0:236-41. 9. World Health Organization (WHO) Task Force. Recommendations on stroke pre- vention, dIagnos1s and merapy. Aepurt of the WHO task force on stroke and other cerebrovascular disorders. Stroke, 1989, 20:1407-31. 10. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the National High Blood Pressure Education Pro- gram Coordim'lting Committoc. Archives of internal medicine, 1 997, 57 :2413. 11. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adull Trec1l!mm\ Pclrrel 11\). E,;- ecutive summary of the third report of the national cholesterol education program (NCEP). Journal of the American Medi- cal Association. ?001. 285( 19):2486- 97 12. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabe- tes Mellltu~. Diabetes care, 1000, 22(suppt. 1):S5-19. 13. The Publications Committee for the trial of ORG 10172 in acute stroke treatment: TOAST investigators. Low muleo.;ular weight heparinoid ORG 10172 (Dana· paroid) and outcome after acute is- chemic stroke. Journal of the American Medical /1ocociation, 1998, ::,7Q· 1 ?AR- 72. 14. Qari F. Profile of stroke in a teaching uni· versity hospital in the Western region Neuw:oviem::es, 2002, 6( 1) :38 41 . 15. Wolf PA et al. Probability of stroke: a risk profile from the Framingham study. Stroke, 1991, 22:312-8 16. Gan R et al. Testing the validity of the la- cunar hypothesis: The Northern Manhat- tan Stroke Study experience. Neurology, 1997, 48(1):1204-11. 17. Conti A et al. Aetiologic diagnosis of ischaemic stroke in the emergency de- partment: relevance for triage and clini- cal management. European journal of emergency medicine, 2000, 7(1):9-14. 18. Niwa J, Kubota T, Chiba M. Acute surgi- cal and endovascular therapy for stroke: especially patients with brain infarction No shinkei geka, 2000, 28(6):499-504 [in Japanese]. 19. Becker E et at. Cardiogenic embolism as the main c.:::111!.P. of ischemic stroke in a city hospital: an interdisciplinary study. Vasa, Zeitschrift fur Getasskrankhe1ten, 2001, 30(1):43-52. 20. Amo.rcnoo P ct :::ti. Athgrosclerotic. rli!.- ease of the aortic arch and the risk of is- chemic stroke. New England Journal of medicine, 1994, 331:1474-9. 2 I. Sc1c:o.;u SE et al. Cpidemiological charac- teristics of lacunar infarcts in a popula- tion. Stroke, 1991, 22:1236-41. 148 Ld Rwue de Same ae la Mediterranee orientale. Vol. 1 O, N° 1/2, 2004 22. Arboix A, Morcillo C, Garcia-Eroles L 27. Kaul S et al. Frequency, clinical features Different vascular risk factor profiles in and risk factors of lacunar infarction ischemic stroke s,ihtyr"'". a ~tudy from (doto from a 3lroke regi:otry i11 Suutt1 In- the Sagrat Cor Hospital of Barcelona dia). Neurology India, 2000. 48(2):116-- stroke registry. Acta neurologies scandi- 9. navica, 2000, 102(4):264-70. 28. Dulli D et a!. Ditterentiation of acute corti- 2::l. Tomita F, l<ohya T, Kitabutokc A. Anti- ,:;al cu1u :su/J(.;urtlcal lschemic strol<e by thrombotic therapy for stroke prevention risk factors and clinical examination find- in patients with atrial fibrillation Nippon ings. Neuroepidemiology, 1998, 17(2): rinsho, 2000, 58( 6): 1 326-34 [in Japa- 80-9. nese]. 29, lbranim SA, Kwoh CK. Underutilization 24. Go AS et al. Prevalence of diagnosed of oral anticoagulant therapy for stroke atrial fibrillation in adults: national impli- prevention in elderly patients with heart cations for rhythm management and failure. American heart journal, 2000, stroke prevention: the AnTicnR011l,;ition 140(2):219 20. and Risk Factors in Atrial Fibrillation 30. Deplanque D et al. Stroke and atrial Ii-{ATRIA) Study. Journal of the American Medical Association, 2001, 285(18): brillation: is stroke prevention treatment 2370-5. appropriate beforehand? SAFE I study investigc1torc,,. H'='afl, 1999, 82(5):563-!c!. 25. Lamassa M et al. Characteristics, out- 31. Vilalta JL. Arboix A. The Barcelona come and care o1 stroke associated with atrial fibrillation (the European Cornmu- stroke registry. European neurology, nity Stroke Project). Stroke, 2001, 32(2): 1999, 41 (3): 135-42 392-8. 32. lkebe T et al. Long-term prognosis after 26. Kazui S el al. Risk factors for lacunar stroke: a community-based study in Ja- stroke: a case-control transesophageal pan. Journal of epidemiology, 2001, echographic studv. Neurolo{Jy, 2000. 11 (1 ):8-15. 54(6): 1385-7. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 Prevalence of atrial fibrillation in a primary health care centre in Fars province, Islamic Republic of Iran F. Habibzadeh, 1 M. Yadollahie, 1 M. Roshanipoor and A. Boroomand Haghighi' 147 iJl.t-! .j ,.r)lj ;i,,J:,\L, J ~J~I ~I 4.t~ )1 _?I~ J ~j'il u\k }I Jl..!.:il J..w ~ .,,;t..,n; \..,;,J ~,_;~'..,';._;;~,~I J,. :..i~ ,o.:ilj ~ JJ;l.t · , , • I , , _ • a t ~I\ • 1o ,. , • '\ -< · . · t • 1 .,, , I\ , • -·, \ , _ • - 1 · '1 ; ~ · • • I _ ... ,1_ I ..J ....... )~ ~""" J. ..,, J. ~· 4<u,,- ,J J"..,,. ..J -$<:, l ~.....,,. .r ) ....... ,., ......... 4-,, ).).j o- c:-" y __ 7\T ;,.,,..,.,.J! ,1,l,.. JI ,$"..., ).J1)· -..1..i.li. •<i ,i ~ -•. i-- ~ ·,,,.J\j, :r..l -,--ll ....;, ll ,._.~ ._s .,J.. i: .li.i • .:JI -:!I • ... J .., J .., _.. .., .,....,. ~ t,,,.,T:--- -- • - .. _;-----" .J · E- ,;__- .. ,,,r I .,..,, .\.i.,,:.;;,...L, ,:,,/-11 .jlv,.)1 ~ 2001 /'U-' . ..,. ..,.:5"i,l,].'j1 -~_:;.:;• -·~j/.)l-...i .,.. i- 01\ • li..J,~1 r . r..Ji· !al '· ,.,,-- Jo., -~ ...... ~~.., ..,.. .. ..1- .. '--' JIJ4.I '< .. ~ _3..;.... 8.9 ± 64,0 ._,)...ul .j ..:.:S} • .:..J.l J-, }I _,..._..!.1 .:.,\5" ..I.ii .µ ;.:,~'JI ~\..ol,.l,4~1 -.$:, ;$.Jt,,.11 ~I _;..u .)\5' l.ls- 79: ~"- ~ ... ) . ..s-i -,.;._.,. Jlj ..:.,,.-VI j 463 r>.:,U . .:; . .;. l:.! .;_y...iJI ~ ) .. :.;;.\ '-) Y, ..:,,~ .:/' j I • C"" (230 ..J!,! .y tO) .. ~1 ,:_,-"~,;,,LS"'_, ,(t...l.,;- 74 ~..il ~ .. Ji ~I) -.>~;,i )\..i.,,.; (1-2,8) i"'P 13 ;w..:;)'1 J-uu .)I,, "-,,"WI .J\..l.y\ ,J ~?-"j l.!><l' ~W, ..:.,L...1.)..1.i• ~-:J.,;,:,J ,(233 .:_,:,; ,:.r- 3) Ji_.,,. )1 ~I,;.. 59-so __....Ji ,.;;,.,! _,;.., ..J zo.6 .:.,.- tii _,,,..i.. i.:t,u .::1_., _jl ..w , _,....,Ji .:."' ~ -11 r· .,__jt...,;,i .:~ J..1 . .u_ .>1.:i ),! ½--:! L. __, .j!.":.~', ..)la>. }I .J\,t ~U\ .)'..l.!.,.\I .... ~ J pi .:i~::, jl C::' ! . 79-70 _,....JI .;.,If-" .J './.6.4 ~ -~YI i..,Jt.J1 ~I..:,~),;_,..~ .a :Y:,L,.:, ..:.,L:s::.... _:r ABSTRACT This study determined the prevalence of atrial fibrillation at a primary health care centre in Fars province of the Islamic Republic of Iran. All ambulatory people aged.: 50 years visiting the centre between April and October 2001 were screened for atrial fibrillation using a standard 12-lead ECG. The mean± SD age of participants was 64 .0 ± B.!I years. Ut 4c.::J part1c1panrs aged ~0-7& years, l 3 (2.Bo/o} 11o1u alrii:11 fiu1 illtllion (median age 74 years), significantly more women (10/230) than men (3/233). Unlike previous studies ln industrialized countries, the prevalence tripled with each decade of life and increased significantly from 0.6% in the 50-59 years to 6.4% in the 70-79 years age group. With increasing longevity in some developing countrloc, atrial fibrillation and consequgntly 1.troke may become ml\jor hAAlth prohlAms. Prevalence de la flbrlllation aurlculaire dans un centre de soins de sante primalres de la province de Fars (Republlque islamlque d'lran) RESUME Cette etude a perm is de determiner la prevalence de la fibrillation auriculaire dans un centre de soins de sante primaires de la province de Fars (Republique islamique d'lran). Tous 1es patients amtx.natoires ages de 50 ans ou plus qui ont consulfe au centre entre avril el octobre 2001 ont subi un examen a la recherche d'une fibrillation en reansant un ECG standard a 12 derivations. L'age moyen des participants etait de 64,0 :t 8,9 ans. Surles 463 participants ages de 50-79 ans, 13 (2,8 %) avaient une fibrillation auriculaire (Age median 74 ans) ; ii y a.vait un nombre signifioativemont pl.is important de fommes (f0/230) qwa d'hommes (3/233). Contrairement aux etudes precedenles realisees dans les pays industrialises, la preva- lence triplait a chaque decennie de vie et augmen!ait de manlere significative, de 0,6 % dans le groupe d'age des 50-59 ans a 6,4 % dans cetui des 70-79 ans. Compte tenu d8 l'accroissement de la longevite dans certains pays en developoement, la fibrillation auriculaire et done les accidents vasculaires cerebraux peuvent devenir des problemes de sante majeurs. 'Shiraz National Iranian Oil Company Medical Education and Research Centre, Shiraz, Islamic Republic of Iran. R11ceiv11d. 12/12102, accepted; OC/05103 148 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1 /2, 2004 Introduction First described almost 100 years ago, atrial fibrillation is now the most common clini- cally important sustained cardiac arrhyth- mia [1.21. Atria! fibrillation is associated •.vith a substantial morbidity [2.3) and is a major health care burden for many coun- tries. The arrhythmia is the complete ab- sence of coordinated atrial systole. charac- terized on the electrocardiogram (ECG) by the absence of' P' waves before each QRS complex and the presence of rapid, irregu- lar ·F' waves that vary in size. shape and timing. Atrial fibrillation is a potent predis- posing factor for ischaemic stroke, and is associated with a 5-fold increase in risk [ 4.51. Tho~c with rheumatic heart disease and atrial fibrillation have an even higher ( 17-fold) increased risk of stroke [J]. lt may also be an independent risk factor for death. with a relative risk of around l .5 for men and 1.9 for ,.vomen after adjustment for known risk factors (6]. The prevalence of atrial fibrillation re- ported in various studies. mostly conduct- ed in industriahz,ed countrici;, doubles with each decade of lite and ranges from 0.05% among persons aged 25-35 years to 13.7% in those aged 80 years or older [7.8). Nev- ertheless, little information is available about the prevalence of the disorder in de- veloping countries. This study ½'as con- ducted to dctennine the prevalence of atrial fibrillation in people aged 50 years and old- er attending a primary health care centre in fars province in the south of the Islamic Republic of Iran. Methods Two general practitioners who pracrisc in a primary health care centre affiliated to the National Iranian Oil Company (NlOC) health care system were assigned to screen patients fm atrial fibrillation between April and Octnher )0111 Thi~ cPnlre '>Ce._ ahoul 400 patients a day in its 8 general practice clinics. The patients arc employees of NIOC and their family members, They then•fore r:cirirf' in :'!gr: frnm children to old people. Around 70%-80% of the attendees are from urban areas and the remaining pa- tients come from suburban/rural regions. P:irtirip,mt,; were ~Plr:decl from thnse who attended the cenlre for either a medical problem or routine check-up through sim- ple random sampling; each patient attend- ing thP hl':ci\th r:circ cr~ntre was a:-: .. igned to l of8 genera! practice clinics at random. The assignment was done by computer pro- gram, so that each doctor sa1.v almost equal 111 m"lhPr of pritir-nt, in e.ach v.nrk ing day. Regardless of their presenting signs and symptoms, al! ambulatory persons aged ~ 50 yearn who were seen by each of the 2 w·nernl prnrtitinners were included in the study. The patients were infonncd of the study objectives, lhc time needed to com- plete it and the procedure in detail. None of lhPm rPfll:-f'rl to participate. The diagnosis of atrial fibrillation (com- plete absence of coordinated o.trial systo!e, characterized by the absence of 'P' waves bPfr:m• Pach ()RS complex and the pres- ence ofraptd, irregular 'F' wa,,es that vary in size, shape and timing) was made after recording a single standard resting 12-kad swrfo.-P: FCC (Fukiula Cardisuny 501 B-IH. Japan) with a I-minute rhythm strip. For analysis, the participants were cate- gorized into 50-59, 60-69, 70 -79 and~ 80 YPflrs age ernup..;_ Data were ana!ys.cd us- ing SPSS. version 10. Results Between April and October 2001, 480 Cau- casian patients were entered into the study. Eastern Mediterranean Health Journal, Vol. iO, Nos 112. 2004 149 As 1mly 1 7 participants were aged '2'. 80 years, further anflly<.i<. nf prevalence was not performed on this age group. The age distribution of the remaining 463 individu~ als (233 males, 230 females} is shown in Table I. The mP,m + SO nee was 64.0 ± 8.9 years. Overall. 13 patients ·were found to have atrial fibrillation, a prevalence of 2.8% (95% confidence> inlf'nal 1.1%-4.31%). The prevalence increased significantly (X2 for trend 9.608, P < 0.002) from 0.6% (SE = 0.6) in patients aged 50-59 years to IA~/~ (SE - 1.0) and 6.4"/4, (SF= ?.O) in the 70-79 year age group (Figure I). The me- dian age (25th percentile, 75th percentile) for those ,vho had atria! fibrillation was 7/4.0 (6R.5, 76.5) years. Of thr, \ 1 patients with atrial fibrillation, women (n = I 0) were affected significantly more than men (n = 3) (Pearson's f ~3.972, df = L P < 0.05). Discussion The epidemiology oratnal hbrillalion in this health centre in the south of the Islamic Republic of Iran is different from that of industrialized countries. In contrast to pre- vious studies that found lugller rates of atri- al fibrillation among men [l,2,5], we found Table 1 Age and sex distribution of participants and prevalence of atrial fibrillation Ago group No. of p:utir.ipants (years) Male Female Total 50-59 89 74 163 6Q---69 ti.! 83 143 70--79 84 73 157 Total 233 230 463 No.(%) with atrial fibrillation (0.6) 2 (1.4) 10 (6.4) 13 (2.8) the prevalence was higher in women ( 10/ 13) than men (3/13) {P < 0.05). Nowadays, atrial fihrillation is more of- ten treated as a sign of an underlying dis- ease than a disease entity in its own right. The most important underlying cardiac dis- orders consist of heart failure, coronary ar- tery disease, hypertensive cardiovascular disease and valvular heart diseases [9.10]. Mitra\ stcnosis is important in the etiology of atrial fibrillation [Jl]. Mitra! stenos is mostly results from rheumatic fever, a dis- ease that is currently not frequent in indus- trialized countries, owing to better treatment with antibiotics and increased health standards [IO]. In developing coun- tries, however, where rheumatic fever is still a health problem, mitral stcnosis is much more frequent. Since mirtal stcnosis affects females twice as often as males [IO], in developing countries the sex ratio of patient:, with atrial fibrillation would be reversed, and women might be expected to develop atrial fibrillation much more often than men. Like previous studies, mostly conduct- ed in industrialized countries. we observed that the prevalence of atrial fibrillation in- creases with age [5]. The median age of74 years in our patients is in keeping with that reported in other studies [4,51. Go et al. [4] reported a prevalence of 1.8% in patients aged 60-69 years and 4. 9% in 70-79 years, compared with 1.4'\i and 6.5% respective- ly in our study. Comparing our results with these, we found no statistically significant difference between the reported pre·,alenc- cs over the age range 60 to 80 years. How- ever, unlike previous reports that show a 2-fold increase in the prevalence of atrial fibrillation with each decade of life f 2,5], in our population this trend was much steeper and instead increased 3-fold with each de- cade over the age range studied. This ac- c e lcra t ed trend may he due to ethnic 150 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 12 6.4 10 -;;- 8 !:.... Q) ~ 0 "' "iij ,. 2.8 w ii. 4 ~ 0 ~50 50-59 60-69 70-79 Ove1d.ll Age group (years) Figure 1 Prevalence of atrial fibrillatlon by age group (error bars represent 95% confidence Interval) differences and/or to the underlying causes in our population. In industrialized coun. tries, ischaemic heart disease is the most impu1Laul i.;aust: [9]. whereas in developing countries, though it was not studied here, valvular heart disease, particularly mitral stenosis. seems to be the cause of atrial fi. brillation in the rn,tju1 ily ur 1.:ases. This study suffers from some limita~ tions. Estimates of the prevalence of atrial fibrillation vary according to the character- istics of the population stw..lic:Ll 1:1.uu Lhe way atrial fibrillation is ascertained. In the cur- rent study, the diagnosis of atrial fibrillation was made on a single ECG. Hence, we might miss some pcupk with nun- sustained atrial fibrillation. Moreover, given the small sample size used in this study as compared -.,vith those conducted in indus- trialized countries, the statistical pmver of the current research is low. Likewise, the sma!I number of cases with atrial fibrilla- tion diagnosed in this study, particularly when they were categorized into age groups, means that we were only able to derive a rough estimate of the prevalence rates. Nevertheless, the results obtained from this work were statistically significant and the steep trend of increasing preva- lence ot atrial fibrillation at older ages is noteworthy. With improved health stan- dards and increasing longevity in some de- veloping countries [ 12, 13], atrial fibrillation and consequently stroke may become in- creasingly important health problems. References 1. Narayan SM, Cain ME, Smith JM. Atrial fibrillation. Lancet, 1997, 350:943-50. 2. Kannel WB et al. Prevalence, 1nc1dence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. American journal of cardiol- ogy, 1998, 82(8A):2N-9N. 3. Benjamin EJ et al. Impact of atrial fibrilla- tion on the risk of death: the Framingham Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 151 Heart Study. C/fcufation, 1998, 98: 946- S2_ 4. Go AS et al. Prevalence of diagnosed atrial fibrillation in adu!ts: national impli- cations for rhythm management and stroke preve-ntinn· thi,, Anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Journal of the American Medical Association, 2001, 285:2370-5. G. nyder KM, Benjamin EJ. Epidemiology and significance of atrial fibrillation. American journal of cardiology, 1999, 84: 131 R-8R. 6. Falk RH. Atrial fibrillation. New England journal of medicine, 2001, 344:1067- 78. 7. Atrial Fibrillation Investigators. Risk fac- tors tor stroke and efficacy ur anti- thrombotic therapy in atrial fibrillation: analysis of pooled data from five ran- domized trials. Archives of fntemaf medi- cine, 199'1, 154:1449-57 8. Furberg CD et al. Prevalence of atrial fi- brillation in elderly subjects (the Gardie- vascular Health Study)_ American jour- nal of cardiology, 1994, 7 4 :236-41. 9. Evers S et aL Epidemiologie und Ursachen von Vorhoff\immern [The epi- demiology and causes of atrial fibril\a- tionl. Herzschrittmachertherapie und Efektrophysiofogie, 2001 , 12:59-67. 10. Braunwald E. Valvular heart disease. In: Braunwald E et al., eds. Harrison's prin- r:iples of internal medicine, 1 5th ed. New York, McGraw-Hill, 2001:1343-6. 11 . Moreyra AE et al. Factors associated with atrial fibrillation in patients with mitrat stemosis: a cardi:;m r..ithP.IArization study. American heart journal, 1998, 135:138- 45. 12. Tucker Kl, Buranapin S. Nutrition and aging in developing countrios . .Journal of nutrition, 2001, 131 :2417S-23S_ 13. Shrestha LB. Population aging in devel- oping countries. Health affairs (Mi/1- wuuu}, 2000, 19:204-12. 152 La Revue de Sanle de la Mediterranee orientate, Vol 10. N"' 1/2.2004 Frequency of Yersinia species infection in paediatric acute diarrhoea in Tehran M. M So!tan-Dal/af and K. Moezarda/arf <)\_;fl' J J\,@½i ._;..U ~'J.-1 ..;'.,,._.'ft\ _j .;..,~'.r-)1 t_1_/-; ..GJ.WI J'j) -J ~,~.,:,- :__'•i-~ ..__;L__"-~:- ._ . .-<.._...f ..l__J_,• -~~•1,::-11 ...;:....-l_,_~11 -~( ..:.:,.,l~1 ,___.. ~ ~"-~· _ ___j1 ~I ~~ ~" ~--....-"_11 ~ .. -~ "/_1 J .._:.,1~(~1 c_1_,~\ ... ..;_1)11L,.!..1 :_,_I"~ "/5.7 ~; ;. 1~·-s~· ~-~I ~-.__!~1 .....s:_I ~,)1'._,. (/.'.:!~7) ...::...,")'L~ X ~)~!-~·1_. ~u ~1 1, ~~~~ 1, ,_) ... ~L-- ~\ ~<J l _,. .~'}U·---1 ~~ /.2 -..} ..:...-')1~~~.J.L...J1 t 11_~i~_. u)1l~1 ,:_.,,i, ~~~ .,~~i~l,I, ~- 1-r~;~II ~-:~-~- ;,l,.~a'1 i ~_.~._ ,) .():.1_, o:~, ~~~lw__:JI ~,~~ i '~I -~i ~ .._.;_~, ~.:J'1 '/_~ ~~~~~}1 ~ 1;_~~ :::-':-- ~~i ~·i.'} .(_4;_,-.~:_;~~---~,I .__;..11~_;}':_~ ii=- __ ~' ~~~~,I) ~~~~'1 L~ ~-I --~' "-::~ ~l.;. ,..-_.i.- ...;;_;~.,·-~1• tl..-~i~ ...£.:~~11 .~:\ ~ .~l:_~_,--<J.\ .; .. ,i·IJ~ 4__ . .1 .\_ii! ~ ~~ 4-:i~ .. . .)I_+; ABSTRACT This study determined the frequency of Yersm1a enterocolitica infection in 300 children with acute d•,arrr,oea aged 0-12 years who were attending a paediatric hospital in Tetuan. Over the 5-month study (May-September 2002). Yers111ia species and othe1· organisms were cultured and serotyped from stool samples or sw:abs YAr.,im;, !':rr weff' fm1nrl in R r::isAs (? 7%) FntP.mri;ithOQAnir. E.,:;chArichiR cnliwRr; isolated in 5. 7%, of cases, Shigella spp. in 3.0% and Salmonella spp. in 2.0%. None of the Y enterocof1t1ca belonged to the common serotypes of 0:3 and 0:9. Atypical Yersimi~ spp (Y intermed1a and Y trederiks- en111 were i_solated. All Venterocolit!caisola.tes had a similar pattern of antimicrobial resistance. Yersinia spp. infections are not common in the summer months in Tehran. Frequence de !'infection par les especes '1e Yersinla dans la diarrhee aigue de renfant a Teheran RESUME Cette etude a determine la frequence de !'infection a V enterocolit1cachez 300 enfants ages de O a12 ans souffrant de diarrhee aigue qui consullaient dans un h6pital pediatnque de Teheran. Pendant l'etude 4ui a uurti cir1<., 1J 1vi::; (111a1·::;t:,µte,-,-,L,,., 2002). II":; e,;p,>,c"s de )er,;imd et d'autrei, org,mismes ont ete miC"> en culture et serotypes a par1ir d'echanllllons lecaux ou de prelevements effectues a l'a1de d'un ecouvillon. On a trouve Yersirnaspp dans 8 cas (2,7 %). Escherichia coiienteropathogene a ete isole dans 5,7 °odes cas Sh1gellaspp dans 3,0 %,. et Salmonellaspp dans 2.0 ~"- Aucune des Y enteroco/itica spp n'appartenait aux ,;i;rntypAs r:nw;mtr; O J Al 0: ~- Des Bspeces .:ityp1que1=: du genre Yersinia (Y.intermedia et Y. fredenkseniil ont ete isolees. Tousles isolats de Y enteroco/ltic,, avaient un prolil de resistance antimicrobienne similaire. Les infections a Yersinia spp ne sont pas frequentes durant les mois d ete a Teheran. 'Department of Pathobiology, Tehran University of !vied/cal Sciences, School of Priblic Health, Tehran, Islamic Republic of Iran. 2Nat1onal Research Department ol Foodbome Diseases, Research Centre of Gastroenterology and Liver Diseases. Tehran, Islamic Republic of Iran. Received: 16 /2i02: accepted.' 22·04i03 Eastern Mediterranean Hea(1h Journal, Vo(. 10, Nos 112, 2004 153 Introduction Diarrhoeal diseases are a major cause of childhontl morbiditv and mortality \Vorld- wide, espcdat!y in developing countries [1]. T!tc, <1C1An1111 fm <11t 1.:~li1u,w;ll airnuiil 5 mill~on death, arnong infants aged under 5 years around the world r 2]. Yersinia cnterocolitica is a pathogen thi'lt c<1u~,;.,; self-limiting gastroenteritis or enteroco!itis [3.4J. The organism is partic- ularlv common anrnng children. causing outb;eaks in day-care centres and schools. Sympton1G rungc from mild (diurrhoc:a, llh- dominal pain) 10 severe (frvTf. severe ab- dominal pain often mistaken f1.H appen- dicitis). Occasionally f. entero,ofitica gas- trointc,stinnl infl:'ction is followt-d by arthri · tis of the peripheral joints l5, 6]. ln different parts of the \.Vorld, such as smnhcrn and western Europe (Scandinavia., Belgium, Hnlbnti, Fni.111.'<', (Jenu:iny, D1_•nmark, etc), the United Stati:s of America, Canada,Aus- trn!ia, Japan and many other countries, Y enterocoli1ica has been shO\'-ill to b(: a pri- marv human pathogen [4.7-1}]. ,~!though Yersinia species {spp.) have been reported in tropical areas [I Ul, infec- tions arc more prevalent in cold European countries and North America r / /. / .?J. Since the first isolation of r'. enrerocolitica in the Islamic Republic of Iran in 1977 [/ JJ, there have been only a te·w studies on 1he epidemiology of this pathogen in our country and only one study has reported its isolation from drinking-water in Tehran [ J 4, J 5]. Y. enterocolilica has bi.:en isolated from humans 1n many countnes with vary- ing rates [ 6, 16]. Infrequent isolation in some areas !ws led some investigators to cone] ude that routine culturing of stoo 1 specimens for Yersinia spp. 1,; n~t cost- effective [17]. The current study aimed to record the frequency and serntypcs of Yersinia spp. and other enteropathogens in children with acure diarrhoea attending a paediatric hospital in Tehran. We focused our study on cl11ldren as they arc two to three times more susceptible to infection with Yersinia spp. than adults. Methods Subjects The subjects were 300 children bctw,x·n t lw ages- of 0 and l 2 years who were su f- fcri ng from acute diarrhoea (3 or more loose or "atery stools per day for a period of less than 2 weeks). V,/c included all pa- tients with a diagnosi, of acute diarrhoea visiting the Children's Trc-.1tment Centre at rvtarkaz Tebbi K0odakan during a 5-month period from May to September 2002. Markaz Tebb1 Knodakan is the largest pae- die1tric hospital in Tehran, the capital city of the Islamic Republic of Iran Data collectlon All the patients' demographic and clinical data ,vere collected by the primary care physicians at the centre using a question~ m1ire. StoL•l :.,u11ples wcrt; 1,:0\lt:cted from the children or. when this was not possible, rectal s1vabs were taken, For the detection of Yasinia spp., the samples ,vcre trans- ported to the laboratory in phosph<1tc- buffered saline transport medium (pH 7,0), according to World Health Organization recommendations lf 8] (0.5-1 g stool in 5 mL of buffer). To i:m!atc Esche:r,chi,;, coli, Salmonella spp. and Shigella spp .. an ad- ditional swab was obtained from the stool sample or directly from the patient and was placed in Cary -Blair transport medium. Laboratory analysis For the detection of Ycrsinia spp. the cold Pnri~hmf'nt method ,vas m:r:d. Samples were incubated at 4 °C frir 4 weeks. At the end of the first, second, third and fourth week of incubation, samples were then cul- 154 La Revue de Sante de la Mediterr.:inee orientale, Vol. 10, N° 1/2, 2004 tured on l'ersinia-sekt.:tive agar (C1N, 1. 164]4.0500, Merck, Darmstadt, Gcnna- ny) with Yersinia-sclective supplement (CJN, L\6466.0001, Merck) and on Mac- Conkey agar (CIN, 1,05465.0500/5000, Mcr.:k, Darmstadt, Germany) and incubat ed at 22 °C for 24 and 48 hours. After 24- hour incubation on Yersinia-selectivc agar, the samples were inspected carefully for suspicious colonies: pinpoint, round pink to red colonies, with a clear colourless sur- rounding halo which was dearly visible af- ter 48 hours. After 24 hours on Mac Conkey agar, tiny, round :\nd colull-rles:s (lactose-negative) colonies were consid- ered suspicious for Y enterocolitica. Be- cause of the lack of necessary anti-sera at thP t1hor!ltnry, the i,;ol:ltes were sent to the Pasteur Institute of Paris for scrotyping. To identify other organism&, the sam- ples were transferred immediately to cul- ture media. E. coli were cultured on Fndo agar metEum (ClN, 1.04044.0500/5000, Merck, Darmstadt, Germany) and suspi- cious colonies (red, sometimes metallic colonies) were transfetTed to differential media (Kliglcr iron agar.. SIM medium, urea agar and Simmons citrate agar) and ini.:u- batcd for 18-24 hours at 37 °C. Identifica- tion of enteropathogcnic £. coli was done by slide agglutination with commercial polyvalent antiscra (BioMericux, Lyon, France). For isolation of Salmonella spp. and Shigella spp. samples were transferred to Salmonella Shigclla (SS) agar (CIN, l.07667 .0500, Merck, Darmstadt, Gcnua- ny ). Selenite-F broth (CIN, BO0354, Ox- oid, UK) was used to augment che isolation of Salmonella spp. Suspicious colonies for Shigella sp. (colourless colonies) and for Salmonella spp. (colourless sometimes with a black precipitate) were transferred to differential media and incubated as be- fore. Salmonella and Shigella spp, were identified through standard techniques I 19] and were seroptyped u~ing commercially available antisera (Difeo, Detroit, Michi- gnn, USA). Stool were examined for ova. and parasites using the formalin ethyl ace- tate concentration method. The in vitro susceptibilities to a range of antibiotics were determined for all isolates by the disk diffusion method [20]. The an- tibiotics tested were: tetracycline, chlo- ramphcnicol, gentamicin, kanamycin, stre- ptomycin, amikacin, colistin, polymyxin R, co-trimoxazole, nitrofurantoin, nalidixic acid, lincomycin, penicillin G, arnpi- cillin, cephalothin and rifampicin. Results A total of 300 children were studied: 122 fcmnk,i (40.7'%), l 78 tnolct. (SIJ.3,%). The mean age ± standard deviation was 3.34 + 3.21 years. Table l shows the age and sex distribution of the children. Most of the pa- tiunts were younger than I year old, fol- lowed by those aged l-3 years. Enteropathogenic E, coli was the most common pathogen isolated (I 7 out of 300 c:1se~, 5 7%). Shig,;,!/n spp. were i,olated from 9 cases (3.0°-"~), Yersinia spp, from 8 (2.71~{,) and Salmonella spp. from 6 (2.0%) (Table 2). More than one pathogen was iso- htteil from ?. children, who were positive T~bfa 1 Ag• and so~ di~tTib\ltlon of ~00 children with acute diarrhoea Age Male Female Total (years) No. No. No. % <1 63 47 110 367 1--3 46 33 79 26.3 1\-6 31 22 53 17.7 7-9 28 14 4.:'. 14.'J 10-12 10 6 16 5.3 Total 178 122 300 100.0 ·--~--.- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 155 for both enteropathogenic E. coli and Shi- gel la spp. . The most common scrotypcs of the ISO- lated E.coli were O26:B6 (8 cases, 47.1%) and O119:B 14 (3 cases, 17. 7%). Among the Shigella spp., Sh. Jlexneri type 2 (4 cases, 44.4%) and Sh. sonnei (2 cases, 22.2%) were most common. In cases of Salmonella spp., the tvm scrotypcs isolat- ed were S. (vphimurium (5 cases, 83.3~~) and S. havana ( I case, I 6. 7%). Among the 8 Yersinia spp. isolates, 5 cases (62.5%) were Y. enterocolitica. The results of the serotyping for isolated Y. en- terocoliticu showed that none of them be- longed to the common serotypes of 0:3 and 0:9, and they were all environmental serotypes. Furthennore, the atypical Yers- inia species Y intermedia or Y frederikse- nii were isolated from the other 3 cases (Table 3). AH of our Y enterocolitica isolates had a similar pattern of antimicrobial resistance (Table 4). The E. coli were all were sensi- tive to nalidixic acid and colistin, while the pattern ofresistancc for the rest of the anti- biotics differed tor each strain. Among the Salmonella and Shigella spp., al\ were sen- sitive to nalidixic acid, colistin and amika- cin and were resistant to the other ant1b1otics. Among the cases with }'. enteroco!ilicu, 60% (3 out of S) lived in rural areas in Tc- Table 2 Distribution of isolated pathogens by sex from 300 children with acute diarrhoea Specloc Mt<ile FAmale Total No. No. No. % Enteropathogenic £coli 10 7 17 5.7 Shigella spp. 5 4 9 3.0 Yersinia spp, 5 3 8 2.7 Salmonetlaspp. 3 3 6 2.0 ·--·-- Table 3 Biotypes and serotypes of Yersinia !<:pec:les isolated from 8 cases of acute diarrhoea Case Species Biotype Serotypes no. 1 Y. enterocolitica 0:7, 0:8, 0:19 2 Y. enterocolitica 0:7, 0:8, 0:19 3 Y. enteroco/itica 18 Autoagglutinable 4 Y. l:!t, t "'' vcaliffGc1 Non outougglutinabla 5 Y. enteroco/ltica No n-autoagglutinable 6 Y. frederiksenii 0:39 7 Y. intermedia 2 0:17 8 Y. intermedia 0:17 ·- -- - ----- bran province where the drinkin~-~at~r supply is from wells; the rest were ltvmg m urban areas. Diarrhoea and abdominal pain and fever (38-39 °C) were the most com- mon cl ini~al manifestations of infection with Yersinia sp. and were observed in all cases. Vomiting, headache and anorexia were seen less frequently. Diarrhoea was sometimes accompanied by mucous but no blood was fowid in stools. All of the 17 patients with enteropatho- genic £. coli had a negative direct smear for parasites, except I patient who was positive for Hymenolepis nana and had a past medical history of long-tenn w~ak- ness, malaise and chronic diarrhoea. Etght (47.1%) of the enteropathogemc L. coll cases were less than l year old. Discussion The main objective of our study was to iso- late Yer:Yinia spp. to find out whether this organism and its common serotypcs exist in the Islamic Republic of Iran or not. We were able to isolate Yersinia spp. from 8 of our patients in whom the other enteric bac- La Revue de Sante de la Mediterranee orientale, Vol. 1 O, N" 1/2, 2004 Table 4 Antimicrobial susceptlbllify of Yersinia species isolated from 8 cases of acute diarrhoe~ Antibiotic Sensitive Resistant No. % No. % Tt:t1c1t:yt:line 8 1UU 0 0 Chloramphenicol 8 100 0 0 Gentamicin 8 100 0 0 Kanamycin 8 100 0 0 Streptomycin 8 100 0 0 Amikacin 8 100 0 0 Colistin 8 100 0 0 PoIymyx1n ti 8 100 0 0 Co-trimoxazole" 8 100 0 0 N 1trotu rantoi n 8 100 0 0 Nalidixic acrd 8 100 0 0 Lincomycin 0 0 8 100 PenicillinG 0 0 8 100 Ampicillin 0 0 8 100 Gephalothin 0 0 8 100 Rifampicin 0 0 8 100 •Sulfametl?oxazole/trimethoprim. terial pathogens mentioned were excluded. Our findings clearly show that Y. entero- culiticu is presem as a pathogen of diar- rhoea in this country and can be isolated from the stool samples of children suffer- in,, from acute diarrhoea. \Ve found a frc- qu:,ncy of 2. 7% frn this organism, which is near the frequency of about 1 % reported by other studi cs in this country [14] but is lower than some parts of the world espe- cially northern European o..:urnitries with a frequency up to 13% [7.11]. This might be partly due to the warmer climate in ~ur country, especially as the study was earned out during summer, and pmtly due to uif- fercnt dietary patterns in the Islamic Re- public of Iran where pork is not consumed. We would expect a higher frequency dur- inu autumn and \Vintcr, based on the fact th;t this organism increases greatly in com- parison with other species in cold seasons [ 4, /6]. We used CTN medium and the cold en- richment method, which has been shown by many researchers to be an effective method for the isolation of Yc,rsinia spp. from stool samples [21-23]. The Y entero- rnlitica isolated were considered to be the cause of the presentation of acute diar- rhoea, despite the fact that none of them belonged to the group of serotypes that are domimml iu Europe, Asia, and Canada (U:J and 0:9) {5,6]. According to previous studies, the high- est frequency of Y enterocolitica is in cool-weather ruin! <11 cas, based on the presence of the most important sources of contamination: pigs, cows, rabbits, and dogs and the surfaces and drinking-water soun.:cs contuminutcd with thci1 foc:1.:es (24-27]. Our findings arc in harmony with the previous studies since 3 out of 5 of our Y. enteroco!itica cases lived in rural areas with a cooler c!imute and probably ue,ul contaminated drinking-water. This might also be the reason why all the isolated spe- cies belonged to the groups \\'hose patho- £'!'nirity ha!. been reported [25.28 30]. The main risk factors for the morbidity and mortality of diarrhoea are well known and relate to a poor quality of lifr, lack of sani- tation an<l clr:m umter ~upply for most of the population living in poor areas of devel- oping countries [29,30]. The clinical manifestations of Y entero- co!i tica infection in our chi 1 <lr~n were mi Id, in accordance with studies from northern Europe [5] and in contrast with the study of Naqvi et al. [4]. Six of them had fever but we did not find any patient<;. with bloody stools. The results of the antimicro- bial sensitivity tests t<Jr Yersiniu spp. iso- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 157 \ates showed a :-.imilar pattern to' other stud- ies [ 4, 5]. Overall, enteropathogenic £. coli was the most common isolaicd pathogen in our study (5.7%), and this i-,; consistent with other studies in the Islamic Republic oflran f 14] and in other developmg countries [31], The findings for Salmonella and Shigel!a spp. isolates were also consistent with these studies [ 14 .31], In spite ot the fact that r. enteroco/trica is an important cause of diarrhoea in some European and Scandinavian countries with a colder climate, this study has shown that this organism is rarely isolateli frur11 Muul cultures of children with diarrh(ica seen in a hospital setting in the summer months in lehran. Acknowledgements We wish to thank Professor E, Carnie!, from the Pasteur Institute of Paris, fi:.1r her kind cooperation in biotyping and serotyp- ing of Yersinia species. We also lhank all ?f our colleagues from the School of Publtc Health of Tehran University of Medical Sci- ences and the Research Centre of Ga,;tro- enterology and Liver Diseases. References 1. Ribeiro H Jr, Diarrheal disease m a de- veloping nation. American journal of gastroenterology, 2000, 95(suppl. 1 ): S14-15. :2. George<, MC; ~, Al. PR.rasitic. bacterial and viral enteric pathogens associated with diarrhoea in the Central African Re- public. Journal of clinical microbiology, 1984, 19:571-5, 3. Marks Ml et aL Yersinia enterocolitica gastroenteritis: a prospective study of clinical and epidemiologic features. Joumat of pediatrics, 1980, 96:26-31. 4, Naqvi SH et aL Presentation of Yersmia enterocofitica enteritis in ct1ildren. Pedi- atric infectious disease journal, 1993, 12:386-9, 5. Hoogkamp-Korstanje JA, Stolk-Enge- llaar VM. Yersinia enterocolitica infection in children. Pediatric infectious disease journal. 1995, i 4:771-F; 6. Bottone EJ. Yersinta enterocolitica: over- view and epidemiologic correlates. Mi- crobes and infection, 1999, 1 :323-3. 7. Ostroff SM et al. Clinical features of spo- radic Yersinia enterocolitica infection in Norway. Journal of infectious diseases, 1992, 166:812-7, 8. Monte Boada RJ et al, Yersinia entercolitica: investigac1on en 7 300 ninos menores de 5 anos con enfermedad diarreica aguda. [Yersinia entero-cofitica; investigation in 1300 children under 5 ycar::i of ago with acl1te diarrhea,] Revista cubana de medicina tropical, 1990, 42:13-18. 9. Ehara A et al. Age-dependent expres- sion or abdomi!1ctl ~yHi!JlOmc-. i11 patienb with Yersinia enteroco!itica infection. Pe- diatrics international, 2000, 42:364-6. 10. Samadi AR et al. An attempt to detect Yersinia enterocom,ca In1ec11on i11 Dacca, Bangladesh. Tropical and geo- graphical medicine. 1982, 34(2): 151-4. 11, Work, ng group on Yersinios1s. Yersi- niosis: report on a WHO meeting, Paris, 1-3 June 1981. EURO reports and stud- ies no. 60. Copenhagen, World Health Organization Regional Office for Eu- 1uptt, 1983, 12, Ostroff S. Yersinia as an emerging infec- tion: ep1demiologic aspects of yersinio- sis. 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Manuel pour r elude au faboratoire des infections intestinales aigues. Geneva, World Health Orqanization. 1987. 19. Bopp CA et al. Escherichia, Shigella, and Salmonella. In: Murray PR et al., eds. Manual of clinical microbiology, 7th ed. Washington, nr:. American Soci11ty of Microbiology, 1999:459-74. 20. Jorgensen JH, Turnidge JD, Washington JA. Antibacterial susceptibility tests: dilu- tion and disk diftuoion methods. In: Murray PR et al., eds. Manual of clinical microbiology, 7th ed. Washington, DC, American Society of Microbiology, 1999: 1526-43. 21. Mollaret HH. Fifteen centuries of Yersiniosis. Contributions to microbiol- ogy and immunology, 1995. 13:1-4. 22. s(;t1iemann DA. synthesis ot a selective agar medium for Yersinia enterocolitica. Canadian journal of microbiology, 1979, 25: 1298-304. 23. Pai C et al. Efficacy of cold enrichment techniques for recovery of Yersinia enterocolitica from human stools. Jour- nal of clinical microbiology, 1979, 9: 712-5. 24. Zheng XB, Xie C. Note: Isolation, charac- terization. and epidemiology of Yersinia enterocolitica from humans and animals. Journal ot applied bacteriology, 1 996, 81 :681-4. 25. Soltan-Dallal MM, Harteman P. A study of atypical Yersinia spp. isolated from Moselle river. Iranian Journal of public health, 1988, 17:69. 26. Thibodeau Vet al. Presence of Yersinia enterocolitica in tissues of orally inocu. lated pigs and the tonsils and faeces of pigs at slaughter. Canadian journal of vetennary research, 1999, 63:96-100. 27. Fukushima H et al lntrorl, 1ction into Ja- pan of pathogenic Yersinia through im- ported pork, beef, and fowl. International journal of food microbiology, 1997, 35: 205-12. 28. Agbonlahor DE. Characteristics of Yersinia intermedia·like bacteria iso- lated from patients with diarrhoea in Ni- geria. Journal of clinical microbioloov. 1986, 23:891-7. 29 Gonul SA, Karapinar M, The microbio- logical quality of drinking water supplies of Izmir city: the incidence of YP-r.<:ini,1 enterocolitica. International journal of food microbiology, 1991, 13:69-74. 30. Toma S et al. Survey on the incidence of Yersini;:i P.nfpmr,n/itica infection in Cana- da. Applied microbiology, 1974, 28:469- 75. 31. Todd EC. Epidemiology of foodborne diseases: n worldwide review. World health statistics quarterly, 1997, 50:30- 50. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 Quinine therapy in severe Plasmodium falciparum malaria during pregnancy in Sudan 159 r Adam, 1 O.A. Mirghani,2 O.K. Saed,2 S. M. Ahmed,2 A.A. Mohamadam/' H.M. Ahmea/ G.D. Mackenzie, 3 M.M.A. Homeida" and Ml. Elbashir6 ,:.i1~ _,...Ji ..J J--.>-' ~wi ~1-.? ~1 .,;;.,1.)~1 ,:,,,s, ~1. .• 11 4J"}.l1 ak-w . . . ;,~I ~i_..... •..$l_L~~ .~_.;,,...l ~ L .>,..( l.:,•-~ ...1.-~ . 1L......,:c <.,;¥',.-,.,. .--"" ,~..,1 __ ..,..__..] ~,1~_.~;....l;-..-- > _j p _;_,b _,.....)I .h.., J _j ¼)".'>'-.!.! 0 fa-,, ,..), -.,,1_,,,.... .:,,-"' dW ,w,_:,, -J ~L,:,,-1 .....,1_.~ ~.r"i ;L.,,~I .;;', ,-...,.:11 , ,.- ~U ~ ~ l,,.J":i~ 4-;L..a,.. ;\..., __ 33 J.--':-<J~ ~-.... ..w .j-J--1 ~Gi ,.:.,,.:,$J, 9 - _, a...-'i.,'.; i.JI >-- ._,_)_, l. - , -:Jl:,, ,~1..,\ ;;,_,,__.. LL-1...11 .;c, r~I, , lsc .....,i 288 ._.,__,_\_] 1----LI ---<- _k.... • _;\S' • U....J.1 .I ~ .,.- ....- ', ~ , .,. ...,... _,,, ,__rv~ ,.__. .r- i..;,· ...,,. ~ ~ ;..,,_,,-,- ._,_j,;) .:/' (0.7 1: 392) 1.-;_,.,.,..,.,. ~ ~1 :.J',:'-11 J-,> .:iJJ: .;,,~ '-'L-1y- 3 J.JJ r,:J..<.\I ~Gi 01 ~ ~ -.J?' r-41 ..:.'o' .Jj, !JL,,, ,:?'I. t 1 .(13 ± 38.7) ...,L....cl-1 i'.J .J .:.i.J_, .,;1,..U', J,,1_,.J-1 J...l! ,.......J--1 :;!_., ,! ._J_,.~~ ~J 'td.Q~:..S ... -.-S::..C.~ -=...-Ub~ j~ .__~ -~!- .L...:>_~\it ~I_-, 9:--5-\~t ~i ½F_r-J1 ~~-bl ~~·' :.:,_,;..... ..w ,lh ~-\ _,...._,..,..,,J ~ ):;+-!- 6 .JJ./' ~ )_;' ~,'i_;' ..c...i: .;;1..u_,.1, .J ~ _;'; ;._,,....~ _;'1 ._l-J.--1 ~GI ~·1 ..;...,\_},,~\ .. :_:,_.;, ~~l.J·1 ~-~\ l":'l_)j\J.l :d-:-W Lyl- ;1.,~ ABSTRACT A prospective study was carried out in an area of unstable malaria transmission in central Sudan to determine the efficacy and toxicity of quinine in pregnancy. Thirty-three pregnant women with severe Pfasmodium fafciparum malaria at mean 28.8 weeks gestational age were treated with quinine for 7 days. The mean body temperature on presentation for 3 patients who delivered prematurely was significantly higher than for those who delivered at term (39.2 ± 0,7 "C versus 38.7 ± 1.3 °C). There were no significant differences between the 2 group:, in other clinical or biochem;cal param,;,l<>rs. Th,m;i w<>rA nn r.linir.,illy detectable congenital malformations and no auditory, visual or other neurological deficits in the babies at birth or 6 months later. Quinine may be safe in the treatment of severe falciparum malaria during pregnancy. Traltement par quinine du paludisme severe a Plasmodium falciparum pendant la grossesse au Soudan RESUME Une elude prospective a eta realisee dans une zone de transmission instable du paludisme au centre du Soudan afin de determiner l'efficacite et la toxicite de la quinine pendant la grossesse. Trente-trois femmes enceintes atteintes de paludisme severe a Plasmodium falciparum a. un age gestationnel moyen de 28,8 comaines ont ata lraite .. s par quinine pendant 7 jour<: I "'tf'!m['lAmt11rf! corporelle moyenne au moment de la presentation pour trois patientes ayant eu un accouchement premature etait significativement plus elevee que pour celles ayant accouche a terme (39 ,2 ± o, 7 °C versus 38, 7 ± 1 ,3 °C), II n'y avail aucune difference significative entre les deux groupes pour les autres parametres cliniques ou biochimiques. II n'y avait pas de malformations congenital es clirnquement delectables ni de deficits auditils, visuals ou autres deficiences neumlogiques chez les oeoes a 1a naissance ou six mols aprei;. Li14ui1 ii, 1t:1 µt:ul 81, e utili:;ee en toute sllcu rite pour le traitement du paludisme severe a Plasmodium fs.lciparum pendant la grossesse. 'New Haifa Hospital, New Haifa, Sudan. 2Facultv of Medicine, University of Gezira, Wad Medani, Sudan. 3Michigan State University, East Lansing, Michigan, United States of America. 4Academy of Medical Science and Technology, Khartoum, Sudan. 'Faculty of Medicine, University of Khartoum, Khartoum, Sudan. Received: 13/04/03; accepted: 20/07/03 160 La Hevue ae ::;ante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Introduction in Africa, each year somo 2-1 million ,vom- en become pregnant in malaria endemic ar- eas. Pregnancy increases susceptibility to malaria and pregnant women are more like- ly to develop clinical attacks ofmuluriu und serious complications than non-pregnant women of the same age. The increased susceptibility ufpregnant women to malar- ia i,; thought to be in part the n.,e;ult vf n certain degree of immune suppression dur- ing pregnancy required for fetal allograft retention(/]. 1\falaria in pregnant women is associated with seriouf; adverse effcct3 on pregnancy causing abortion, preterm la- bour, low birth weight, intrauterine fetal 1.kath and maternal death [2-4]. The epidcmiologic:ul profile imd clinical pattern of malaria vary according to the en- demicity of the disease. In areas where ma- laria transmission is seasonal and unstable, both the mother and her fotuG t;uffer from severe complications of the disease [5]. High-grade resistance of the malaria parasite to chloroquine has been reported in eastern and central Sudan l 6, 7J. Thi» ho,; led tn the use of alternative drugs, such as quinine. There an:: few dctaik<l reports on the effect of quinine in pregnant women and its dl(?ct on the outcome of pregnuncy. and doubts remain about its safety in preg- nancy. Through its oxytocic effect, quinine is capable of inducing abortion and labour [RJ. Moreover_ it can cause maternal hv poglycaemia through the release of insulin f Yl. However, quinine is still the drug <if choice for treatment of severe folciparum in:ilaria in Sudan. The objectiveea pf thi,a work were to study the clinical efficacy and toxicity of quinine on mothers with se- vere falciparum malaria and their babies and to demoirntratc tho manifestations of severe falciparum malaria during pregn::rn- cy in the study group Methods Study :irea and patient$ This study was carried out at \Vad rvtedani teaching hospital. Gczira state. central Sudan, an area of seasonal unstable malaria !rnn<:mi,;:,;:inn [ 6]. It is the main ho~pital where all serii)usly i II patients are referred from health centres and other single-doctor hospitals in the area. 4. 11 p;iti en ts incl udcJ in the i; tudy \Vere selected from around 850 pregnant women seen and admitted to the hospital during the period September 1997 to January 1998 (thr mJ:lin malaria transmission season). Pregnant women were included in the study if they had a positive blood film for Plusmodium Jt!cij>urum and l or more of the fn 1!.-nMing criteria for severe malariu [JO]: C<.'rcbral malaria (unarou~abk coma fix> 30 min), repeated gcnerah1.ed convul- sions, hyperpyrexi:1 (rectal temperature > 40 °rL SC\!Prf'. :in;iemia (haematocrit <C 15% or haemoglobin < 50g/L). hypotcn- sion or shock ( systolic blood pressure< 70 nunHg). jaundice (high serum bilirubin), ("lulmnm1ry nedPm>1. hypoglycaemia (blood glucose< 2.2 mmol/L), renal failure(< 400 ml urinc/24h despite rehydration, and sc- rum ncatininc > 265 ~tmol/L), spontaneous hlccdinp nr eviclPncc of di,-sc-minatt:?<l intra- vascular coagulation and hyperparasitaemia (> 250 000 ringsiµL). Patients in lahour, and those with twin pregnancy, intrauterine fetal death or v:1r;in:11 h]N,,.Jing w,:.-rc- ex dud- ed from the study. The patients or their relativ("s gave oral consent for admission to the study after full explanation nf 1hi: p1irpn~,, of the study and its expected risks. Data collection A full medical and oh,;li·Jri~ hi,:tory and physical examination were performed on Eastern Mediterranean Health Journal, Vol. 1 O, Nos 1/2, 2004 161 the participants and recorded using a case report form. Parasitological diagnosis of malaria was confirmed by thick and thin blood films us- ing Giemsa stain. The parasite was counted against 200 white blood cells and the extent of parasitacmia was calculated using the patients' white blood cells. The following investigations were per- formed for all patients included in the study. Urine analysis was carried out (in- cluding presence of haemoglobin). Blood was analysed for haemoglobin level, white blood cell count and reticulocytc count. Serum levels of hilirubin, albumin, urea, creatinine, calcium alkaline phosphatase, alanine aminotransferase (ALT) and aspar- tate aminotransferase (AST) were also de- termined. Blo,1d glucose level \vas determined on presentation and repeated if hypoglycaemia was suspected clinically. Ultrasound examination to confirm the gestational age and viability of the fetus was performed on admission and every 4- 6 weeks. Chest X-ray was performed us- ing necessary protective precautions if pulmonary oedema was suspected and the pregnancy was more than 28 weeks. Treatment and follow-up The women were treated with qummc (Laboratoires Renaudin, France) at a dose of 30 mg salt/kg per day for 7 days. It was given first by intravenous infusion in 5% dextrose solution over 2--4 hours J tunes a day, and when the patient could tolerate it therapy was continued orally in the form of tablets. Paracetamol was used to lower the fever. When haemoglobin was less than 1D g/L, packed red cells were infused as nec- essary. The patients ,vere discharged after completing the full dose of quinine on day 8. They ,verc seen at the antenatal clinic every 2 weeks until delivery. The obstetrician supervised all hospital deliveries and kept close links with those who decided to deliver at home. Ddivc:1y followed thc standard management proce- dure adopted in Wad Medani teaching hos- pital. A paediatrician examined and followed up all the babies to exclude congt:nilal 111al- formations. Weight and head circumfer- ence were recorded for babies delivered in hospital or at home. All the babies, whether hospital or home delivered, were fullowi.:Ll up until 6 months of age by the same paedi- atrician to make an initial assessment of hearing (ability to respond to a rattle in a calm quite room) and vision (ability tu 1i.:- spond to a coloured object moving in front of the child). If defects were suspected, more specialized tests would be perfonned, e.g. bram stem test and fundoscopy. Definitions Abortion was defined as expulsion of a dead fetus before 28 wt:t:k.s uf gc:-.tdtion. Premature labour was delivery after 28 ,veeks of gestation and before the 37 weeks. Perinatal death was death of the baby trom 28 weeks tn utem uutil the a.gc of l week. Anaemia was defined as haemo- globin < I 00 g/L. Stathstics Data was entered into the computer using SPSS, version 10.0 batching for data analy- sis. Simple frequency distributions, de- scnpnve sutl1:,t1t,::,. mean, standard deviation (SD), t-test and chi-squared tests were used, with a probability level of < 0.05 for statistical tests. Ethics Ethical clearance for the study was ob- tained from the ethical committee of the Fa1:uhy uf Medicine University of Khar 102 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 toum and national ethical committee at the Sudanese Federal Ministry of Health. Results Clinical presentation on admission Thirty-five pregnant women with severe P. falciparum infection were initially admitted to the study; 33 patients completed the study and 2 patients decided to discontinue after the first dose of quinine (initial data collected from these patients is reported here), The mean ± SD parity was 1.8 ± 2.2. Of the 35 patients, l l were primigravidae, 9 were in the second pregnancy and l 5 were in the third pregnancy or mnrc ( 1 pa- tient was a grand multipara in her ninth pregnancy). On presentation, the mean gestational age was 28.8 + 8.7 weeks, One patient had received quinine during the first 8 weeks of pregnancy. The main presenting symptoms among the initial sample were: fever (77. I%), vomiting (68.6%). headache (57. l %), cough (22.9%) and diarrhoea (14.3%). Ta- ble I summarizes the clinical and laboratory findings obtained on admission. The mean values for all biochemical parameters mea- sured were within normal ranges, except for bilirubin which was s1ightly raised. The major manifestations of severe ma- laria among the 35 patients who started qui- nine therapy were: cerebral malaria (unarousable coma) (2 patients), severe anaemia (4), jaundice ( 11), hyperpyrcxia (17), haemoglobinuria (11). hypotension (2), hypoglycaemia ( 1 ), and pulmonary oedema (l). Some patients presented with more than 1 symptom and l patient devel- oped hypoglycaemia on day 7 of quinine treatment. However, no patient presented with renal failure or spontaneous bleeding from the gums or nose, and none were de- Table 1 Major clinical and laboratory findings on admission in 35 pregnant women with severe malaria Parameter Mean SD Age (years) 26.3 4.7 Gravidity (No.) 3.2 2.5 Parity (No.) 1.8 2.2 Weight(kg) 60.5 10.9 Gee.tatio11t1.I i:IYt! (we!;lkS) 28.8 tl.7 Systolic blood pressure {mmHg) 102.3 11.5 Temperature (°C) 38.8 1.3 Parasite count (rings/µL) 18735 21819 Haemoglobin (g/L) 89 25 White blood cells (cells/mm3) dA.{)(I <;JOO Blood urea (mmol/L) 23.7 5.5 Blood glucose {mmol/L) 5.70 2.50 Creatinine (mg/dL) 083 0.11 Bilirubin (mg/dl) 1.90 1.40 Albumin (g/L) 31.4 5.2 Calcium (mg/dl) 10.2 0.4 ALT (IU/L)" 5.14 9.70 AST (IU/L)" 3.17 6.11 Alkaline phosphatase (IU/L) 23.6 12.1 "ALT= alanine aminotransferase: normal values 0-- 45 /Uil. "AST"- aspartate aminotransferase; normal values 0-41 IU/L SD "' standard deviation. fined with hyperparasitaemia (> 250 000 rings/µL). The spleen was palpable in 8 pa- tients on aclmi"<:inn The 2 comatose patients {with cerebral malaria) also had repeated generalized con- vulsions, haemoglobinuria, body tempera- tures of 38.6 °C' ~nd .38.9 °C, parasite counts of 7600 rings/µL and 6250 rings/ µL, haemoglobin concentrations of 98 g/L Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 163 aml 91 g/L, and blood glucose levels of 7.8 mmol/L and 3.9 mmol/L, respectively. The mean± SD haemoglobin of all the patients was 89 ± 25 g/L. However, 4 pa- tients presented with severe anaemia (hae- moglobin< 50 g/L). ln these patients the peripheral blood picture shO\,ved normocyt- ic normochromic red cells, with aniso- poikilocytosis, and the sickling test was negative. Treatment response Twenty-one of the patients included in the study had received chloroquine before ad- mission and had not improved. /\11 patients responded well to quinine with dramatic re- lief of symptoms. The comatose patients recovered consciousness within 24 hours, and the lever subsided within 72 hours. Vomiting was not noticed in any of the pa- tients after 72 hours and treatment was continued with oral quinine. Jaundice dis- appeared within 5 days ln all except 2 pa- tients where it persisted for 7 days. Severe anaemia was corrected by transfusion of packed red ce \ls and the response was ~at- isfacrnry. Quinim: was wdl tukrntcd by the patients with limited side-effects (tinnitus and dizziness in about 54% of patients), which were mild and transient. All J.ntlicub had negative blood films on day 7. However, 2/33 ( 6.1 °;~) patients pre- sented on days 17 and 20 \vith recurrence of malaria symptoms and their blood films were po5itivc. They were admitted and giv- en artemether intramuscularly, 80 mg ini- tially then 80 mg after 12 hours and then daily for 4 days. They were discharged af- ter completing the treatment with foll re- covery and \Vere followed up closely until delivery. Pregnancy outcome Thirty patients delivered at term and 3 pa- tients delivered prematurely (at 32, 33, 34 weeks). One of these 3 patients delivered after the third dose of quinine; the other 2 patients delivered prematurely, but 30 and 50 days after compkting quinine therapy which makes it unlikely to be due to qui- rnne. When we compared the clinical and lab- oratory findings in the 2 groups of patients (term and pre-term deliveries), there was no significant difference bet\veen them re- garding mother's age, parity, gestational age when they received quinine therapy, systolic blood pressure, parasitaemia or biochemical findings (blood glucose level, scrum bilirnbin, blood urea level and hae- moglobin concentration). However, the mean ± SD temperature on presentation for the 3 patients who delivered prematurely was 39.2 ± 0.7 °C, whereas it was 38.7 ± 1.3 °C in those who delivered at term. a di !Terence that was significant (P = 0.05). On the third day, the temperature was nor- mal in both groups (Table 2). Fifteen patients delivered in Wad Med- ani hospital and 18 at home. The mean birth weight of the babies delivered at hospital and at home was 3.0 kg (range 2.2-4.0 kg); the mean head circumference at birth was 35.5 cm. There were no auditory, vi- sual or neurological defects recorded. There were no maternal deaths, abortions, stillbirths or perinatal deaths. Discussion The present study was carried out in an area of unstable malaria transmission. More than 50% of the women were parous and di ffcrent forms of clinical presentation of severe malaria were observed among our study group, including cerebral malaria and hyperpyrexia. This supports the belief that falciparum malaria in areas of low and un- stable transmission is usually symptomatic and affects all parities, whereas in areas of 164 La Aevue de ::.ante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Table 2. Comparison of the major characteristics of severe malaria in women with term and pre-term deliveries Parameter Women with term Women with pre-term P.value• delivery {n = 30) delivery (n = 3) Mean SD Mean SD Age (ycora) 26.8 46 22.~ ti.ti 0.42 Gravldity (No.) 3.2 2.5 3.3 3.2 0.70 Parity (No.) 1.8 2.2 2.3 3.2 0.34 Gestational age at treatment (weeks) 29.3 9.0 29.3 6.0 0.50 Temperature on admission (·C) 38.7 1.3 39.2 0.7 0.05 Temperature on day 3 (~Cl 37.2 0.8 '.'l7:;? 0.9 0.90 Systolic blood pressure (mmHg) 102.3 12.1 103.3 16.7 0.12 Pam.&ilo oount (ring3/µL} 10005 23472 10200 826:J U.02 Haemoglobin (g/L) 87 Random blood glucose {mg/dL) 106.6 Blood urea (mg/dl) 24.1 Serum bilirubin (mg/dl) 1.90 •UsingHest SD~ standard dAViAtinn high endemicity, falciparum malaria is more common 11mong primigravidae and patients are usually asymptomatic or present with severe anaemia [JJ-13], It is of interest to note that, although the patient,;_ presented with severe illneim, the mean parasite count was relatively low at 18 735 rings/µL, and the highest count was 100 380 rings/µL. The explanation of this phP.nnmenon is not dear. It is possible that the threshold for complications is low in this epidemiological setting. Hypoglycae- mia was found in I patient on presentation, and nnly I patient developed hypoglycae- mia after quinine therapy. However, hy- poglycaemia has been reported in around 26 104 12 0.24 44.7 80.6 13.6 0.33 5.3 23.3 5.8 090 1.50 2.50 0.63 0.38 50% of pregnant ,.vomen at one stage or another of .severe fokipmum 1m1laria [9]. In this study, the patients responded readily to quinine and all symptoms cleared rapidly as described m the results. Only 2 patienh (6%) <lcvdopcd :,_ymplurns uf ma- laria with detectable parasitaemia in the third week. \Ve are not sure if this was due to some degree of declining efficacy or even rcsi.'lt<1n\Oc to qui11i11c 01 liue lO re- infection. Quinine resistance or failure has been reported in the ea stem parts of Sudan among non-pregnant patients l 7, 14], and quinine resistance duriug pn:gnam:y of around 30% has been documented in Thai- land [ 15.l 6]. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2. 2004 165 Quinine \Vas well tolerated by the moth- ers and had no adversf' pfff'1't on the chil- dren up to the age of 6 months. There were no maternal deaths, abortilms, stillbirths or perinatal deaths. The mean gestational age of the patients at the time, of e,nrnlment was 28.8 weeks, which might explain why there was no abortion. This was also re- ported in 2 recent studies [I 5,161. In the present reporl, Wf' shnwed that 3 patients (9~-o) had pre-term labour~ I of them delivered during quinine therapy and the other 2 patients delivered prematurely, 30 and SO days after ('nmpldinn of quinine therapy. This makes it difficult to relate premature labour to quinine. However, no pre-term labour was reported by Mc Gready ct al. in lQQR Fiml 2000 [15.16]. This might be explained by the difference in morbidity of the patients included in those studies. In our study, all patients presented to hospital ,.vith m:mi festations nf severe falciparum malaria, whereas in the above- mentioned studies, which were community based, the patients presented with uncom- plicated m:e1 hiriA Only 16%and 18'%ofthe patients presented with fever, whereas the mean temperature of our patients on pre- sentation was 38.8 °C. Furthem10rc, in our study 17 pFitif'nts presented with hyperpyr- exia and the difference in temperature on presentation between patients who deliv- ered prematurely and those who delivered at tenn w;i,;; -:ipnifi1'a11tly higher. High tem- perature was the main reason for uterine contraction [9]. Malaria can cause abortion and pre-term labour as well f 2] and in cen- tral Sudan it was found to be the leading cause of low birth weight by causing pre- term labour [17]. However, the oxytocic effect of quinine on the pregnant uterus cannot be excluded totally, at least in the patient who delivered during quinine treat- ment. Quinine has been used as an abortifa- cient and labour inducing agent [8]. In this study, the paediatrician did not note any hearing or visual defects, and no congenital or developmental abnormalities in the babies. This agrees with other recent studies fl 5, 16]. However, deafness and hypoplasia of the optic nerve have been de- scribed in children born after unsuccessful attempts to induce abortion in women tak~ ing quinine overdoses [18]. Tn humans, or- ganogencsis is in the first 12 weeks of intrauterine life, and during this time only 1 patient in this study received quinine. Very few studies have been made on the safety of quinine during early pregnancy. We think it is necessary to carry out such studies in view of the emerging multidrug-rcsistant strains of P. falciparum and the limited choice of alternative safe and effective drugs for malaria treatment. Acknowledgements We wish to thank all the patients and their families for excellent cooperation and the nursing and technical staff at Wad Medani Lt:rtdiing hospital. This study wos partially supported by funds from WHO Regional Office for the Eastern Medeterranean. Reterences 1. Fievet Net al. Immune response to Plas- modium falciparum antigens in Came- rnoni.<in primigravidae: evolution after delivery and during second pregnancy, Clinical and experimental immunology, 1997, 107:462-7. 2. Menon R. Pregnancy and malaria. Medi- cal journal of Malaysia, 1972, 27:115-9. 3. McGregor IA. Epidemiology, malaria and pregnancy. American journal of tropical 16!1 La Revue de Santa de la Mediterranee orientale, Vol. iO, N° 1/2, 2004 medicine and hygiene, 1984, 33:517- 25. 4. Brabin BJ et al. A study of the conse- Ql}ences of malaria infection in pregnant women and their infants. Parassitologia, 1993, 35(suppl.):9-11. 5. Menendez C. Malaria during pregnancy: priority area of malaria research and control. Parasitology today, 1995, 11: 178-83. 6. Ibrahim AM. Response of Plasmodium falciparum lo antimalarial drugs in vitro at Wad Medani, Sudan. APMIS Suppfementum, 1988, 3:44-6. 7. Adam I et al. In the Sudan: chloroquine resistance is worsening and quinine re- sistance is emerging. Sudan medical journal, 2001, 39(3):5-11. 8. Mukherjee S, Bhose LN. Induction of labour and abortion with quinine infu- sion in the intrauterine fetal death. American journal of oh.c;fAtrir..c; and gy- necology, 1968, 101:853-4. 9. Looareesuwan S et al. Quinine and se- vere falciparum malaria in late preg- n;ml'.'y Lanc,;;.f, 1985, .2:4-8. 10. Severe falciparum malaria. World Health Organization, Communicable Diseases Ctuster. Transactions of the Royal Soci- ety of Tropical Medicine and I lygie11e, 2000, 94(suppl. 1):$1-90. 11 . Brabin BJ et al. Consequences of mater- nal anaemia on the outcome of preg- nancy in a mi:ilc::11ic1. endemic area In Papua New Guinea. Annals of tropical medicine and parasitology, 1990, 84: 11-24. 12. Nosten Fetal. Malaria during pregnancy in the area of unstable endemicity. Trans- 1:1r.;tions or me Royal ::;oc,ety ot Tropical Medicine and Hygiene, 1991, 85:424-9. 13. Verhoeff FH et al. An analysis of the de- terminants of anaemia in pregnant women in rural Malawi-a basis for ac- tion. Annals of tropical medicine and parasitology, 1999, 93(2): 119-33. 14. Elhassan IM et al. The efficacy of artemether in the treatment of Plasmo- dium falciparum malaria in Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1993, 87:685-6. 15. McGready R et al. Quinine and meflo- quine in the treatment of multidrug-resis- tant Plasmodium falciparum malaria in pregnancy. Annals of tropical medicine and parasitology, 1998, 9:643-53. 16. McGready R et al. Randomized compari- son of mefloquine-artesunate versus quinine in the treatment of multidrug-re- sistant falciparum malaria in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000, 04:689-90. 17. Taha Tel T, Gray RH, Mohamedani AA. Malaria and low birth weight in central Sudan. American journal of epidemiol- uyy, 1993, !38:315-25. 18_ Briggs GC, Freeman AK, Yaffe SJ, eds. Drugs in pregnancy and lactation, 2nd ed. Baltimore, William and Wilkins, 1986: oor-53. Eastern Mediterranean Health Journal, Vol. 1 O. Nos 1/2, 2004 Anopheles arabiensis: abundance and insecticide resistance in an irrigated area of eastern Sudan Y. EI-S. HimeiU,m', M. Y. Dvkeerf', Cl-A. El-nayah2 and I. Adam,' 1G7 .jl~ .,_II J ,rJ .j a:iJy ~ .j .,:.,\~ ~ JW J i.:-!~1 ll,,! y'J\ }ly , "I\ 1 11 - ''I,'.--, ,I ·,1,,._-' -11 · :-~-0~~"'c.~r·.JY'.1 •i_.,~ .... ~'-~l...<,A -....;1,..,..,::2.; ._,t....,.,~"r! ,j'")__;,:.. ,,Jl;._,,_JI .J_,..;:, •.o..i....,,...i..Jc-1 Li.:.,..~ '<I ..::.,',..y.l i_..;t; _;;.v) ½.,.._l', 4_y)11 _,,Jly ._fJ;:,, ;;\...,.p')l»-1 \.,,,;.~ _._i._. ;)I,~ j ;J1 ..::.,'}.,; ,/t, ._.. ..:..,'ci'{, ~ .,_.. • .2000 J-=' .:/.)I ~T-, 1999 ,-,),•/f:,l ·~• •j..,JI ~ • "rF' .,,, l ~- M _;, ......... ~ ~· ._.. _,/ • - .... ~ ...;~ """ ........ .,__,. 2! .;;___,,;_,,.._,...;, ..::.,')'-=-y'li·, .:.,,... (/.0.1) 4....- 7 JIS" ·.....,,; -½!",.,..!', .:..,;·'--oi_.,.81 y (/.99.9) 1+· 4847 .)15' 4854 J"L~ -....,.J......-\ ,._;....£J•, ~~-:,.:'----=-(.•-ti - 1', ,!Jo (t...,,;\.5".::) t...,,[,,._, ~I_.:; L_,,._h ,.:.,'y._,,./:JI _'.-' ..':...,\.;)'l J)'.__,;. . ,;c\..:]\J ( .:..,L...J,. ,~ J~ .J ..::.,IJ ,.,!I _y 84. 7 t' o }Jl/r ,,J1,/_,;:.i 158.4 .:..,.Lo,- J ~) ,.,.1:J.1 ,_J .. ..,..Ji J\..S) .(..:.,L...-jc ~ jS .J ..:.,Li)!.:__,.,.... 44.8 c° .;,._;JI /r.,..Ji/..:;.,l,'JI ,:_,-- 136.8 .J.>..) ..:;_,,,..) ..,,)l ~ .. ', ·__ll ~ 1G:- _,,G,:. ~ • ; w.JI J·',_:_. ~ ..::.,~1', p J- ~, ,½J1i ~/~ 28.8 .;;,..J1 ..'.:,W...., .1,..., ,::.. -~ l· ,_.. ....r -..J u~ i..;, '-- . ..,. ..,. , . ......r · I--' .,,. ..J..,.,_;½1 ,:;l ./100 .J.,-iJ.,.,,;.lL-J /96.3 .J_,./YJ.L,: /.97.8 ..::.,_;. J.Ji.; ;; .. ,u,ll -:..,)1_,;_,.;\· 1 _;t. J..i..... J,S J..JJ Jy J----' ._r"- _,.-ci,: ':,' _: _-L,J, _yi.5' ~ J,,Lc...; ..;.,I., ,/' J , :,,..Jd I _J l;J ;/,..JJ ..Ly-- _,)1 J-iLl' ,/' ½ _,,JI . _r'-1 ABSTRACT The abundance of Anopheles arabiens1:S and its susceptibility to insecticides was studied in New Haifa, eastern Sudan, from March 1999 to June 2000. Of 4854 females anophelines collected, 4847 (99.9%) were An. arabiensis and 7 (0.1 %) An.pharoensis. Female An. arabIenstswere breeding throughout the year, with 2 peak densities, during the rainy (158.4 females/room/day and 84.7 larvae/10 dips) and irrigated seasons ( 136. 8 temales/roonvaay and 44.e l;;uvc:1.tl/ 1 o <Ji1-1s). The mean biting activity woo 28.8 bites.I parson/ night, found throughout the night, mainly outdoors. Susceptibility of An. arabiensis to insecticides dichloro- diphenyl-trichloroethane (DDT), malathion and fenitrothion was 97 .8%, 96.3'% and 100% respectively. An. arabiensisis the sole malaria vector in the area and is perennial rather than seasonal. Anopheles arsbiensis: abondance et resistance aux Insecticides dans une zone lrrlguee du Soudan oriental RESUME L'abondance d' Anopheles arabiensis et sa sensibilite aux insecticides ontfait l'objet d 'une etude a New Haifa (Soudan oriental} de mars 1999 a juin 2000. Sur 4854 anopheles femelles recoltees, 4847 (99.9 %) appartenaient a l'espece An. arabiensiset 7 (O, 1 %) a An. pharoensis. Les temenes An. arao1enstsse reproduisaient toute l'annee, avec 2 pies de densite, pendant la saison des pluies (158,4 femelles/piece/jour et 84,7 larves/1 O prelevements) et la saison d'irrigation (136,8 femelles/piece/jouret44,8 larves/1 O preleve- ments). La den site agressive moyenne eta it de 28,8 piqures/personne/nuit, constatee pendant toute la nuit, pnnc1pa1emem a I' exterleur. Lc:1 sl:!1 or,ibilite d'An. arc1.bi~n:.,i:., aux inacotioidec dichloro-diphonyl-trichlorogthane (DDT), malathionetfenitrothion etaitde 97,8 %, 96,3 % et 100 % respectivement. An. arabiensisest le seul vecteu r du paludisme dans la region et la transmission y est perenne plut6t que saisonniere. 'Ur!l'vt:1:jity of l<e1'5'5t1la, l<euu,ala, Sudan. 2Faculty of Science, Umversity of Khartoum, Khartoum, Sudan. 3New Haifa Hospital, New Haifa, Sudan. Received: 07111102; accepted: 22/06103 188 Ll:l RBVue de same de ra Medilerranee orientale, Vol. 10, N° 112, 2004 Introduction Malari::i j._ a major health problem in the tropical countries. especially sub-Saharan Africa, where about 90% of the clinical cases occur. There are nearly 500 million clinical C:1'-1"'- nf malaria worldwide each year and l .1 to 2. 7 million people die annu- ally (/]. The Anopheles gambiae complex is the main malaria vector [2]. In Sudan, mal aril'l cnn ~ti tut,:,;; around 40% of all in foe tious diseases and Plasmodium falciparnm is the predominant species, v,rhich is re- sponsible for over 90% of the infections [3]. Thi" ._pread of drug-resistant P. falci parum strains worldwide has hampered the control of malaria, and vector control re- mains the best approach for protecting the community :1e:,iin,;;t malaria 14]. An. arabiensis is the major malaria vec- tor reported from a!I parts of the country, co-existing with An. gambiae sensu stricto (s.s.) and An .f1mPsf11s in southern Sudan [5-8]. Vector control by chlorinated hydro- carbon insecticides was started in Sudan in l 948, when dichloro-diphenyl-trichloroet- hane (DDT) spniyo>rl with oil was used as a residual indoor insecticide. Thereafter, or- ganized control by these chemicals was ini- tiated in 1950/51 in the Gezira scheme (central Sudan) hut hy the early 1970s, re- sistance to DDT was reported. Thereafter, the organophosphate insecticides malathion and fcnitrothion replaced DDT [9, 1 O]. Understanrlinr; tho> behaviour of the ma- laria vectors and their abw1dancc is essen- tial for malaria control operations. Furthermore, understanding the resting, biting and hrceiiing habits of the vectors and their susceptibility to insecticides is ex- tremely important for planning, implement- ing and monitoring vector control measures. The objective of this study was to establish this data for the New Haifa area of Sudan. Methods Study area The study was carried out at 2 localities (Dibaira camp and Heielrnasakine) in the north and south of New Halfa town, an arcu which i~ ~urrounl.h:U by freehold farms. The New Hal fa area is located in the semi-arid belt of the Sudan approximately 500 km east of Khartoum in the middle of un agricultural :sche1m:. During the smcty period, the total rainfall was 431.6 mm and the average temperature was 30 °C. P.ful- ciparum is the predominant malaria parasite species, und ha:s been :,;liuwn lU be 7:'5% and 9.6% resistant to chloroquine and qui- nine respectively l l I]. Mosquito collection Hand capture and pyrethrum spray meth- ods were used to make monthly collections of indoor resting mosquitoes during the pe- riod March 1999 to June 2000. Colkdiu11 by hand capture \Vas carried out from 06:00 to 08:00 hours. Two collectors spent about 10-15 minutes in each hut (total I 0 huts) using a torch, uspirators and pap..:;1 cups to search for resting anophcline mos- quitoes. Then 0.3% pyrethrum in kerosene was sprayed and knocked-down mosqui- toes were collected from 08:00 tu l 0;00 hours. Females collected were classified as according to their blood meal stages unfed, fed, half-gravid/gravid. The monthly night biting collection wa:s carried out in fixed collection sites during the main transmission season by 2 people ( 1 indoors and l outdoor) sitting from I R:00 to 06:00 hours. Females co!k..:tcli were kept in separate paper cups until iden- tification and dissection for parity detenni- nation. The ovaries were dissected to determino the parity rate using the mcthou of Detinova [ / 2]. Blood spots from freshly fed females of An. arahiensis caught by Eastern Mediterranean Health Journal, Vol. 10, Nos 1 /2, 2004 169 pyrethrum spray catches were harvested on filter paper, the source of each blood determined (human biting index, using the Ouchterlony radial diffusion technique \ H]. The surveys of immature stages ,vere carried out from 13:00 to 15:30 hours using a standard dipper. Monthly samples of 100 dips were taken at IO positive breeding sites selected randomly to cover the Vihole town. Adult and larvae mosquitoes were identified on a morphological basis using the standard keys [13.14]. Susceptibility testing The susceptibility ot An. arabiens1s to DDT, malathion and fcnitrothion was ex- amined in 3 locations (Wad el Naeem, Heielmasakine and Umgargoor). According to World Health Organization (WHO) rec- ommendations [J 5], fed females were ex- posed for l hour to 4°-;, DDT, 5°/~ malathion and I% fenitrothion to determine their susceptibility 10 1llese insectici<lc!,. Statistical analysis Data was entered into a computer database antl SPSS ::;uflw,uc was u~cd for stnti:;ticul analysis. The difference between variables was evaluated using the chi-squared test. Student !-test was used to evaluate the di f- fc1encc in the density of the vector in the 2 localities and the human biting rate between the outdoor and the indoor sites. One-way analysis of variance was used to compare the human biting rates at different times of the night. A P value of Less than 0.05 was considered significant. Results Out of 4854 females collected, 484 7 (99 .9%) were An. arahiensis and 7 (0.1 %) were An. pharoensis. Most of the An. ara- hiensis specimens were collected by pyre- thrum spray (4164, 85.9%) rather than hand capture (683, 14.1%). The mean vector density in the Heiel- masakine area (pyrcthrum collection) was 29.3 females/room/day, while it was 23.1 females/room/day in Dibaira camp (Table 1 ). The highest density was recorded in September 1999 by the end of the rainy season ( 158.4 females/room/day) in Heiel- masakine while the lowest density in this area was recorded in April 1999 (0.2 fe- males/room/ day). The peak density of adults was reflected by the peak of imma- ture stages in the same month (84.7 larvae/ IO dips). The Lowest density of adult fe- males was recorded in March 2000 (0.4 females/room/day) in Dibaira camp_ The lable 1 rotal numr:ier of aelult Auupllt1ft1li ma/Ji1:Jm;i;5 apeclmen3 ,;ollected during the study period by hand capture and pyrethrum spray and mean density per room per day in the 2 localities Locality Pyrethrum spray Hand capture Total Total Mean:SE Total Mean:tSE Total Meim:s:51; collected density collected density collected density No. NoJroom/day No. No/room/day No. No/room/day Dibaira camp 1821 23.1±8.8 311 3.7 ± 1.4 2132 26.9±10.1 Heielmasakine 2343 29.3± 13.0 372 4.6 ± 1.5 2715 33.9± 14.5 Total 4164 26.0 :t 7.9 683 4.2± 1.0 4847 30.3±8,9 SE= standard error. 170 Lo Rtwue oe same oe 1a Meorterranee orientale, Vol. 1 O, N° 1/2, 2004 lowest density of immature stages was re- corded in that month (0.54 larvac/10 dips). A minor peok of female dcn~ity was re- corded during the period of irrigation (March 1999). 136.8 females/room/day in Dibaira camp, coupled with a minor peak of immature stage~ (44.8 larnic/10 dips) in the same month (Figures 1 and 2). Of 2132 females collected from indoors resting sites in Dibaira camp, 14.1 %, 112.5% and 43.3 % were unfed, fod am.I half-gravid/gravid respectively. While from Heiclmasakine, 14.4%, 36.5%, and 49.1 % were unfed, fed and half-gravid/gravid. The ratio of fed to gravid/half gravid fe- males in the 2 localities considered together was ! : 1.2 in favour of gravid/half-gravid. This indicates that this species is more en- dophilic than exophilic. A total of 4. I fe- males/room/day were captured on thatched 250 200 150 100 50 0 ~ ~~ ~'f,.\ ,;:.'Z ~'fl ~<:;. -:,v walls compared with 1.6 females/room/day on mud walls. or the An. arabiensis females captured while trying to bile human baits, 76.2% were caught outdoors and 23.~% indoors. The average human biting rate during the 1 c1i11y ~c:asun was significantly higher for outdoor biting activity (28.8 bites/person/ night) than indoors (9.0 bites/person/night) (P < 0.001). The indoor biting activity stc1rlt":U initially ,virh a moderate value at 18:00-02:00 hours (0.88 bites/person/ hour), followed by a peak of biting activity at 20:00-22:00 (1. 13 bites/person/hour) am.I thc:n dropped to lower activity at 24:00-02:00 (0.25 bites/person/hour). A minor peak was observed at 02:00-06:00 (0. 75 bites/person/hour). In contrast, the outduu1 biting aclivity sranect with a peak value at 18.00-20.00 hours (5.0 bites/per- --v- Larvae/10 alps ---- t--emales/room/day ---Ir- Rainfall ~ Relative humidity ......._ Temperature Figure 1 Abundance of both adult females end larvae of Anopheles arabiensis in relation to rainfall (mm), relative humidity(%) and temperature (°C) in Olbalra camp Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 171 180 160 140 120 100 80 60 40 -------+-- Larv ae/1 0 dips ---0- F emales/roomlday -fr- Rainfall -----)f-- Relative humidity ......,.__ Temperature Figuu,? Abundance of both adult females and larvae of Anopheles arabiensis in relation to rainfall (mm), relative humidity(%) and temperature (°C) in Heielmasaklne son/huu.r) tlc1,;1ca5cd at 20:0(l~-22:00 to 3.25 bites/person/hour and dropped to lower values (0.25 bites/person/hour) bet\veen 02:00--06:00. The difference was not sta- tislically siguificant (I'> 0.05). The monthly parity rates of An. arahi- ensis during the rainy season were 2 l .4°lo, 6. 7%, 42.5% and 36.4% in July, August, Scplcm\J.::1 and Qc;tobcr respectively, with a mean of 32.2°,i, during this period. The human biting index of the 2 localities were 76 .4%, and 81.1 % in Dibaira camp and Hcid1m1.sak.inc rcspcctivdy, with u mean of 78.7% of the total mosquitoes examined. Out of a total of 3849 larvae collected, 2 LI%, 29 .2 %, 24.6% and 15. 7% were fo:;t, stcond, third and fourth instar larvae respectively. Most (82.5%) of these lan1ae were collected from the shallow sunlit pools resulting from broken w,itf',r pipes. Other breeding sites were rain pools {11.6%), leakage from irrigation canals (3.1 %) and water excavations for human and animal use (2.9%). The mean to1al number of larvae collected during the study period \'las 24.3 larvae/ 10 dips. The susceptibility of An. arahiensis to the 3 insecticides v.,·as 97.8'%, Q(i 1°i;, anrl 100.0~-~ for 4%, DDT, 5% malathion and 1 % fenitrothion respectively (Table 2). Discussion This entomological study was conducted in an agricultural area in eastern Sudan, char- acterized by a high level of chloroquine-re- sistant falciparum malaria (11]. An. 172 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1 /2, 2004 Table 2 Susceptibility to insecticides of adult A. arabiensis collected from 3 localities Locality DDT4o/o Total St.lscep Resist Total tested tested No. % % No. W(Jd el Naeern 75 97.3 Z/ 75 Heielmasakine 60 98.3 1.7 40 Umgargoor 100 100.0 0 100 Total 235 97.8 2.2 215 Suscep = susr::eptible. Resist resistant. arahiensis was the mam vector (99.9%) found in the area; only 0. l % were An. pharoensis and no other species were de- tected. This agrees with a previous study from the nearby area (Gectaret) m the east- ern Sudan where An. arabiensis was the main vector, besides 2 other species, An. pharoensis and An. fimestus [8]. An. arahiensis existed throughout the year with 2 peaks, a major one at the end of the rainy season (September) and the other during the irrigated season of the scheme. Tlit: second peak is most likely due to pres- ence of breeding sites that were formed from the puddles of irrigation canals around the area. Thus An. arabiensis has bernme perennial instead of seasonal be- cause of irrigation and agricultural practic- es. Similar findings were reported from an irrigated area in the Gczira scheme in cen- tral Sudan (16], but unlike our study, a sin- gle peak of vector density was observed at the end of the short rainy season that dropped gradually to disappear in the long, hot dry scason [8]. lhe most important factor leading to high breeding density dur- ing the rainy season was the optimal tem- perature (28.9-30.1 °C) and high relative humidity, as it is known that high tempera- ture and low humidity adversely affect adult and immature stages [17]. This trend Malathion 5% Fenitrothlon 1% Suscep Resist Total Suscep Resist tasted % % No. % % 98.7 1.3 75 100.0 0 100.0 0 40 100.0 0 93.0 7.0 100 100.0 0 9R::J .'3.7 215 100.0 0 of mosquito abundance differs from other tropical areas that arc characterized by longer rainy sca~ons and more humid con- ditions, e.g. southern Sudan and many oth- er African countries. In th('se regions, anophcline mosquitoes arc known to be prevalent throughout the year [18J. Our study sho\ved that An. arabiensi.1 clearly preferred thatched to mud walls as a resting surface. A similar finding was ob- served from central Ethiopia [19]. In this area An. arabiensis is strongly exophagic. This finding is supported by the previous study in Gcdaref state and central Ethiopia [8.19]. Three factors seem to de- termine the biting cycle of the An. arabien- sis: rhythmic activity of the mosquitoes, the microclimate and human habits [ 20]. Winds and temperature arc the climatic fac- tors affecting the peaks of the biting cycle [18]. In the Z\vai area of central Ethiopia the peak of outdoor biting occurred from 22:00 to 24:00 hours, whereas the peak of indoor biting took place early in the evening from I 8:00 to 20:00 [!9]. However, the vector was aggressive throughout the night and exhibited 2 peaks in the indoor biting activitv at 20:00 to 22:00 and later at 02:00 to 06:00, with the peak outdoor biting ac- tivity at l 8:00 to 22:00. Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 173 The low parity rate of female mosqui- toes in this area is likely to be related to the application of the insecticide K-Othrine (a water-based fonnulation of dehamethrin) during the period of the study in August I 999. as shown by the low parity rate that month (6.7%). Mixed feeding by mosqui- toes is common, but with An. arabiensis this may be determined by the host avail- able [21]. Tn this area, the presence of do- mestic animals is most likely to be very rare in human dwellings. Therefore, th.: human biting index recorded (78.7%) was relative- ly high, similar to that in Gedaref state f8l Although there is seldom a large differ- ence in susceptibility between the sexes, female mosquitoes (preferably blood-fed) should be used exclusively in fidd tests. This is because they survive better and show lower control mortality [ 15]. The susceptibility to DDT, malathion and feni- trothion was found to be 97.8%, 96.3°1<:, and I 00.0~-o respectively, indicating that the mosquito population in this area had a low level of resistance tn insecticides. Similar findings were reported in central Ethiopia f /91- The comeback susceptibility of An. arabiensis to DDT may be due to stoppage of chlorinated hydrocarbon insecticides for more than 20 years. Nevertheless, in the Gczira irrigated sch.eme the vector devel- oped resistance to several insecticides in the 1970s, which was influenced by the overuse of crop-spraying with insecticides f/Ol It is important to note that the establish- ment of the New Haifa agricultural scheme in the area has resulted in a serious abun- dance of An. arabiensis throughout the year. More studies are needed in order to assess the role of this species in malaria transmission in different seasons. References 1. WHO expert committee on malaria, 20th report. Geneva, World Health Organiza- tion, 2000 (WI 10 Technical neport Sc ries, No. 892). 2. Colling FH, Bsansky NGJ. Vector biology and the control of malaria in Africa. Sci- ence, 1994, 264: 1074-~. 3. El Gaddal AA. The experience of the Blue Nile Health Project in the control of malaria and other water associated dis- eases. ln: American AssocIatIon tor Ad- vancement of Science. Malaria and development in Africa. A cross-sectoral approach. Washington DC, AAAS, 1991 {http: //www . .:iaac. o rg/i nta rn a I io nal/ africa/malaria91 /index. html). 4. A global strategy for malaria control. Bul- letin of the World Health Organization, 1993, 71:261-4. 5. Petrarca V et al. Cytogenetics of the Anopheles gambiae complex in Sudan, with special reference to An. arabiensis. relationships with East and West Africa populations. M0dicaf and veterinary tm- tomofogy, 2000, 14:149--64. 6. Dukeen MY, Omer SM. Ecology of the malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) by the Nile in northern Sudan. Bulletin of entomologi- cal research, 1986, 76:451-67. 7. El Sayed BB et al. Study of the urban malaria transrnissiur, !Jiulilern in Khartoum. Acta tropica, 2000, 75:163- 71. 8. Hamad AA et al. Marked seasonality of malaria transmIssIon In two rural sites In eastern Sudan. Acta tropica, 2002, 83: 71-82. 9. Abdelrahman AA. The integrated pest management strategy and its expected environmental and economical impact 174 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 in Sudan. Albuhuth, 1994, 4(1-B):164- 75. 10. Haridi AM. Inheritance of DDT resistance in species A and B of the Anopheles gambiae complex. BulleNn of the World Health Organization, 1972, 47:619-26. 11. Adam I et al. In Sudan chloroquine resis- tance is worsening and quinine resis- tance is emerging. Sudan medical journal, 2001, 39:5-11. 12. Gi!Hes MT. The duration of the gono- trophic cycle in Anopheles gambiae and Anopheles funestus. with a note on the efficiency of hand catching. East African medical journal, 1952, 30:129-35. 13. Verron A. Outline of the determination of malaria mosquito in Ethiopia. Part I: adult female anopheline. Mosquito new.~. 1962, 22:37-49. 14. Verron A. Outline of the determination of malaria mosquito in Ethiopia. Part II: anophAlinP. /;:i rv~<=> Mos:quito news, 1962, 22:394-401. 15. Annex of 22nd report of the WHO Expert Committee on Insecticide-Resistance of Vectors and Rcacrvoira of Disee:ses. Geneva, World Health Organization, 1976 (WHO Technical Report Series, No. 585). 16. Cl Gaddal AA et al. Malcuict w11trul in the Gezira-Managil Irrigated Scheme of the Sudan. Joumal of tropical medicine and hygiene, 1985, 88: 153-9. 17. Molineaux Let a!. The epidemiology of malaria and tis measurement. In: Wernsdorfer WH, McGregor I, eds. Ma- laria: principles and practice of malariol- ogy. Edinburgh, Churchill Livingstone. 1988:999-1090. 18. Crees MJ. Biting activity of mosquitoes and malaria incidence in the southeast lowveld of Zimbabwe. Transactions of the Zimbabwe Scientific Association, 1996, 70:21-7. 19. Abase T et al. Re-orientation anrl r/1:ifini- tion of the role of malaria vector control in Ethiopia. Geneva, World Health Organi- zation, 1998 (WHO/MAL /98. 1085). ?O C.illies MT. Anopheline mosquitoes: voe tor behaviour and bionomic. In: Wernsdorter WH, McGregor I, eds. Ma- laria: principles and practice of malario!- ogy Edinburgh, Churchill Livingstone, 1988:453-86. 21. Bruce-Chwatt LJ et al. Ten years study (1955-1964) of host selection by anopholine mosouitoes. Bulletin of the World Health Organization, 1966, 35: 405-39. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 Characteristics of tuberculosis patients in Vazd province, Islamic Republic of Iran, 1997-99 M.H. SalarP andA.B. Kalantarr 175 1999-1997 .:.i1_)'!! .J !I).. :W,,\A.,o J J,-J1 ..r _r __,.a..il.A;- ..,s;',.;.j':/\5' ,,,PJ4 r ~) ,,_;;')_,, ~ ..i..,..;. ..:_.,I,.:..., 3 j')1.,.:- _.;, J., ._. 604 -5.\.l y\ .;.; ... J·, ,..,.,L.,,J--1 ,,-,,.,...J L. \; ;,- ,. ' J..:....., ~IJ..U' ..:..,~...b-- :L..,",\j-1 _.1 0 .J .,__, ~ .I ...., w ....,---- \_,_-' - ~i c.- t<: ,, 26.8 U, ., J +', J,,..,. J, ,._,; ..:...JI J...wl .:.it ,...__;.,;1 ..UJ ,.:JI ytl j ~ .i,! i.....1,Ll_. j (1999-1997) w- u ..__..,, ..., ...,;; .-, ~ 7--· ._ ~ ~ ... .--ls- ,..I>____,._.:. -L, -., .... .:_:-, w _; ......... )..:-i ;)IS" ..u. '(..__.;Ji ;;.:_. L(J ..:..,\.;')I .._-; ... :.l 31.0. ) ,S jjl _; ... i.J 22.9) ~ \ ~ ~...t~ ........ ••' ... - .... i,_,. ~ ..,( ~ -.$ ..J jl ,:"" JW-- • /75.8 c.£ ..J J\ '~I ~'.,IL.,:... .,4.,, J\ c.;' ,-;-J', ;..1.,J\ J\.5" • , ( ._)JI ,._Lo l;J 111.1} l,l_.. 5U y ...I ..., i.__.. .,.. ~ ..-' J i,_. ,.;, -' T..,. ..I I_. .:_:-' ;-+'-' / 17.7 j~.: ,.u.l:.:,.:. <-Ip-\ ._,a,Lo 0) /8.4 ~l_,ij L...,. c/.66,7 ~I <5" ,r• ~,-' ~ ... \J j '"/24.2 .:.ii....i~1 _:.,:,, .. c>:-")'JL ~,-.> '/.36.lJ ,:.,~,,;1_...,:l ~ /63.2 JIS ..:..-::~'- ,:.,·::i _:,r') ·;>-r" /.7.1 ~.Jc .• _, ,:;.J,.W1? ubL~.'.i. 1 0 ~ ..j ~~ ~ --~-:_.~.,f-~ ..__~·-·Jl .:,:µ ._:,,~."YJ; ~..r_..JJ ~-~ 1._,~11._; s_.-·..._,..:...;,,.-~-~I\J J_:li_....J 1, -=,~ ~-..JJ ABSTRACT We determined the incidence of tuberculosis and some demographic characteristics among 604 patients in a 3-year period (1997-99) in Yazd province, Islamic Republic of Iran. The average annual rate of tuberculosis was26.8 per 100 000 (22.9 in males and 31.0 per 100 000 in females). I ne nignest rate or tuberculosis was in the> 50 years age group (111.1 per 100 000). The average annual proportion of pulmonary and extra-pulmonary tuberculosis cases was 75.8% and 24.2% respectively. On average 66. 7°/o o!TB patients were cured, 8.4% transferred to a different catchment area, 17.7% were treatment failures and 7. 1% llitl\J. or l11tl lul1:1I, 63.2% were Iranian, 00.1 % Afghan relu9cc::i. Dcopitc offorli;: in prevention, diagnosis and treatment of patients and refugees, tuberculosis is sUII an important problem in this province. Car:aet~ristlques d"'"' rmtt ... nti; tuberculeux dans la province de Vazd (Republique islamique d' Iran), 1997-1999 RESUME Cetta etude a perm is de determiner !'incidence de la tuberculose ainsi que certaines caracteris- tiques demographiques chez 604 patients sur une periode de trois ans (1997-1999) dans la province de Yazd (Republique islamique d'lran). L'.incidence annuelle moyenne de la tuberculose etait de 26,B pour 1 oo 000 (22, 9 chez les horn mes et 31,0 chez les femmes). LJnc1dence 1a plus e1evae se trouvan dam, le gmupe d'age des plus de 50 ans (111, 1 pour 100 000). La proportion annuelle moyenne de cas de tubercu- lose pulmonaire et extrapufmonaire etait de 75,8 ~" et 24,2 % respectivement. En moyenne, 66,7 '% des patients tuberculeux ont gueri, 8,4 % ont ete transferes a un autre secteu r, 17, 7 % ont con nu un echec therapeulique et 7, 1 % 3ont decedea. Au total, 63,::! % 6tuionl doc Iranians, 36, 1 % dgs refugioi!s afghans Malgre les efforts deployes pour la prevention, le diagnostic et le traitement des patients, la tuberculose demeure un probleme important dans cette province. 'Department of Pathobiology, School of Public Health; ~lns11tute of Public Health Research, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. Received· 09/10/02; accepted: 22106/03 176 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Introduction Tubcrculo:,is (TB) remain, a mujm global public health problem. The World Health Organization (WHO) estimated that in 1997 there were about 8 million new cases of TB and 2 million deaths worldwide; the grci!.t majority (95%) of these cases and deaths (98%) were in developing countries [J,2]. It was estimated that by 2000, the annual global number of new cu;;c:; would lurvc: increased to over 10 million (163 per I 00 000 population), and the annual ex- pected number of deaths to 3.5 million per year (nearly 46 per I 00 000 population) [3,4]. Today. TB remains common throughout most of the world with one- third of the world's population estimated to be infected with !t,1_vcoha,:;;tc:rium tuhoculu- si.1. The incidence of TB has recently start- ed to rise again due to increased migration, a higher rate or direct transmission of M. tuberculosis and co infection with IIIV [5). In ! 999, the highest and lowest rates of TB in provinces of the Islamic Republic of Iran were reported to be 13 7 per I 00 000 and IO per 100 000 rc3pcctivcly [6). The .main goal of this study was to describe the incidence of TB and some demographic characteristics of TB patients over a 3-ycar period (1997 99) in Yozd province, in the central part of the Islamic Republic oflran. Methods Yazd province covers an area of about 74 214 km2 and has an estimated popula- tion of 750 769 (385 936 males and 364 833 fomaks). The study participants were patients with TB aged 8-65 years who were referred to the Yaz<l referral hos- pital during the study period ( 1997 99). Samples of sputum, tissue or body flu- ids were obtained and investigated by Ziehl-Neelscn staining and culture meth- ods. Specimens were transported in broth media (Becton Dickinson, Maryland, USA) and processed on the same day if possible, or if delay was unavoidable, the specimens were stored at 4 °C for not more than l night before processing. On arrival at the laboratory, the presence of visible fibrinous clots was noted and Ziehl-Nedsen staining was applied. Cultures were obtained by in- oculation into conventional solid Lowen- stein-Jensen media (U1ko). All inoculated cultures were incuhakd at 37 °C under 5% CO,. The culture media were investigated twice a week for the first 3 weeks and thereafter weekly tor a total of 6 weeks in- cubation. All isolates were initially con- firmed by Ziehl--Neelsen staining and subsequently identified by standard bio- chemical tests L /,.S j. The collected data and results of labora- tory tests were analysed by SPSS, version 6. Results A total of 604 cR,;c,; of TR were identified during the study period. The overall mean annual rate or TB over the 3-year period was 26.8 per 100 000 population (Table I). There were :2S6 mHlc"l Hnri ~~9 females. There was no significant difference in the rate of TR between the sexes (P > 0.05); the mean annual rate was 22. 9 per I 00 000 for males and 31.0 per 100 000 for fp_ males. Breakdown of the data by age shov,·ed the lowest rate of TB was in the S: IO years age group (7.0 per JOO 000) and the highest rate among the > 50 years aee group ( 111. l per I 00 000). Data analysis revealed that those aged > 50 years had a significantly higher rate than those in the younger age groups (P < 0.05), The nationality of the TB patients over the 3-year period showed a high proportion of the group were Afghan refugees Eastern Mediterranean Health Journal, Vol. 10. Nos 1/2, 2004 177 Table 1 Number of tuberculosis patients and rate per 100 000 population by sex and ago Variable Population 1997 1998 1999 Total Mean No. Rate No. Rate No. Rate No. annual rate Sex Male 385936 87 22.5 107 27.7 71 18.4 265 22.9 Female 364 833 112 30.7 122 33.4 105 28.8 339 31.0 Age (years) ,;: 10 171738 ?? 1?.R 10 5.8 4 2.3 36 7.0 11-19 210 309 18 8.6 25 11.9 20 9.5 63 10.0 20-29 120 355 19 15.8 3.5 29.1 23 19.1 77 21.3 30-39 94622 14 14.8 23 24.3 13 13.7 50 17.6 4(}-49 58922 25 424 21 35.6 16 27.2 62 35.1 >50 94823 101 106.5 115 121.3 100 1 Ot>.~ 316 11 I. 1 Total 750 769 199 26.5 229 30.5 176 23.4 604 26.8 -- -- ·---- (36.1 %); 63.2% were Iranian and 0.7% TB. The mean annual percentage of extra- other nationalities (Table 2). pulmonary TB cases (24.2%) was much Of the 604 patients, 458 patients had lower than for pulmonary TB cases pulmonary TB and 146 extra-pulmonary (75 .8°-io) (Table 2). Table 2 Distribution of patients by natlonallty, type of tuberculosis and treatment outcomes Variable 1997 1998 1999 Total Mean (n = 199) (n = 229) (n= 176) (n= 604) annual No. % No. % No. % No. % Nationality Iranian 121 60.8 155 67.7 106 60.2 382 63.2 Afghan (refugee) 75 37.7 73 31.9 70 39.8 218 36.1 Other 3 1.5 0.4 4 0.7 Type of tuberculosis Pulmonary 147 73.9 186 81.2 125 71.0 458 75.8 Extra-pulmonary 52 26.1 43 18.8 51 29.0 146 24.2 0U{CUI//B Cured 132 66.3 149 65.1 122 69.3 403 66.7 Treatment failure 49 24.6 34 14.8 24 13.6 107 17.7 Transferred to diffP.mnl ama 3 1.5 40 17.5 8 4.5 51 8.4 Death 15 7.5 6 2.6 22 12.5 43 71 n = total number of TB patients. 178 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2. 2004 The outcome of TB for this group of patients shmwd that on average 66.7% of p<tlicuts wen: cured, ~.4% transferred to a different catchment area, 17. 7~,o were treatment failures and 7. 10,-~ died (Table 2). Discussion The technologically under-developed and developing countries carry an cnorrnnu~ share of the world's TB burden. The dis- ease is not uniformly distributed and some countries show a continuing increase in TB infection rates. whereas other!l. show ilf>- clining infection rates [9--1 !]. In industrial- ized centres, a rise of TB incidence has been observed, due to incrcase.d migration, a hi.gher rate of direct ,\f tuhPrc11/nl"i,· transmission and the HIV epidemic. TB is a continuing threat to health in all parts the world [5]. The present study was carried out to monitor the incidence of TB and some de- mographic characteristics of TB patients in Yazd province in a 3-ycar period (1997- 99). The average annual rate of TR dnring the study period was 26.8 per I 00 000 pop- ulation (23 per l 00 000 among males and 31 per 100 000 among females). The rate of TB in our study is higher than the rll M in some other areas in the world [ 6, 12 -15]. But, it is nearly equal to the lowest rate for developing countries (25 per I 00 000). and one-ninth the highest rate for developing countries (240 per 100 000) [16J. Real increases in the numbers of TB pa- tients cured will only occur when the Irani- an Ministry of Health and ~1e<lic/ll Education is able to either directly treat all cases of TB in Yazd province or at least in- tluence the method of treatment applied in private practice and other health care ser- vices, such as university hospitals and mil- itary services. If the National TB Control Programme can achieve its target of DOTS [ directly observed treatment, short-course] for all, it will have had a real impact on the problem ofTB, not only immediately on in- c1dence and mortality rates, but also in the longer tem1 on TR prevalence. In addition, clinical mycobacteriology laboratories play an important role in the control of the spread of TB through the timely detection, isolation, identification and drng suscepti- bility testing of Ai tuhemdosis [ I 7]. Today's worldwide TR epidemic and the movement of a growing number of ref- ugees have made TB control in refugee populations an issue of increasing impor- tance. However, in developing countries 18 control in refugee populations remams a largely unmet need. Experience shows that despite difficult field conditions, TB control programmes can be managed successfully m th is setting [ 18]. It seems that despite the efforts which have been made in preven- tion, diagnosis and treatment of patients and refugees, TB is still a problem in this province. Acknowledgements The authors wish to thank Dr K. Ghazi- Saecdi, Dr M. Karimi, Dr M. Shayegh, A.A Sadrabadi, A.A. Hanafi-Bojd and F. Falah for their kind assistance in thir, study. References 1. Mum1y CJ, Styblo K, Rou111on A. luber· culosis in developing countries: burden inteNention and cost Bulletin of the In- temationa/ Union against Tuberculosis and Lung Disease, 1990, 65:6-24. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 179 2. Dye C et al. Consensus statement. Glo- bal burden of tuberculosis: estimated in- cidence, prevalence and mortality by country. WHO Global Surveillance and Monitoring Project. Journal of the Ameri- can Medical Association, 1999, 282: 677-86. 3. Dolin PJ. Global tuberculosis incidence and mortality during 1990-2000. Bulle- tin of the World Health Organization, 1994, 72:213-20. 4. Dolin PJ, Rav1glione MC, Kochi A. A re- view of the current epidemiological data and estimation of the future tuberculosis incidence and mortality. Geneva, World Health Organization, 1993. 5. Opravil M. Epidemiological and clinical flsru~r:ts of mycobacterial infections. In- fection, 1997, 25(1 ):56-9. 6. Seloudeh Maram E, Fararoei M. Inci- dence of tuberculosis in the cities of Fars. Journal of Oazvin Univ@r.<:ity nf Medical Sciences, 1999, 11:74. 7. Eisenstadt J et al. Mycobacterium tuber- culosis and other nontuberculous Myco- bm;teria. In: Mo.hon CR, Manu1.elis G. Textbook of diagnostic microbiology, 2nd ed. Philadelphia, WB Saunders, 1995: 635-76. 6. Ru11yu11 EH. Mycobacterium. In: Lenncttc EH, Balows A, Housler WJ, eds. Manual of clinical microbiology. Washington DC, American Society of Microbiology, 1980: 160-7~ 9. Hershfield ES. Tuberculosis in the world. Chest, 1979, 76:805-11. 10. Sutherland I et al. [Risques annuels d 'infection tuberculeuse dans 14 pays d'apres les resultats d'enquetes tuber- culinques effectuees de 1948 a 1952. Annual risks of tuberculous infection in 14 countries derived rrom me results of tuberculin surveys in 1948-1952.] Bulle- tin of the International Union against Tu- berculosis, 1971, 45:75-96. 11 . Bleiker MA, Styblo K. The annual tuber- culosis infection rate and its trend in de- veloping countries. Bulletin of the Inter- national Union against Tuberculosis, 1978, 53:295-8. 12. Miller M, Leowski J. Epidemiology of tu- berculosis in Poland and in the wortd. Przeglad epidemiologiczny, 1997, 51(4):38!::l-4U4 [In Polish]. 13. Zuber P. Epidemiology of persistent tu- berculosis in DeKalb county, Georgia, 1990-1996. Journal of the Medical As- sociation of Georgia, 1999, 8t:I( 1 ):42-o. 14. Rivest P, Tannenbaum T, Bedard L. Epi- demiology of tuberculosis in Montreal. Canadian Medical Association journal, 1998, 151(5):605-9. 15. Baldo V et al. Epidemiological aspects of tuberculosis in Padua Health District rnP.S-1996. European ioumal of epide- miology, 1998, 14(2): 125---8. 16. Global tuberculosis control. WHO Re- port 2000. Geneva, World Health Orga- nization, 2000. 17. Beverly G et al. Mycobacterium. In: Murray PR et al., eds. Manual of clinical microbiology, 7th ed. Washington DC, American Socioty for Microbiology, 1999. 18. Kessler C et al. Tuberculosis contra, in refugee populations. International jour- nal of lu/.J1:11i;ufo5i:5 dnd lung diacaso, 1998, 2(2):105-10. 180 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 La fievre typhoide au nord du Liban : etude sur 8 ans (1992-1999) utilisant le test de Widal M. Hamze 1 et P. Vincenf' JI~ ~w ~I~~ (1999-1992) ~l_,.:...i 8 oJJ. L\J.) :~l.;J J~ ~ l_o_-11 ~I j\.....;.o J~4 '".r'" J..i..:,. ..;J.J (1999-1992) 11ri :;,,;L1 ...,...i... J.s;- JL.,.\ JI.P .:, ~1 ~1 Lh .Ii :.....1,,.i11 ~ :t..,.:,~1 ~\ J.-1" ..Li.., -~4 r-t=iL:,! ~ sr11_.,1, .J ,/')...,..'ii (f.P.""1 ~I Jl 1__,.L,-.JI .,:r-.i.ll ~)\ ~; ~I ...:..;IS_, .~_, Ji..y j.-u; ~I~~ ,_.;._-Ji .,;..,~}LJL; r,_;_,.J..JI ._f_;>.::J :a.,,L..z.. ~ 739 ~_,,.,.i ~L.. .,;..,l.,.l,,.:i J .,;..,..t...=,\ a...,; ...,,. )) 160/1 ~ -4.Y- ,,1.,,,,.; 0 ~l; ....,.,.1_,,J1 ..:., _,.i,... ...,,. i.5 _,..wl .:.,-- pi (i.15.3) 4,;.- 1131 ,_) ...,...1;J1 ..!l,,.- .:.,tS' 7 391 \.io.:,..1..- ~ ._;)I ..::..,l..:..,JI _:.'!,-1 ~J .(.....k.:.l.l ._,..i; J. C:°) . .__.o )1 t_} _, Jly _) .:. _,.6.. ._,..ail..i .:.)L,,. Ji.5' 4.il ;JWI ..;..,1_,....JI 1.5..Lo J.;,. .w _,JI ~ .,i ..l.i J .160/1 r:?'J' -li_, -·~ ul,.!,1..o ...,...,_.; .JJ_, a...,bJ.l J ;d,p -wl ~\ fr"O ~_,.,.... ,Jl,.. ~ ~ -4j,! L,. ..:.;_,.A>- .~\;;.!j\ _J./4 .J lo _;>--L.- <..r'L, C: ~I ~ J i.-L,..:. jl .!.IL,,. J( (f ~\ ~\ RESUME Nous avons evalue la frequence de la fievre typho"ide au nord du Li ban sur une periode de 8 ans (1992-1999): 7391 serums ont ete analyses pour rechercher une infection par Salmonella typhiparletest de Widal et Felix. La valeur seuil retenue pour I' infection etait celle d'un titre en agglutinine O superieur ou egal a 1/160 (valeur validee par un travail anterieur mene dans cette meme region). Surles 7391 serums, 1131 (15,3 %) presentaient un titre en agglutinine O .: 1/160. La surveillance sur le5 8 annees a pennis de mettre en evidence une baisse progressive de la frequence de la maladie. Mais avec plus de 100 cas chaque annee, la typhoi"de reste dans cette region une pathologie endemique qui peut s'aggraver d'episodes epidemiques majeurs. L'analyse mensuelle montre qu'a la classique pous.see estivale s'ajoute une recrudes- cence hivemale. "Typhoid fever In north Lebanon: a 8-yeer study (1992-1999) using the Wida I test ABSTRACT We evaluated the frequency of typhoid fever in north Lebanon over an 8-year period ( 1992- 1999) in patients admitted with fever to the lslami de Bienfaisance Hospital in Tripoli. We analysed 7391 serum samples for Salmonella tv,uh/infection using the Widal and Felix tests. The cut-off value for infection was an agglutinin O titre~ 1/160 (a value validated in an earlier study in the same region). Of the 7391 samples, 1131 (15.3%) had an agglutinin O titre~ 1/160. The 8-year surveillance showed there was a progressive decrease in the frequency of the disease. However with over 100 cases annually, typhoid is endemic in the area and could cause major outbreaks. The monthly analysis shows that we have an increase in summer, whilst a decrease is observed in winter. 'Universite libanaise, Faculte de Sante publique, Tripoli (Liban) (Courriel: mhamze@fnco.com.lb). 2Service de Bacterio/ogie, CHR de Lille, Facufte de medecine, Lille (France}. Reyu : 22110/02: accepte: 17/08/03 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 181 Introduction Alors qu'elle est devenue rare dans les pays industrialises, la fievre typhorde reste un probleme de sante publique clans les pays ou l'hygiene collective et individuelle est deficiente. La maladie reste en effet endc- mique en Afrique, en Asie du Sud-Est, en Amerique centrale et en Amerique du Sud [1-3]. Dans Ies pays developpes, le diagnostic repose sur l'isolement du germe. Mais en pays d'endemie, ou les moyens de culture peuvent faire defaut [2,4~7], le serodiag- nostic de Widal-Felix reste le plus econo- mique des moyens diagnostiques. Par ailleurs, dans ces regions, la prevalence plus forte de la maladie renforce la valeur predictive positive de ce test. 11 reste par consequent couramment employe et il constitue la base du plus grand nombre de diagnostics {8-10). Au Liban, Ia fievre typhoi'de sevit de maniere endemique. Deja par le passe, un rapport datant de 1895 avait signale une epidemie survenue a Beyrouth, touchant 2 % de la population (2000 cas), avec un taux de mortalite de plus de 15 % [ 11]. Au cours des dernieres decennies, et du fait de la guerre civile (1975-1990), la si- tuation s'est aggravee dans le pays, en rela- tion avec la degradation ou la destruction des infrastructures ; traitement et distribu- tion des eaux potables, evacuation des eaux usees et evacuation des dechets. Au nord du pays, de graves episodes de la maladie sont surveous. En effet, la plupart de la population de cette region consomme de l'eau non traitee. A cela s'ajoute l'absence totale de traitement pour les eaux usees et les dechets (menagers mais egalement hos- pitaliers). Au total, la fievre typho'ide fait partie des infections endemiques qui persis- tent dans cette region. Le but de ce travail est de faire le point actuel sur la frequence de la fievre typhoide au nord du Liban et d'etudier revolution survenue au cours des demieres annees (periode 1992-1999), Methodes Periode et lieu de l'etude L'etude s'est deroulee de janvier 1992 a decembre 199Q ctans le laboratoire de mi- crobiologie de l'hopital Islami de Bienfai- sance a Tripoli. Cette ville (situee a 80 km au nord de Reyrm1th) est la capitale du nord du Liban. C'est la deuxieme ville du pays. Le centre hospitalier comprend 189 lits, ou la plupart des specialites sont exercees (a ]'exception des operations a cceur ouvert et des transplantations). C'est le plus impor~ tant au nord du Lihan. II est dote d'un sec- teur public et d'un secteur prive, et dessert toute la population de Ia region. Dans la mesure ou les autres hopitaux de la region sont principalement prives (9/10), on peut considerer que la pathologie vue dans ce centre reflete la situation de la population generale de la region. Patients Pendant les 96 mois de r etude, 7391 pa- ti en ts ont fait l'objet d'une recherche serologique de typhoide par le test de Widal. Ce serodiagnostic est demande pour tout patient presentant des signes compati- bles avec le diagnostic de typhoi'de, nne diarrhee febrile ou une fievre isolee qui per- siste pendant plus de trois jours avec une temperature jusqu'a 40 a 41 °C associee ii des cephalees, a une alteration de l'etat general et a des frissons. Avec celui de Wright, ii constitue un examen de routine devant toute fievre au Liban. Le test de Widal Pour chaque sujet, 5 ml de sang etaient pre)eves clans un tube sec sans anticoagu- lant. Apres coagulation. le tube etait cen- 182 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 trifuge a une vitesse de 3000 t/rnn pen<lw1l 3 a 5 minutes. Le serum obtenu etait analyse en utilisant des antigenes O et H commercialises par la societe Sclavo (Ila- lie), suivant le protocole propose par le fa- briquant. Les serums etaient dilues en serie de 1/20 a 1/2560. Selon la definition habi- tuelle, le titre retenu correspondait a l' inverse de la plus forte dilution pour laquelle on observait encore um: agglutina- tion. Chaque serum avec un titre en aggluti- nine O Superieur OU egal a 1/160 etait considere positif. Ce seuil provit:nl <l'um: etude anterieure OU nous avons montre que la valeur critique qui permet la meilleure discrimination entre les sujets infectes et les autres dans cette population est un titre en agglutinine O superieur ou egal a 1/160 [I 2} : dans cette etu<le, ct: st:uil donnerait une specificite de 100 % par rapport aux donne1,1rs, et de 94 % par rapport aux sujets febriles sans typhoYde. L'c:lt:valion du seuil a 160 a pennis de reduire le risque de porter a tort le diagnostic. L'association des ag- glutinines H ne pt:11nt:t rualheureusement pas d'ameliorer la fiabilite du test. En effet, s'ils sont plus faciles a detecter (taux plus eleves), ks anticorps anti-H sont uussi plus frequents dans la population generale en zone d'endemie. Observation a partir de janvier 1996 Les resultats ont ete enregistres mois par mois ct lcs 4 dcmieres annees de l 'etude (1996-1999) ont done fait l'objet d'une analyse saisonniere. Resultats Les fievres non typhoidiennes {TO< 1/160) Entre 1992 et 1999, les fievres (avec ou sans diarrhee) necessitant une hospitalisa, tion ont augmente progressivement (Ta- bleau 1) passant de 641-645 cas annuels en: 1992-1993 a plus de 800 a partir de 1996 (avec une poussee supplementaire en, 1999 : 1014 cas). La periode 1996-1999 permet d' ana .. lyser les variations saisonnieres (Figure 1): d'une annee a l'autre, on a retrouve une poussee estivale et un creux hivemal. Les trois premieres annees ( 1996, 1997 et Tableau 1 Distribution annuelle des cas de 1992 a 1999 Annee Patients Flevresnon Typho'ide hospitalises typhoidlennes (TO~ 1/160) pourfievre Nbre Nbredec11s Nbrede cas Proportion (%) 1992 812 641 171 21,0 1993 841 645 196 23,3 1994 877 716 161 18,4 1995 926 784 142 15,3 1996 9'..:!4 807 117 12,7 1997 1000 823 177 17,7 1998 904 830 74 8,2 1999 1107 1014 93 7,8 Ensemble 7391 6260 1131 15,3 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 183 200 160 120 80 40 0..---o---- ---~ -a-- 1996-1998 .......... 1999 0 -t---,---.---r----.--y-----r--,---..-----.--.....----~ .m .9i V, = ·.a ,!;; i - Q) Cl) Q) ... ~ ,:::, a:, > > ro ::!? :::, 0 ... l5 .0 ... .:; ::!? .., :::, <( .0 .0 m '(I) -, E 0 ~ E .., u. Q) t, Gl ii 0 > .a; Q) 0 U) z 0 Figure 1 Aspect Aaisonnier des dlarrhees febrlles non typhoidiennea (TO.;:; 1/160} ; moyenne pour les annees 1996-1998, et annee 1999 1998) etaient tres homogenes, avec 80 a 100 cas mensuels en ete contre 40 a 60 en hiver. En 1999, 2 poussees se sont ajoutees a ce profil (janvier/fevrier d'une part, et juillet d'autre part) expliquant a elles seules I' exces de cette annee par rapport aux precedentes. Typho"ide (TO ~ 1/160) Pendant la periode de 1992 a 1999, le nom- bre de cas de fievre typhorde diagnostiques par titrage des agglutinines TO a diminue, passant progressivement de 171 cas en 1992 a 93 cas en 1999 (Tableau 1), a !'exception d'um:: breve recrudescence en 1997 (177 cas). Les variations saisonnieres ont ete itudi6es sm ht p!Sriode 1996-1999 (Figure 2). Les annees 1997 a 1999 ont montre un meme profil, avec un minimum au prin- tcmps (le mois de mai etant la periode la mains touchee) suivi d'une poussee esti- vale avec un creux vers le mois d' octobre puis une recrudescence hivernale. Con- trastant avec ce profil, l 'annee 1996 a ete marquee par une incidence elevee tout au long de I' annee, et particulierement pendant l'hiver 1996-1997 ou il ya eu 15 a 40 cas mensuels de novembre jusqu'a avril (mas- quant ainsi l'habituelle recession post- estivale). Discussion Le serodiagnostic de Widal, pratique au cours des fievres hospitalisees a l'hopital Islami de Tripoli (Liban) entre 1992 et 1999, revele done la situation epide- miologique dans le nord du pays. Alors que les hospitalisations pour fievres justifiant une recherche par serodiagnostic de Wida! ont augmente regulieremcnt, la typhoi'de (TO ~ 1/160) qui represente mains de 20 % de ces cas a haisse progressivement. Cependant, elle persiste tout au long de l'annee avec une poussee estivale et une legere recrudescence hivemale et elle peut dormer des epidemies importontes commc celle survenue pendant l'hiver 1996-1997. 184 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Novembre 1999 Mai 1999 Mars 1999 Novembre 1998 Septembre 1998 t:::==::::::::i Juillet 1998 Mal 1998 Mars 1998 Janvier 1998 Novembre 1997 Mai 1997 Mars 1997 Septembre 1996 Juillet 1996 Mai 1996 Mars 1996 0 10 20 30 40 50 Nombre de cas par mois Figure 2 Nombre de cas mensuels de typhoid11t (TO~ 1/160) de Janvier 1996 a decembre 1999 Les limites du test de Widal sont con- nues. Ce test comporte en effet un risque de faux positifs par reactions croisees (au- tres salmonelles, Yersinia pseudo tuberculo- sis type IV, autres enterobacteries) et un risque de faux negatifs (periode initiate de !'infection, infection decapitee). Malgre ces limites, plusieurs travaux menes en zone d'endemie ont montre qu'en contrepartie d 'un manque de sensibilite, l' augmentation du seuil de decision confere au test de Widal une haute specificite [8,13,14], et plusieurs etudes ant conclu a l'interet de choisir pour le titre O une valeur de 160 ou plus pour affinner la presence de l'infec- tion [6,15-17] dans !es pays en developpe- ment. Il est done possible que cette observa- tion sous-estime le nombre de cas de ty- phoide reellement survenus dans cette population pendant cette periode, mais la valeur elevee du seuil retenue garantit par contre une bonne specificite et nous assure que le phenomene n'est pas surevalue. De plus, l'emploi du meme test avec la meme valeur seuil tout au long de l'etude pennet de comparer les annees et les mois entre eux. L'augmentation des fievres non typhoi:- diennes montre que la population recourant aux soins de notre hopital n'a pas diminue pendant Ia periode etudiee et permet done de conclure, malgre le risque constant d'episodes epidemiques, a une baisse reelle du niveau endemique de la typhoide. Cette baisse est a rapprocher de !'amelioration relative des conditions sanitaires dans la re- gion, tout particulierement dans la ville de Tripoli, ou depuis 1998 la station de traite- ment de l'eau potable a ete remise en fonc- tionnement. Depuis plusieurs annees, l'evolution saisonniere de la typhoide dans notre region semble stabilisee. avec ses periodes creuses d'avril a juin (respective- ment 8, 6 et 7 cas cumules sur les 3 mois Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 185 pour 1997, 199R et 1999), et novembre/ decembre (respectivement 11, 5 et 13). Le profil de l'hiver 1996-1997 (22 cas pour avril, mai/juin, et 44 cas pour novembre/ decembre) montre que l'absence de ces creux correspond a une poussee epide- mique. Le suivi mensuel du test de Widal apparait done comme un bon outil de veille sanitaire. Conclusion Cette etude a montre que la fievre typhoide reste endemique dans le nord du Liban et presente toujours un risque de survenue d'episodes epidemiques. Cependant l'rune- lioration des conditions sanitaires depuis la fin de la guerre civile s'accompagne d'une diminution relative du niveau d'endemie. Dans cette region ou les difficultes eco- nomiques persistent, le test de Widal reste un hon moyen pour diagnostiquer !'infec- tion. De plus, la surveillance de l'evolution au fil des mois permet d'utiliser oe test pour surveiller Ies epidemies. References 1. Coovadia YM et al. An outbreak multire- sistant S13.lmone/la typhi in South Africa. Quarterly Journal of medicine, 1992, 82(298):91-100. 2. Gallals H et al. La fievre typhoide en Afrique noire. A propos de 213 cas. Medecine tropicafe : revue du corps de sante colonial, 1983, 43:367-70. 3. Trabelsi M et al. Typhoid fever in children in Tunisian rural areas, Epidemiofogic and clinical study, Me<iecin tropicate : re- vue du corps de sante colonial, 1986, 46(4):349-54. 4. Choo KE et al. Usefulness of the Widal test in diagnosing typhoid fever in en- demic areas. Joumal of paediatrics and child health, 1993, 29:36-9. 5. Pang T, Puthucheary SD. Significance and value of the Widaf test in the diagno- sis of typhoid fever in an endemic area. Journal of clinical pathology, 1983, 36: 471-5. 6. Saha SK et al. Interpretation of the Widal test in the diagnosis of typhoid fever in Bangladishi children. Annals of tropical paediatrics, 1996, 16(1 }:75-8. 7. Shukla S. Patel B, Chitnis OS. 100 years or Wida! test and Its reappraisal \n an endemic area. Indian Journal of medical research, 1997, 105:53-7. 8. Buck RL et al. Diagnostic value of a single pre-treatment Widal test in sus- pected enteric fever cases in the Philip- pines. Transa.cNons of the Royal Sof.1ety of Tropical Medicine, 1987, 81:871-3. 9. Gupta Vet al. An outbreak of typhoid fe- ver in Chandigarh, north India. Tropical and geographical medicine, 1986, 38(1):51-4. 10. Rasaily R et aL Value of a single Wida! test in the diagnosis of typhoid fever. In- dian Journal of medical research, 1993, 97:104-7, 11. Wortabex Y. Al Moktatat, 1896, 268-4. 12. Hamze M, Naboulsi M, Vincent P. Evalu- ation du test de Wida! pour le diagnostic de la fievre typhoide au Liban. Patho- logie Biologie, 1998, 613-6. 13. Abraham G et al. Diagnostic value of the Widal test. Tropical and geographical medicine, 1981, OS:329-33. 186 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 14. Coovadia YM et al. Comparison of pas- sive haemagglutination test with Widal agglutination test for serological diagno- sis of typhoid fever in an endemic area. Journal of clinical pathology, 1986, 39: 680-3. 15. Kulkarni ML. Rego SJ. Value of single Widal test in the diagnosis of typhoid fe- ver. Indian paediatrics, 1994, 31 (11 ): 1373-7. Note from the Editor 16. Mohammed I, Chikwem JO, Gashau W. Determination by Widal agglutination of the baseline titre tor the diagnosis of ty- phoid fever in two Nigerian states. Scan- dtnav,an Journal or Immunology. supple- ment, 1992, 11:15&--6. 17. EI-Shafie S. The Wida! test in a normal healthy population in the Sudan. East African medical Journal, 1991 , 68( 4): 266-9. The EMHJ website (http://www.emro.who.int/EMHJ.htm) contains all Issues of the Journal published to date from which the full text of all papers can De obtained free or charge. we would like to draw our readers' attention to the onllne evaluation form. We welcome com- ments from our readers and would appreciate it if readers could kindly take the time to complete this form. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 Visual outcome of extracapsular cataract extraction and intraocular lens replacement in leprosy patients A. Derakhshan1 187 ?\~\ ,.r f J lli\,\ ...,1.:,.,1~ L.,.w, ;i..,;ol.-..;..,,"'JIJ ~I ~.Ji.,:. .:iW\ JL.A:;;....";i 4/.Jl..4.i~\ ~\ _:.1L..:...,.:.\J~ /$i .J.,...J-.1 ~~';,' ,2000: 1998 ; 1.s- _:_-,, o)'...i.ll ,.) ,,:)l_;:1i .J ,~ ½.l.-o ,.J LI;..-]·, ...:...,_,,.,.1 :4.-,p')\j.-l (_,-' 18 ._;;_i.} ~ 1 J--.,.:.') L..i....,, :i...pl....::..-:/1 (:' ~I ~JI,. )L....\I _;.'-....=.-'j ~ i.>-\r ~1..r"') "-!./-.a.,)11 ;,_. ,J·, J.ii ..., A.W l<;. ,._;.. s:;..,~1 ..... ;,.l", .c5"1 ;)"1 • L.<. .,, ~ ! ... ;;,_,..t.,.,. ....;. .:,., .,.,.i .u.;,.1 . _::, ..A L, ..,/ ., _./ , ..-'Y ,r- I ~ .,_r..,r-·- i,,5'- ../ · I r_,/ " 1, ~ · .J ~I;): if "-?--1.f-1 1..,,4,J• .__Y ;l-.a...:)11 ;.b-- -.:_:.-_:lj .J.i_: .(/.55) y}JI ~~I __ ,.....;,.;/ (/.90) .__,...,,,.l_,,i-1_: :i,,)l;JI __,; )...\.,,.)' .1; . ._,..;., )' ,/ /55 c.5_i.; 10/8) 10/5 ~"':! l, J! ~~- ;.,.._ij:.i --'-"i ~ ~ 10/1 J: '--~I . ' i_L.!-1 ~_! ,lJ',J> ~-~J l-uj, -~1_, ~~_,,_. ~~ ~-G-- .JJ ~I (,~~ '-:-"',1.+01 j~ i..;,;.)! j'J ~\~ ~' ,i' ..U • . S::...,I ,-.,._.;;;.... J Q _ . ..._, lw ..,L..,'::,11, ~, :._ \) 1,$',..;;. . __:.., I · ____,.) • ,:.di , ,;., , • [\ a, ,..,,,J\ '-- ff I _.J j ~ ...s~ i.._· ...I ~...1 ,.___. ...,, "T- . .. ~ ...., Y_,/ .. ,, • ,'4-'-' /25 .) "?'" _;,,), )U • ...,'•_: ,,.;;.,'_i' 1J..I .:..,,_,. /70 ;_S..l.l ?UJ,-1 ._j c:.,-• _).: 4,.:-Jl .._,., 1+:!1 ~,s;- ~\.;.;1 ~ _;.JI Ji...=J', .·~-;. 10.:; ~ ;JI .J .J..t:.,,_1., )~'.: ,~ ns .J ...,._,_;1fa1 ..::.,i_,... ;Ji: ABSTRACT The study was carried out in Meshed, Islamic Republic of I ran, from 1998 to 2000 to explore the visual outcome of eye surgery with extracapsular cataract extraction and intraocular lens replacement on 18 leprosy patients (20 eyes). The most common comp Ii cations of leprosy were madaros1s ( 90%) and partial or total corneal opacity (90%). Visual acuity before surgery ranged from 'light perception' to 1/10, and this improved after surgery to 5/10-tlll u Tor ooy/o 01 patients. Po:.tuf)tll alivtl inleo.:.tion lea.ding to endophtholmitic occurred in only 1 patient and was treated with drugs; this patient's visual acuity remained at 10 cm finger count. Posterior synechia due to chronic uveitis in leprosy was diagnosed in 70% of eyes, obstructed iris in 25%, keratic precipitates in 25% and moderate ins atrophia in 10% .. Resultat optique de !'extraction extracapsulaire du cristallln et du remp1acement par une lentllle lntraoculaire chez des patients lepreux RESUME Celle etudea ete realiseea Meshed (Republique islamiqued'lran) de 1998a2000 pour explorer le rt'l:;ul\al vµlique de la. chirurgie oculaire par extraction oxtracapsula.in, du cristallin "'' rl'!mJ11flr.P.ment par une lentille intraoculaire chez 18 patients lepreux (20 yeux). Les complications les plus courantes de la lepre etaient la madarose (90 %) et une opacite corneenne partielle ou totale (90 %). L.:acuite visuelle avant l'inteivention chirurgicale allait d'une " perception faible,, a 1/1 O, et ii ya eu une amelioration apres l'interJP.ntion allanljusau'a 5/10-8/10 oour 55 % des patients. Une infection postoperatoire enlrainant une endophtalmie est survenue chez un seul patient et a ete traitee par medicaments ; l'acuite visuelle aux doigts de ce patient est restee a 1 O cm. Une synechie posterieure due a une uveite chronique dans la lepre a ete diagnostiquee pour 70 % des yeux, une obstruction de l'iris pour 25 %, des precipites keratiques pour 25 % et uneatrophie moderee de l'iris pour 10 %. 'Department of Ophthalmology, Imam Reza Hospital and Meshed University of Medical Sciences, Meshed, Islamic Republic of Iran. Received· 11/11/02; accepted· 26/05!03 'I'• • i , 'I'-\ ,jl~._w', , .?~-', ~I ,.,,.LW, ~\ .....k;_. ,.k..- ,_.11 J? ..,_,.._..,J, .w;I 186 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Introduction Leprosy is u stigmatizing di:scasc affi;;1..:tiug mainly the skin, peripheral nerves, and eyes and nose and is a notorious cause of blind- ness and nasal, hand and foot deformities. In 1986, 5.4 million lcpro:a;y p<tticnt:s wc1c registered worldwide, a figure that had fa]]. en to 3.1 million by 1992 [J]. The overall prevalence ofleprosy in the Eastern Mcditcrrancun Region in 199.'.i w11:s 0.4 per IO 000. Although the prevaknce in the Islamic Republic of Iran is less than 1 per 10 000, there arc localized areas where it exceeds 1 per IO 000. Regional :stialcgic:s are emphasized for the elimination and con- trol of leprosy, early case detection, treat- ment with mu!tidrug therapy and disability prev,;ntion. \VHO :;upporb m1tional 1..:u11uul programmes, providing technical assis- tance to the Islamic Republic of Iran in the promotion of surgery for leprosy impair- ment [1]. The rate of ocular involvement in lepro- sy ranges from 6'%-90% in different stud- ies. In a study in Nepal, the incidence of blindness ( eyesight less thun 2/200 or 6/60) was 3%-8% in patients with duration of ill- ness up to 10 years, and 30% in patients with more than 20 years of illness [ 3]. In a study in Nigeria, the rote of blindnc5s iu leprosy patients was 8. 7%, i.e. I 0-fold more than the general population in the area, and one of the most common causes of blindness in thut study was caturnd [ 4]. The rate of eye problems and blindness vary with the type ofleprosy; inflammatory eye is a common finding that can cause problems for eye surgery. Leprosy, c~pc- cially the lepromatous type, causes impair- ment of the immune system. which increases the success of extracapsular cat- aract extraction and intrnncular lcn:,; n::· placement surgery. In one study, blindness in patients who had aphakic surgery and pseudophakic surgery was 71% and 14% respectively ! 5]. Considering the high level of physical and psychological impairment associated with leprosy. all efforts should made to de- velop the full potential of leprosy patients. Kehabilitation of eyesight, even at finger count level is a valuable help to the patients. As there is little information about the na- ture or incidence of ocular pathology in lep- rosy patients and about the effectiveness of ocular surgery, the present study was con- ducted to explore the visual outcome of eye surgery with extracapsular cataract extrac- tion and intraocular lens replacement. The study was carried out on leprosy patients in Imam Rc,:a Hospital in Meshed, Islamic Republic of Iran. from 1998 to 2000. Methods In thi<: ,;tudy, 18 cured leproi;y patients with cataracts (20 eyes) underwent extra- capsular cataract extraction and ocular lens replacement surgery. For each patient, a prim;ciry ophthalmologic examination was conducted in the ophthalmology clinic of Imam Reza Hospital in Meshed. After confirming leprosy and cataract, the p;cit1e-nt was referred to the ophthnlmol- ogy ward and a clinical assessment was perfonncd by ophthalmologists or ophthal- mology residents, Before the operation, in- traoc-11br pressure was measured. Surgery was performed on the eye with better vi- sion. except for 1 patient ,vho had no light perception in the other eye. After s.urgery, all patients received bc- tam ethas one and chloramphcnicol eye drops. All patients were followed on the 1st, 3rd and 7th days postoperation and at the end of th,:.- 3rd and 6th months and 1st year, and were examined by surgeons or ophthalmology residents. Postoperative vi- Eastern Mediterranean Health Journal, Vol, 10. Nos 1/2, 2004 189 sual acuity was defined by the eyesight at the end of the 1st year postoperation. Results The ;,,tudy sample was 12 males and 6 fe- males, aged 54 70 years; operations were ma~c on 20 eyes. The preoperative compli- cattons of the eyelid and cornea due to lep- rosy arc presented in Table I. Madarosis (loss of eyelashes) ,:vas the most common eyelid complication in 901% of eyes, fol- lowed by loss of eyebrows (65%), \agoph- thalm.os (50%) and corneal hypoacsthc::siu {35%). Corneal problems were corneal in- filtration (45%) and corneal neovascula- rization (45%), and partial or total corneal opacity (90%). In all cases, intraocular pressure was normal before and after operation; no cases of increased intraocular pressure were de- tected. l\1ild postoperative ocular inflam- mation was seen in all cases, but the intraocular lens was \veil tolerated. In 14 ~~ses (70%), in spite of iridotomy, slight mdoavulsion occurred at the time of the lens nucleus extraction, which is not a seri- ous problem in intraocular lens replace- !flent. B~cause of multiple ocular problems m 5 palicnts, tarsorrhaphy and corneal im- plantation was also performed in their oper- ations. In all cases, visual acuity before surgery ranged from 'light perception' to 1/10, and th_is improved in all cases after surgery, with 55% of eyes regaining a visual acuity from 5/10 to 8/10 (Table 2). The postoperative complications were low. Posterior synechia was diagnosed in 14 eyes (70% ), a very mild case in 1 eye. Obstructed iris was seen in 5 eyes (25%) and a mikl case in I . Keratic precipitates occurred in 5 eyes (25%) and very mildly in l eye. Iris atrophia was seen mildly in 14 eyes (70%) and moderately in 2 eyes (I 0%). Postoperative infection occurred in Table 1 Complications of the eyelid and cornea in 20 eyes from leprosy patients with cataract Complir,alinn Mild Moderate Seven! Total No. % No. % No. % No. % Eyelid Madarosis 16 00 5 5 18 90 Lo,i,i of eyebrows 10 so 2 10 5 13 66 Lagophthalmos 5 25 4 20 5 10 50 Corneal hypoaesthesia 4 20 3 15 0 7 35 Ectropion 3 15 2 10 0 5 25 Trichiasis 3 15 2 10 0 5 25 Cornea Inflammatory pannus 13 65 5 5 15 75 Partial corneal opacity 7 35 2 10 2 10 11 55 Total corneal opacity 4 20 3 15 0 7 35 Corneal infiltration 6 30 1 5 2 10 9 45 Corneal neovascularization 2 10 7 35 0 9 45 190 La Revue de Sante de la Maditerranee orientale, Vol. 10, N° 112, 2004 Table 2 Vlsual acuity in 20 eyes from leprosy patients with cataract 1 year after uxtracapsular cataract extraction and ocular lens replacement surgery Visual acuity No. of patients % ~l 1)---lj/l u 11 55 1 /1Q----4/10 5 25 CF=S 2 15 Not determined 2 10 CF= counting fingers at 5 m. 1 patient, which led to endophthalmitis and was treated with drugs; this patient's visual acuity remained at IO cm finger count. Discussion The prevalence of cataract in leprosy pa- tients will increase as life expectancy con- tinues to increase, Leprosy control pro- grammes need to develop activities aimed at reducing the burden of cataract. Extra- capsular cataract extraction and intraocular lens replacement is a suitable treatment for cataract in cured leprosy patients. The postoperative complications, followed up for I year, were very low in this ~tndy. In our sample, the most common pre~ operative complication of leprosy was ma- darosi s, which was similar to a study performed in the USA [6]. Loss of eye- brows, inflammatory pannus and partial corneal opacity were the next most com- mon complications; conjunctiva\ fibrosis was the second most common complic:1- tion in leprosy patients in the American study [6]. Symptoms of neuromuscular involve- ment of leprosy, such as lagophthalmos and C(lfneal hypoaesthesia, were more common in our study than other studies, In the USA, the rate or lagophthalmos was 11 % and the rate of corneal hypoacsthesia was 16%; in our sample the rates of these complications were 50':·c, and 35'Vii respec- tively, This can be explamed by the d1tfor- ent rates of tuberculoid and lcpromatous types of leprosy that occurred in these re- gions, which result in different complica- tions. Tn a study in south India ot 63 leprosy patients admitted for treatment of corneal ulcers, 34 had lagophthalmos, 28 had madarosis, 9 had cctropion, 6 had blocked nasolacnmal ducts, J had tnchiasis and 39 had decreased corneal sensation [7]. Indigenous treatment and late presen- tation were notable in many cases and visu- al outcomes were not good, In the present study, all patients had low visual acuity before surgery (between light perception and I/ 10). One year after sur- gery 80'}\, of them Ila ct h 1ghly improved vi- sual acuity, which indicates the effecti- veness of extracapsular cataract extraction and intraocular lens replacement in leprosy patiems. In a study in Korea among patients with aphakie surgery, 71 % were still blind in the operated eye, while among patients vvho had pseudophakic surgery, 14% re- mained blind [5]. Tn our study, postopera- tive posterior synechia was seen in 75<'.o of patients due to chronic uvcitis, which is one of the major causes of blindness in lep- rosy, Considering the good visual outcomes in operated patients and the low rates of in- tra ocular inflammation and reaction, we conclude that the results of intraocu.lar .lens replacement surgery for cured leprosy pa- tients with cataract are satisfactory and can be recommended, Eastern Mediterranean Health Journal, Val. 10, Nos 1/2, 2004 191 References 1, Pirouzi MA, Pirouzi P. The Canadian encyclopaedia of dermatology. Canada, Pirouzi Scientific and Interactive Labora- tories, 1998 (http://www.fortunecity.com/ marina/v1ctory11 1 /leprosy.mm, accessed 20 June 2004). 5. Courtright P et al. Cataract in leprosy pa- tients: cataract surgical coverage, barri- ers to acceptance of surgery, and outcome in a population based survey in Kurtla. Brifi1,h jowma.f of ophthalmology, 2001, 85(6):643-7. 2. The work of WHO in the Eastern Mediter- ranean Region. Annual report of the Re- gional Director. 1 January-31 Decem- ber 1995. Cairo, World Health Organiza- tion, 1995. 6. Dana MR. Ocular manifestations of lep- rosy in a noninstitutionalized community 1n the united states. Archives of opf1//1c1r- mofogy, 1994, 112(5):626-9. 3. Daniel AE. lntraocular pressure in lep- rosy patients without clinically apparent anterior segment pathology. Indian jour- nal of leprosy, 1994, 66(2):165-72. 7. John D, Daniel E. Infectious keratitis in leprosy. British journal of ophthalmology, 1999, 83(2): 173-6. 4 Nwosu SN. Ocular findinas in leprosy patients in Nigeria. East Africa medical journal, 1994, 71 (7):441-4. Leprosy elimination Leprosy continues to have public health Importance In some coun- tries of the Region at sub-national levels, although the number of newly registered leprosy cases has decreased slgnlflcantly during the past several vears. Druqs for treatment of leprosy are available free in all endemic countries, and diagnosis and treatment are Inte- grated In the maJority of countries, either within the primary health care system, or with other communicable diseases programmes. The main challenctes for the endemic countries relate to reducing the backlog of untreated cases through passive and active case detection, achieving full compliance of cases with multidrug therapy (MDT), changing the negative Image of leprosy and eliminating stigma throuqh increased community awareness, preventing dis- abllltles among cases, and achieving sustainability In diagnosis and treatment of cases In countries that have already ellmlnated lep- rosy. Suurce: The work of WHO in the Eastern Mediterranean Region: annual report of the Reg10na! Director, 1 January 31 Decemher 21103 \., __ _ / 192 La Revue de Santa de la Mediterranee orientale, Vol. 10. N° 1/2, 2004 Distichiasis and dysplastic eyelashes in trachomatous trichiasis cases in Oman: a case series R. Klli:lf/Uf;!Ki:lr,' s. Kldlyul" and A. AI-Raisf' ..::..,':i\J-.1 ,:r a..J....., : .:,J4S, J \..o ~I_JJI .:.,,S, U:-ull ~ ~1 ..::.,':IL<-- .j yl.U.':il ~ Jb'-J i:. 1 J~ jl ~l_)I ~I ..y> , ;y.~ .._,a...,.;L- "JL~ ..1.,;L-,:. __;..,.,..,.J ..... •.-':-u, • .....:...IL, ·...,La.11 J,.c· ._,,-J.;,,';,", ;,,.-e., '.G-. _, • .,_)., ,\....:.,;;1 J......l L...L.;;.,.,1 0 .__.1 ,..i.J1.....; ::i..J')ul,-1 Lr ., -- - ' ~-· ~- • ,..:..,. '- ..,I ~ .,,, ., ' • -.. .,,, ~..j ..\.ii .2000 i~ .J.+"' ,.';~; ~~' oJ-* ,j .:_,w -.:..•~ ..l.;,-i..) ,.:.~I ...,...1J i..l.;,-.l .J Lo.)""'-',_;JI J., ·;/" ,:i"1l -~ 11..i.,,:.:._,L, ~,_;,..,.,,. ,_,,,_.....::; u. ..s_,..,.i..J ..:.,')IL.J...1 .1-.. .:.,s_,.,,.J1 ...,..1,., ---~ Jr. ~ ..:....- :;_.,-..•.; o_.......;;, J.l :UL;.,)'\....,,_,_. ~ ._,..,i..u,J (/.72.5) ~-_. 58 ,.;.,J ,:,ilj" .,;_,,_.J~.J...i.1 .;.,,_Lcl1 __, :.._)I .:,.,, y.. ... L,i o:21.3J zs.2 ..:.~ c.,1y..,., /.95...: :;,l_,.,Ll.,) z13_a ...,...1 ...... ~, c'J-') J-"""" .:.il.5" ...,J .i.,...,_,..,)J1 .:r- (1/.34.5 J! /.15.5) c+"' /.25 .jl$. L...,.i ,(/.44.1J /235 :.."o/ CJ1,;,,.J) /33.8 .j\S' ..w ...,_.,1.a\' 1 ~ LA ~..;.I ;J•, ,$- :;,..~LJI ; ~I ,L.,;.c;i ·-• 0 <i ~·\..U, \:I ,.,_._;,; ~ < ,-I-~ ;I ,~\ .jl5• ,Jj, . lo.• -., _}'JI "}5 _,, f L, - _, .,,, '--- 7-' - i.,:_ .,_.. _., ~ J _., _,.. J v-J --r'\ I~,.,_~!\ c--~ j-J...-' _;. c._1..,~.iij\ .;i._r~, _) .:.:; .~\J.,,\1 ~4 ..:..~\.....all, -...>...:Jj ~'._i,u- L....~ ~ ~)L.a,.s.i -½_r' :.....,_,,. sJJ ~1,_..:;J~ .,:_..A ..J.S .... t:'.11! ~--)-Ill .:i~ -½-5_..,_...;J ~L . .,.,1_JJJ·1 ,._..,..... ~i~).! '--;-'-~ ~__...~--.:__\_JJ\ .__~ ~t..J\ O~l ~':lL.-- ,C"' -~c_;-...,..,....J' ABSTRACT The study was a prospective evalm1tinn of thF! JlrAw,lence, of di,;:tichiasis and/or dysplactic eyelashes among trachomatous trichiasis cases at the oculoplasty unit of a hospital in Oman over 3 months in 2000. An oculoplasty surgeon examined and photographed cases using a bio-microscope. Out ol 80 cases, 58 (72.5%) had abnormal eyelashes in addition to trachomatous trichiasis. The rate of distichiasis and dysplastic lashes were 13.8'% (95% Cl 6.2%-21.3%) and 33.8% (95% Cl 23,5%-44.1'%) respectively; ~o.uu,;,, {~:>%, GI 15.5%-34.5%) had both. Dysplastic and dislichiasis eyelashes were significantly more prevalent in trachomatous trichiasis cases aged< 50 years and those with entropion. Presence of distichi- asis and/or dysplastic eyelashes in trachomatous trichiasis cases warrants further analytical studies to confirm the observation and establish any causal association. La dlslichiase et les cils dysplasiques dans les cas de trichiasis trachomateux a Oman: serle decas RESUME Cette elude etait une evaluation prospective de la prevalence de la distichiase eUou des cils dysplasiques chez les cas de trichiasis trachomateux au Service d'oc1Jloplm:;ti,:. rl'11n hArital 21 Oman, portant su r 3 mois en 2000. Un specialiste de chirurgie oculoplastique a examine et photographie des cas a l'aide d'un biomicroscope. Surles 80 cas. 58 (72,5 %) avaient des cils anormaux en plus d'un trichiasis trachoma- teux. Le taux de dist1chiase et de cils dysplasiques s'elevait a 13,8 % (IC 95 ~·;,: 6,2-21,3 '"lo) et a 33,8 % (IC 95%: 23,5-44, 1 %) respeclivement; 25,0 % (IC 95% ·. 15,5-34,5 %} avaient les deux. La distichiase el 1es c11s aysp1as1ques eta1ent s1gmt1cativernent plus courants chez les cas de tnchiasis trachomateux Ages de plus de 50 ans et les cas d'entropion. La presence de distichiase et/ou de cils dysplasiques dans les cas de trichiasis trachomateux justifie la realisation d'autres eludes analytiques pour confirmer cette observation et etablir toute association causale. 'National Eye Health Care Programme,' 20culoplasty Unit. Department of Ophthalmology, Al Nahdhah Hospital,· 30phthalmic Services. Ministry of Health, Muscat, Oman. Received: 15109/02; accepted: 01106103 Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 193 Introduction Trachomatous trichiasis as graded by the World Health Organization (WHO) docs not specify the presence of distichiasis and dysplastic eyelashes and limited informa- tion is available about these conditions among trachomatous trichiasis cases. In a long-term fo11ow-up study of trachoma- tous trichiasis cases managed by the bilat- eral tarsal rotation procedure in Oman, the prevalence of distichiasis and dysplastic eyelashes were not noted [1]. The 61.8% recurrence rate of trichiasis observed in that study is very high an<l clinicians have proposed that this is due to dysplastic and distichiasis eyelashes which were not man- aged separately in addition to the bilateral tarsal rotation procedure. Our study was therefore undertaken to determine the fre- quency an<l determinants of dysplastic and distichiasis eyelashes among trachomatous trichiasis cases in Oman. Methods This was a case series study based at the Oculoplasty Unit of Al Nahdhah Hospital in Muscat, Oman. The study included all tra- chomutous trichiasis cases reporting to the unit between May 2000 and August 2000. The field investigator was an oculoplas- ty surgeon. The ocular status of each pa- tient wro cvnlu.uted using a bio microscope with an attached photography unit. Pa- tients' eyes were photographed after taking their written consent. The following were noted for each patient: personal details (age, sex), date of examination. details of trichiasis, past history of lid surgery, type of trichiasis, eye involved, presence of dis- tichiasis or dysplastic lashes. The trachoma gradings recommended by WHO in the I 0th revision of the Interna- tional classification of diseases [2] \Vere used to define the i.:ye conditions. Distichia- sis was defined as the presence of an addi- tional row of eyelashes at the lid margin. Dysplastic eyelash {Figure 1) \\'as de-fined as any abnormal eyelash originating from the area of the lid margin posterior to the grey line or at the conjunctiva! edge of the lid margin of an in-turned eyelid. Presence of abnormal eyelashes in either eye was counted as one person with abnonnal eye- lashes. The patients were offered laser treat- ment free of cost at the time of examination and then given bilateral tarsal rotation sur- gery. Figure1 Dysplasticeyelashes In left upper lid with trachomatous trlchiasis 1Y4 La Revue cle Sante de la Mecliterranee orientate, Vol. 10, N° 1/2, 2004 The data were collected on a standard form and entered into a Microsoft Excel :?000 database. Two researchers computed th~ data separately using a pre-tested for- mat. The frequency and percentage of pa- tients and 95% confidence intervals were 1:alculated. Relative risk (RR) and P values were calculated for comparison of sub- groups. Results Eighty ( 80) trachomatous trichiasis cases were examined, 23 males and 57 females. They were divided into age groups < 50 years and 50+ years. Females in the age group 50+ years were the largest group in the study (Table l ). Distichiasis and/or dysplastic eyelashes were observed in 58 (72.5%) of trachoma- tous trichiasis cases ( Table 2). Analysing the data by sex showed that 17 of 21 ma le cases (73.9%) had abnormal eyelashes (distichiasis or dysplastic lashes) compared with 41 of 57 female cases (71.9%). Male cases had higher rates of dysplastic and distichiasis lashes than female cases. Ho,v- ever, the difference was not statistically significant. Table 1 Age-sex distribution of trachomatous trichiasls cases and age distribution nf r.JUIO!l.s with abnormal eyelashes Age Male Female Total Abnormal (years) No. No. No. eyelashes No. % 25--49 7 15 22 20 90.9 50+ 15 41 56 38 67.9 NR 2 0 Total 23 57 00 58 725 NR = not recorded. Table 2 Abnormal (distlchiasis and/or dysplastic) and normal eyelashes among 80 patients with trachomatous trlchlasls Condition of No. %, 95%CI eyelashes Abnormal eyelashes Distichiasis 11 13.8 6.20 to 21.30 Dysplastic eyelashes 27 33.8 23.49 to 44.11 Doth of above 20 25.0 15.:> 1 to 34.49 Total 58 72.5 62.721082.28 Normal eyelashes 22 27.5 17.72to37.28 n "' total number of cases. Analysmg the data by age group (Table l) showed that 20 of 23 cases < 50 years old (90.9%) had abnormal eyelashes (7 dis- tichiasis, 5 dysplastic lashes, 8 both) com- pared with 38 of :,t, cases aged 50+ years (67.9%) (13 distichiasis, 6 dysplastic lash- es, 19 both). The relative risk for abnonnal eyelashes among those < 50 years was 1.3 (95°:'o CI: 1.03-l.ooJ compared with those aged 50+ years. Of 59 cases of trachomatous trichiasis with a history of lid surgery in the past, 46 (78.0%) had abnormal lashes. However, the presence of abnonnal eyelashes with past lid surgery was not significant. The severity of trachornatous trichiasis cases was graded as 'm-tumed eyelashes only' (no cntropion) or 'in-turned lid mar- gin' ( entropion). The distribution of abnor- mal eyelashes by the severity of trachomatous trichiasis ts given m Table 3. Severe distichiasis/dysplastic eyelashes were seen in a significantly larger propor- tion of cases with entropion than those with trichias1s only. Eastern Mediterranean Health Journal, VoL 10, Nos 1/2, 2004 195 Table 3 Abnormal (distichlasis and/or dysplastlc) and norm11t ""Y""lashes among patients with trachomatous trlchlasls by severity of trichiasls Condition of eyelashes Abnonnaf eyelashes Distichiasis LJyspIas11c eyelasnes Both of above Total Nonna! eyelashes' Severity of trichiasls No entropion Entroplon (n ~ 14) (n ~ 66) No. % No. % 0 0.0 20 30.3 I 7.1 10 1::u:> 6 42.9 21 31.8 7 50.0 51 n.3 7 50.0 15 22.7 •RR 1.55; P = 0.05 (2-tailed Fisher exact test}. n = total number of cases. Discussion Oman is a trachoma-endemic country (Th- ylefors B, unpublished report). The national prevalence of trachomatous trichiasis has been recorded as 1.1 % [1]. The bilateral tarsal rotation procedure for managing tra- chomatous trichiasis cases has been shown to have a recurrence rate of 23~--;, as a short-term outcome and 60''.o as a long- tenn outcome in Oman [ 3,4], The present study attempted to determine the preva- lence of distichiasis and dysplastic eyelash- es among trachomatous trichiasis cases. The trachomatous trichiasis cases seen at the tertiary ophthalmic centre of Oman are likely to be cases in the advanced stages and thus they are not representative of all the trachomatous trichiasis cases of Oman. The oculoplasty surgeon used standard definitions to minimize the chances of mis- classification bias. Use of records to deter- mine the past history, and other factors related to exposure, minimized the recall bias. Age-sex. stratification enabled us to control for these and other unknown con- founders in the study. Thus, the outcome of the study is likely to be true picture of the examined sample. The study showed that a large propor- tion of the trachomatous trichiasis cases had dysplastic eyelashes and/or distichia- sis. Dysplastic and distichiasis eyelashes were more common in the younger age group as well as those having entropion. Even though male trachomatous trichiasis cases had a higher rate of these conditions, the difference was not statistically signifi- cant. Ocular conditions with chronic irrita- tion, such as Stevens-Johnson syndrome. ocular pemphigoid and the sequel of chem- ical bums to the eyelids and conjunctiva are known to cause metaplasia of the conjunc- tiva and skin cells and dysplastk eyelashes [51. Chlamydia trachomatis causing chron- ic conjunctivitis with elements of scarring also could cause similar rnetaplastic chang- es resulting in the growth of eyelashes at aberrant places. Thus a causal association of dysplastic and distichiasis to the chronic trachoma infection might be a possibility. 198 La Hevue de Sante de la Mediterranee orientale, Vol. 10. N° 1/2, 2004 Trachomatous trichiasis as a cause of chronic irritation resulting in dysplastic cycla:,h could not ln:: established in this study as no temporal relation could be not- ed because both events occurred at the time of examination. Omw ha.s <1. high pn:vaknct: of genetic disorders [6]. It has a high level of risk fac- tors, such as consanguinity, which are known to be responsible for different ge- netic di5ordcn [7]. Tlu: cxlt:nl and kinetics of genetic change in the outer membrane protein ( omp-1} gene of C. trachomatis in endemic areas of trachoma suggested a possible M5ociation al the mukcular level between the trachoma organisms and the host susceptibility [8,9J. Thus, genetic and molecular alterations might influence the cellular rc.spon:scc to C. truc.:hummts infec~ tion in the Omani population. Different types of human leukocyte an- tigen (HLA) markers for blinding trachoma in Oma.n have been ul,:;i.;rve:LI [IO]. They could be responsible for the different re- sponses to trachoma organisms at molecu- lar level. The abnormal cell growth rc3uJting in blinding lii1d1uma cases might be linked to different HLA markers. These observations suggest that ac- quired factors might be changing the host cellular environment causing an altered re- sponse to Chlamydia spp. organisms. The findings of the present study in the presence of the above-mentioned biologi- cally plausible corroborative evidence favours the hypothesis of a causal link be- tween trachomatous trichiasis and dysplas- tic and distichiasis. Further analytical epidemiological studies with larger sample are needed. Acknowledgements The authors are thankful to the Ministry of Health and the staff of Al N ahdhah Hospital for their Sllppnrt A special thanks to Mr Salah Al Harby and Mr Henry Doss for as- sisting in compiling the information, The authors acknowledge the active participa- tion of the pi'lli~nt" in this study. The preliminary report of first 30 cases was presented in at the Third Meeting of the Global Alliance for the Elimination of Trachoma held ::i.t Geneva in December 2000, Refarences: 1. Khandekar R et al. The prevalence and causes of blindness in the Sultanate of Oman: the Oman Eye study (OES). Brit- ish journal of ophthalmology, 2002, 66. 957-62. 2. International Statistical Classification of Diseases and Related Health Problems, 1989 Revision. ICD-10. Geneva, WorlCJ Health Organization. 1992. 3. Khandekar R, Mohamed AJ, Courtright P. Recurrence of trichiasis: a long-term follow-up study in the 8ullanate of Oman. Ophthalmic epidemiology, 2001, 8:155- 61. 4. Reacher MH et al. A controlled trial of surgery for trachomatous trichiasis of the upper lid. Archives of ophthalmology, 1992, I I 0:667-74. 5. Kanski JJ. Clinical ophthalmology: a sys- tematic approach, 4th ed. United King- dom, Reed Educational and Pro- tessiona! Publishing, 1999:3. 6. AI-Riyami AA et al. A community based study of common hereditary blood disor- ders in Oman, Eastern Mediterranean health joumal, 2001, 7(6): 1004-11. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 197 7. Sulaiman AJ et al. Oman Family Health Survey, 1995. Journal of tropical pediat" rics, 2001 ;47(suppl.1 ):1-33. 8. Smith A et al. OmpA genotypic evidence for persistent ocular Chlamydia tracho- m:;i tis infAr.tion in Tanzanian villaoe women. Ophthalmic epidemiology, 2001, 8:127-35. 9. Hayes LJ et al. Extent and kinetics of ge- noti o ohangee in the amp 1 ggne of Note from the Editor Chlamydia trachomatis in two villages with endemic trachoma. Journal of infec- tious diseases, 1995, 172:268-72. 1 O. White AG et al. HLA antigens in Oman is with blinding trachoma: markers for dis- ease susceptibility and resistance. Brit- ish Journal of ophthalmology, 1997, 81: 431-4. We wish to draw the kind attention of our potential authors to the importance of applylna thP Priitnrl,:il rP(]uirements of the EMHJ when preparing their manuscripts for submission for publ1cat1on. These provisions can be seen in the Guidelines for Authors, which are published at the end of every issue of the Journal. We regret that we are unable to acr:@pt r,,:ipers that do not conform to the editorial requirements. 198 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Review ..;.., ~ I .r JP} I ..:;.J ~ ~ J ½-".: . kt 1 ~ W:! ~ 1 ~ ~ J W \ ::, y:--:...,, ..l..#- ..:iii -1/ . ::, ~) ,._,..kll .__,., )..l ~ J _,..Lll ~4-iiJI 1~ J , ~II .h,I ~I ,j> ...,.;:;, iL: o.:W -.....1_,JJI o..\.b J_16 :.i.,,:,~I µ1) ~JJ.I r-WI) µ\l; ~ Jl µ1 ~I j_,,- 1,.A •~J ,~.JJ..I _,.-.\I c) ~I) ~I t~I Jj ..Li _jl ..::.,w.w.11) ~I iJ.J..I J;:J 1-+-,; ,.k_...dl (':" ... ~I -..JJ_;.-, ~ ~_,..;.JI ;}t) ,•-i"y.,:.)11 .h;I;~½ fW'. J. ..,....hJI .,;.,L,_~-- J. ~I ....;;_, ..:.,y")'.,:.( ~,....,J~ a,..IJ.,ul ..r'iJ ·,,?'";WI J..cli ~ ..::,.,J.i -_,5"'.>l.. • .':JI t 'wl .jl...u, ~ .j .._,.,. .r=-JI ~I .)l.,,.1II ),'-' __k,....; c:,• '../":},..,,'jl Medical practice with regard to physicians' mistakes and disease compllcatlons SUMMARY Thi,:; _c;t11rly oive,:;"' historical background on rngulations implamontod by lalamic achotara lo codify medical practice, and highlights the advance of science and technology in the modem era and the need for physicians (along with science and technology) to adhere to religious values. It discusses physi- cians' responsibilities, the issue of malpractice, and the difference between malpractice and complications. Recommendations are proposed to implement medical ethics in the curriculum of medical colleQes around the fslamic world and to promote the role of medical religious committees in Islamic world as is being done in Saudi Arabia. ,)"' ~L,.1,\1 1 c:,-<':"- E (~i) _:__~ ~ .:~ 1..,_,..,,1,~:> ~ <r';_.J_i> ..,,.-wJ, .,;,µ., _,.t ~~-""-" 319 /'~ cj .J Jl.b, 'u:. WJ .J --5) (•} _:.,~ ~\J _:.,,-! ,)L-) rJ ~I db J ~I.J,,~i ._,~J ~I ._:,,.- ':I; ~WI ~ _,t .. :J _j~ ';ii I y> --1, t _:.,,;jJi, I~ ( L.-,1, 800) .!,\1.i:.o) t..,,..i.,... 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I.Ii /Li.JI ;,a .. ~.l.h .__,,_...i_.;; --=i, ; • "' .....:.,/ '-- .., I._..~ I,,..• I..>..,..- ~ I ._.i,:;-- \...---.:r"" f-----;.. \ -.-,' ,,_;L,.._.<(!.1 J-~· ..:.,~ .;., ~) 'c.;..,.;.:..,,->_, o .,..-.LaJ1., y ;_, G _,s:;,_, i .,.~H_i .,1~ !) :;_,.,b cf )J.... _: _?I_;-' ' ~ ..J....ii ,..._;.,-, L.S, ,...,;.,_..;:,,_. J l,L::.,;.', ._$.:>J .. ., _,.-,)..UI oh .:.r" c_.,,-,,:...;.\.I 01.5'.J .b.>\'.,)1J cl._J1.! ,L.-1_,J.,.IJ .[ ?I ------kl',""· .J,1, .... - ... ._j, ,......., ,,...,,.-"'oJ o .1~-. ,.-,'c.JI ,- J.;.; ..__,;.l!I \,,,'c..J,.1 ,______hl1 .~·, H_l,~~ 1,l ._w;...·, 'I . """"'"'a""" ,.,, J V ' ..; . I J-----.. ~ i.... ...... ,., V ' U• .., ........--- .., . [ 3J (,:rWo * .:JJ~ j,i ~lj 4J,. ~ ,f ) ~ if) .....;,., _r!-)1 ~.J.).., <)) 'A.M. Mangoud. Department of Community and Family Medicine, Faculty of Medicine, King Faisal University Hospital, AI-Khobar, Saudi Arabia. Received. 27/05102; accepted: 08/03/04 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 199 ' ~ J ... :_,,.. i__w ,4, .i,:.'.JI r:f J..JOI_,; ,;,_,,,,h)i oL ... }-•-..:.J ~fJ ,..::...,_JJ..I .,..,,_,JI,_) lli,.,.,_i..,, l,J..i; ~I r:U. ctiJ ,..,.-:-1~:.1 :·: .·,•J ,,...;...Ji ~I .,_11 ,.;~_;: .. \1 o;")'JI ..:.,Lt/;Jt, .L..i)1 1 , 1.L:J1 j_l1 .;._,Ji.:ll ~ p)\k':,'1 ..__ \ - I "- ~ • ~ - · • \ • , t.~ ~ T 1. " .._-;~ L ~I o ·--'--"'"i ,>I._::; 'J _l.oJ ,a_,..I.J•, ..;..,l,;\S:,.'1\, .)tS'.:il J')\;,.:.l, .:,~W';, ~I 11\...., 1 ~ J.i, ,----\.J.', ,.__, - _..,---er-· ..,,. ..,: -I_.,. . _, i._.. ~ V __,. _.,. . . 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'JI ~ .1..,.:,.\ri :;_,,-L<h .y Y' .J.,]£ ~wt.i ~I --,--1,.)i r ~ j-,,-,,G e (1) (2) 212/4 ,~U--1; ,370 ..Ja,f-L!I_, -3466 ;,_,,.1_. ..:,,,I} ,53/8 ,_Jt.......;!1_, ,4586 :,)',::, yi "->:-_,>I :..::.....,JJ....1 . [228/2 ~II ~..\l-)11 :,Ji,,.!'il) ..,s,"J..1 1 w1n ,::,L')". ~ ::--5'LL1 Ji...i . .: -141 ,_.,4-,.,.:1 J (3) ( 4) The Use of Essential Drugs, Report of the WHO Expert Committee. Geneva. World Health organization, 2000 (Technical Report Series, No. 895). Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 207 (5) Evidence-based medicine: principles for applying the users' guides to patient care. Joumat of the American Medical Association, 2000, 384(10):1290-6 (6) Integrating research evidence with the care of the individual patient Journal of the American Medical Association, 2000, 283(21):2829-36. (7) U~ing electronic health information r"•ources in svid,;.nc.a-bA~ practice. Journal of the Am&rican Medical Association, 2000, 283(14):1875-9 . . 1980 ..,..JWI );; -J).ill <,Aall L) ~I a.lJ..l--" =(i...JI J.,&- -~pl (8) .1983 .1, 136 c..-"' ,_l'/.,.J1 ~I ,_;i)I i_1',,J_,, ~JI ~~J-·" :._:,eJJI Jr' .l.<"-i .;; (9) .l.a..u</ Lo) 154/1 1")1..JI ~ .;_,,1 01..ul _,J 'i"'L;'.Ji tl...,.a... J 1l5:.,...\J1 ..\;l.,_i, (10) .2000 J}';JI ~'._,.-!'WI)"'~\ ~1 '.\s'-r}-" _, __ ..:. 1..>-I ~,1.< (11) .93/5 .,j.t-'-!\..- .;I (13) ,<3<~1 ~ ,457_454 <...,, ,~ ~;J.t }J';IIJ ~I :\...:,,-1):-1 1~i :).,,.:,.ll ~ ~I {14) . 1993 Jjlk)l .560/._j 945 /2 ~Li~,)1 u-1 ~ ~j tWl ~I j,"-...ll.1 l15) .";1J_p":. ;Jt-/ IJ/'Y:-1 Jtu J.J. JP.ill -.,;.,i...,...__)1 J,_;li .J a.,,,k!1 ~..,;-J.1 (16) 206 La Hevue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Review The district health system: a challenge that remains B. T. Shaikh1 and F. RabbanP SUMMARY The health care system in Pakistan has been confronted with problems of inequity, scarcity of resources, inefficient and untrained human resources, gender insensitivity and structural mismanagement. With the !Jr ~riuus nealttl status or me peopre and poor indicators of health in the region, health care reforms were finally launched by the government in 2001, There are, however, numerous challenges and constraints in the system. The future health of the nation depends on this decentralization initiative. All our efforts should be concerted to support and facilitate the new system, which wil! mature into institutionalization of the health services ;it thl'! rfo;:trict ,~~I. Most importantly, lt wm holp in otrcngthening the primary heal ti, r..:cut:i :s1trvlces catering to the major fraction of the population. Besides political commitment, we ought to maintain attitudinal, behavioural and cultural conditions conducive to letting this system flourish. Introduction Health is a basic human right, and must be av:iil;:ihle and accessible to all in an afford able framework. To this end, an integrated approach to public health would combine preventive, promotive and curative health :it all levels. Promoting good governance and fairness in the health sector through meaningful and consistent emphasis on prompt delivery, equitable and professional SP.rvires, transparency and accountability must become a cardinal principle of the health sector, where social sector invest- ment is perceived as a mathematical equa- ti rm In many parts of the world, progress towards the goal of 'health for all by 2000' has been slow and in some cases unachiev- :ih 1 e. Whilst most developing countries for mulated broad policies, strategies and plans with this goal in mind, the modus operandi has been ·weak and questionable. In recent years, reforms in Malaysia, the Philippines, Suulh Kvn:-:a, Spain, Tanzania and Uganda have had mixed results [1,2]. The objec- tives were common: improving 'allocative' and technical efficiency; innovating service delivery, impruving quali1y, rransparency and accountability; and achieving greater equity in the distribution of resources [3]. All these efforts may also be aimed at add- ing new rc:;oun;i;;;~, cin.:umventing ineffi- cient bureaucracies and assuring em- powem1ent of the people ( 4]. This article is based on a thorough liter- ature ri.;vicw, not only from llie lrn:al jour- nals but also from some international ones. A few publications of the United Nations Development Programme and the World Bunk on the cmbjcct of dect:11lrnliF.ctlion were consulted to revie\v best practices in 'Health Systems DiVision, Department of Community Health Sciences, Aga Khan Umversity, Karachi, Pakistan. Received: 15/06103; accepted: 20/08/03 Eastern Mediterranean Health Journal, Vol. 1 0, Nos 1/2, 2004 209 various countries. Several types of decen- tralization case studies were included, and the official policy documents of the gov- ernment of Pakistan were also referred to verify certain details. Current situation in Pakistan Healthy public policy co"vcrs policy deci- cdons in any oector or o.t any level of gov- ernment and is characterized by an explicit concern for health and accountability for health impact [5]. It is an established fact that most of the developing countries :irE'" not spending more than 2% of their gross national product (GNP) on health, resulting in poor coverage of public health services. The Government of Pakistan spends r1bo11t 0.81h1 of GNP on health care, v.hich is low- er than some neighbouring countries such as Bangladesh (1.2%) and Sri Lanka (1.4%) (6]. In Pakistan, only 107%, of the total annual budget is allocated for econom- ic, social and community services, and 43 out of I 00 Pakistan rupees are spent on debt servicing [ 7] A further increase in the allocation for the health budget may not be possible for many years to come, there-· fore, alternative methods of health financ- ing, im~luding cost-sharing, have to be considered. In most of the developing countries of Suuth Asia, out-of-pocket household expenditure on health is at times as much as 80% of medical expenditure [8]. For health expenditure in Pakistan, it is about USS 17 per head per year. out of which $ I 3 is out-of-pocket private expen- diture [9]. Our country spends 80So of its meagre health budget on tertiary care ser- vices, which are utilized by only l 5~o of the population. In contrast, only 15% is spent on primary health care services, used by 80% of the population [J(J]. Quality o"f health care is questionable, with consider- able expenditure on unnecessary and inap- propriate (and sometimes unsafe) care. De- spite Pakistan being an advocate of the Alma Ata Ueclaration and having a hugt: primary health care infrastructure ( set up in the early 1970s, but having declined over the past 2 or 3 decades), there is still a dearth ottraincd human resources, im:4uity in financing of health care and a scarcity of reliable information. In this scenario, the devolved district health services are also presented with an opponuniry to tack.k Ll11; health-financing situation. It is obvious that there is willingness to pay for primary health care in the public sector services if users receive improved care. Distrii..:ts would in this case be able to recover sub- stantial costs and maintain their incomes. Ha!f a century down the road from in- dependence, social and demographic imli- cators in Pakistan present a gloomy picture, despite advancement in the eco- nomic sector. The current effort of the government to decentralize the sysu::m ur governance included the health sector, as- signing responsibility for health to the newly-created local governments. The dis- tnct governments, however, srill la..:k lh.: capacity and powers to cope with their new responsibilities. There are a few questions which arise nght away while considering rhe pruc.:ss of devolution. Arc basic data on the charac- teristics of the population, levd of health, major health problems and coverage of es- sential health care readily availabk i11 t\11:: district? Have district priorities been ap- praised? Have targets and objectives for health and health care been set? Docs the district have a plan of ac1ion for impurtaul programmes such as health promotion, maternal and child health, school health, environmental sanitation, occupational health, control of diseases and curati vc sci - vices? Are there effective mechanisms to make communities and the public and pri- 210 La Revue de S,mtti ll'-l la Medtterra.nee or1enta.1e, Vol. 10, Nv 1/2, 2004 vatc health sectors work together? Are there adequate resources, logistics, organi- :zational arrangements and inccnti vc~ to ensure prompt implementation of pro- grammes? Will activities be monitored reg- ularly? ls there a mechanism for quality m:st1rance? Will periodi'° evaluotion be cnr- ried out? Many of these remain unan- swered, even after the passage of 2 years. Devolution of power in the health department There has been an obvious political, snc-ial, economic, demographic and epidemiologi- cal need for health sector refonn in Paki- stan [11]. The ultimate goal of any health sector reform is to improve the aggreg:Hl' health status of the people, whether through de-concentration, devolution or delegation [ / 2, I 3]. It includes packaging of services; the structures and organization of service delivery; financing; and the con- sumer-provider relationship [14]. All these efforts are geared towards the cmpovver- mcnt of the people at grass roots level. The district will be the dominant revel for decision-making in the health department. The quantity, quality and access of inte- grated health care delivery will he im- proved. This will promote good gover- nance and human resource development for sustainable development. These steps shou Id be the answer to cha! knges I ike high infant and maternal mortality rates, low prevalence of contraceptive use and a high population growth rate, along with scarce income and health resources. The devolution plan in general as well as the health-related section can be analysed in 4 different respects: <lcvolution (political power), decentralization (administrative authority), deconcentration (management functions) and diffusion (j)ower-authority nexus) (J 5, 16]. Therefore, the aim is to es- tablish a set of activities that include im- proved access Lo aml utilization of services; community involvement; local accountabil- ity [17]; integrated, comprehensive health care deli very; in tcrsectoral collaboration; and a :strvJJg 'hollum-up' approach to plan- ning, policy development and management, Hence, attaining equity, effectiveness and efficiency in the health sector should, in principk, kwJ ll' sustainability in the sys- tem. Responsibilities/functions at the provincial and district level The responsibility of the provincial govem- mPnt will cover policy-making and kgic;Ja tinn for the province; drug control under the Drug Control Act; monitoring and regu- latory functions of medical and allied insti- h1tion~: h,•;i 1th re~e11rch and related health infom1ation gathering; interacting with do- norn and international agencies: personnel management; provincial procurements; and supervision anrl mnnitnring of he:1lth pro- grammes [ I 8]. Reproductive health and nutrition edu- cation; prevention and control of commu- nicable- and noncomm11niC'::ihlP diseasei1; food and sanitation; health management in- formation system; envuonmcntal and oc- cupational health; ho;;pital referral systems; ambulance services: and financilll ,1ml rf'r- sonnel management will be the responsibil- ity of the district government. The district government will also look after primary and secondary level health facilities. Besides these, there \.Viii be a district health management team, which will com- prise a district health officer, managers from other relevant departments, puhlic and private sector health care providers and community representatives. The district Eastern Mediterranean Health Journal, VoL 10, Nos 1/2.2004 211 health management team will adopt a team 11rprnach, share and exchange views, and reduce the workload of the district health officer, optimizing the utilization of human resources and improving cooperation and l'ollaboration between stakeholders [191. It is expected that well-defined structures; meaningful partnerships; capacity-building at provincial, district, sub-district and com- m1 mit y leveh; detailed mapping of resourc- es and services; and integrated approaches tmvards programme planning will emerge as desired outcomes. The district will get its hudget share according tu population size, socioeconomic development, health infrastmcture, health needs and problems, and indicator-based performance evalua- tion. This will contribute to and maintain equitable allocation of health resources be- tween different districts with different pri- orities. Challenges and constraints The new actors in the health svstcm arc looking for motivaliun arnl im;i:.utive5 for their new assignments. Defining their ad- ministrative roles and jurisdiction still rc- mai ns a challenge. The distribution of financial puwi:r bi:Lwi:i.::u .111 ~,v iu1,;ial and di:;- trict representatives is mandatory. The new political government of Pakistan is still in the early stages of dealing with this dilem- ma. Thuugh Lili:,; is the plmse uf tnmsfor- mative learning and transition, the jurisdiction of the Public Service Commis- sion; medical colleges; tertiary hospitals; am.I foucntl i11ilitttivi:~ like the programmes for AIDS, malaria, tuberculosis and lady health workers, and the Expanded Pro- gramme on Immunization need to be dc- fini:d. Tiu: nul'ial sti:p, however is building awareness in the general public. ln countries where the administrative machinery has been decentralized to dis- trict level successfully, the development of the district health systems has been re- markable, despite an initial decrease in pro- ductivity, reluctance of the centre to share power and instability of the polit1cal frame- work [20]. Decentralization without dele- gation of appropriate financial and administrative powers does not work. There is also a need to ensure political com- mitment inside the district to create a fis- cally and socially responsible management. The process requires trained health manag- ers at ct1stnct level, a team approach and planning support from the centre in the form of clear job descriptions, guidelines and advisory staff [21]. Devolution to the district level is impera1ive, am! l.Crul.Cial if primary health care is to be improved. The advantages are a manageable size at district level, easily obtainable information and smooth communil:alion ui:twecn different stakeholders [22]. Moreover, decentralized programmes can be designed with a knO\vledge of the local culture and circum- M<1m.;c::., thereby improving technical and allocative efficiency with appropriate local institutional capacity building [23]. District health managers need to be trained in arcus like HIV/AIDS, control of diarrhoeal disease/acute respiratory infec- tion, the Expanded Programme on Immuni- zation, maternal and child health/family planning, health education, health manage- ment information system, nutrition, envi- ronment and sanitation, community mobilization, personnel and project man- agement, etc. [14]. lnfonnMinn ancl data regarding population, health indicators, de- ployment of funds and coverage will be needed to appraise the district priorities and to set future ohjeetives and targets. It will only then be possible to ascertain the 212 La Revue de same de ra Medi!erranee orientale, Vol. 10, N° 1/2, 2004 strenglhs and weaknesses of the existing district system, and take measures to im- prove it. The district health C'\)':Sk111 lids of- ficially been with us for more than 2 years. The transformation of the fragmented and inefficient apartheid health system into a coherent health 5ystcm ca pa.bk of at.:h.ln:~:;- ing the health needs of the vulnerable and marginalized population was, and still is, a massive challenge. At the same time a:s a.dopting llii~ m;w system, we cannot ignore ambitious targets 1 ike gender equality, empowerment of women, reduction in mortality rates for in- fants und chi ldrcn, reducing rnatcrm1l mu1 - tality, improving primary health care and reproductive health services and poverty reduction. In order to meet such challeng- es, the dcccnlrulizcd 5y3tcm ha:s lo fu1:u:; on equity, efficiency and good governance [4,25] and on developing tools to monitor and assess health system needs, especially in rural areas [26,27]. Tod,:iy, about 67% uf Pakistani people live in rural areas [28], but they have been completely neglected and disenfranchised in the decision-making processes thut affect their daily live~. L.:~- sons could be learned from the best prac- tices of Brazil, Columbia, Morocco, South Africa and Chile [29,30]. Conclusion With the transfer of administrative and fi- nancial powers to district authorities/local bodies, programmes relevant to the local needs and priorities will be facilitated [21], resources will be mobiliLcd and greater community participation wiU be ensured [JO]. There will be continuous monitoring and surveillance of continuity and quality of services, thus ensuring sustainability. This will create motivation, confidence and a sense of ownership. The strengthening of the first level care facility will bring an im- provement m various health indices. The services and programmes could be de- signed on rhc concept "by the people, tor the people, of the people" through more meaningful community participation, mobi- lization and empowerment. Of course, lit:alth system research should be part ot every plan now. It will assist the newly- created district health system in defining clear goals and objectives, formulating strategies and providing quality services to the most underserved groups in the popula- tion. Only this approach can provide evidence-based services and address the nt:t:ds of lhe community. Decentralization has considerable promise. The empowem1ent of the decen- tralized bodies will lead to institutionaliza- tion ur democracy, which is lhe key to · progress. It will promote greater communi- ty participation, responsiveness of govern- ment institutions and increased flow of infunnation between people and govern- ment [31]. This will not only make devel- opment programmes more flexible in catering to local need,, but also transparent uud sustainable. Health care is a right and not a privilege. Today, we are living in an epoch of urban- ization, industrialization, demographic tran- si tiun and globalization and thci r repercussions. Pakistan needs increased political freedom, economic facilities, so- cial opportunities and transparency to brt:ak. Lht: vicious cycle of corruption and underdevelopment. This devolution plan, if granted full legitimacy, presents an oppor- tunity to usher in a more democratic sys- tt:m uf governance and effective and transparent health care delivery and man- agement. For that to happen the citizens of Pakistan will need to participate proactivcly in lht: cunstrnction and functioning of the new in~titutions, and take advantage of the new environment for self-emprnvenncnt. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 213 References 1. Healtn sector rerorm m Asia and the Pa- 11. l::;lam A. Health ::iector reform in Paki,:;tan: cific: options tor developing countries. Why it is needed? Journal of the Paki- Manila, Asian Development Bank, 1999. stan Medical Association, 2002, 52(3): 2. Rodriguez E, De Puelles P, Jovell A. The 95-100. 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Decentralization and primary health care: some negative im- plications in developing countries. Inter- national journal of health services, 1994, 24(3): 459-75. 23. Ruualir10 DA, Picazo OF, VoetOerg A. Does fiscal decentralization improve health outcomes? Evidence from a cross country analysis. Washington DC, World R;mk, ?001 (Polley l=le,;;garch PapGr No. 2565). 24, Vaughan JP, Morrow RH. Manual of epi- demiology for district health managers. GGneva, World Hcolth Organization, 1989. 25. Roy A. Efficiency and equity implications of the health care reforms. Social sci- en,:;~ ~nd medir:;ine, 1994, 39(9).1189- 201. 26. Cassels A, Janovsky K. Strengthening health management in districts and prov- inces. Geneva, worIa Health Organiza- tion, 1995. 27. District Health Council. Local voice in health planning. Ontario, Canada, Minis- try of I lealth, 2002. 28. World population data sheet. Washing- ton DC, Population Reference Bureau, 2002. 29. Bossert T J et al. Decentralization and equity of resource allocation: evidence from Columbia and Chile. Bulletin of the World Health Organization, 2003, 81 (2): 95-100. 30. Quraishi S. Decentralization to district level. Background paper prepared for the second local dialogue _qroup meet- ing, Islamabad, 12-13 March 1988. Islamabad, UNDP Pakistan, 1988. 31. Janovsky K. The challenge of implemen- tation: district health systems for primary health care. Geneva, World Health Orga- nization, 1988. 32. Manor J. The promise and limits of de- centrati?atinn Pciper pro.>se-ntgd at thG FAO Technical Consultation on Decen- tralization, Rome, 16-18 December, 1997. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 215 Repot1 Development of the Regional Malaria Training Centre in Bandar-e Abbas, Islamic Republic of Iran H. Vatandoost, 1 A.R. Mesdaghinia, 1 G. Zamani, 1 R. Madjdzadeh, 1 K Holakouie, 1 B. Sadrizadeh,2 H. Atta3 and P.F. Bea/es4 SUMMARY The resurgence of malaria has highlighted the need for training health professionals in malaria control planning. The course described here was organized jointly by the World Health Organization, the Ministry of Health and Medical Education and the School of Public Health in Iran. The first course was held in 1997 and the fifth WHO-approved course is now in progress. The course focuses on dynamic, interactive, practical and problem-solving learning methods. It provides the participants with the knowledge, skills, competence and confidence to be able to analyse the malaria problem. The course fulfils the requirements of the Roll Back Malaria campaign. In the 8-week training period subjects such as basic bio-statistics and epidemiology, microcomputing, malaria parasitology, malaria entomology, vector control, case management, epidemiological approach to malaria control, field work and planning for malaria control are taught. Each participant is evaluated in each subject. A total of 71 participants from 17 countries in the WHO African and Eastern Mediterranean Regions, mainly those with a malaria problem, have graduated. Introduction The WHO Regional Malaria Training Cen- tre in Bandar-e Abbas, southern Iran, was inaugurated in 1996 and held its first inter- national training course in 1997. Since that time there have been courses annually, the fourth of which is presently in progress. The development of the centre, and of the international course, is a collaboration be- tween the Ministry of Health and Medical Education, the School of Public Health of the Tehran University of Medical Sciences, the WHO Regional Office for the Eastern Mediterranean and WHO Headquarters. The purpose of this report is to put into perspective and on record, the develop- ment of the Regional Malaria Training Cen- tre and the series of 4 international training courses that have been held there and our vision for the future. The Regional Malaria Training Centre Historical evolution In February 1992, the first Iranian Con- gress of Malaria was held in Zahedan, Sis- tan and Baluchistan province. This coincided with a revamping of the national malaria control programme to accelerate control of this disease in the 3 most affect- ed provinces in the country, Hormozgan, 'School of Public Health and Institute of Health Research, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. 2 Ministry of Health and Medical Education Tehran, Islamic Republic of Iran. 3 World Health Organization, Regional Office for the Eastern Mediterranean, Cairo, Egypt. •world Health Organization, Geneva, Switzerland. Received: 01/05/03: accepted: 22/06/03 216 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Kerman and Sis tan and Baluchistan. Advan- tag~ was taken of the presence of WHO to organize rapidly and conduct a short work- shop on planning and management of ma- laria control programmes for senior staff of the Ministry of Health and Medical Educa- tion. The value of this for the realization of the accelerated control programme was very soon recognized and discussions were held between the Ministry of Health and Medical Education, the dean of the School of Public Health and WHO on the possibili- ty of developing a training programme in the Islamic Republic of Iran for national staff at the district level. A technical review of global malaria control efforts was carried out during the l 980s by WHO through the expert com- mittee meetings on malaria (18th and 19th) and the scientific working groups. This culminated in the endorsement of the Glo- bal Malaria Control Strategy by the Minis- ters of Health of more than 90 countries at the WHO Ministerial Conference on Malar- ia held in Amsterdam in October 1992. The strategy was also endorsed in subsequent years by the Economic and Social Develop- ment Committee of the United Nations. This political endorsement of the way for- ward opened up opportunities for a wider global recognition of the malaria problem and its impact on the global economy. It also raised awareness among the peoples of the world of the plight of the millions of persons affected, especially children, in malaria-endemic parts ofthe globe. In 1997 and 1998, WHO provided US$ 10 million each year for accelerated malaria control in Africa, much of it spent on pro- gramme planning and human resources de- velopment. Building on the momentum created, WHO established the Roll Back Malaria·campaign in 1998, directed princi- pally, though not exclusively, to the prob- lem in Africa. Spurred on by these events, the Islamic Republic oflran began developing a nation- al training programme for district health centre managers to plan and manage malar- ia control activities. The need for this was recognized following the revamping of the malaria control programme in the 3 south- ern provinces of the country and imple- mentation through the primary health care system. In 1996, the WHO Regional Committee for the Eastern Mediterranean Region dis- cussed the malaria problem in the Region and the approach to control. A resolution was passed fully supporting the establish- . ment of a regional malaria training centre in the Islamic Republic of Iran. This fitted in well with the development of the training programme in Iran. The Centre for Health Education and Research in the Tehran School of Public Health, situ- ated in Bandar-e Abbas, Hormozgan prov- ince, was considered ideal for the purpose. It was, therefore, designated as the WHO Regional Malaria Training Centre in 1996. Relevance to the local health care · structure In Iran, each province has a University of Medical Sciences as part of the structure of the Ministry of Health and Medical Educa- tion. The vice-chancellor for health affairs of each of these universities is the person responsible for the delivery of health ser- vices to the population. During 1996, dis- cussions were intensified between WHO Headquarters, the Regional Office for the Eastern Mediterranean, the Ministry of Health and Medical Education and the Dean of the School of Public Health regarding the development of the Regional Training Cen- tre. A decision was made to hold the first international course at the centre in 1997 as a means of precipitating its further develop- ment A 12-week course was designed on Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 · 217 malaria and other tropical diseases and the planning and control of these diseases. The curriculum wa_s developed during 1996 and 1997, and faculty members of the School of Public Health were identified as tutors and facilitators to cover as many subjects as possible. The close collabora- tion between the provincial universities, the training centre in Bandar-e Abbas and the Tehran School of Public Health was crucial for the success of this activity and was, therefore, cultivated from the very begin- ning to facilitate the smooth running of the course and especially for the development of the field training sites and the field exer- . cises. Principal objectives of the training centre From the very outset, the authorities in Iran identified the need for training in planning and management for malaria control. The academic stmcture of the Tehran Universi- ty of Medical Sciences School of Public Health, with satellite research stations dis- tributed in 10 of the 30 provinces in the country, is such that basic subjects such as parasitology, medical entomology, vector control, general epidemiology and simple statistics could be adequately covered. However, the more malaria-specific sub- jects such as the epidemiological approach to malaria control, clinical management of the severely ill patient and planning and management were not areas for which ex- perienced and knowledgeable teaching staff were readily available. In addition, with the revamping of the national malaria control programme by the Ministry of Health and Medical Education and planning the accelerated control programme for the 3 southern provinces of Hormozgan, Ker- man and Sistan and Baluchistan, the need for well-trained health professionals to plan and manage the programme at district level was recognized. Thus, it was primarily to meet this national need and to comply with the WHO Regional Committee resolution that the Bandar-e Abbas centre was devel- oped for international training courses in planning and management. The preparatory period was the latter part of 1996 and the first 7-8 months of 1997. During that time the physical facility was set up, the tutors and facilitators prepared themselves, the evaluation instruments were developed, the training materials completed and printed, supplies and eq~ipment procured, books ordered and delivered for the library and trainees and the course advertised within the Region and world-wide to recruit train- ees. The training courses The first course was for 12 weeks, from 27 September to 18 December 1997. It was on "Malaria and other tropical diseases and planning their control" and included, besides malaria, leishmaniasis, schistoso- miasis and filariasis. There were 17 partici- pants, of whom 10 were from Iran and the remainder from Afghanistan (2), Sudan (3), Yemen (1) and Zambia (1). Field train- ing was for only 3 days in Siahu district of Hormozgan province. Two teams were formed; one stayed and worked in the vil- lage ofSagazAhmadi and the other in Siahu town. A joint WHO, Ministry of Health and Medical Education and School of Public Health certificate of achievement was awarded to those reaching the required standard. The second course was held at the Re- gional Training Centre in 1998 from 22Au- gust to 24 October. This was the first part of an 8-week course, which did not include other tropical diseases. It was on "Malaria and planning its control" and all 21 places on the course were filled. Participants came from Egypt (1 ), Islamic Republic of 218 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Iran (13), Namibia (1), Somalia (3), South Africa (1) and Yemen (2). This was the first course which had a female participant. The third course was for 8 weeks, from 22 September to 18 November 1999. A to- tal of 20 participants attended, of whom 8 were Iranian and the remainder from Botswana ( 1 ), Egypt (1 ), Iraq (I), Jordan (1), Saudi Arabia (1), Somalia (2), Sudan (I), Syrian Arab Republic (1 ), Yemen (2) and Zimbabwe ( 1 ). This was the first course where the intt:malional participants outnumbered the nationals. The fourth course is presently under way, running for 8 weeks from 6 Septem- ber to 2 November 2000. Unfortunately there are only 13 participants, 9 Iranians and the remainder from Afghanistan (1 ), Egypt (1), Pakistan (1) and Saudi Arabia ( 1 ). There are 2 women on the course, 1 from Iran and 1 from Pakistan, making a total of 3 since these courses began. During these courses, 71 participants have been trained, a total of 40 (56.3%) were from the Islamic Republic oflran and 55 (77.5%) were medical doctors. The learning approach Since the inception of the training course, a participatory approach to learning has been adopted, with the learning being dynamic, interactive, practical and problem-solving. E111phasis has been placed on p~~cals, sma11 group discussions, individual projects and team fieldwork to develop the skills and competence necessary to plan and manage a malaria control programme. Lectures have been kept to a minimum with a few guest speakers only being invit- ed. Tutors have been encouraged to reduce lectures to short introductions to the sub- ject with discussions and exchange of ex- perience and ideas predominating the sessions. This approach to learning has taken time to be accepted by all the tutors involved in the course. All tuition is in the English language. The faculty To ensure the sustainability of the course and the potential of the training centre, at- tention has been directed towards develop- ing a national faculty to teach all 8 disciplines presently in the course curricu- lum. This has been a gradual process. Since the beginning, external tutors have been required for clinical malaria, epidemi- ological approach to malaria control and planning and management. All other sub- jects were taught by national specialists in the field. As an approach to strengthening the na- tional capacity to manage the whole curric- ulum "shadow tutors" were appointed to teach alongside the external tutors. It was difficult at first to find suitable young staff for this purpose, to ensure continuity and sustainability. However by this year's course (2000), the difficuity has been solved. A national clinician working in the private medical sector, who is very knowl- edgeable in clinical malaria, managed the teaching of those sessions with compe- tence. An epidemiologist from the School of Public Health, who has been appointed Director of the Training Centre, and a PhD graduate are gradually assuming responsi- bility for the course in epidemiological ap- proach to malaria control. For the first time 2 national tutors have been assigned as "shadow tutors" for planning and manage- ment, an MD and the PhD graduate who is also taking over the epidemiological ap- proach to malaria control. These 2 are graduates from the first international course held in 1997. Thus, in a year or two all subjects will he adequately taught entire- ly by Iranian tutors. Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 219 Curriculum development The curriculum has been evolving over these past 4 years. Changes have been made as a result of feedback from the par- ticipants themselves and from the tutors. The content has been updated in line with the WHO general approach to malaria con- trol, in particular the Roll Back Malaria ob- jectives and main thrust. Twelve weeks was clearly too long for senior managers to be away from their duty stations. The training period has, therefore, been reduced to 8 weeks. Even this is felt to be too long by some; it is, however, dif- ficult to reduce the time further without a large investment of time and money. There are 3 objectives to be achieved by the end of the course, when the partici- pants should have gained sufficient knowl- edge and skills to be able to: • analyse the malaria situation and prob- lems and find solutions, • plan, impkment, manage and evaluate antimalaria programmes, • develop a training programme for ca- pacity building for malaria control. The basic subjects are oriented towards malaria control and have heen found to he necessary in view of the heterogeneity among the participants on entering the training programme. The course is aimed at providing district level, responsible, health professionals with the skills and compe- tence to be able to plan, manage, evaluate and replan malaria control programmes with the resources available and as an inte- gral part of the health system of the coun- try. The course is not designed to train the participants in research methodology and its implementation, nor is it intended to pro- duce microscopists, parasitologists, ento- mologists or vector control specialists. The time spent on the basic subjects is justified to bring the participants up-to-date. In ad- dition, it provides them with the skills, competence and confidence to supervise the diagnostic, entomological, vector con- trol and other services under their authori- ty. Furthermore, a thorough knowledge of these subjects is essential to be able to un- derstand the epidemiological approach to malaria control and for programme plan- ning purposes. The structure and content of the course can best be illustrated diagrammatically (Figure 1). Field training The field experience is a critical part of this programme. This has taken longer to devel- op for a variety of reasons. The experience in the year 2000 has been the best to date but improvement is still required. The first course in 1997 provided only a 3-day field experience in 2 health districts of Hormozgan province, Ahmadi and Si- ahu. There had been no preparation ahead of time and thus the experience was very limited. Accommodation could not be found and participants travelled daily to the fieldwork sites. In 1998 the field experience was for 5 working days in 3 districts of Hormozgan province, Minab, Roudan and Siahu. Ow- ing to the absence of suitable accommoda- tion, the participants travelled to the sites from the training centre in Bandar-e Abbas by road on a daily basis, a 1 ½-hour journey. In 1999 WHO provided a consultant from 9 to 28 May to help select and develop 3 field-training sites for the 1999 course. These were the health districts of Minab in Hormozgan province, Kahriuj in Kerman province and Iranshar in Sistan and Bal- uchistan province. They are accessible by road from the training centre in Bandar-e Abbas with the exception of lranshar. The 220 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 Basic epidemiology and simple statistics Weeks 1-3 The use of microcomputers Malaria parasitology Malaria disease management Malaria entomology Week4 Epidemiological approach to malaria control Weeks Field exercise on situation analysis and stratification in a h ealtn district WEteks 6-8 Planning and management of malaria control programmes: theory and practice Figure 1 Course structure team of participants travelling to Iranshar will first have to fly to Chabahar and then travel by road for 5 hours to Iranshar. Nev- ertheless, they represent excellent exam- ples of the different epidemiological types of malaria in Iran and thus can be expected to provide the participants with the best possible experience. A list of data that need- ed to be compiled and translated into En- glish well before the course commenced was drawn up and left with the heads of the Development of a plan for malaria control by each participant for the country, or part of the country, where the participant is working, using data brought to the course by the participant district health centres. During the remain- der of 1999 this data was collected, com- piled and translated. Unfortunately, at the time of conducting the 1999 training course, owing to security issues, the par- ticipants were nut permitted to travel to Kahnuj and Iranshar. Thus, they were as- signed to the same 3 areas in Hormozgan province as in the 3 previous courses, but only the statistics for Minab were readily available as planned. The outcome was al- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 221 most the same as in previous years: accom- modation in Siahu was very poor and the participants had difficulties. The exercise was nevertheless useful but not implement- ed as planned. In 2000 there were only 11 participants, which was not enough for 3 field teams, so only 2 field sites were needed. The course manager and coordinator decided to select Minab health district in Hormozgan prov- ince, which had been used in the 3 previous courses, and Chabahar city and health dis- trict in Sistan and Baluchistan province. The former was accessible by road and the latter by a 50-minute flight from Bandar-e Abbas. The experience was much im- proved and appreciated by all participants. Accreditation Since the inception of the course, 2 certifi- cates have been awarded jointly by WHO and the School of Public Health, a certifi- cate of achievement for those reaching the required standard and a certificate of atten- dance for those who satisfied the atten- dance requirement but who did not come up to standard otherwise. Following long-standing discussions with the university, the course has now been accredited as a diploma course of Te- hran University of Medical Sciences. The tutor/trainee contact is 350 hours and the standard of tuition has reached an accept- able level for the award of a diploma. The diploma is in "Malaria and planning its con- trol," designated DMPC. The year 2000 class will be the first to graduate with this university diploma. This is a major step forward in the de- velopment of the course and is expected to increase the attractiveness of this course to overseas participants as well as nationals and contribute to its sustainability. Course management The course is organized and managed joint- ly by WHO (WHO Representative, Islamic Republic of Iran; the Regional Office for the Eastern Mediterranean; and Headquar- ters), the School of Public Health of Tehran University of Medical Sciences and the Ministry of Health and Medical Education. The course director is the dean of the School of Public Health; the course manag- er is the head of the Entomology Depart- ment in the School of Public Health in Tehran. The management of the course has also evolved over the 4 years that it has been running. The long experience that WHO has in planning, organizing and implement- ing international courses on malaria has been fully exploited in establishing the Re- gional Malaria Training Centre and the in- ternational course. For the first 3 courses, WHO provided the technical coordinator for the whole period of the course, and the School of Public Health a national counter- part. From the present course, the course administration will be carried out by the course manager and the role of technical course coordinator has been shared be- tween the course manager and the director of the training centre in Bandar-e Abbas. Financial management and accountabili- ty is the responsibility of the course direc- tor. Requests for allocations are made to the course director by the course manager. The actual accounts are maintained with the assistance of the School of Public Health, Tehran University of Medical Sci- ences. Multisectoral collaboration The structure of the health system in the Islamic Republic of Iran greatly facilitates the possibility for close multisectoral col- 222 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 laboration. The establishment and develop- ment of the Regional Training Centre, and in particular the malaria training course, have fostered close collaboration with the provincial universities of medical sciences ofHormozgan, Kerman and Sistan and Ba- luchistan. Working closely with the vice chancellors for health affairs of these uni- versities, good collaboration has been es- tablished with the district health authorities, especially in the districts where the field training exercises have been carried out. The chancellors of the universities of me- dical sciences in each of these provinces and the vice chancellors for health affairs have welcomed the extension of this inter- national training activity into these provin- ces and pledged their full support. Benefits are expected to accrue by having the na- tional and international participants carry out a situation analysis in the selected health districts. It was agreed that, for the period of the field training, a field facilitator (who will be a past participant on this course) from the School of Public Health and a field coordinator appointed by the chancellor of the provincial university would be provided in each province. The terms of reference of these two key pro- fessionals were agreed upon. Thus, in 1999 and 2000 the heads of the district health centres were appointed as the field coordi- nators. Further close cooperation was received from the Hormozgan University of Medical Sciences in 2000 in the form of permission to use their server to provide internet ac- cess for the participants. This has proved to be an excellent arrangement, and more cost effective with only a local telephone call instead of long distance to Tehran as in the previous year. Since 1997, close collaboration has been promoted with the Vice Chancellor for Health Affairs of Hormozgan University of Medical Sciences, which is situated in Ban- dar-e Abbas, and with the director in charge of the provincial malaria pro- gramme. Both were past participants on the WHO Italy-Thailand course. Sustainability of this course is to a large extent dependent upon a commitment on the part of, and close practical collabora- tion between, the School of Public Health in Tehran; the Ministry of Health and Medical Education; the universities of medical sciences ofSistan and Baluchistan, Kerman and Hormozgan provinces; and the provin- cial health authorities. This collaboration will be seen and felt by the international and national participants of this course. It will demonstrate that multisectoral collabora- tion is a key element to sustaining capacity- building for the control of communicable diseases. Participants will return to their places of work as ambassadors for the course and with a model of how this could be made to work well. The other strength in running the course in the Islamic Repu- blic of Iran is the excellent primary health care system and through that, the delivery of malaria control activities. Outcome to date In summary, the Regional Malaria Training Centre has been developed from the Centre for Health Education and Research situated in Bandar-e Abbas, which is one of the field stations belonging to the School of Public Health in Tehran. The government has been fully committed to developing the centre and the training activities. Over the past 4 years, the facilities have been renovated and further developed, equipped and staffed for the courses. The School of Public Health has provided members of its faculty as tutors and facilitators. The World Health Organization has pro- vided full support in the form of fellow- ships for participants; staff members as Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 223 tutors; consultants as technical coordina- tors and tutors; and books, equipment, training materials and evaluation instru- ments. The courses have a built-in system for evaluation of both participant and tutor per- formance and for feedback from the par- ticipants and tutors on the organization and functioning of the course. It is through this mechanism that improvements have been made each year to facilities, training mate- rials, evaluation instruments and choice of tutors and facilitators. Relevance to Roll Back Malaria The training being offered in the Regional Malaria Training Centre in Bandar-e Abbas provides the participants with the knowl- edge, skills, competence and confidence to be able to analyse the malaria problem and develop from first principles approaches to controlling the disease according to the prevailing epidemiological situation. Participants are taught how to conduct knowledge, attitude and practices studies and have the opportunity to carry out such studies themselves in order to und~rstand the communities in which they are work- ing. During the situation analysis they iden- tify the at-risk population and devise approaches to controlling the disease and to protecting people from malaria. Their train- ing includes the use of comparatively new technologies, in particular the use of a geo- graphic information system for slratifica- tion and surveillance. The experience in the Islamic Republic of Iran provides participants with the op- portunity to examine the primary health care system and how it functions to ac- complish malaria control; community mo- bilization is very much to the forefront. The educational process follows the 6 key ele- ments of Roll Back Malaria, in particular, effective case management; detection and control of, and preparedness for, epidem- ics; early diagnosis· and prompt treatment of cases and monitoring of treatment fail- ures; multiple and cost-effective approach- es to preventing infection; sector-wide capacity-building and intensified communi- ty efforts; partnerships for action, especial- ly with the provincial universities, the health system and the private sector; and a research and development approach along with the in-depth analysis and critique of published articles. The training is all about effective man- agement, and in the implementation of the learning experience participants are given the responsibility to manage their own re- sources, including time, and to organize their own teamwork. Thus, the process of education at the training centre embodies team building, wide collaboration, effective management practices and modern ap- proaches to learning. Vision for the future In the first 4 years of the Regional Malaria Training Centre there has been remarkable progress in all aspects: administrative, con- structive and educational. There are still several areas for improvement and these are in the medium-term plan for the centre and the diploma course. They include fur- ther improvement of the physical facilities, strengthening the library, improving the field experience and the field training sites and improving the evaluation instruments. The course has reached the point of curriculum development whereby very lit- tle can be cut or added within the same tiine frame. However, there is one way in which learning can be improved and made more enjoyable, and possibly reduce the length of the course, and that is through computer assisted learning. The basic modules used during the first 4 weeks of the course could be developed as computer assisted learning 224 La Revue de Santa de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 modules. This would mean that partici- pants could bring themselves up to date faster by using these learning tools under tutor guidance and learning at their own rate, depending on their basic knowledge of the subject Practical work and group dis- cussions would continue and eventually the length of the course could be slightly re- duced without damaging the learning expe- rience. Consideration would, however, still need to be given to the minimum number of contact hours needed to maintain the ac- creditation. The potential value of this course to the national malaria control programme in the Islamic Republic of Iran and to the health system has not yet been fully exploited, nor has the capacity of the Iranian health sys- tem to improve the learning experience. The future augurs well for both. Any gains achieved in malaria control with the full support of the Roll Back Ma- laria campaign will not be sustained without continuing development of human resourc- es and improved management effective- ness throughout the health systems. Strengthening and supporting the manage- ment of health systems and services is vital to the success of communicable disease control programmes, especially those as complicated as malaria. The opportunity in the Islamic Republic of Iran for a pilot training course in malaria control through primary health care, supported by Roll Back Malaria, and improved health sys- tems, supported by the Management Effec- tiveness Programme, provide evidence that the strategy is sound and can provide an ideal training ground for participants on the diploma course and, through them, subse- quent dissemination to other countries of the Region and to other WHO Regions. Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 225 Casereporl Rothmund-Thomson syndrome in a young man without cataract involvement I. Esfandiarpoor, 1 S. ShamsadlnP and S. Farajzadeh1 Introduction Rothmund-Thornson syndrome is a rare disorder that is inherited as an autosomal recessive trait occurring predominantly m females at the age of 3-6 months or later [J]. It is characterized by light sensitivity and some degrees of poikiloderma. The disease has a worldwide distribution. One review of the literature showed 200 cases up to \992 [2]. Rothmund-Thomson syndrome was probably first described by Rothmund, an ophthalmologist, in 1868. All reported cas- es suffered from premature cataracts rJl Later, Thomson described sisters with sim- ilar skin changes in 1923 and subsequently the disorder was labelled as poikilodenna congenita [4]. Cataracts were not a funda- mental finding in them. Taylor reviewed all the literatun.' and proposed the eponym of Rothmund-Thomson syndrome [ 5 J. We report a case of the syndwrne in a young man without any problems with vi- sion or premature cataracts or malignant transformation. Facial photoscnsitivity and involvement of his skin, such as sparse scalp and eyebrow hair, with involvement of the fingernails were also noted. We re- ·vicw some of the relevant literature. Case report An 18-year-old man was seen with,photo- sensitivity of the face, neck and ears, with warty papules on his exm:milics. A bird-like face and poikilodermic skin were promi- nent signs in this case. In the physical ex- aminatilln, he was slightly short in stature, but small hands and feet wt:n: uvtcd. Pigmentation, telangicctasia and reticu- late crythcma were seen all over the face except on the upper lids. under the nose, lower lip and dorsum ofbulh ca1s. Eiythc- ma had appeared when he was 6 months old. The eyebrows were thin with loss of bilateral end parts. Hypo- and hypcrpig- mentation areas, with partial JJ!aqucs or keratosis pilaris, \vere seen on the neck. trnnk and distal parts of the limbs. Bilateral partial ill defined brown scaly plaques were found in both axillac. Warty hn.11:d,cratotic papules were seen on the palms, soles. and the back of his hands and feet Papyrus scars were present on his knees. He had a hisrnry of righl fuiearm frac- ture at the age of 16 years that fused after 2 years. No history of ocular problems or convulsion was reported, Genital examina- tion revealed normal c.kvdopment, and hy- popigmen ted macules were seen on the 'Department of Dermatology, Kerman University of Medical Sciences, Kerman Darman Hospital, Kerman, Islamic Republic of Iran. Received: 18103/02; accepted: 03108/03 226 La Revuo do So.ntc de la Mediterranee 01ie,11lal", Yul. I 0, N° 1/2, 2UU4 penile shaft His fingemaik were thin, but mucous membranes were normal in ap- pearance exi:P.pt for mild gingivitis. In the laboratory evaluation, fasting blood sugar, complete blood cell count, and liver and renal function tests were normal. The serum levels of sodium, calcium and phosphorus were nom1al. The serum alka- line phosphatase level was raised at 368 IU/L (nonnal range 100-290 JU/L). Radiogrnphir reports of the pelvis, hands, skull, chest, foreanns and the lower extremities were normal, without any patchy sclerosis, cystic changes or os- teolytic le.~ion;: f'xrept mild osteoporosis in the bones of the right hand. Discussion Rothmund-Thomson syndrome is a rare, inherited disease [l]. The disease is an au- tosomai recessive disorder and a world- wide review of literature m LYY2 showed that 200 cases had been published up to that time [2]. Heterozygous carriers are virtually nor- mal bur may be identifiable by a minor sign such as light sensitivity. The parents of our case suffer from mild photosensitivity without any other signs of the syn<lrome. The genodermatosis of l{othmund- Thomson syndrome can be diagnosed by clinical findings such as short stature, cs- pecia! ly in the limbs, light sensitivity and poikiloderma. Children are usually normal at birth and have minimal findings in the first 3 months of life [ 6]. Cataract was not seen in this case. Bilateral cataracts can de- velop between the fourth and seventh :.,·car, usually in about 40% of reported cases, but they are more frequent in some families than in others f 2,5]. The diagnosis of Kothmund-Thomson syndrome is made on dinical grounds as no consistent laboratory test has been identi- fied [ 7]. The essential features in the differ- ential diagnosis are the age u/' uuset, the distribution of the lesions, and the combi- nation of atrophy, tclangiectasia and mot- tled pigmentation, most intense on light exposed skin but not nccc;i;:;<11 ily con- fined to it [8]. Short stature with photosen- sitivity and radiodcrmatitis of the facial skin were seen; skin signs such as loss of scalp and eyebrow hair with nail iuvulvt:ment were seen in this case. Scalp hair is often sparse and fine, and may be absent. Eye- brows, eyelashes, and pubic and axillary hairs arc often sparse or db:;t:ul. Naib arc nonnal, or small an<l dystrophic. Teeth arc often normal, but rnicrodontia and early caries have been reported [ 3, 7J. Short limbs without uny mali1,;11a11l tn:rns- formation were prominent features in our case. Squamous cell carcinoma may devel- op in the keratosis or in the surrounding atrophic skin. After cutaneom, t:pitlidiuma, ostcosarcoma is the most frequent malig- nancy [fl. Thus patients with Rothmund- Thomson syndrome need a 1.,;uu;ful ~urvt:y [3]. Physical development is frequently re- tarded; most patients are of small stature and some arc dwarfs, The dwarfism is pro- portionate, with slender di,;1 i1,;alc; I imbs, small hands and feet, and short stubby fin- gers. The skull may be small and bird lik..:, sometimes with a saddle nose. Aminoaci- duria hus occasionally been n::pu1 tell uuL has not been a consistent finding [}]. One report described ostcogenesis impcrfccta in a patient [9]. Hypogonndism und the inci1..k111.;;;: ufhy- pcrparathyroidism also appear to be in- creased [JO]. Mental development is usually normal, but may be retarded. Neu- rologicul examination of OU.f case ~huwt:LI no abnormality, and genital organs also had Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 227 normal development, but hypopigmented maculcs were detected on his penile shaft. In excised biopsy specimens. flattening of the epidermis with dennocpidemial junc- tion oedema \Vere seen. Acrogeria, Kindler syndrome, dyskeratosis congenita, xero- dcnna pigmentosa, and tlloom and Cock- ayne syndromes must be differentiated from Rothmund-Thomson syndrome [I]. Ligh1 sensitivity hi a l.'UllllllOLl feature in patients with Rothmund-Thomson syn- J.rome [/,2,3,8]. High sun protective sun- screen is thus recommended for all patients with this syndrorm::. References 1. Harper JI, Trembath RC. Genetics and genodermatoses. In: Burns ST, et al., eds. Rooks textbook of dermatology, 7th ed. Oxford, Blackwell Scientific Publica- Liuri:;, 2004. 2. Vennos EM, James WD. Rothmund- Thomson syndrome. Dermatology clin- 1cs, 1995, 13(1):143-50. 3. Cumin I et al. Rothmund-Thornson syn- drome and osteosarcoma. Medical and pediatric oncology, 1996, 26(6):414-6. 4. Thomcon MS. A hith<::Jrto undgscrib,;,d fa- milial disease. British journal of derma- tology, 1923, 35:455-62. 5. Taylor WB. Rothmund's syndrome; Tl1ome.011';,, ;,,yndrome; congenital poiki- loderma with or without juvenile cata- racts. AMA archives of dermatology, i957, 75:236-44. 6. Berg E, Ghuang TY, Cripps D. Aothmund-Thomson syndrome. A case report, phototesting and literature re- view. Journal of the American Academy of Dermatology, 1987, 17:332-8. 7. Lindor NM et al. Rothmund-Thomson syndrome in siblings: evidence tor ac- quired in vivo mosaicism. Clinical genet- i1,·,:;,·, 1996, 49(3):124-G. 8. Simmons LJ. Rothmund-Thomson syn- drome: case report. Australian journal of dermatology, 1980, 21 :96-9. 9. Reid J. Congenital poikiloderrna with osteogenesis lmperfecta. Bntish journal of dermatology, 1967, 79(4):243-4. 10. Wcrdcr EA et al. Hypogonadism and p8- rathyroid adenoma in congenital poikilo~ derma (Rothmund-Thornson syndro- me). Clinical endocnnology, 1975, 4(1 ): 75-82. La nevuo de Sant,!, ,Jt, l<1 M1:1ulterranee orlentale, VOi. 10, Nu 1/2, 2004 Case report Molecular basis of RhD-positive/D- negative chimerism in two patients S.S. Eicf SUMMARY This study investigated two patients with Rh chimerism: patient A, a healthy individual, and patient B with myelolibrosis. Flow cytometry studies showed two red blood cell populations of Rh phenotypes R,r and rr at percentages of about 25% and 75% respectively, Normal RhD transcript sequenr,m: w"'"" found following RT-PCR. Genomic DNA (gDNA) showed normal exon, intron, GATA regions and exon/intron boundary sequences except for a single base change in intron 7 (C"-7A) of exon 7 in patient A. The major change found in both patients was the absence of RHD exon 9 DNA in gDNA isolated from peripheral blood. These findings suggest a somatic mutation, probably in a stem cell common to the myeloid lineage of both paticnta, and indicate that pat,.,, ,t A may undergo malignant transtormation in the future. Introduction Rh blood group and gene complex The Rhesus (Rh) blood group system plays a key role in immunohaematology and transfusion medicine. The Rh antigens are the most immunogenic red blood cell pro- tein antigens in humans. Antigens of the Rh blood group system are carried on two pro- teins encoded by genes denoted RHD and RHCE. RecentJy, it has been established that the Rh locus on chromosome 1 p34.3- p36. l comprises at least two distinct but highly homologous genes, a D gene and a CcEe gene (Figure I) [1]. The D and CE polypeptides both consist of 417 amino acids, which differ by 35 amino acids as a result of 44 nucleotide substitutions in the coding sequence (2]. Cherif.-Zahar ct a!. first described the in- tron-exon organization of the 10-exon RHCE gene. The organization of the close- ly linked and highly homologous RHD gene appears to be similar [3]. Genetic basis of the RH locus polymorphism The RH locus is highly polymorphic. The structure of the RH locus was first estab- lished by studying blood samples collected from the Caucasian population where llu; R HD gene is completely deleted in a D-neg- ative phenotype [1]. RIID gene deletion ac- counts for almost all D-negative pheno- types [ l, 1]. An intuct but dy5fu111vtion11l RHD gene was reported in a small number of phcnotypically D-negative Caucasians. Two examples of such individuals have bc"1n studied ut the molecular level. Avent cl al. [ 4] reported a nonsense mutation in the RHD gene, while Andrews et at. [5] repor- ted a four-nucleotide deletion in exon 4 of the RJJD gene. In the Africun population a significantly higher proportion (up to 60%) of serologically D-negative individuals car- ry RHD genes compared with Europeans (6]. Among fapuncsc people that arc typed as D-negative by standard serology, two different RH genotypes can be defined. 'Princess Iman Centre for Research and Laboratory Sciences, Department of Haematology, King Hussein Medical Centre, Amman, Jordan. Received: 27102/01; accepted: 13/10101 Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 229 RHCE RHD gene completely deleted D Figure 1 Proposed molecular organization of the Rh genes The first group of individuals lack RHD genes (that is, are genotypical!y similar to Caucasian D-negatives) and the <:?rnnd group possesses RHD genes. Two groups of workers reported that this second Japa- nese D-negative allele appears to be of Dc1 (D-elute) phenotype, which um nnly hP identified by complicated adsorption and elution tests [ 7.8]. HO\vever, Okuda et al. [9) stated that this group does not corre- spond to the Dd phenotype, and rnndnrlP.rl that the RHD gene is highly detectable among Japanese D-negative individuals. D01 has recently been correlated with a l O 13 bp deletion, including cxon () [ In] in thP RH!) gene. Rh mosaicism and myP.loprt1I iferative disorders Disease-related abnormal expression of blood group antigens has been recognized for a long time. Rh group changes charac- t P.ri zerl hy the presence of NiO populations of red cells with different phenotypes (Rh mosaicism) have been reported in some pa- tients suffering from acute or chronic my- dogennus leukaemia. myeloid metaplasia, polycythaemia and myelofibrosis [ ll 14]. The myeloproliferative disorders arc thought to have a clonal origin arising from ll mutation in the haematopoietic pluripo- tential stem cell [ J 5). Occasionally the clone has an associated chromosome anomaly or a change in antigenic character- 1stics. Cooper et al. thought that these changes might also have a clonal origin [In]. Although in some cases there was an association of Rh loss \vith chromosome aberrations [ 16-18], no detectable abnor- mlllity of chromosome 1. \Vhere the RH lo- cus is located (I p34-p3 6 ), has been noticed in other cases. In these examples the Rh mosaicism most probably resulted in the expression of an abnormal clone of stem cells (somatic mutation), which occasion- ally disappeared during clinical remission with a return to a normal Rh phenotype [ / R. J 9]. However. it is not clear whether the leukaemic process itself causes these changes in Rh blood group expression or not Rh mosaicism was also found in ap- rarently healthy individuals in whom chi- merism could be eliminated as a possible explanation [ 13, 20, 21]. In one case a so- matic mutation affecting only one of monozygotic twins was suspected f 221. In a healthy donor and a patient suffering from a non-haematological disease (pro- lapse of an invcrkbral disc) a mosaicism for the blood group RH and FY locus (chromosome l q) was noticed [23,24). In these studies, serological Rh typing established that persons who had initially typed D' subsequently had mixed field re- actions indicating RhD chimerism. Meth- ods for direct detection of the RHD gene were not available when these studies were 230 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 reported. The subsequent availability of polymerase chain reaction (PCR) for de- tecting genes eneodmg Rh proteins has made it possible to demonstrate the Rl!D gene even when conventional serological methods do not detect D antigen. Although the mokcular basis ot KH genes has been largely clarified [25], there is currently no information availabk regarding the molecu- lar alterations causing Rh blood group changes in rnallgnant d11.cases, except for one report [14] which studied the molecu- lar basis of RH ehimerism in two patients who were about 75% RhD-negative and 25% RhD-posit1ve. Une patient suffered from chronic myeloid leukaemia and the other was a normal patient whose Rh chi- merism was detected on preoperative blood typing. Both patients were tound to have RHCE and not RHD at cxon 9. Methods Patients Patient A was a woman aged 25 years old with no haematnlngical cli~nrnn~ or other malignancies. She was found to have Rh chimerism after preoperative (laminecto- my) blood group typing. She had not been transfused and does not have a twin Patient B was a 79-year-old Caucasian woman, referred by her general practitio- ner to the haematology outpatients clinic at Norfolk and Norwich hospital for investi- gation of persistent mild anaemia and leu- kocytosis. Her blood film and bone marrow aspirate suggested a diagnosis of myeloii- brosis. Blood samples Blood samples were sent to the Internation- al Blood Group Reference Laboratory, Bris- tol, by the University of Cambridge Divi- sion of Transfusion Medicine, where sero- logical tests and flow cytometry were per- formed and hoth patients were diagnosed with Rh chimarism. The International Blood Group Reference Laboratory sup~ plied DNA and cDNA from common RhD- positive and RhD-negative phenotypes. Genomic DNA extraction and analysis Genomic DNA (gDNA) was extracted from peripheral blood as described by Avent and Martm L 26 J. PCR reactions were carried out using gDNA templates derived as previously described. Each PCR reac- tion mix had a final volume of 50 µL con- sisting of 2.5 mmol/L MgCl 2, 10 mmol/L Tris pH 8.3, 1.25 mmol/L dNTPs, 25 µmol/L diluted stocks of primers, I 00 ng gDNA and 2.6 U Expand 1M High Fidelity enzyme mix. The PCR reactions were car- ried out on a Perkin Elmer-Cetus DNA ther- mal cycler TC I. The PCR conditions and the sets of primers used in the amplification uf exuns 1-10 are shown in Table I and Table 2 respectively. The PCR products were gel-purified using a Qiaex IT kit (Qiagen) following the manufacturer's ins- Lru.:tiuns. Purified DNA was sequenced using dye-labelled terminator cycle se- quencing chemistry on an Applied Biosys- tems 373A DNA sequencer. PCR amplification of Rh transcripts Rh transcripts from two overlapping frag- ments (cxon 1-7 and exon 7-10) were iso- lated, followillg RT-PCR un LOtal RNA trom peripheral blood reticulocytes using Dyna- beads Oligo (dT\5 • cDNA was prepared as described by Sambrook et al. [27]. Two :.tot:; uf primers were used to am- plify the Rh transcripts. The first set of primers ,vas used to amplify the region from exon 1 to exon 7 and had the follow- ing :scquem;c:,. • Exon I RHD forward (sense) amplimer: 5 '-TCCCCATCATAGTCCCTCTG-3' Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 231 Table 1 PCR conditions for ampllfylng genomic DNA Exon Initial Denaturation Annealing Elongation No.of no. deneturation (OC) (OC) (extension) cycles (°C) (OC) 94 for 5 min 04for 1 min 60 for 1 min 72 for2 min '.li) 2 94for Smin 94 for 1 min 58for 1 min 72for2 min :l) 3 94 for 5 min 94for 1 min 65for 1 min 72 tor2 min 30 4 94 for 5 min 94for 1 min 60 for 1 min 72 for2 min :l) 5 94for Smin 94 for 1 min 60for 1 min 72for2 min ~ 6 94 for5 min 94for 1 min 65 for 1 min 72 for2 min 30 10 94for5min 94 for 1 min 60for 1 min 72 for 2 min :l) long PCR conditions were used to amplify exons 7 and 8/9. For exons 819. initial denaturation 4 min at 94 °c. denaturation 20 s at 94 °C, annealing 30 sat 60 ''C, extension 8 min at 68 "C for 10 cycles, /hen another 20 cycles under the following conditions: denaturation 20 s at 94 "C, annealing 30 sat 60 °G, extension 8 min and 20 sat 68 "C. ~Of 0XOr1 ( me Same COndff(Qf!S W8ff1 U,:;t:<.1, e,,;~·t:pl (he "-nnUJ/ing f.-,mperaturc was 58 'C, • Exon 7 RHD reverse (antisense) arn- plimer: 5. -AAGGTAGGGGCTGGA- CAG-3' The second set of primers W'aS used to amplify the region from exon 7 to f'Xon 1 0 and had the following sequences: Exon 7 RHO forward (sense) amplimcr: 5 '-TGGTGCTTGATACCGCGGAG-3' • Exon 10 RHD n:verst: (amisi.:H1s1::) am- plimer: 5. -AGTGCATAATAAATGGT- GAG-3' PCR reactions were carried out using the following cond1t10ns: Y4 °C for l min, 55 °C for 1 min and 72 °C for 3 min for 35 cycles in a 50 µL reaction mix composed of: IO mmol/L Tris-HCl pH 8.3, 2.5 mmol/L MgCl2, I µm/L each pnmer, 1.2~ mmol/L each dNTP, I 00 ng cDNA, and 2.6 U Ex- pand1M High Fidelity enzyme mix. PCR products were gel purified on 1.5% agar- ose gel using a Qiaex unit (Qiagen) and cloned into a PCR1M fl vector following the manufacturer's instructions. Sequence analysis of cloned PCR products was per- fonned using dye-labelled terminator cycle sequencing chemistry on an Applied Bio- systems 373A DNA sequencer with 0.5 to 1.0 µg plasmid DNA as template. Both strands of DNA were sequenced. Results Rh transcript analysis Reticulocyte RNA isolated from the patient was reverse transcribed and transcripts arising from the RHD gene were umplified using t\vo overlapping Set:'> of primers ( ex- ons 1-7 and 7-10). PCR products of the expected sizes ( 1200 and 3 87 b-p for 1-7, 7-10 respectively) (Figure 2) were cloned into PCR™ II plasmid as described in the M cthods. Six clones of each transcript ( I - 7, 7- IO) were isolated and fully sequenced on both strands, The re~sults revealed that all these clones' sequences are identical to the RHD gene sequence in both patients. N Tabb 2 Sets of primers used and their product sizes ... N Exon Primer Diriectlon Specificity Primer position Sequence (5' to 3') Product name size (bp) 1 "RH1F F CCE Promoter -675 to -652 CTAGAGCCAAACCCACATCTCCTT 952 'AH1A R CCE lntron 1 129 to106 AGAAGATGGGGGAATCTTTTTCCT •RHJ 1F F C Promoter -149 :o - 132 ATAGN3AGGCCAGCACAA 42E bRHDIN1R R CCE. lntron 1 84 to 34 TCTGTGCCCCTGGA3AACCAC -'( . 2 •AH EX2 IN 1F . F COE lntron1 -72 to-53 ACTCTAATTTCATACCACCC 4& ,., bRHDC2A (M) DC lntron 2 225to205 TGGAT"CCTTGTGATACTCG A :.; r I 3 •RH3F F COE lntrcn 2 2823 to 2842 GTGCCACTTGACTTGGGACT 389C ru _,,. :D (,.· •Rf--'3A R COE lntrc,n 3 28to 11 AGGTCCCTCCTCCAGCAC :g c- C: l 4 bRHDIN 3F F D lntrc,n 3 -36to-16 GCCGACACTCACTGCTCTTAC 390 (D a. (D \,, 0 Rl-4R R D lntrcn4 198 to 175 TCCTGAACCTGCTCTGTGAAGTGC CJ) II) E=- 5 0 Rl-5F F D tntrcn4 -267tc -243 TACCTTTG~ATTAAGCACTTCACAG 507 ::::, <ii- ~ CRHD IN SA A CO;; lntrcn 5 73 to 56 GTGGGGAGGGGCATAAAT a. (D iii" ,t.'. 6 "Rl-6F F CD:: lntrcn 5 -332 to-314 CAAM°'CCCATTCTTCCCG 511 ;;:: CD• ~ 'RHO N 6A R D lntron 6 41 to21 CTTCAGCCAAAGCAGAGGAGG 9: [ 7 •RHO IN 6F F D Intra, 6 -102 to -85 CATCC-:::CCTTTGGTGGCC 400 ~ ji; ::, "RHO N 7A A D Intro, 7 169 to 152 AAGGTAGGGGCTGGACAG <lh (D F 0EX7 FOR2 F 0 Exon 7 949 to ~67 AACCGAGTGCTGGGGATTC 3500 S! a;· :, 0 RH7R =i COE lntror, 7 -3000 GCTTGAAATAGAAGGGAAATGGGAGG ill" r 15" •AHO EX7R =i D Exon 7 100810985 ACCCAGCAAGCTGAAGTTGTAGCC 3600 . 'r.,.. a: - RH5F :: CDE Intro, 5 -332 to-314 CAAAAACCCATTCTTCCCG ~ (.. ~ t. 8 anc9 "RH8'9R A COE Intro, 9 - 300 CACCCGCATGTCAGACTAmGGC 500 z ,t' 0EX9 l'J BF F COE Intro, 8 -165 to -144 GCTGGTCGAGGAATGACAGGGC 0 t 1\3 bRH If~ BF F COE Intro, 8 69to S1 CGTGTGGCTGGATGTCTATGTGC 5000 . J\:) />' 0 i- 0 Ex 9A R D Exon9 1219to1193 AM CTT GGT CAT CAA AAT ATT TAA CCT 0 . - .I>, ----------------------------------------- Eastern Mediterranean Health Journal, Vol. 10, Nos 1/2, 2004 233 --.... 0 ... "" i 'iii 0 c.. ... fl) .E ... a. w w w 0 0 0 0 u u (.) LI.. a: u... u: 0 PCR amplification of the gDNA All gDNA PCR products {Figure 3) were excised, gel-purified, and the two DNA strands sequenced using the same sets of primers used in the amplification. Almost all exons. introns, GATA regions within the promoter region, and exon-intron splicing boundaries were found to be identical to the normal RHD gene. The single exception was intron 7: the primers RHD IN 6F, RHD IN 7R gave no product for patient A, while patient B and the control gave a product with a size of 400 bp (Figures 3 and 4b). When primers RHD EX 7R and RH D 6f were used, there was a product of 3600 bp, Cl.~ .c " o.,, u= N~ 1= 0 ~ I n_ {a) Exon 1-7 fragment PCR product Ol ,0: : : • • - • - - -- .. - .. .. - (b) Exon 1-7 fragment PCR product 1200 bp f--· Figures ::>i:i and ::>h PCR products of cDNA obtained by the amplification of 2 overlapping fragments: exon 1-7 and exon 7-10 La Revue de Sante de la Mediterranee orientale, Vol. 10, N° 1/2, 2004 952 bp ____ ..,. ,. 426 bp l!xon 5 (507 l;p) , l!xon 6 _j (511 bp) 0 r Ell'.On 1 (COE) Exon 1 (D specific) ·7 UJ ... ~ ~ :g 0 .:.. ;.;;;.: C: -£~8'..8 Exon4 ~ --··1 (Cl<(: C: 1= 0 Cl..1,_ ~ Q),:::.C!l) Q ',.;;;;i ._ L 0"0 J:N ~ t]J_ 8 ~~ 390bp ,......__ I EKon 7 I /400bpl •I Exon 10 0 Ill <( O O Ill<( O CL<i, (3SO bp) Icc~£t:c~~:g ii8 ~~8~.S i:&.. ~ u..u.. J ~ __J - ___ ,I. EKon 5 EKon 6 EKon 7 EKon 10 Figure 3 PCR products, stained with ethldlum bromide, include exon 1 (CDE), exon 1 (D specific), exon 4, exon 5, exon 6, exon 7 and exon 1 O for both patients (no product is seen for patient A In exon 7) which indicates that at kast the 5' half of exon 7D is present. When primers EX 7FOR2 and RH 7R were used to amplify the 3' regions of exon 7 and intron 7 PCR gave a 3500 bp product (Figure 4a). When sequenced this gave A instead of C ( 151 cxon 7 position) at the 3' end of primer RHD IN 7R which is located on intron 7 (Figure 5), that is, the CE sequence not the D sequence. This explains why PCR with D IN 6F and DIN 7R failed. When RH COE IN 7F and RH IN SR primers were used to amplify exon 8. the PCR gave one product of about 3 511 bp for both patients. An interesting finding was that on one oc- casion, patient A gave two products (Figure 6). This raises the possibility ofa mutation, deletion or insertion in intron 8. When puri- fied, these products gave very poor quality DNA and therefore no sequencing was (:;ir- ried out. The same PCR was repeated more than once. Each time, a single product was obtained (Figure 7a). When EX 9 IN 8F and RH 8/9R primers were used. the P,R gave a 580 bp product (Figure 7b). Patient A and patient B both gave CE-specific se- quences only, that is, C at nucleotide ll 70 and Tat nucleotide 1193 (Figure R) Eastern Mediterra11ean Health Journal, Vol. 10, Nos 1/2, 2004 235 2 (D specific) 3 (D specific) 1 (D specific) ~II~ r ? C C C ~ ~ 8 Q.. -~ 8 0 u..Q::C: CLQJ:N <Cl .· - .. 3500 bp _______.. 3600 bp ~ (a) - .... .. .. ••• {b) 400 bp ..__ t-Igures 4a and 4b Ampllflcatlon proctucts uf exun 7 in ptolitml A, u:1>in9 a c,;,nfrol and J primcra: {1) DIN 6F, DIN 7R (400 bp) (2) EX 7 FOR 2, RH 7R (3511 bp) (3) RHD1R, RHD 6F (3511 bp) Discussion This study presents the results from two patients. one suffering from a mycloprolif- erative disorder and the other a healthy indi- vidual, Both were females having a mixture of R 1r, rr cell populations as demonstrated by serological tests and flow cytometry, which has become a valuable tool in the de- tection of minority red cell populations. Loss ofRhD antigen in malignant haem- opathies and in healthy individuals is ex- tremely rare and molecular infonnation on the blood group changes of these patients is lacking. The molecular basis of Rh chimer- ism in both patients was studied to find out whether the 2 patients had the same molec- ular basis, and compare them with those described by Cherif-Zahar et al. (<lei G600) [J 4]. The RHD transcripts were s.tudied using two overlapping fragments, exon l-7 and exon 7-10. The PCR products of both frag- ments were cloned and sequenced for both patients. As the results indicated, no change was detected in the coding region. Howev- er, since the D antigen was not detectable on about 75%J of native red cells. either a mutant transcript or truncated protein might be degraded within the cells so that the 7-10 fragment PCR might not amplify immature fragments and pick up only the normal transcript. As a result, no mutant RHD was found because no transcription from the mutant gene occurs. When these PCR amplificatio;s were carried out for all IO cxons of the RHD gene in patients A and B, all cxon/intron boundaries, exon, intron, and GA TA regions were found to be normal, except for intron 7 in patient A where a sin- gle base change was found (C~A) at the 151 exon 7 position, which is at the 3 · end of primer RJJD IN 7R. that is, in the CE and not the D sequence. This explains why PCR with RHD IN 6F and RHD IN 7 failed (Fig- ures 3 and 4b). This minor change does not --"{ ... --"{ _!, C· t \. ~ t ,c:, ~ t f. r 't- (., t. t f , en s:- '!a ::!1 (I) :::r C, -3 ,g :::ro::z, ., O:f::t:5''° ;i!!Ou, 01 ,.:::rlll CDC :::r C, ::Jo..c ~ Illa, c- 3CD:t:JCD11> st ~g! ~:::irrr•li g28[g a-e:~! m clif2.mo ::I ... Ul ..... C. CD • 8 ID s·;:l 3 S - GI '0 ~ :I er ID - ,.. CD ""I: ::::, ai m::- :::i rp O 0 .... (D :I:::, I» :I :r .... ... :t:J Ill "' .... :::r: C'::r ~ 0 111 i 1111» i-· )( ::I (D ::, OCL CDCQ ::,l:J :::IUI "ti :::r: (D _g 2 C') ~ C ;;;: I'll :I Ill -· :::, :I 0 :::, O :I .+ ID -- a 3 0 :I Ill a; ...,.g ...... "':::r . !g Ii i i=: 3 (D :I Ill -0 :::r ..., ID "CJ to1 ID ' = CD ~ :::, :, 0. ,. fll Jioo Ill - :, -1:1. :::r CD Rfflli,nllill RHCExm~i,I Pa:ie11:, Rf{(} r•oo i. seq RT!CE own 1. seq RHDccnwl RHCE@mrnl f'J1i:ruA RKDooi 7 ~ ' RJI( fooo i 5eq RHDco1rrol Rl!CE,lllrrr,I Pal~m/. RHDeiia 7 ,-;g I RHCFe:0n1 ~ RHDoortm RHCEcmrrol Patient,\ RHDcxm 7. '.11:q RHCEe:oal.scq :n ~ - 31 I 'C:~~ l<I'~~~7:'~:~A cu,rrnn TATAAIA\CA CTllilCCACA k IIJIJ u, llO . I '.'_'_'::~:~'.G.T Ll_r:~-~C~~~~~::A~.I:~ '. . (nUYGGGT CTGCT:GC,AG .~G.,K\Cff4 CTTGOGGGI CTGrTIGGAG AGATCATCTA CTl(ifYGGG I CTGl'TlGGAG AGAT{Alm CT:"(i(JGGGT crr{TIGGAG Ii;) TA\CCCCATC TACC(CCATC HCUCCAJC CCCTPACAC CCCTTMCAC CCCTTMCAC 1<1 AGAffA((]A TCCCC[CCA:1 TC'OCCTl'CAA TC(\TTCA.-\. ;10 .;1 ;o --· l--·· ._j___ GGGHf,TTGT ~A[(ll'IGTC( TGG<:rGnrcc GG{r(TGTTGI AACCG\GIGC -(iGifGTR,T 'v\C'CC1\GiliC -·······-- CTGfGJ"Vil "A(((j\GTGC _l( 11U TG{,GiiATTCC TGOOiATTCC --------·]! TGGGr,mrA j_ __ ___j______ CA nG,U'l'I ~TGGTrJ1.1TG ATACCGTCGG CATTGHil.Tri CA!T!TGCrn CAllU(i(TG • ~ • - - •- r rt l T(iGHrTTC llfi(iTIJCTf(i l'HiGT!iCITG CATTHGCTG r!GGTltm: c.,"I) 1--:1 -- •. t ..• 11:L ATACTJ[CTG ATACCJTCGG ATACC'.iTCG{i ····*---·- A 1 An,rn G 611 1;0 70 ~II --- L--- C(A(~GCl(C .\TC.U:iGDCT ACATC1CC' CCAC\GOCC (CAnGCTCC ;C. ~ - - .• :t •• GTCAFiCACT ATCAlGGGCT A TCA T1)GGCT 'ill AC,\ACTIClf, i - - t - .... ~ C(ATCTTAlr ACAACTTCAG ACMClTMi O rLL, ~ • ••• .t O ~ ~ ~ •. ;a: O • t LL ,i; • (C-\C\TCTCC vTCATliCACT n:,nmci,:J l&i 1r,:1 ____ ;. ___ .L ____ - AGCC1,GC.AAT CoGCAmGGG TCACTG(ffT ... •••••• T• GAAC,)G(A:IT AG<.UGCAAT AGCO)G(AAT :ttl•-·-···- G{j('AmCT(i{r GGCATGTGGG GGCAT --·· GA.Af~GCAAT GGCAT ·•• ICAClli(firT TCACTGfGCT ~'-) ~50 'I.I ::r;) CTCAfrt,MGA AAff,TCTGCA AATGfClGCA ,.\ATGTCrCiCA NAGTCTTAG CT<iGUi({ITG TUCACTCGGG TGCACTrGGG TGCACTGl'ii GCCAGGJGCT GCC~GG!GCT (,CCAGGM7 lTCAWMGA crq1)GAA1:iA OT••••••~~ --~---•••• 'iAGW]TAG nG()((iCGTG NAGTO:TTAG C'IGG(GCGTG 1i ~ jOO ~10 ;11;' jJU J'-~ ~~ ~~I ___ I _______ . _ __L_ .____]__ _ __ . ·---- .--- .______i__ .. ____J_- ___ I CAGTIGGCTT COClG~ATAT IlGlTCGCTG AITTATTCAA AA.sTT,:GTC CAGCCOCTAC CTTGCAIGGA IDATC,CCT CTCTAGO:CA CAliT.ICiGCTT CACT!i,GCH ----···-·· I . ·······-·· CGCTGJ\.\TAT C GGTG.¾I TA l TICiTTCGC'ffi m,TTCGCTG ATTHfRAA ATfiAIT(M ... ~ ... AAATT,lGTC M.~Tr_, l(rTC ····t-·· CAG!HCIAC CAGCCCCTAC llTGG\TGfiA nTGGHGGA ITTATC.1CCT ITTATCJCCT CTCCAGlifCA ClC(AGGCC,~ "' "' Cl\ i;;- jJ ~ ,:: CD a. CD g, ::, c;. Q. <I> iii' ~ C!>-g, $' i (D 0 ::,_ a) ::, S' _ro ~ ... .0 z 0 f3: N 0 0 .j>,. Eastern Mediterranean Health Journal, Vol. 10, Nos 112, 2004 237 3511 bp --+- C. ~ .0 <l> ,.., "O ou N~ 2 r:= R b 2 r:= R b (a) -,; CD E c Q) .!!! 'i\i ON ;f Q__ :I: Figure 6a Amplification products of exon 8 using primer RH COE IN 7F, RH IN SR (CDE) 3511 bp _____.. Q) "O ~lg Cl. c; .c R = 0 c N t (COE) 0 -,; al t E E 0 .!!! .~ b '" i,:i Q__ Q__ 2 (0 specific) II~ g -,; al <: E c g R Q) i ON .fa b ::c: C Q__ Q,. (a) ~- 3511 bp +---- Figure 6b Further migration for patient A (two products) 5000 bp ~ Q) .,,, -0 ~ C. .0 8 N g <:: R 0 3 (COE) -,; al E E .!!! <l> ta ~ Q__ (b) n £ 580 bp ~ Figures 7a and 7b Amplification products of exon 819, using thee primers: (1) RH COE IN 7F, RH IN SR (2) RH IN SF, EX 9R (3) RH 8/9 R, EX 9 IN SF ,,., a' . ..,. <C 5 .! .1 g ~~~ La Aovue de 8e.nte de la Mediterranee orientale, VoL 10, Nn 1/2, 2004 F. ,, Figure 8 DNA sequences of exon/intron 9 showing sequence match between the 3' ends of the primer. Sequence shows a comparison Iha between exonnntron 9 sequences of patient A and the RHDand RHCE oontrole. ·Shows the sequence difference between RHDand RHCE. J. Shows that both patients have RHCE sequences not RHD. Eastern Mediterranean Health Journal, Vol. 1 0, Nos 1/2, 2004 239 provide an explanation for the patient chi- mcrism, but the presence of CE-specific bases in intron 7 of RHD may suggest that part of the RHD gene in patient A has been replaced by RHCE, resulting in an RHD- CE-D hybrid gene. Hov.·ever, more experi- ments are needed to see if this is the case. An alternative explanation is that this change may affect the end part of RHO gene, which results in the loss of RhD anti- gen. This is supported by the tindmg that the RHD cxon 9 is absent in both patients, with no RHD exon 9 isolated from periph- eral blood gDNA. This may be explained by an insertion of DNA (possibly a replace- ment with part of RHCE) or the deletion of a segment of DNA in intron 8 including cxon 9. Any alteration in the amino acid se- quence can impair stability, resultmg m an unstable molecule that degrades almost as quickly as it is synthesized. As a result no RHD gene is expressed. Possible support for this hypothesis comes from the obser- vation that another primer (D 8/9F, RH IN 8R) produced a large product in high yield (Figure 6a). In patient A, further migration gave two bands m one occasion (Figure 6b ), but on other occasions both patients A and B gave only one large product which could not be resolved into discrete bands (Figure 7a). This product needs to be cloned and sequenced to sec if any mutation is present in intron 8 which may cause de- fective processing or splicing of the prima- ry rn.K.NA transcript, resulting in improper translation and the absence of RHD exon 9. When 0-spccific primers were used (Fig- ure 7a) weak PCR products for RHD exon 9 were produced in patients A and 8, stron- ger in patient B. This may be explained by the high leukocyte count. The presence of these products in both patients when D- spec1fic primers were used may be due to amplification of exon 9 from the minority of cells that are RHD-positive. The high ratio of myeloid cells to reticulocytes may ex- plain why this change could be detected more easily in the gDNA than in the Rh tran- scripts in patient B, which is not the case for patient A. Weak D phenotypes are associated with severely depressed D expression. Wagner et al. [28] detected two changes in cxon 9: a substitution at nucleotide 1177 (T ----')G) changing tryptophan to arginine and giving nse to a weak D type 9 phenotype, and an- other at nucleotide 1154 (G-----;)C) which changes glycine to alanine, and gives rise to a weak D type 2 phenotype. In our patient thts ts not the case, since the whole RHD exon 9 is absence. In a Japanese population a deletion in l O 13 bp in the RHD gene that includes cxon 9 has been reported [JO]. Thts deletion is correlated with the D e1 (D- elute) phenotype (which can only be de- fined by sophisticated adsorption and elution tests), whereas in our case D anti- gen expression is severely depressed. Any RHD alteration to exon 9 affects D antigen expression. These findings differ from Chcrif-Zahar et al.'s finding [/4] ofa CML patient whose RhD-positive phenotype shifted to RhD-negative, where sequence analysis of Rh transcripts amplified from reticulocytes revealed a single nucleotide deletion (del G600) localized in a region en- coded by exon 4 of the RHD gene. Comparing the tv.'o patients with some of the D-ncgative phenotypes, it is most likely that the two cases showed a genuine D-negative phenotype caused by clonal changes accompanied by absence of RHD cxon 9. More analysis is needed to define the precise mechanism of RhD chimerism, but our results indicate that the defect is within the region of exon 9 in both patients. Northern blotting is helpful in detecting any changes in the RNA level. The M9 PCR product (Figure 7a), using primer I, should be cloned and sequenced. Clinically, the 240 La Revue I.I"' S<111t~ I.lid 1 .. Mli:uilerrc111B-e urlemale, VOi. 10, N" 1/2, 2004 healthy patient has been advised to have regular check-ups to rule out any clonal chungea that may develop over time. In the case of the myelofibrosis patient, it may be that during the myelodyplastic process a downregulating gene is activated, inhibiting RHD gene expression. Acknowledgements I am most grateful to my supervisor, Dr N. Avent, for his help and guidance throughout this project. Rsfsrsncss 1. Colin Y et al. Genetic basis of the RhD- 8. Sun CF et al. RHD gene polymorphisms positive and RhD-negalive blood group among RhD-negative Chinese in Tai- polymorphism as determined by South- wan. Vox sanguinis, 1998, 751:52-7. em analysis. Blood, 1991, 78:27 4 7-52. 2. Arce MA et al. Molecular cloning of RhD cDNA derived from a gene present in RhD-posilive, but not RhD-negative in- dividuals. Blood, 1993, 82:651-5. 3. Cherif-Zahar B et al. Organization of the gene (RHCE) encoding the human blood group RhCcEe antigens and char- acterization of the promoter region. Genomics, 1994, 19:68-74. 4. Avent ND et al. Evidence of genetic di- versity underlying RhD-, weak D (Du), and partial D phenotypes as determined by multiplex polymerase chain reaction analysis of the RHD gene. Blood, 1997, 89:2568-77. 5. Andrews KT et al. The RhD- trait in a white paUent with the RhCCee pheno- type attributed to a four-nucleotide dele- tion in the RHD gene. Blood, 1998, 92: 1839-40. 6. Daniels G, Green C, Smart E. Differ- ences between RhD-negative Africans and RhD-negative Europeans. Lancet, 1997, 350:862-3. 7_ Fukumori Y et al. Further analysis of Del (D-elute) using polymerase chain reac- tion (PCR) with RHD gene-specific prim- ers. Transfusion medicine. 1997. 7: 227-31. 9. Okuda H et al. The RHn gRnR ii:: highly detectable in RhD-negative Japanese donors. Journal of clinical investigation, 1997, 100:373-9. 10. Chang JG et al. Human RhDel is caucod by a deletion of 1,013 bp between in- trons 8 and 9 including exon 9 of RHO gene. Blood, 1998, 92:2602---4. 11. Majaky A. Some ca:se:s of leukaemia with modifications of the D(Rho)-receptor. Neoplasma, 1967, 14:335---44. 12. Habibi B, Lopez M, Salmon C. Two new t;ct:.e:. ur Rt1 mosalclsm. Selective stuay of red cell populations. Vox sanguinis, 1974, 27:232-42. 13. Mertens Get al. Loss of D and C expres- sion m chronic myelomonocytic leuke- mia. Transfusion, 1997, 37:880-1. 14. Cherif-Zahar B et al. Shift from Rh-posi- tive to Rh-negative phenotype caused by a somatic mutation within the RHD gene in a patient with chronic myelocytic leukaemia. British journal of haemato- ogy, 1998, 102:1263-70. 15. Barr RD. Fialkow PJ. Clonal origin of chronic myelocytic leukaemia. New En- gland journal of medicine, 1973, 289: 307-9. Eastern Mediterranean Health Journal. Vol. 10, Nos 1/2.2004 241 16. Cooper B et al. Loss of Rh antigen asso- ciated with acquired Rh antibodies and a chromosome translocation in a patient with myeloid metaplasia. Blood, 1979, 54:642-7. 17. Marsh WL et al. Mappinq human auto- somes: evidence supporting assignment of rhesus to the short arm chromosome no.1. Science, 1974, 183:966-8. 1R. Mnh;mrl;rn V P.t ;ail. I oss ;ainrl rf!ArreAr- ance of Rh 0 (D) antigen in an individual with acute myelogenous leukemia. Transfusion, 1993, 33:24s. 19. Bracey AW et al. Rh mosaicism and ab·- errant MNSs antigen expression in a pa- tient with chronic rnyelogenous leukaemia. American journal of clinical pathology, 1983. 79:397-401. 20. Race RR. Sanger R. Blood groups in man. Oxford, Blackwell, 1975:178-260. 21. Salaru NN, Lay WH. Rh blood group mo- :;cti<.;i:;111 i11 ct !11:1tdtl1y t1l<.J1:.nly wu111ct11. VuA sanguinis, 1985, 48:362-5. 22. Muller A et al. Mosaicisme Rh par muta- tion dans une gemellite monozygote. Genetics in developing countries [Rh mosaicism by mutation in monozy- gottc twins.] Revue franr;aise de transfu- sion et immuno-hematologie, 1978, 21 : 151-64. 23. Jenkins WJ, Marsh WL. Somatic muta- tion affecting the Rhesus and Duffy blood group systems. Transfusion, 1965, 20:6-10. 24. Northoff H et al. A patient mosaic for Rh and Fy antigens lackino other sions of chimerism or chromosomal disorder. Vax sanguinis, 1984, 47:164-9. 25. Avent ND. The rhesus blood group sys- tem: insights from recent acivanrp_c; in molecular biology. Transfusion medicine reviews, 1999, 13:245-66. 26 Avent ND, Martin PG. Kell typing by al- lele specific PCR (/\SP), Britich journal of haematology, 1996, 93:728-70. 27. Sambrook J, Fritsch E, Maniatis T Mo- lecular cloning: a laboratory manual, 2nd ic:d. N.;,w York, Cold Spring Harbor, 1989. 28. Wagner FF. Molecular basis of weak D phenotypes. Blood, 1999, 93:385-93. Low- to middle-income countries vary in their capacities In medical genetics. Some may not have the resources to set up appropriate genetic services. Others provide genetic services but need assist- ance to improve equity of access to these services. The World Health Organization Is supporting country capacity building by con- structing educational modules and pilot studies to develop national community genetics, Including the ethical, legal and societal impli- cations (ELSI) Smm:e.· /VHO F<Jcl she el: genetics and heal!h (hltp. ilwww. whu. intigenumicsieni[_ j hgn- jinal.pJI) 242 La Revue de Sante de la Mediterranee orientale, Vol. 1 o, N° 1 /2, 2004 Guidelines for authors 1. Papers submitted for publication must not have been published or accepted for publication elsewhere. The Eastern Mediterranean Regional Office reserves all rights of reproduction and republication of material that appears in the Eastern Mediterranean health journal (EMHJ). 2. 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')~Lall ,Jl..u,t,11 :"-::JGI .1,WI ,~i.ll 4-A>,-l)IJ c.:;,l~'}I ..:.,'}Ll..,. J_,L:.; .)i ~ ., • . ..:.,\.>,\.;.;:;_..'}I)\..,,~) ..:.,L,bJ.I ' J . . ' o~l,_J-~ 'J_, .:i..,........,L',11 ~...l;l..1 c>-1)1? ,~I_) ""J~ w,1 c.,s-1 .:_,.,.~~'}\~JI~.,' .)\) ,~I .j..:., __,....;.-1; L$ 'c>-1}1 ~ _,; r j--1,J .~..t...:.ll ..:.,'}WI ,l:.::...,½ ,p~l j>- b.--_r' H ~ e-1)1 .j ,~ ~ .j ,;;_.jf' Wu .j e-1)1 • ..0, J-Jx ~ W- -[~J" c.J"l_,il] __ ~1_,;i ..:.,"o! ¼f' ~1~14-); ,~l....i:--1 .:_,-- j}JI j )_,...,ll) ,~ j--11 ,l....i:--1 )f , .... ,Jjll i'""'"I :§_.i Jl ,;,_,)\.:;JI ..:.,\.... ,,Wt ~ .)1) ,o J_,ll "-,:4' \..:.,l>...i......aJI ~..LJ-) ,,.M.1 r-') C::_' ,j--1.5:l½ :\L;l;I i-"I) ,~) j\ s.jl_;,( ,,.,,L/;1 W]I .j -.,.,1..:...<J1 __,( ;\i ;_}I .)lpc) ~I ..:.,\_j J_,ll o~Lv; r.::... j y) . _,.!-:.ii (:!-J\:j) \(..0.,JI) ~..UI) _,.!-:.ii Jl.5:.. J •(.,,,----_;ii _Ji c,;;).,,..:JI) _,.;,\.JI l'""""IJ y}--'>U ;bl_}..\....))-~ ,JJ_;ll Jl ,(.pyl o.l,,, ~ 4_;' y,j- _Ji ,U.1.5' y,j- t>-"1)1 4-,J .:ifa :,._;;, .)I .k....., -1\ i •.i ~I :w\-1 L...:,..i.; ejJI 1......-~ r v..r- .. (,.,,' "? .-..,..1:5' Al Hamza B, Smith A. The fifth sign of identity. Cairo, American University Press, 1990. : JU, i) if tk Jones A et al. One day in Tibet. Journal Of tautology, 1993, 13(5): 23-7. :U,,:_j Al-ltneen M, ed. The principles of uncertainty. Geneva, World Health Organization, 1985 (document WHO/DOC/537) . • ~ ~ J 4:--jS ~;i .:ii~ -Gk> ,w')l.11 c_J?½ ~µ1 ,J.,1..LJ,-1-' ..:.,\...._,,...)½ JL.::; 1.... 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J-:i_ Ji_, ,..:.,L,b].1 o.l,,, ½-"""La; JI~ ,..:.,L,bJ.I ~ ~I ..:.,\...._,,...)I .)~ 1.....1? .a....lS' . ·_r'\/1~ -~} J]_,11 j-" ...,_l1, ~ ~\..:, 'll ,~~I ..:.,~_;)1_, ..:.,L;J_,ll ~) '} ., f O• ~ ~} ,.....__j_;il J-~ L..;.,.i ,Lil.al 9 ~J-,s..\.11 ~.WI J ;i_,;.__; j>- J.,_.J_;il ~,_,.!-:JI~., t J! , }• . ......., ~I J_J-'>" ..:.,\...... ~ ? _,I ,~I j-" ~)\ J>- J_r-=JJ ..:.,L,lhll 1~) · Jy:.J.1 _:_.;,..J1 .:.r' ~ • ,r.!__,,...:ll c.r)) 246 La Revue de Sante de la Mediterranee orientale, Vol. 1 0, N° 1 /2, 2004 WHO sales and discount policy Objective Within the financial obligations of the publishing and distribution process, prices of WHO publica- tions are kept as low as possible in order to maximize their dissemination and reach readers for whom they are intended. 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Box 7608 Correspondence Editor-in-chief WHO Eastern Mediterranean Regional Office Tel: (202) 670 2535 Nasr City, Cairo 11371 Arab Republic of Egypt email: khayat@emro.who.int emhj@emro.who.int Fax: (202) 670 2492 (202) 670 2494 Subscription details Individual copies: US$ 15.00 Annual subscription: US$ 60.00 There is a 50% discount for orders from developing countries Prices include cost of dispatch Subscription orders should be sent to the Editor-in-chief Letter from the Editor ......................... .............. ........................................................................................ 4 Hepatitis B infection among Iraqi children: the impact of sanctions ........................................................... 6 Correction. Relationship between depression and non-adherence to anticoagulant therapy aftervalvereplacement ................... ... ................ .............. .. ................................................................... 11 Supplementary feeding of malnourished children in northern Iraq ........... .. ............................................ 12 Pakistan's experience of a bioterrorism-related anthrax scare . . . . . . . . . . . . .. . . . ... . . ........... .. . . . .. . . ... .. . ... . ..... .... 19 Anthrax: pathological aspects in autopsy cases in Shiraz, Islamic Republic of Iran, 1960-2001 ........... 27 CoOt des soins de sante de base dans une circonscription sanitaire en Tunisia ................................. 37 Life expecf!lncy and cause of death in the Kuwaiti population 1987-2000 . .. . . . . . . . . . .. . . . . . . . . . . . . . . ...... .. . . ... . . .. 45 Capture--NCapture methods for estimation offertility and mortality in a rural district of Turkey •.. . . ...... .. . 56 AdoleecenlB' use of health services in Alexandria, Egypt: association with mental health problems .••... 64 Practice and awareness of health risk behaviou~among Egyptian university studentst ...... .... ...... ..... ... 72 Opioid use in patients presenting with pain in Zahedan, Islamic Republic of Iran ........... ........................ 82 Right heart haemodynamic values and respiratory function test parameters in chronic smokers .......... 90 Detection of cotinine in neonate meconium as a marker for nicotine exposure in utero ......... .... ............ 96 Contents Growth charts of Egyptian children with Down syndrome (D-36 months) . . . . .. .. . .. . . . .. . . . . . . . . . . . . . .. . ..... ...... 106 Fragile X syndrome: aclinico-genetic study of mentally retarded patients in Kuwait . . . . . . . . .. . . .. . . . . .. . ..... .. 116 Apollpoprotein B gene polymorphisms in people in the East Mediterranean area ofTurkey . . . . . . . . . . . . . . . .. 125 Improved serum HDL cholesterol profile among Bangladeshi male students during Ranladanfaating ............... ... .... .......... ..... ... ...... ...... .. . . . ... . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... ... . . . . . ..... ..... 131 lschaemic stroke In Jordan: a 2-year hospital-based study of subtypes and risk factors ................... 138 Prevalence of atrial fibrillation In a primary health care centre in Fars province, lllamlc Republic of Iran .. ...... ............. ..... ... . . . . . . . . . . . . ... . .... ... .. . . . . . . . . . . . . . . . . . ... . . ... . . . ... . ...... ..... .. . . .. . . . ..... ...... 147 P'NquencyofYersiniaspecies infection in paediatric acute diarrhoea in Tehran ............. .. . .. .. . .. .....•.... 162 Qulnlne~ln severe Plasmodium falciparum malaria during pregnancy in Sudan .... .... ..... .... ...... 159 ~ : abundanceandlnsecticideresistanceinan irrigated area of eastetnSudll'I ...................................................................................................................... .... ......... 167 C'*adlNll~oftuberculosis patients In Yazd province, Islamic Republic of Iran, 1997-99 .. .. ..... ..... 175 au nord du Liban : elude sur 8 ans ( 1992-1999) utilisant le test de Widal . . . . .. .•.. ...... 180 larcataract extraction and intraocular lens replacement