Eastern Mediterranean Health Journal [2004; Vol.10, Issue 4-5]

468 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Prevalence of measles antibody in children of different ages in Shiraz, Islamic Republic of Iran A. Karimi,1 A. Arjomandi,1 A. Alborzi,1 M. Rasouli,1 M.R. Kadivar,1 B. Obood1 and B. Pourabbas1 1Clinical Microbiology Research Centre, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran. Received : 10/10/02; accepted: 21/09/03 ABSTRACT An outbreak of measles due to secondary vaccine failure prompted this investigation into the prevalence of measles antibody in children. We studied 608 children in 7 different age groups: 6, 9, 14 and 18 months and 6, 10 and 15 years. Children in the 2 youngest groups received no vaccination; the rest were vaccinated at 9 months and 15 months. The 15-year-old age group received an additional vaccination. Transplacental measles antibody (Ab) decreased from 10.0% at 6 months to 0% at 9 months. Measles Ab was positive in 52.9% (14 months), 89.4% (18 months), 60.8% 96 years), 45.0% (10 years) and 96.8% (15 years). To increase Ab levels, a booster vaccination is recommended, administered either with the second DPT booster or at pre-high school age. Prévalence des anticorps antirougeoleux chez des enfants de différents âges à Chiraz (Répu- blique islamique d’Iran) RÉSUMÉ Une flambée de rougeole due à l’échec de la vaccination secondaire a conduit à effectuer une étude de la prévalence des anticorps antirougeoleux chez les enfants. Nous avons étudié 608 enfants dans sept groupes d’âge différents : 6, 9, 14 et 18 mois et 6, 10 et 15 ans. Les enfants des deux groupes d’âge les plus jeunes n’avaient pas été vaccinés ; le reste des enfants avaient été vaccinés à l’âge de 9 et 15 mois. Le groupe des enfants de 15 ans avait eu une vaccination supplémentaire. Les anticorps transplacentaires diminuaient, passant de 10,0 % à l’âge de 6 mois à 0 % à l’âge de 9 mois. Dans les groupes d’âge étudiés, la proportion des enfants présentant des anticorps antirougeoleux par âge était de 52,9 % (14 mois), 89,4% (18 mois), 60,8 % (6 ans), 45,0 % (10 ans) et 96,8 % (15 ans). Afin d’augmenter les taux d’anticorps, une vaccination de rappel est recommandée, à administrer soit avec le deuxième rappel DTC soit à l’âge correspondant au cycle d’enseignement pré-secondaire. 01 Prevalence of measles.pmd 8/17/2005, 11:03 AM468 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 469 Introduction Prevention of measles using vaccination is still the most important task in developing countries. The disease is a substantial cause of mortality and morbidity in chil- dren. It is highly contagious but prevent- able [1]. Mortality has declined drama- tically since the introduction of a live atten- uated vaccine. Despite an 85% decrease in mortality, however, outbreaks of measles have been reported due to secondary vac- cine failure in older age groups (10–24 years), e.g. in a study of measles epidemi- ology by the Iranian Minister of Health and Medical Education in 1998 [2]. This has led some countries, including the United States of America, to introduce an additional dose of vaccine in school-age children. In the Is- lamic Republic of Iran, the decline in mea- sles incidence due to the vaccination programme has been noticed in children; cases in older age groups are, however, still emerging. This might be due to immigra- tion from neighbouring countries such as Afghanistan and Pakistan, which have a vaccine coverage of less than 80% (unpub- lished report, Ministry of Health and Medi- cal Education, 1988). Our study was conducted to disclose the prevalence of measles antibodies in dif- ferent age groups and to evaluate the ne- cessity of administering additional doses of vaccine. The study was prompted by an outbreak of measles in our country in 1997. Methods Over the period 2001–02 we enrolled 608 children into the study in 7 different age groups. Details of the groups and their vac- cination history are given in Table 1. The children were selected by random cluster sampling of children referred to the Motah- hari out-patient clinic or from primary schools in Shiraz. The epidemiological data including sex, age, socioeconomic status, number of family members and vaccination history were obtained. For antibody (Ab) testing, 5 mL of blood was drawn and se- rum was separated and frozen at –20 °C. The sera were examined using an enzyme- linked immunosorbent assay IgG kit (Mor- billio, Radim SpA, Pomezia, Italy). Samples with optical density (OD) lower than the cut-off control (OD < 0.200) were consid- ered non-reactive for measles IgG antibod- ies. Samples with OD higher than the cut-off control (OD > 0.700) were consid- ered reactive for measles IgG antibodies. Samples with absorbance values ± 10% of the cut-off (OD 0.200 to 0.700) control were considered questionable and were re- tested for confirmation. Results We enrolled 608 children, 52% male and 48% female, in the study. Table 2 shows Table1 Vaccination history for children in seven different age groups Group No. Age Vaccination history 1 70 6 m No vaccination 2 62 9 m No vaccination 3 70 14 m Vaccinated at 9 m 4 66 18 m Vaccinated at 9 m and 15 m 5 97 6 y Vaccinated at 9 m and 15 m 6 149 10 y Vaccinated at 9 m and 15 m 7 94 15 y Vaccinated at 9 m, 15 months and 9 m prior to the study m = months. y = years. 01 Prevalence of measles.pmd 8/17/2005, 11:03 AM469 470 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 the frequency of measles Ab prevalence in each age group. Antibody prevalence was higher in girls, although the result was not statistically significant. The Ab prevalence was significantly different in all consecu- tive age groups (P = 0.00001). The P-val- ues for the different age groups are shown in Table 2. Number of family members, so- cioeconomic status and literacy of parents were not significant (data not shown). Transplacental IgG from mothers de- clined from 10.0% at 6 months to 0% at 9 months of age in non-vaccinated children. Although this is unusual and we do not have good explanation for it, it is possible the titre of measles Ab in our pregnant women was very low due to low contact with wild measles viruses. However, in in- fants more than 9 months old, the preva- lence of Ab increased owing to vaccination at 9 months and 15 months of age, and de- clined over time thereafter. Primary vaccine failure is defined as a no detectable antibody after vaccination. It can be caused by interaction of maternal antibody to the vaccine by immunological response, technical problems, and so on. Primary vaccine failure in our study was 47.1% in the 14-month-old group, reduc- ing to about 10.6% in the 18-month-old group due to the second dose of vaccine given at 15 months. Primary vaccine failure was 55% at age 10, reducing to 3.2% at 15 due to the third vaccine administration. Discussion Measles is a highly contagious, preventable disease. The incidence has shown a re- markable decline in our county over recent years due to routine administration of live, attenuated vaccine at the ages of 9 months and 15 months, but several reports of dis- ease outbreak in older age groups have been documented [2,3]. The presence of measles Ab indicates previous infection, active immunization or, at ages below 9 months, maternal Ab transmission, all of which offer immunity. Our study was conducted to determine the pattern of Ab prevalence in different age groups of children. In this study, transpla- cental Ab was detected in only 10.0% of 6- month-old infants, declining to 0% at 9 months. This finding is in accord with pre- Table 2 Prevalence of measles antibody (Ab) in children in seven different age groups in Shiraz Age Total Ab positive Ab negative P-values between different age groups No. No. % No. % 6 m 70 7 10.0 63 90.0 9 m 62 0 – 62 100.0 6 m and 9 m 0.014 14 m 70 37 52.9 33 47.1 9 m and 14 m 0.00001 18 m 66 59 89.4 7 10.6 18 m and 6 y 0.00006 6 y 97 59 60.8 38 39.2 6 y and 10 y 0.016 10 y 149 67 45.0 82 55.0 10 y and 15 y 0.00001 15 y 94 91 96.8 3 3.2 All age groups 0.00001 Total 608 320 50.7 288 49.3 m = months. y = years. 01 Prevalence of measles.pmd 8/17/2005, 11:03 AM470 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 471 vious studies from Iran [4,5]. The decline of maternal antibody in infants in different geographic areas is dependent on socioeco- nomic states, catabolism of antibody, amount of antibody transmission to fetus, level of maternal antibody, and so on. In some studies it was shown to be between 0% and 10% at about 11 months of age [2,4]. Therefore, a high percentage of chil- dren at 6 months of age are also susceptible in an outbreak of the disease. It has been documented that the Schwarz type vaccine that is used in the Islamic Republic of Iran is not so effective for 6-month-old infants [6,7]. The absence of Abs during outbreaks was 47.1% at 14 months, 1 month before the second vaccination and 10.6% 3 months afterwards. This finding was in ac- cordance with previous studies [8–10]. High primary vaccine failure at 9 months of age might be related to trans-placental Ab from mothers [8]. Other possible factors responsible for this high primary vaccine failure include nutritional status of children [11], acute disease during vaccination [12–14] and concomitant administration of gamma globulin [15], race, environmental factors [16,17], sex [18] and immunity status of those being vaccinated [19,20]. In our study, sex and literacy were not statistically important factors in primary vaccine fail- ure. Measles Ab was positive in 89.4% of the 18-month-old children and 60.8% at 6 years of age, which was statistically signif- icant (P < 0.001). In the 10-year-old group, only 45.0% of the children were positive for measles Ab (P = 0.016). This Ab- waning phenomenon is reported to be about 2%–20% in several studies [21–24]. The presence of Ab may be due to the vac- cine effect or to previous infection with wild virus. The waning of Ab titre is greater in subjects who produce lower initial Ab ti- tres. Accordingly, a single vaccination pro- duces more significant Ab waning [25]. An important observation was the significant rise in the Ab titre of the 15-year-old age group following the administration of an additional booster dose of the vaccine, compared to the 10-year-old age group (P < 0.00001) (Table 2). The necessity for an additional immunization is also emphasized in a report from Singapore [26] and in oth- er countries [27,28]. Therefore, an addi- tional dose of measles vaccine is recommended for Iranian children around high-school age. Acknowledgement The authors wish to thank Dr A. Japoni for his help in preparing the manuscript. References 1. Issacs D, Menser M. Modern vaccines, measles, mumps, rubella, and varicella. Lancet, 1990, 335:1384–7. 2. Study of measles epidemiology in Iran during 1991 to 1998. Annual report of the Minister of Health and Medical Educa- tion. Tehran, Ministry of Health and Medi- cal Education, 1998. 3. Health picture. Annual report of the Min- ister of Health and Medical Education. Tehran, Ministry of Health and Medical Education, 2002. 4. Mirchamsy H et al. Age of measles im- munization in tropics. Developments in biological standardization, 1978, 41: 191–4. 5. Mokhtariazad T. Evaluation of measles vaccination in 6-month infants [thesis]. Tehran, Tehran University of Medical Sciences, 1982. 01 Prevalence of measles.pmd 8/17/2005, 11:03 AM471 472 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 6. Markowitz LE et al. Immunization of six- month-old infants to different doses of Edmonston–Zagreb and Schwarz measles vaccine New England journal of medicine, 1990, 322:580–7. 7. Tidjani O et al. Serological effects of Edmonston–Zagreb, Schwarz and AIK- C measles vaccine strains given at ages 4–5 or 8–10 months. Lancet, 1989, 11: 1357–60. 8. Shelton JD et al. Measles vaccine effi- cacy: Influence of age at vaccination vs duration of time since vaccination. Pedi- atrics, 1978, 62:961–4. 9. Mirchamsy H et al. Comparative field trial of five measles vaccines produced in human diploid cell, MRC-S. Journal of biological standardization, 1977, 5:1– 18. 10. Mirchamsy H et al. Mass immunization of children in Iran with live attenuated Sugiyama virus adapted to calf kidney cell cultures. Japanese journal of experi- mental medicine, 1971, 41:39–40. 11. Wesley A, Coovadia HM, Henderson L. Immunological recovery after measles. Clinical and experimental immunology, 1978, 32:540–4. 12. Krober MS, Stracener CE, Bass JW. De- creased measles antibody response af- ter measles–mumps–rubella vaccine in infants with colds. Journal of the Ameri- can Medical Association, 1991, 265(16): 2095–6. 13. Halsey NA et al. Response to measles vaccine in Haitian infants 6 to12 months old. New England journal of medicine, 1985, 313(9):544–9. 14. Ndikuyeze A et al. Immunogenicity and safety of measles vaccines in ill African children. International journal of epide- miology, 1988, 17(2):448–55. 15. Krugman S. Present studies of measles and rubella immunization in the United States: a medical program report. Pediat- rics, 1971, 78:1–16. 16. Black FL et al. Geographic variation in infant loss of maternal measles antibody and in prevalence of rubella antibody. American journal of epidemiology, 1986, 124(3):442–52. 17. Neiburg P, Dibley MJ. Risk factors for fatal measles infection. International journal of epidemiology, 1980, 15(3): 309–11. 18. Bromberg K et al. Maternal immunity to measles and infant immunity at less than twelve months of age relative to mater- nal place of birth. Journal of pediatracs, 1994, 125(4):579–81. 19. Dai B et al. Duration of immunity follow- ing immunization of live measles vac- cine. Bulletin of the World Health Organization, 1991, 69(4):415–23. 20. Markowitz LE et al. Persistence of measles antibody after revaccination. Journal of infectious diseases, 1992, 166(1):205–8. 21. Climie A, Andre FE. Field trial of heat- stable measles vaccine in Papua New Guinea. Journal of tropical medicine and hygiene, 1984, 87(6):249–55. 22. Zhuji Measles Vaccine Study Group. Epi- demiologic examination of immunity period of measles vaccine. Chinese medical journal, 1987, 67:19–22 [in Chi- nese]. 23. Xiang JZ, Chen AH. Measles vaccine in the People’s of Republic of China. Re- views of infectious diseases, 1983, 5(3): 506–10. 24. Gdalevich M et al. Measles epidemic in Israel—successful containment in the military. Preventive medicine, 2000, 31(6):469–51. 25. Smith FR et al. Reported measles in per- sons immunologically primed by prior 01 Prevalence of measles.pmd 8/17/2005, 11:03 AM472 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 473 vaccination. Journal of pediatrics, 1982, 101(3):391–3. 26. Goh D et al. Resurgence of measles in Singapore: profile of hospital cases. Journal of paediatrics and child health, 1999, 35(5):493–6. 27. Christenson B, Bottiger M. Measles anti- body comparison of long-term vaccina- tion titer, early vaccination titers and naturally acquired immunity. Vaccine, 1994, 12(2):129–33. 28. Olsha M et al. Measles immunity in Is- raeli young adults. Israel journal of medi- cal sciences, 1994, 30:596–9. Measles mortality reduction Measles remains a leading cause of death among young children, despite the availability of a safe and effective vaccine for the past 40 years. More than half a million people, the majority of them chil- dren, died from measles in 2003; in the Eastern Mediterranean Re- gion (EMR) there were an estimated 69 000 deaths from measles. WHO and UNICEF have developed a joint Strategic Plan for Measles Mortality Reduction and Regional Elimination 2001–2005. The over- riding goal of this plan is to reduce the number of global measles deaths (from the 1999 level) by 50% by the end of 2005. The priority countries in EMR are Afghanistan, Djibouti, Pakistan, Somalia and Sudan. The four-pronged strategy for sustainable measles mortality reduction is based on: providing strong routine immunization; pro- viding a “second opportunity” for measles immunization to all chil- dren; surveillance; improvement in the clinical management of measles cases. Thus, from 1999 to 2003, more than 350 million children globally received measles vaccine through supplementary immunization activities. Moreover, improvements were made in rou- tine immunization over this period. These accelerated activities have resulted in a significant reduction in estimated global measles deaths. Overall, global measles mortality decreased by 39% be- tween 1999 and 2003. Given the progress made to date, it is ex- pected that the 2005 global measles mortality reduction goal will be achieved. Source: WHO Fact sheet No. 286 Available at: http://www.who.int/mediacentre/factsheets/fs286/en/ 01 Prevalence of measles.pmd 8/17/2005, 11:03 AM473 474 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Évaluation de la réponse vaccinale contre la poliomyélite et la rougeole chez les enfants malnutris au Maroc H. Caidi, 1 F. Bennis, 2 N. Mouan 2 et R. El Aouad 1 1Département d’Immuno-Virologie, Institut national d’Hygiène, Rabat (Maroc). Courriel : hcaidi@mailcity.com. 2Service de Pédiatrie III, C.H.U. Avicenne, Rabat (Maroc). Reçu : 07/02/02 ; accepté : 26/10/03 RÉSUMÉ Il s’agit d’une étude comparative de la séroprévalence des anticorps anti-poliovirus type 1, anti- poliovirus type 2, anti-poliovirus type 3 et des anticorps anti-rougeole chez les enfants malnutris (37) et complètement vaccinés et les enfants dont l’état nutritionnel est normal (34). L’âge est compris entre 10 mois et 5 ans. Les enfants souffrant d’une malnutrition protéino-calorique présentaient un taux d’immunisation vis-à-vis du vaccin poliomyélitique et du vaccin antirougeoleux très faible en comparaison avec les enfants témoins. En effet, 94,1 % des enfants témoins sont immunisés contre le poliovirus type 1, 97,1 % contre le poliovirus type 2 et 91,2 % contre le poliovirus type 3. Chez les enfants malnutris, ces taux étaient dans certains cas significativement plus faibles : 40,5 % (p = 0,001), 59,5 % (p = 0,001) et 40,5 % respectivement. La même baisse de la réponse vaccinale a été notée concernant le vaccin antirougeo- leux: le taux d’immunisation est de 82,4 % chez les enfants témoins contre 35,1 % chez les enfants malnutris. La malnutrition est le facteur majeur de l’échec de la réponse vaccinale qui nous interpelle pour adopter les attitudes adéquates en vue d’éviter les échecs de vaccination. Evaluation of the response to vaccination against poliomyelitis and measles in malnourished chil- dren in Morocco ABSTRACT We made a comparative survey of the poliovirus antibodies (anti-poliovirus type 1, anti-poliovirus type 2 and anti-poliovirus type 3) and the measles antibodies in malnourished but completely vaccinated children (37) and control children (34). The age range was 10 months to 5 years. Immunization in children with protein–energy malnutrition was low for both vaccines. Seroprevalence rates of the polio 1, polio 2, polio 3 antibodies and the measles antibodies in the control group were 94.1%, 97.1%, 91.2% and 82.4% respectively. In malnourished children the respective rates were in some cases significantly lower being: 40.5% (P = 0.001), 59.5% (P = 0.001), 40.5% and 35.1%. Malnutrition is a major determinant of the humoral response to oral polio and measles vaccines and must be given due consideration to prevent vaccination failure. 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM474 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 475 Introduction La malnutrition protéino-calorique (MPC) représente dans les pays en développement l’un des principaux problèmes de santé publique, responsable d’une forte mortalité infantile [1,2]. D’après des analyses ré- centes des causes de décès chez l’enfant, la malnutrition, mesurée par les paramètres anthropométriques, serait associée au décès dans près de la moitié des cas dans les pays en développement [1]. Elle est par ailleurs fréquemment associée sous une forme grave ou modérée à de très nom- breuses affections où elle intervient comme facteur aggravant [1,2,3]. Plusieurs mécanismes immunitaires sont défaillants chez les enfants malnutris qui, de ce fait, sont victimes de sévères in- fections et du cycle vicieux infection- malnutrition [4]. La malnutrition constitue un problème majeur de l’échec des pro- grammes de vaccination dans les pays où la malnutrition est répandue. Des études ont montré la faible réponse au vaccin vivant atténué contre la rougeole et la poliomyélite en comparaison avec les enfants témoins [5,2,6,7]. L’objectif de notre étude consiste à évaluer la séroprévalence des anticorps anti-poliovirus type 1, anti-poliovirus type 2 et anti-poliovirus type 3 ainsi que des an- ticorps anti-rougeole chez les enfants malnutris, complètement vaccinés. La prévalence de ces mêmes anticorps est dé- terminée en parallèle chez les enfants complètement vaccinés et dont l’état nutri- tionnel est normal. Méthodes Enfants malades et enfants témoins L’étude est réalisée sur 37 enfants (20 garçons et 17 filles) âgés de 10 mois à 5 ans auprès du service de Pédiatrie III, Hôpital d’enfants du Centre hospitalier uni- versitaire (C.H.U.) de Rabat. Tous ces en- fants sont vaccinés contre la poliomyélite (vaccin antipoliomyélitique oral trivalent ; fabricants : Bucham & Clyron) et la rou- geole (vaccin antirougeoleux ; fabricants : Serum Institut of India et Aventis) et rem- plissent les critères de malnutrition qui sont vérifiés au préalable grâce à un question- naire validé par le clinicien. Ils sont alors classés selon l’âge (Tableau 1), le type de malnutrition (Tableau 2) et le degré de mai- greur (Tableau 3). Le calendrier vaccinal au Maroc prévoit une première dose de vaccin poliomyéli- tique oral à la naissance et 3 doses de rappel à un intervalle d’un mois, et une dose de vaccin antirougeoleux à 9 mois. Le groupe témoin a été recueilli égale- ment auprès du même service. Il s’agit de 20 garçons et 14 filles (34 enfants) âgés de 10 mois à 5 ans. Ces enfants sont tous vac- cinés contre la poliomyélite et la rougeole et ne présentent aucun signe de malnutrition. Le prélèvement sanguin est fait dans le ca- dre d’un bilan destiné à l’exploration de la pathologie qui a motivé leur hospitalisation. Tableau 1 Répartition des enfants malnutris et des enfants témoins en fonction de l’âge et du sexe Variable Enfants malnutris Enfants témoins Nombre % Nombre % Âge (mois) 10-12 16 34,2 14 41,1 13-15 10 27,0 9 26,4 16-24 7 18,9 6 17,6 >24 4 10,8 5 14,7 Sexe Masculin 20 54,0 20 58,8 Féminin 17 45,9 14 41,1 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM475 476 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Prélèvement sanguin Un prélèvement sanguin (5 ml) veineux est recueilli dans un tube sec pour chaque en- fant. Le sang est centrifugé (500 g pendant 10 minutes) et le sérum est stocké congelé à - 80 °C jusqu’à son utilisation. Titrage des anticorps anti-polio 1, 2 et 3 et des anticorps anti- rougeole Le titrage des anticorps anti-poliovirus 1, 2 et 3 ainsi que des anticorps anti-rougeole est réalisé par réaction de séroneutralisation sur cultures cellulaires. Deux lignées sont utilisées : la lignée HEp-2 pour le titrage des anticorps anti-poliovirus 1, 2 et 3, et la lignée Vero pour le titrage des anticorps anti-rougeole. Le choix de ces techniques était justifié par leur grande maîtrise dans notre laboratoire. Pour le poliovirus, le titre du sérum est donné par la plus forte dilution sérique qui neutralise 50 % des cultures cellulaires contre 100 DI50 de virus d’épreuve. Les ré- sultats des titres d’anticorps sont normale- ment exprimés par leur réciproque (Manual for the virological investigation of the po- liomyelitis). La DCP 50 % est calculée par la mé- thode de Reed et Munch. Log DCP 50% = log (dilution 50 % d’effet cytopathogène) + DP corrigé Pour le titrage du taux d’anticorps con- tre le vaccin antirougeoleux, le titre du sérum est calculé par la méthode de Kärber (Manual for the laboratory diagnosis of measles virus infection). Log10 (inverse) de la plus grande dilution - (somme des moyennes des plages de lyse (UFP) ÷ titre inverse du virus contrôle - 0,5) × log10 du facteur de dilution. Résultats La tranche d’âge la plus touchée par la carence nutritionnelle se situe entre 9 mois et 2 ans et touche aussi bien le sexe mascu- lin que le sexe féminin. Tableau 2 Répartition des enfants malnutris en fonction du type de malnutrition Type de Garçons Filles Total malnutrition (%) Kwashiorkor 2 2 4 (10,8) Marasme 6 0 6 (16,2) Autres hypotrophies 12 15 27 (27,9) Syndromes anémiques 3 0 3 Vomissements associés à une béance du cardia 1 1 2 Infections parasitaires 2 0 2 Infections mycobactériennes 0 1 1 Avitaminose 2 0 2 Maladie cœliaque 4 3 7 Cardiopathie congénitale 1 0 1 Diarrhées avec déshydratation 6 4 10 Total (%) 20 (54) 17 (45,9) 37 (100) Tableau 3 Répartition des enfants malnutris en fonction du degré de maigreur Degré de Nombre % maigreur (%) de cas < 60 14 37,8 70 10 27,0 80 8 21,6 90 5 13,5 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM476 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 477 Les résultats de séroneutralisation pour le vaccin antipoliomyélitique chez les en- fants témoins montrent qu’après trois do- ses de vaccin antipoliomyélitique oral trivalent (VPOT), la proportion d’enfants témoins présentant des titres ≥ 8 est de 94,1 % (32/34) pour le type 1, de 97,1 % (33/34) pour le type 2 et de 91,2 % (31/34) pour le type 3. Chez les 37 enfants de notre étude souf- frant d’une malnutrition protéino-calorique et en comparaison avec le groupe témoin, le taux d’immunisation est beaucoup plus faible aussi bien pour le poliovirus type 1 que pour le poliovirus type 2 et le poliovirus type 3. En effet, la séroconversion est de 40,5 % (15/37) pour le poliovirus type 1, 59,5 % (22/37) pour le poliovirus type 2 et 40,5 % (15/37) pour le poliovirus type 3. Le pourcentage d’enfants triple positifs est de 37,8 % (14/37) seulement (Tableau 4). Pour le vaccin antirougeoleux, les résul- tats de la séroneutralisation ont révélé que malgré une couverture vaccinale de 100 % chez les enfants témoins, le taux de séro- conversion contre le vaccin est de 82,4 % (28/34) ; 70 % présentent un taux d’anticorps compris entre 120 et 899 UFP et seulement 12,4 % des enfants présentent un titre supérieur à 900 UFP. Le taux de séroconversion négatif chez ce groupe d’enfants est de 17,6 % (6/34). Chez les enfants malades, le taux d’immunisation contre la rougeole est beaucoup plus abaissé par rapport au groupe témoin. Ainsi, la présence d’anti- corps neutralisant le virus de la rougeole révélé par la réaction de séroneutralisation est notée chez seulement 35,1 % (13/37) des enfants, le titre des anticorps étant en- tre 120 et 899 UFP. La majorité des enfants de ce groupe sont séronégatifs (24/34), soit un pourcentage de 64,8 % ; le titre des anti- corps neutralisants est inférieur à 8 UFP. Par ailleurs, aucun enfant ne présente un taux d’anticorps supérieur à 900 UFP. On a également pu comparer le taux d’immunisation contre la poliomyélite et la rougeole chez les enfants malnutris en fonction de deux paramètres : le type de malnutrition et le degré de maigreur. Chez les cas de kwashiorkor (4 cas) et de marasme (6 cas), le taux d’immunisa- tion est nul aussi bien pour les trois types de poliovirus que pour le virus de la rou- geole. Pour les autres hypotrophies (27 cas), 12 présentent un statut immunitaire normal pour le vaccin antipoliomyélitique et le vaccin antirougeoleux avec un pourcen- tage de 44,4 % et 13 enfants ont des tests négatifs pour la poliomyélite et la rougeole, soit un pourcentage de 48,1 %. Les deux hypotrophes restants ont des tests positifs pour la poliomyélite et négatifs pour la rou- geole (7,4 %). L’immunisation la plus défaillante est celle trouvée chez les enfants avec un degré de maigreur < 60 % et un degré de mai- greur de 90 % : 3 enfants seulement sur 14 (21,4 %) avec un degré de maigreur < 60 % présentent une séroconversion vis- à-vis du vaccin antipoliomyélitique contre 2 cas (14,2 %) pour le vaccin antirougeo- leux ; un seul cas sur 5 (20,0 %) avec un degré de maigreur de 90 % (les enfants avec un degré de maigreur de 90 % sont Tableau 4 Taux d’immunisation contre le poliovirus et le virus de la rougeole chez les enfants témoins et les enfants malnutris Immunisation Enfants Enfants p contre témoins malnutris % % Poliovirus Type 1 94,0 40,5 < 0,001 Type 2 97,0 59,0 < 0,001 Type 3 91,0 40,5 < 0,001 Virus de la rougeole 82,3 35,1 < 0,001 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM477 478 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 tous des formes œdémateuses où le degré de maigreur n’est pas un bon indicateur de l’état nutritionnel du malade) est séropositif aussi bien pour le virus poliomyélitique que pour le virus de la rougeole. Trois cas sur 10 (30,0 %) avec un de- gré de maigreur de 70 % montrent une séroconversion positive vis-à-vis du polio- virus et 4 enfants sur 10 (40,0 %) une séroconversion positive vis-à-vis du virus de la rougeole ; 7 enfants sur 8 ayant un degré de maigreur de 80 % sont séroposi- tifs pour le poliovirus (87,5 %) contre 6 cas (75,0 %) pour le virus de la rougeole. Discussion Comme déjà mentionné, la tranche d’âge la plus touchée par la carence nutritionnelle se situe entre 10 mois et deux ans ; cette prédilection trouve son explication dans le sevrage de l’allaitement au sein et la grande fréquence des maladies associées à cet âge [2,3]. Par ailleurs, la malnutrition touche aussi bien les garçons (54 %) que les filles (45,9 %), la différence n’étant pas statis- tiquement significative (p = 0,48). Pour les résultats de séroneutralisation, notre étude montre que le taux d’immunisation aussi bien pour le vaccin antipoliomyélitique que pour le vaccin antirougeoleux chez les en- fants malnutris est plus faible en comparai- son avec les enfants dont l’état nutritionnel est normal. Pour le vaccin antipoliomyéli- tique, le taux de séroconversion pour le type 1 est de 94 % chez les enfants té- moins, alors que chez les enfants malades il est de 40,5 %, la différence étant statis- tiquement très significative (p = 0,001). Pour le poliovirus type 2, la proportion d’enfants présentant des titres d’anticorps ≥ 8 est de 97 % chez les enfants témoins contre 59 % chez les enfants malades (p = 0,001). Il n’en reste pas moins que l’immunité contre le poliovirus type 1 constitue un atout majeur dans la lutte con- tre la poliomyélite antérieure aiguë puisqu’il s’agit à la fois du type le plus fréquent et le plus pathogène. La même différence est notée pour le poliovirus type 3 : 91 % pour les témoins contre 40,5 % pour les enfants souffrant d’une malnutrition protéino- calorique (p = 0,001). Ces résultats sont tout à fait comparables à ceux rapportés par d’autres auteurs, le poliovirus type 3 étant connu pour sa faible immunogénicité [8]. En effet, les carences en protéines et en apport énergétique ont une influence di- recte sur l’immunité et plus particulière- ment sur la production d’anticorps qui sont des glycoprotéines [4]. Ainsi l’absence de réponse immunitaire vaccinale, plus parti- culièrement dans les formes œdémateuses (kwashiorkor) où le taux d’immunisation est nul aussi bien pour le vaccin antipo- liomyélitique que pour le vaccin antirougeo- leux, trouve son explication dans le défaut de protéosynthèse. Dans ces formes œdé- mateuses, la protidémie est très basse, elle atteint 38 g/L ; l’électrophorèse des frac- tions protéiques a révélé une hypoalbumi- némie (< 18 g/L) et une hypogammaglo- bulémie (< 3 g/L). Dans la malnutrition protéino-énergé- tique, le système du complément, surtout la fraction C3, est déficiente et par con- séquent la production d’anticorps est dé- ficiente elle aussi. Cette déficience en pro- duction des anticorps aussi bien pour le vaccin trivalent oral (VPOT) que pour le vaccin antirougeoleux est beaucoup plus marquée chez les cas de kwashiorkor et de marasme [9] ; ceci explique la susceptibi- lité sinon la confirmation d’une réinfection par la poliomyélite et par la rougeole chez les enfants souffrant de MPC. D’autres facteurs peuvent expliquer la faible réponse vaccinale antipoliomyéli- tique, comme les diarrhées chroniques et 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM478 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 479 l’interférence des entérovirus non po- liomyélitiques qui sévissent pendant la pé- riode sèche. Deux études ont permis d’illustrer le rôle de ces deux facteurs. Ain- si, une étude menée en Tunisie en 1997 sur 121 enfants ayant reçu 3 doses du vaccin VPOT a montré que les taux de sérocon- version pour le poliovirus type 1, le poliovi- rus type 2 et le poliovirus type 3 sont de 94,7 %, 100 % et 89,5 % respectivement. Le faible taux de séroconversion a été noté surtout pour le poliovirus 3 comparé à celui du poliovirus 2 et du poliovirus 1. L’inter- férence virale avec les entérovirus a été notée dans 50 % de la non-réponse à un type de poliovirus ou à un autre. L’étude a montré que la faible réponse vaccinale peut aussi être associée à d’autres facteurs comme la présence d’anticorps maternels et la malnutrition [10]. Une étude menée en Chine (province de Guangdong) a permis d’illustrer le rôle de la saison de vaccination dans la séroconver- sion vaccinale antipoliomyélitique chez 82 enfants vaccinés en été et 106 enfants vaccinés en hiver. Le dosage des anticorps a été testé avant et après vaccination. Le taux de séroconversion est de deux à sept fois plus important en hiver qu’en été. L’interférence virale avec les entérovirus non poliomyélitiques a été notée dans 75,6 % et 38 % des cas en été et en hiver respectivement ; ceci laisse apparaître que la fréquence des infections à entérovirus pendant la période sèche, période où l’incidence de la malnutrition est à son pic, peut être la cause principale de l’échec de la réponse vaccinale antipoliomyélitique. Une suggestion proposée par l’auteur de l’étude est de donner une dose de vaccin supplé- mentaire en dehors de la période sèche, surtout chez les enfants à risque de malnu- trition [11]. Ceci donc laisse comprendre que l’infection par des virus autres que le poliovirus pourra diminuer la réponse vac- cinale vis-à-vis du vaccin contre la po- liomyélite, surtout chez les enfants à risque pour la malnutrition où l’infection par d’autres virus est plus fréquente [12]. La malnutrition et les maladies diar- rhéiques très fréquentes dans les pays en développement sont les causes majeures de l’échec vaccinal. Une étude similaire a été réalisée en 1996 aux Philippines sur l’évaluation de la réponse vaccinale vis-à- vis du vaccin poliomyélitique oral chez les enfants dénutris suite à des diarrhées chro- niques. Les résultats montrent que le taux d’immunisation chez les enfants est di- minué de 26 à 34 % en comparaison avec le groupe témoin (p < 0,002) [13]. En effet, les diarrhées fréquentes chez les enfants souffrant de MPC peuvent expliquer la non-fixation du virus dans la paroi intesti- nale, soit par un phénomène d’inférence vi- rale avec les anticorps en réponse au VPOT (l’adénovirus, l’entérovirus et le rotavirus), bactérienne ou parasitaire, soit en favo- risant une élimination trop rapide du virus [10,14]. Pour le vaccin antirougeoleux comme pour le vaccin antipoliomyélitique, la séro- conversion vis-à-vis du virus de la rougeole est bien plus diminuée dans le cas d’une dénutrition sévère. Ainsi, le taux d’immuni- sation chez les témoins est de 82,3 % (28/ 34) ; ce taux est abaissé à 35,1 % (13/37) chez les enfants malnutris (p = 0,001). Une étude sur la réponse vaccinale vis- à-vis du vaccin vivant atténué de la rou- geole a été réalisée au Soudan chez 35 enfants malnutris en comparaison avec 35 enfants témoins dont l’état nutritionnel est normal. Un prélèvement sanguin a été effectué avant et après vaccination, et le dosage des anticorps a été réalisé par réac- tion d’inhibition d’hémagglutination. Le taux de séroconversion chez les enfants malnutris et les enfants témoins est de 92 % et 96 % respectivement (p < 0,02) ; 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM479 480 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 le faible taux de séroconversion a été noté chez les cas de kwashiorkor [15]. La baisse de la réponse vaccinale est la conséquence d’un état nutritionnel défail- lant. Des études ont rapporté que le taux d’immunisation ou de séroconversion vis- à-vis du virus de la rougeole est beaucoup plus abaissé chez les enfants malnutris [16] en comparaison avec les enfants dont l’état nutritionnel est normal. Ainsi, une bonne couverture vaccinale ne garantit pas une bonne immunité sérologique chez les en- fants souffrant de MPC. La supplémentation en vitamine A chez les mères après l’accouchement et les nouveau-nés pourra remédier à ce problème et pourra augmenter la produc- tion des anticorps en réponse à la vaccina- tion. Une étude menée en Inde consistait à donner de la vitamine A (60 mg de rétinol) aux mères ainsi qu’à leur bébé (7,5 mg) à chaque administration d’une dose de VPO. Cette supplémentation a amélioré le taux d’immunisation vis-à-vis du vaccin de la poliomyélite, surtout pour le poliovirus de type 3 [17]. Conclusion Au vu de ces résultats qui démontrent les faibles taux de séroconversion vis-à-vis du vaccin poliomyélitique oral et du vaccin an- tirougeoleux chez les enfants malnutris comparés à des enfants témoins, il nous paraît urgent de discuter d’une conduite pour améliorer l’état vaccinal de ces en- fants et de s’assurer que les taux satisfai- sants de couverture vaccinale (> 95 % pour la poliomyélite et 92 % pour la rou- geole à l’échelle nationale) permettront d’atteindre les objectifs assignés, à savoir l’éradication de la poliomyélite d’ici l’an 2005 et l’élimination de la rougeole d’ici 2010. Si la malnutrition protéino-calorique a légèrement reculé ces dernières années au Maroc (de 28 % à 24 %), il n’en reste pas moins que les cas de malnutrition que l’on continue à enregistrer constituent un obsta- cle qui ralentit, voire compromet, le succès des programmes d’éradication de la po- liomyélite et d’élimination de la rougeole. L’évaluation de l’importance de la mal- nutrition protéino-calorique au Maroc per- mettrait de proposer une attitude adaptée pour prévenir ces échecs de la vaccination. L’impact de la supplémentation en vitamine A, qui est actuellement intégrée dans les activités du programme de vaccination, sur la séroconversion vis-à-vis du VPO et du vaccin antirougeoleux chez les enfants mal- nutris doit être apprécié lorsque l’admi- nistration d’une dose supplémentaire de vaccin antipoliomyélitique et antirougeo- leux, une fois la malnutrition protéino- calorique jugulée, pourrait être une alterna- tive pour prévenir ces échecs de vaccina- tion. Ceci suppose néanmoins qu’un dépistage ciblé de la malnutrition protéino- calorique dans les régions à risque doit être entrepris, ce qui pourrait être d’une grande importance à la phase finale d’éradication de la poliomyélite et d’élimination de la rou- geole. Remerciements Nous tenons à remercier tout le personnel du service de Pédiatrie III pour leur aide précieuse. Nous tenons à remercier égale- ment nos collègues du laboratoire de virolo- gie de l’Institut national d’Hygiène à Rabat. 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:04 AM480 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 481 Références 1. Rice AL et al. Malnutrition as an underly- ing cause of childhood deaths associ- ated with infectious diseases in develo- ping countries. Bulletin of the World Health Organization, 2000, 78(10): 1207–21. 2. El Khaier A. Etude épidémiologique étiologique clinique évolutive et théra- peutique des malnutritions protéino- caloriques de l’enfant. Thèse n° 376 ; 1987 3. Bhaskaram P. Nutritional modulation of immunity to infection. Indian journal of pathology and microbiology, 1992, 35(4):392–40. 4. Pastoret PP. Nutrition et réponse im- mune. In : Pastoret PP, Govaerts A, Bazin H. Immunologie animale. Paris, Flamma- rion Médecine Sciences, 1990. 5. Bhaskaram P. Measles and malnutrition. Indian journal of medical research, 1995, 102:195–9 6. Powell GM. Response to live attenuated measles vaccine in children with severe kwashiorkor. Annals of tropical paedia- trics, 1982, 2(3):143–5. 7. Chandra RK. Reduced secretory antibody response to live attenuated measles and poliovirus vaccines in mal- nourished children. British medical jour- nal, 1975, 2(5971):583–5. 8. Jody R et al. Sabin inactivated trivalent poliovirus vaccine : first clinical trial and seroimmunity survey. Pediatric infectious diseases journal, 1988, 7:760–5. 9. Hafez M et al. Antibody production and complement system in protein energy malnutrition. Journal of tropical medicine and hygiene, 1977, 80(2):36–9 10. Triki H, Abdallah MV, Ben Aissa R. Influ- ence of host related factors on the anti- body response to trivalent oral polio vac- cine in Tunisian infants. Vaccine, 1997, 15(10):1123–9. 11. Wu CM, Zheng HY, Ren YL. [Immune in- terference of enteroviruses to immune response of TOPV in subtropical areas.] Zhonghua liu xing bing Xne za zhi, 1996, 17(4): 233–5 [In Chinese]. 12. Faden H, Duffy L. Effect of concurrent vi- ral infection on systemic and local anti- body response to live attenuated and enhanced-potency inactivated poliovi- rus vaccines. American journal of diseases of children, 1992, 146(11): 1320–3 13. Yoon PW, Black RE, Moulton LH. The ef- fect of malnutrition on the risk of diar- rheal and respiratory mortality in children < 2 years of age in Cebu, Philip- pines. American journal of clinical nutri- tion, 1997, 65(4):1070–7. 14. Myaux JA et al. Effect of diarrhea on the humoral response to oral polio vaccina- tion. Pediatric infectious diseases jour- nal, 1996, 15(3):204–9. 15. Idriss S, El Seed AM. Measles vaccina- tion in severely malnourished Sudanese children. Annals of tropical pediatrics, 1983, 3(2):6–7. 16. Halsey NA et al. Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition and concurrent illnesses. New England journal of medicine, 1985, 313(9):544–9. 17. Bahl R et al. Effect of vitamin A adminis- tered at Expanded Programme on Immu- nization contacts on antibody response to oral polio vaccine. European journal of clinical nutrition, 2002, 56(4):321–5. 02 Evaluation de la rÈponse.pmd 8/17/2005, 11:05 AM481 482 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Detection of pneumonia among children under six years by clinical evaluation H. Shamo’on,1 A. Hawamdah,1 R. Haddadin1 and S. Jmeian 2 1Department of Paediatrics; 2Ear, Nose and Throat Department, Queen Alia Military Hospital, Royal Medical Services, Amman, Jordan. Received: 09/12/03; accepted: 17/03/04 ABSTRACT To determine the most useful clinical symptoms and signs for detection of pneumonia in children, we carried out a prospective clinical study at Queen Alia Hospital, Amman, on 147 children admitted between August 2002 and January 2003 with clinical pneumonia. All the children had chest X-rays, which were read by the same radiologist. The most sensitive and specific signs and symptoms for prediction of pneumonia were coughing, tachypnoea (respiratory rate > 50/min) and chest wall indrawing. We found that presence of tachypnoea and lower chest wall indrawing can detect most cases of pneumonia. If all clinical signs are negative, chest X-ray findings are unlikely to be positive. Dépistage de la pneumonie chez des enfants de moins de six ans par évaluation clinique RÉSUMÉ Afin de déterminer les symptômes et les signes cliniques les plus utiles pour le dépistage de la pneumonie chez l’enfant, nous avons réalisé une étude clinique prospective à l’hôpital Reine Alia d’Amman chez 147 enfants hospitalisés entre août 2002 et janvier 2003 pour un épisode de pneumonie avec diagnos- tic clinique. Tous les enfants ont eu des radiographies pulmonaires interprétées par le même radiologue. La toux, la tachypnée (rythme respiratoire > 50/min) et le tirage respiratoire étaient les signes et les symptômes les plus sensibles et les plus spécifiques pour prédire une pneumonie. Nous avons trouvé que la présence de tachypnée et d’un tirage sous-sternal permet de dépister la plupart des cas de pneumonie. Si tous les signes cliniques sont négatifs, il est peu probable que les résultats de la radiographie pulmonaire soient positifs. 03 Detection of pneumonia.pmd 8/17/2005, 11:05 AM482 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 483 Introduction Acute lower respiratory tract illness (ALRI) is common among children seen in primary care [1], and accounts for slightly less than 50% of deaths in children under 1 year and about 20% of deaths in all hospi- talized children under 15 years [2]. The physical differences between the chests of children and adults account for some of the differences in physical signs [3]. Small children find it difficult to take large breaths, so crackles and wheezes which may be expected only during such a manoeuvre will not be heard. In ALRI, when the history and physical examination suggest the same diagnosis, chest radiogra- phy is rarely necessary; when the 2 are in- consistent, then a radiograph may be helpful [4]. The identification of signs such as rapid breathing and chest retraction is very important in deciding who needs ex- pensive treatment and who does not [5]. Also important is the decision to refer a child to hospital, which may be many miles away for many people living in rural areas in developing countries. Our aim was to emphasize the impor- tance of using simple clinical signs such as respiratory rate and chest wall indrawing in detecting ALRI, especially pneumonia, in children. Methods We did a prospective clinical observation study at Queen Alia Military Hospital, Am- man, Jordan over a 6-month period (Au- gust 2002–January 2003) for all children below 6 years of age admitted with clinical pneumonia (most cases admitted were be- low this age). All patients were admitted via the outpatient clinic at Marqa, which is about 20 km from the hospital. This clinic sees patients from areas surrounding Am- man (suburban areas) but does not always have radiology facilities available. The pae- diatrician admitted all cases on a clinical basis according to World Health Organiza- tion criteria: cough with tachypnoea (respi- ratory rate > 50/min in infants or > 40/min in older children), indrawing or wheezing. The respiratory rate was counted for a full minute after lowering the temperature (us- ing cold compresses or paracetamol) to < 38 °C rectally or 37.5 °C axillary and be- fore the routine extraction of blood. All children admitted were examined by a specialist in paediatrics and the same ear, nose and throat specialist to exclude severe upper respiratory tract infection and all had chest X-rays which were assessed by the same radiologist. No clinical findings were written on the X-ray request. Exclusion criteria from the study were children with immune deficiency, those known to have asthma, history of foreign body aspiration or chemical pneumonitis, children with failure to thrive and malnutri- tion, and children with severe upper res- piratory tract infection. Malnourished chil- dren were excluded because tachypnoea and lower chest wall indrawing are not suf- ficiently sensitive as predictors of pneumo- nia in these children [6]. The 147 patients in our study were di- vided into 2 groups according to the chest X-ray findings: those having lobar pneumo- nia or bronchopneumonia in 1 or more lobes, and those having normal or hyperin- flated chest X-rays. The clinical signs and symptoms of the 2 groups were analysed and compared with the radiological evi- dence of pneumonia (gold standard) and their sensitivity and specificity calculated. Results Our study included 147 children admitted with clinical pneumonia, 72 (49%) male 03 Detection of pneumonia.pmd 8/17/2005, 11:05 AM483 484 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 and 75 (51%) female. The ages of the chil- dren were: 1–12 months 92 (63%), 13–36 months 47 (32%) and 37–72 months 8 (5%). Mean duration of admission was 5 days for the first and second age groups and 2 days for the third age group. From the chest X-ray findings, 40 chil- dren (27%) had lobar pneumonia in 1 or 2 lobes and 50 children (34%) had broncho- pneumonia, a total of 90 children (61%) with pneumonia diagnosed on a radiological basis. Fifty-seven children (39%) had nor- mal or hyperinflated chest X-rays. A family history of bronchial asthma or allergy was discovered in 15 children (10%). Table 1 shows the overall frequency of symptoms and signs of pneumonia and Ta- ble 2 shows their sensitivity and specificity compared with radiology results (gold standard). Cough, fever, tachypnoea and chest indrawing were the most frequently observed signs and symptoms, while tac- hypnoea was both the most sensitive (99%) and most specific (88%) sign of pneumonia and cough the most sensitive (98%) symptom. Most of the children (146) received antibiotics; 2 patients need- ed a respirator (1 developed pneumotho- rax) and 3 had pleural effusion. There were no deaths. Discussion In developing countries, the case fatality rate from ALRI in children could to be re- duced if the most serious forms of ALRI were identified and dealt with appropriately. Our study showed that the most sensi- tive symptom was cough 98%, with 70% specificity. The most sensitive signs in de- creasing order were: tachypnoea (99%), chest wall indrawing (88%), and fever (78%), while the most specific were tachy- pnoea (88%) followed by chest wall in- drawing (77%). Anadol found that tachypnoea had a specificity of 99% and a sensitivity of 61% and was the most important sign in diag- nosing pneumonia [7]. Another study showed that the best screen for pneumonia was the presence of fever along with tachypnoea [8]. A study done in China showed that tachypnoea was more reliable than auscultation in predicting pneumonia [9]. Most of our children were infants, so in our study clinical signs appear to predict pneumonia in infants more reliably than in older children. A study done by Redd et al. comparing the clinical and radiological di- agnosis of pneumonia found that children with a radiographic diagnosis tended to have been ill longer and to be older because mothers may have tended to take febrile children with mild ALRI to the health centre or hospital more often than non-febrile chil- dren with mild ALRI [10]. In the absence of respiratory signs, febrile infants are un- likely to have abnormal chest radiography [11,12]. Wheezing was found in 33% of the chil- dren in our study and was not a useful sign Table 1 Frequency of symptoms and signs in children with pneumonia (n = 147) Clinical sign or symptom No. % Cough 105 71 Fever 103 70 Tachypnoea 96 65 Chest indrawing 92 63 Poor feeding 79 54 Grunting 79 54 Diminished air entry 58 40 Crepitation 52 35 Wheezes 49 33 03 Detection of pneumonia.pmd 8/17/2005, 11:05 AM484 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 485 for determining pneumonia in children. This is in agreement with a study done by Mahabee-Gittens et al., who found that in wheezy infants and toddlers, grunting along with oxygen saturation is highly spe- cific and can be used to help diagnose pneumonia in wheezing infants and tod- dlers [13]. We did not differentiate ALRI from bronchial asthma so it is possible that chil- dren were overtreated for ALRI and under- treated for asthma. In regions where wheezing illness is prevalent, the specifici- ty of the World Health Organization pneu- monia algorithm is reduced and this may lead to unnecessary use of antibiotics or underutilization of bronchodilators [14]. Simple physical signs that require minimal expertise to recognize can be used to deter- mine oxygen therapy and to aid in screen- ing for referral [15–17]. There may be poor agreement, even among experienced physicians, on the presence of rales in young children, and this was the case in our study. Subcostal or intercostal recessions (difficulty in breath- ing) are generally more often seen in infants than in older children because the chest wall is more compliant than that of the old- er child. The most useful single factor for ruling out pneumonia in an infant is the absence of tachypnoea [18]. We found that tachyp- noea and chest wall indrawing in the pres- ence of cough can help the clinician to determine the need for chest radiography in the paediatric emergency clinic. A study done in Brazil showed that the clinical symptoms taken together contribute more than the signs and are on a par with X-ray in importance [19]. Another study found that age-specific respiratory rate (recom- mended by the World Health Organization, with or without chest wall indrawing) is a sensitive and specific indicator of pneumo- nia in almost all age groups [20]. Careful attention to specific clinical factors and use of adjunct radiographs and laboratory tests Table 2 Sensitivity and specificity of clinical symptoms and signs at presentation for predicting pneumonia Clinical sign or Chest X-ray Sensitivity Specificity symptom Pneumonia Normal or (%) (%) detected hyperinflated (n = 90) (n = 57) No. positive for No. positive for symptom/sign symptom/sign Tachypnoea 89 7 99 88 Cough 88 17 98 70 Chest indrawing 79 13 88 77 Fever 70 33 78 42 Poor feeding 52 27 58 53 Grunting 52 27 58 53 Diminished air entry 30 28 33 51 Crepitation 27 25 30 56 Wheezes 20 29 22 49 03 Detection of pneumonia.pmd 8/17/2005, 11:05 AM485 486 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 should guide physicians in selection of anti- biotics and decisions regarding hospitaliza- tion [21]. The employment of simple clinical cri- teria gives a good indication of pneumonia and can decrease unnecessary referral and admissions to hospital and thus result in cost-savings. Most of the children in our study re- ceived antibiotics, which appear to be used in a high percentage of cases, even if inap- propriate for the condition, because these clinical signs do not distinguish viral from bacterial pneumonia, nor do chest X-ray, temperature measurement or duration of fever [22]. Our study justifies the premise that pneumonia case detection does not require auscultation, chest X-ray or laboratory testing, and that observation of the respira- tory rate and lower chest wall indrawing are the key elements of assessment in young children. Conclusions Initial observation of the infant may be the most critical component for the diagnosis of pneumonia. Tachypnoea is the most valuable of the individual clinical signs for prediction of radiological pneumonia and can be a sensi- tive and reasonably specific indicator of respiratory infection. The absence of tachypnoea and chest wall indrawing can safely be used to reduce the number of chest X-rays ordered for children under investigation. These find- ings have relevance for assessment proto- cols and resulting treatment decisions when chest X-ray is not routinely available. These methods for pneumonia case de- tection could be taught to primary care physicians, nurses and even mothers, al- lowing them to seek medical advice early. This would lead to a decrease in the pneu- monia mortality rate in children. References 1. Margolis P, Gadomski A. Does this infant have pneumonia? Journal of the Ameri- can Medical Association, 1998, 279(4): 308–13. 2. Larsen GL et al. Respiratory tract and mediastinum. In: Hay WW et al., eds. Cur- rent pediatric diagnosis and treatment, 13th ed. Stamford City, Appleton & Lange, 1997:420–74. 3. Helms P, Henderson J, eds. Respiratory disorders. In: Campbell AGM, McIntosh N, eds. Forfar and Arneil’s textbook of pediatrics, 5th ed. London, Churchill Livingstone, 1998, 12:489–583. 4. Alario AJ et al. Usefulness of chest radio- graphs in children with acute lower respiratory tract disease. Journal of pedi- atrics, 1987, 111(2):187–93. 5. Cherian T et al. Evaluation of simple clinical signs for the diagnosis of acute lower respiratory tract infections. Lancet, 1988, 2(8603):125–8. 6. Falade AG et al. Use of simple clinical signs to predict pneumonia in young Gambian children: the influence of mal- nutrition. Bulletin of the World Health Or- ganization, 1995, 73(3):299–304. 7. Anadol D, Aydin YZ, Gocmen A. Over- diagnosis of pneumonia in children. Turkish journal of pediatrics, 43(3):205– 9. 8. Zukin DD et al. Correlation of pulmonary signs and symptoms with chest radio- graphs in the pediatric age group. Annals of emergency medicine, 1986, 15(7):792–6. 03 Detection of pneumonia.pmd 8/17/2005, 11:05 AM486 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 487 9. Dai Y et al. Respiratory rate and signs in roentgenographically confirmed pneu- monia among children in China. Pediat- ric infectious disease journal, 1995, 14 (1):48–50. 10. Redd SC et al. Comparison of the clinical and radiographic diagnosis of paediatric pneumonia. Transactions of the Royal Society of Tropical Medicine and Hy- giene, 1994, 88(3):307–10. 11. Crain EF et al. Is a chest radiograph nec- essary in the evaluation of every febrile infant less than 8 weeks of age? Pediat- rics, 1991, 88(4):821–4. 12. Taylor JA et al. Establishing clinically rel- evant standards for tachypnea in febrile children younger than 2 years. Archives of pediatrics & adolescent medicine, 1995, 149(3):283–7. 13. Mahabee-Gittens EM et al. Clinical fac- tors associated with focal infiltrates in wheezing infants and toddlers. Clinical pediatrics, 2000, 39(7):387–93. 14. Nascimento-Carvalho CM et al. Child- hood pneumonia: clinical aspects asso- ciated with hospitalization or death. Brazilian journal of infectious diseases, 2002, 6(1):22–8. 15. Margolis PA et al. Accuracy of the clinical examination in detecting hypoxemia in infants with respiratory illness. Journal of pediatrics, 1994, 124(4):552–60. 16. Usen S et al. Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: prospective cohort study. British medical journal, 1999, 318(7176):86–91. 17. Weber MW et al. Predictors of hypo- xaemia in hospital admission with acute lower respiratory tract infection in a de- veloping country. Archives of disease in childhood, 1997, 76(4):310–4. 18. Bloomfield D. Tachypnea. Pediatrics in review, 2002, 23(8):294–5. 19. Pereira JC, Escuder MM. The importance of clinical symptoms and signs in the di- agnosis of community-acquired pneu- monia. Journal of tropical pediatrics, 1998, 44(1):18–24. 20. Singhi S et al. Validity of clinical signs for the identification of pneumonia in chil- dren. Annals of tropical paediatrics, 1994, 14(1):53–8. 21. Lichenstein R, Suggs AH, Campbell J. Pediatric pneumonia. Emergency medi- cine clinics of North America, 2003, 21(2):437–51. 22. Korppi M et al. Comparison of radiologi- cal findings and microbial aetiology of childhood pneumonia. Acta paediatrica, 1993, 82(4):360–3. 03 Detection of pneumonia.pmd 8/17/2005, 11:05 AM487 488 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Group A streptococci in children with acute pharyngitis in Sousse, Tunisia R. Mzoughi,1 O. Bouallègue,1 H. Selmi,2 H. Ben Said,3 A.S. Essoussi2 and M. Jeddi1 1Microbiology Laboratory; 2Paediatric Service, Farhat Hached Hospital, Sousse, Tunisia. 3Centre de Protection Maternelle et Infantile (Centre PMI), Erriadh, Sousse, Tunisia. Received: 16/01/03; accepted: 07/10/03 ABSTRACT A 1-year prospective study in 2 paediatric outpatient clinics in Sousse, Tunisia, aimed to determine the presence of group A streptococci in acute pharyngitis cases and carriers, and the distribution of the serotypes and biotypes. Group A streptococci were found in 9.0% of throat swabs from 155 controls and 17.7% from 474 patients (P < 0.05). Of 43 strains isolated from patients and submitted for typing, 15 different types were identified, the most common being M75 (14 strains; 32.5%), M9 (6 strains; 14.0%), M76 (5 strains; 11.6%) and M12 (4 strains; 9.3%). Three strains were non-typeable (7.0%). Biotyping of the strains showed 3 predominant biotypes: biotype 3 (n = 14), biotype 2 (n = 11), and biotype 1 (n = 7). Les streptocoques du groupe A chez des enfants atteints de pharyngite aiguë à Sousse (Tunisie) RÉSUMÉ Une étude prospective sur un an réalisée dans deux services de consultations externes pédiatriques à Sousse (Tunisie) avait pour objectif de déterminer la présence de streptocoques du groupe A dans les cas de pharyngite aiguë et chez les porteurs, ainsi que la répartition des sérotypes et biotypes. On a trouvé des streptocoques du groupe A dans 9,0 % des prélèvements de gorge de 155 sujets témoins et chez 17,7 % des 474 patients (p < 0,05). Parmi les 43 souches isolées chez les patients et soumises au typage, 15 types différents ont été identifiés, les plus courants étant M75 (14 souches ; 32,5 %), M9 (6 souches ; 14,0 %), M76 (5 souches ; 11,6 %) et M12 (4 souches ; 9,3 %). Trois souches étaient non typables (7,0 %). Le biotypage des souches a montré trois biotypes prédominants : le biotype 3 (n = 14), le biotype 2 (n = 11) et le biotype 1 (n = 7). 04 Group A streptococci.pmd 8/17/2005, 11:05 AM488 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 489 Introduction Streptococcus pyogenes (group A strepto- coccus) is still the most frequent cause of pharyngitis in children and can lead to se- vere post-infection sequelae including rheumatic fever and glomerulonephritis [1]. The incidence of rheumatic fever has declined rapidly in developed countries where improved living conditions and sys- tematic antibiotic therapy with penicillin have limited the spread of bacterial strains in the population [2–4]. However, unex- pected outbreaks of rheumatic fever have occurred in the United States of America [5]. The changing epidemiology of group A streptococci and rheumatic fever is said to be related to changes in the distribution of serotypes [6,7], where certain virulent M types have been associated with invasive disease [5,8–10]. Thus, it is important to establish the epidemiological patterns of group A streptococci in different countries and regions, and especially to serotype the strains that have been isolated. This knowl- edge will be important for the development and use of vaccines [11]. In Tunisia, rheumatic fever remains an important health problem in children, with an incidence of 57 cases per 100 000 in- habitants in 2001 [12]. As a part of the na- tional effort to clarify the epidemiological pattern of group A streptococci in our country the present study was conducted to determine the presence of group A strep- tococci in acute pharyngitis cases and in carriers in the city of Sousse, and the dis- tribution of serotypes and biotypes. Methods A 1-year prospective study, between 1 Oc- tober 1994 and 20 September 1995, was conducted in 2 paediatric outpatient clinics in Sousse: Farhat Hached Hospital and Centre de Protection Maternelle et Infantile (Centre PMI) Erriadh. Samples were col- lected from patients with acute pharyngitis, diagnosed on the basis of fever over 38 °C, sore throat, pharyngeal exudates and acute inflammatory tonsillitis. A total of 474 patients, age 2 to 8 years, living in a populous district around Sousse were monitored by 3 general practitioners and 1 paediatrician. Samples were also col- lected from 155 healthy paediatric patients who were attending for vaccination. A swab was applied over both tonsils and the posterior pharynx and was transferred to the Microbiology Laboratory of Farhat Hached Hospital as soon as possible (2 to 3 hours after sampling). Samples were col- lected from patients before any antibiotic therapy. All swabs were inoculated onto 5% horse blood agar plates, with nalidixic acid and colistin and incubated in a CO2-en- riched atmosphere for 24 hours at 37 °C. The cultures negative for beta-haemolytic streptococci were incubated during 24 hours under the same conditions. The pos- itive beta-haemolytic colonies were isolated and applied to a 0.04 U bacitracin disk, the halo was measured and the strains were identified by latex agglutination (Strepto- kit, bioMérieux, France). Forty-three (43) strains of group A streptococci isolated from the patients were serotyped by stan- dard methods [13] at the Institut Für Ex- perimentelle Mikrobiologie, Jena, Germany. The biotypes were determined with a com- mercially available identification system (rapid ID 32 STREP, bioMérieux, France), using the classification of Bouvet et al. [14]. Statistical analysis was carried out using chi-squared tests. 04 Group A streptococci.pmd 8/17/2005, 11:05 AM489 490 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Results Streptococcal strains were found in 12.9% of the controls and 20.7% of the patients. Group A streptococci had a frequency of 9.0% and 17.7% in the controls and the patients respectively (significant differ- ence, P < 0.05) (Table 1). The isolation rates of group A strepto- cocci peaked twice during the year from October to December and in June (Figure 1). Of the 43 strains analysed, 93.0% were typeable. Fifteen different types were iden- tified, the most common being M75 (32.5% of strains), M9 (14.0%), M76 (11.6%), and M12 (9.3%) (Figure 2). The remaining serotypes (< 3% each) were: M1, M14, M25, M2, M3, M11, M28, M8 and M49. Only 3 strains (7.0%) were non- typeable. Three biotypes were predominant: bio- type 3, biotype 2 and biotype 1 (Table 2). Table 1 Throat swab culture results in patients with acute pharyngitis and healthy controls Patient group No. of Group A Group C, G, F Positive culture patients streptococci streptococci No. of % No. of % No. of % strains strains strains Acute pharyngitis 474 84 17.7 14 3.0 98 20.7 Controls (carrier state) 155 14 9.0 6 3.9 20 12.9 Figure 1 Monthly isolation rates of group A streptococci in patients with pharyngitis 04 Group A streptococci.pmd 8/17/2005, 11:05 AM490 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 491 Discussion Little is known about the group A strepto- cocci serotypes circulating in the Maghreb area and North Africa. To the best of our knowledge, the present study is the first Tunisian report of the serotypes of group A streptococci isolated from children with pharyngitis. M serotyping might not adequately re- flect the clonal diversity of bacterial strains, as suggested by the finding that isolates expressing the same M serotype can be distinguished by genetic methods [15–17]. Our results suggest that strepto- coccal pharyngitis is caused by a wide vari- ety of strains, although 4 serotypes predominated (M75, M9, M76 and M12). Continued study may help define the epide- miology of group A streptococci in Tunisia. Most isolates of group A streptococci described in developing countries, especial- ly in the Middle East region, are untypeable [7,18]. Among typeable strains, M type 1 is usually one of the predominant serotypes, as it was reported in Kuwait [7], Islamic Republic of Iran [18], and the United Arab Emirates [19]. In contrast, the high rate of typeable isolates in our study (93.0%) suggests that group A streptococci strains in our city are similar but not necessarily related to those commonly found in Europe and North America. Furthermore, our findings high- light the low rate (< 3%) of M type 1, which has been associated with serious diseases such as rheumatic fever, a recog- nized problem in Tunisia, and toxic shock syndrome [9,20], which has not yet been reported from our area. Although the number of isolates was not sufficient to make any epidemiological conclusions, this data could be useful for further understanding the epidemiology of group A streptococcal infections, and for the development and use of a vaccine. Acknowledgements This work was supported by the Tunisian Ministry of Scientific Research. We thank Drs E. Günther and E. Straube (Institut Für experimentelle Mikrobiologie, Jena, Ger- many) for their help in serotyping the strains. Table 2 Biotype distribution of group A streptococci associated with acute pharyngitis (n = 43 strains) Biotype 1 2 3 4 5 8 10 No. of strains 7 11 14 5 4 1 1 Figure 2 Distribution of M types of group A streptococci associated with acute pharyngitis (n = 43 strains) 04 Group A streptococci.pmd 8/17/2005, 11:05 AM491 492 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 References 1. Bisno AL. Group streptococcal infections and acute rheumatic fever. New England journal of medicine, 1991, 325:783–93. 2. Bach JF et al. 10-year educational programme aimed at rheumatic fever in two French Caribbean islands. Lancet, 1996, 347:644–8. 3. Markowitz M, Gerber MA, Kaplan EL. Treatment of streptococcal pharyngoton- sillitis: reports of penicillin’s demise are premature. Journal of pediatrics, 1993, 123:679–85. 4. Massel BF et al. Penicillin and the marked decrease in morbidity and mor- tality from rheumatic fever in the United States. New England journal of medi- cine, 1988, 318:280–6. 5. Veasy LG et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. New England journal of medicine, 1987, 316:421–7. 6. Kaplan EL, Wotton JT, Johnson DR. Dy- namic epidemiology of group A strepto- coccal serotypes associated with pharyngitis. Lancet, 2002, 358:1334–7. 7. Majeed HA et al. The concurrent asso- ciations of group A streptococcal sero- types in children with acute rheumatic fever or pharyngitis-associated glom- erulonephritis and their families in Ku- wait. Zentralblatt für Bakteriologie, Mikrobiologie, und Hygiene. Series A, 1986, 262:346–56. 8. Bryant AE, Hayes-Schroer SM, Stevens DL. M type 1 and 3 group A streptococci stimulate tissue factor-mediated pro- coagulant activity in human monocytes and endothelial cells. Infection and im- munity, 2003, 71:1903–10. 9. Schwartz B, Facklam RR, Breiman RF. Changing epidemiology of group A streptococcal infection in the USA. Lan- cet, 1990, 336:1167–71. 10. Stollerman GH. Rheumatic group A streptococci and the return of rheumatic fever. Archives of internal medicine, 1990, 35:1–26. 11. Olive C et al. Protection of mice from Group A streptococcal infection by intra- nasal immunisation with a peptide vac- cine that contains a conserved M protein B cell epitope and lacks a T cell epitope. Vaccine, 2002, 20:2816–25. 12. Bulletin épidémiologique. Direction des soins de santé de base. Tunis, Ministère de la Santé Publique, 2001. 13. Johnson DR et al. Laboratory diagnosis of group A streptococcal infections. Geneva, World Health Organization, 1997. 14. Bouvet A et al. Restricted association between biotypes and serotypes within group A streptococci. Journal of clinical microbiology, 1994, 32:1312–7. 15. Muotiala A et al. Molecular comparison of group A streptococci of T1M1 serotype from invasive and non invasive infec- tions in Finland. Journal of infectious dis- eases, 1997, 175:392–9. 16. Nguyen L et al. Molecular epidemiology of streptococcus pyogenes in an area where acute pharyngotonsillitis is en- demic. Journal of clinical microbiology, 1997, 35:2111–4. 17. Murase T et al. Characteristics of Strepto- coccus pyogenes serotype M1 and M3 isolates from patients in Japan from 1981 to 1997. Journal of clinical microbi- ology, 1999, 37:4131–34. 18. Fazeli MR et al. Group A streptococcal serotypes isolated from healthy school children in Iran. European journal of clinical microbiology and infectious dis- eases, 2003, 22:475–8. 04 Group A streptococci.pmd 8/17/2005, 11:05 AM492 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 493 19. Ameen AS et al. Serotypes of group A streptococci isolated from healthy schoolchildren in the United Arab Emir- ates. Bulletin of the World Health Organi- zation, 1997, 75(4):355–9. 20. Johnson DR, Stevens DL, Kaplan EL. Epidemiologic analysis of group A strep- tococcal serotypes associated with se- vere systemic infections, rheumatic fe- ver, or uncomplicated pharyngitis. Journal of infectious diseases, 1992, 166:374–82. Active tuberculosis among Iraqi schoolchildren with positive skin tests and their household contacts. W. Al Kubaisy, A. Al Dulayme and D.S. Hashim. Eastern Mediterranean Health Journal, 2003, Vol. 9 No. 4, pages 675–88. The authors’ names in Arabic should read: The affiliation of Professor Al Kubaisy should read: College of Medicine, Al Nahrain University, Baghdad, Iraq. Correction Knowledge, attitudes and practices survey among health care workers and tuberculosis patients in Iraq. D.S. Hashim, W. Al Kubaisy and A. Al Dulayme. Eastern Mediterranean Health Journal, 2003, Vol. 9 No. 4, pages 718–31. The authors’ names in Arabic should read: The affiliation of Professor Al Kubaisy should read: College of Medicine, Al Nahrain University, Baghdad, Iraq. 04 Group A streptococci.pmd 8/17/2005, 11:05 AM493 494 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Cryptosporidiosis in children in a north Jordanian paediatric hospital E.S. Mahgoub,1 A. Almahbashi2 and B. Abdulatif3 1Department of Microbiology, Faculty of Medicine; 2Faculty of Applied Medical Science; 3Faculty of Veterinary Science, Jordan University of Science and Technology, Irbid, Jordan. Received: 27/10/02; accepted: 14/09/03 ABSTRACT We investigated the rate of infection by Cryptosporidium parvum among children from birth to 12 years attending Princess Rahma Teaching Hospital in Irbid, Jordan and evaluated various diagnostic meth- ods. We collected single stool specimens from 300 children; 7 specimens were from children undergoing chemotherapy treatment for cancer. Diagnostic methods used for detection of infection were direct wet mount preparation, flotation concentration, cold Kinyoun Ziehl–Neelsen stain and direct immunofluores- cence. We detected C. parvum oocysts in 112 samples (37.3%) using direct immunofluorescence, which showed the highest sensitivity. Source of drinking water appeared to be an important risk factor for transmis- sion of infection. A higher incidence of infection was recorded during January–May, the rainy season. La cryptosporidiose chez l’enfant dans un hôpital pédiatrique du nord de la Jordanie RÉSUMÉ Nous avons étudié le taux d’infection par Cryptosporidium parvum chez des enfants de la nais- sance à l’âge de 12 ans consultant à l’hôpital universitaire Princesse Rahma d’Irbid (Jordanie) et évalué diverses méthodes diagnostiques. Nous avons recueilli un échantillon unique de selles chez 300 enfants ; 7 échantillons provenaient d’enfants sous chimiothérapie anticancéreuse. Les méthodes de diagnostic uti- lisées pour le dépistage de l’infection était l’examen direct de préparation à l’état frais, la concentration par flottation, la coloration de Ziehl-Neelsen, la coloration de Kinyoun à froid et l’immunofluorescence directe. Nous avons détecté des oocystes de C. parvum dans 112 échantillons (37,3 %) par immunofluorescence directe, méthode qui a montré la plus forte sensibilité. La source d’eau de boisson semblait être un important facteur de risque de transmission de l’infection. Une incidence plus élevée de l’infection a été enregistrée entre janvier et mai, la saison des pluies. 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM494 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 495 Introduction Cryptosporidium parvum is a coccidian protozoan parasite found in the brush- border of the enterocytes of the small intes- tine in many vertebrates, including humans [1]. Cryptosporidiosis is recognized as a cause of diarrhoeal illness in man and sev- eral mammalian species [2]. The first cases of human cryptosporidiosis were reported in 1976, and there are increasing numbers of reports of patients with documented in- fection with C. parvum. It is now consid- ered a common enteric pathogen in humans and domestic animals worldwide [3]. Cry- ptosporidiosis can induce self-limiting diar- rhoea in immunocompetent people or severe and prolonged diarrhoea in immuno- compromised patients, such as those with AIDS, transplant recipients, those receiv- ing chemotherapy for cancer, institutional- ized patients, and patients with immuno- suppressive infectious disease [4]. A study in the same area of Jordan in 1994 reported that the rate of infection among elementary-school children was 7% [5]. Diagnosis of the infection generally re- quires the observation of the infective stage (oocysts 4–6 µm). Owing to the small size of the oocysts, the routine wet mount prep- aration and concentration methods have limited value for detection of C. parvum in faecal samples, where oocysts can easily be confused with other materials present in the sample [6]. We conducted this study because of the increasing international documentation of infection by C. parvum and the fact that it is under-diagnosed in most Jordanian hos- pital laboratories. We also wanted to com- pare the different methods used for the diagnosis of C. parvum including the direct immunofluorescence test which was used for the first time in Jordan in this study. In addition, we tried to focus on some epide- miological factors that lead to infection in children. Methods Patients Over a period of 11 months, 300 single stool specimens were collected from chil- dren attending outpatient clinics as well as inpatients in Princess Rahma Teaching Hospital. Requests for stool examinations were made by paediatricians who deemed it necessary for diagnosis and follow-up of their patients. Princess Rahma Teaching Hospital is the hospital for medical care of children under 12 years of age. Faecal sam- ples were taken from children with diar- rhoea who were sent to the laboratory for investigation. Seven of the children were undergoing chemotherapy for cancer. There were no exclusion criteria. The purpose of the study was verbally explained to the parents who agreed to give samples from their children. Paeditricians filled in the clinical information and supplied data on drugs as well as chemo- therapeutic agents used for treatment. Ad- ditional information about the children was obtained by means of a questionnaire filled in with the assistance of the parents. Infor- mation requested included name, age, sex and residence (urban/rural). The source of drinking water was also ascertained (well, spring, tap, filtered, boiled). Parents were also asked whether they kept animals in the home. Laboratory tests Stool specimens were collected in the labo- ratory facilities at Princess Rahma Teach- ing Hospital and transported in a cool box to the laboratory in the Department of Mi- crobiology at Jordan University of Science 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM495 496 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 and Technology in Irbid. Each sample, whether liquid, semi-solid or formed, was divided in 4 aliquots and processed accord- ing to each of the 4 methods described here. In all methods used, a positive slide was read by at least 2 of the investigators. Direct wet mount The direct wet mount preparation was used according to the World Health Organization Bench aids for the diagnosis of intestinal parasites [7]. Lugol’s 1% iodine was used to differentiate C. parvum oocysts from yeast cells: C. parvum oocysts do not ac- cept the iodine stain, so they appear trans- parent; yeast cells accept the stain and appear deep yellow. Sugar flotation concentration method Sheather’s sugar flotation technique was used (specific gravity of solution 1.20– 1.25). The high specific gravity allows the oocysts to float on the top of the solution in the test tube. Briefly, a suspension of stool in sugar solution was made in a test tube filled to the brim with Sheather’s sugar so- lution. A cover slip was put on top of the test tube in contact with the solution for 15 minutes. The cover slip was placed down- wards on a microscope slide and the oo- cysts were visualized microscopically at × 400 magnification [8,9]. Cold Kinyoun staining Differential staining using a modified Ziehl– Neelsen technique, the cold Kinyoun technique (TCS Biosciences Limited, Buckingham, United Kingdon), was em- ployed to differentiate C. parvum oocysts from other cells and artefacts. The oocysts are acid-fast so they accept the stain and appear pink to red in colour (4–6 mm) against a blue background of debris. Direct immunofluorescent antibody staining MeriFluor™ Cryptosporidium/Giardia (Meridian Diagnostic Incorporated, Cincin- nati, United States of America) is an in vitro direct immunofluorescence kit for the si- multaneous detection of Cryptosporidium oocysts and Giardia cysts in faecal materi- al. The detection reagent contains a mixture of fluorescein isothiocynate-labelled mono- clonal antibodies directed against cell wall antigens of Cryptosporidium oocysts. Pos- itive and negative controls were provided with the kit by the manufacturing company and manufacturer’s instructions were fol- lowed. Statistical analysis Statistical analysis was performed using SPSS. Results Of 300 stool samples, 112 (37.3%) were positive for C. parvum. According to the consistency of the sample, oocysts were detected in 27.2% of liquid samples, 51.1% of semi-solid samples and 12.5% of formed samples. Among the 7 children who were on chemotherapy for cancer, C. parvum was detected in the stools of 4 (57.1%). The monoclonal direct immunofluores- cence method gave the highest rate of pos- itive samples (37.3%) (Table 1) and was statistically the most sensitive compared with the other 3 methods (Table 2). In addi- tion, under ultraviolet light, the direct im- munofluorescence slide showed clear, oval, fluorescent green oocysts against an orange to dark background. When the results were examined ac- cording to the children’s age, the highest 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM496 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 497 rate of infection (57%) was noted among those in the age group 5–< 7 years (Figure 1). The relation of infection to locality, sex, presence of animals in the home and source of drinking water is illustrated in Table 3. There was no significant difference in the distribution of cases between males and fe- males. Out of 138 samples from children who lived in rural areas, 60 (43.5%) were positive for C. parvum oocysts, whereas of the 162 samples from children who lived in urban areas only 52 (32.1%) were posi- tive. In regard to the presence of animals, the infection rate was 36.2% among chil- dren who lived in compounds with no ani- mals in comparison with 45.0% among those who lived in association with ani- mals. In the children who drank tap water, the infection rate was 35.3%. In those who drank well water or spring water, however, infection rates were 48.4% and 42.9% re- spectively. The seasonal pattern of C. parvum in- fection showed that a higher rate of inci- dence was recorded in the periods from January to July 2001, the first 5 months of which represent the rainy months for that year (Figure 2). Table 2 shows the comparative results between the 4 methods usually used for di- agnosis of C.parvum in stools. Comparison of the various methods revealed the superi- ority of immunofluorescence followed by the modified Ziehl–Neelsen, sugar flotation and the direct methods. Discussion Our findings showed a high incidence of cryptosporidiosis in the 300 children whose stools we examined. Oocysts of C. parvum were detected in 37.3% of samples using the immunofluorescence technique. This is the first time the immunofluores- Table 1 Comparison of four methods for diagnosis of Cryptosporidium parvum Method Samples positive, n = 300 No. % Direct wet mount 52 17.3 Sheather’s flotation 68 22.6 Cold Kinyoun stain 92 30.6 Direct immunofluorescence 112 37.3 Table 2 Specificity, sensitivity and efficiency of the 4 diagnostic methods used for the detection of Cryptosporidium parvum oocysts in stool samples from children in Irbid Method Specificity Sensitivity Efficiency (%) (%) (%) Direct wet mount 95 47 81 Sheather’s flotation 96 61 85 Cold Kinyoun stain 100 82 94 Direct immunofluorescence 100 98 99 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM497 498 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 cence test has been used in Jordan. Al- though this figure is higher than the one re- ported before from Jordan [10], it is similar to high figures from other countries as cit- ed below. It is also worth noting that previ- ous workers from Jordan took specimens from healthy schoolchildren while ours were sick children reporting to a paediatric hospital. Our colleagues used a single method, namely the modified Ziehl– Neelsen, while we used 4 methods. A number of other studies on preva- lence of cryptosporidiosis have been re- ported from different parts of the world. The incidence rates vary according to sam- ple collection, which depends on clinical judgement; diagnostic tests, where some methods are better than others; availability of facilities; and reporting systems. Inci- dence rates of 13.5% to 19.5% have been reported from Egypt [11,12], and 10% in Kuwaiti children [13]. Very high rates have been reported in Israeli children 48% [14], from the Texas–Mexico border 70.2% [15] and from the Republic of Korea 57% [16]. Figure 1 Incidence of cryptosporidiosis according to age Table 3 The rate of infection by Cryptosporidium parvum in relation to sociodemographic characteristics and source of drinking water Variable Positive No. % Sexa Male 72/186 38.7 Female 40/114 35.1 Localityb Rural 60/138 43.5 Urban 52/162 32.1 Animals at residencec With 18/40 45.0 Without 94/206 36.2 Source of drinking waterd Well water 31/64 48.4 Spring water 3/7 42.9 Tap water 73/207 35.3 Filtered water 4/14 28.6 Boiled water 0/7 – aP = 0.529, degrees of freedom = 1, χ2 = 0.40. bP = 0.042, degrees of freedom = 1, χ2 = 4.12. cP = 0.282, degrees of freedom = 1, χ2 = 1.16. dP = 0.425, degrees of freedom = 3, χ2 = 1.71. 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM498 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 499 A review of several human population- based studies, especially on immunocom- promised patients in less-developed countries, reported prevalence ranging from 9% to 48% in Africa and Asia [17]. In this study, 4 different methods were used to detect and identify C. parvum oo- cysts in children’s stool samples. The di- rect wet mount with iodine identified the lowest number of samples, 52 (17.3%), positive for oocysts. The C. parvum oo- cyst is very small in size and can easily be mistaken in stool debris for artefacts. Also, it is easy to confuse with other oocysts, such as those of Cyclospora spp., and cells, especially yeast cells, which resemble C. parvum oocysts in size and morphology [18]. The number of oocysts detected in- creased to 68 (22.6%) using the flotation concentration method. This procedure showed a clear slide picture during micro- scopic examination yet the oocysts did not appear pink and refractile, and other para- sites cannot be detected by this method. Also, this procedure necessitated reading the results within 15 minutes of preparation because the oocysts tend to collapse and disappear if left for a long time. Moreover, the presence of Sheather’s sugar solution inhibits the staining procedure [19]. The cold Kinyoun acid-fast staining technique yielded a higher rate of oocyst identification, 92 (30.6%). Using this meth- od we could differentiate between C. par- vum oocysts, which take a red to pink colour, and other faecal components, espe- cially yeast cells, which take the colour of the counterstain, i.e. blue if using methyl- ene blue, or green using malachite green. The direct immunofluorescence meth- od gave the highest number of positive samples, 112 (37.3%). In comparison with other methods, this method showed high sensitivity so we were able to detect oo- cysts even when present in low numbers in the samples and large numbers of samples could be scanned. Figure 2 Seasonal variation of cryptosporidiosis, November 2000 to September 2001 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM499 500 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Our findings support and agree with other studies which reported that using flu- orescent monoclonal reagents increased the sensitivity and specificity of the detec- tion of C. parvum oocysts. It provides an excellent screening method and offers a useful technique for epidemiological stud- ies, and hence, control of the parasite [20– 22] Source of drinking water plays an im- portant role in the transmission of infec- tion. Many people in Irbid depend on untreated rainwater collected directly from the roof, then stored in metal or cement tanks. This is why most of our cases were diagnosed during April–May, during the rainy season. Some families use wells or spring water for drinking. The results showed that the rate of infection among those who drink from wells was 48.4%, compared to those who use only tap water, 35.3%. We know that the oocysts of Cryptosporidium spp. can survive in con- centrations of chlorine used for water treatment, let alone untreated water [23]. Considering the locality, we found that the infection rate in children who lived in rural areas was 43.5% whereas in children in urban areas it was 32%. Seasonal or temporal trends associated with increased incidence vary from coun- try to country. Our result agrees with other studies from Central America, South Afri- ca, and India that reported a high peak inci- dence in rainy season [24]. Also, our findings were similar to those of another study conducted in Kuwait to detect the in- cidence and seasonality of cryptosporidio- sis in Kuwaiti children. The results of that study showed that the maximum numbers of cases were recorded during the months January to April [13]. Acknowledgement This study was supported by the Deanship of Research, Jordan University of Science and Technology. References 1. Tzipori S. Cryptosporidiosis in animals and humans. Microbiological reviews, 1983, 47(1):84–96. 2. Fayer R, Ungar BL. Cryptosporidium spp. and cryptosporidiosis. Microbiological reviews, 1986, 50(4):458–83. 3. Meisel JL et al. Overwhelming watery diarrhea associated with a cryptospo- ridium in an immunosuppressed patient. Gastroenterology, 1976, 70(6):1156–60. 4. Fayer R, Morgan U, Upton SJ. Epidemi- ology of Cryptosporidium: transmission, detection and identification. Interna- tional journal for parasitology, 2000, 30(12–13):1305–22. 5. Nemri LF and Hijazi SS. Cryptospo- ridium a cause of gastroenteritis in pre- school children in Jordan. Journal of clinical gastroenterology, 1994, 19(4): 288–91. 6. Weber R et al. Threshold of detection of Cryptosporidium oocysts in human stool specimens: evidence for low sensitivity of current diagnostic methods. Journal of clinical microbiology, 1991, 29(7): 1323–7. 7. O‘Donoghue JP. Cryptosporidium and cryptosporidiosis in man and animals. International journal for parasitology, 1995, 25(2):139–95. 8. Bench aids for the diagnosis of intestinal parasites. Geneva, World Health Organi- zation, 1994. 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM500 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 501 9. Garcia LS. Practical guide to diagnostic parasitology. Washington DC, ASM Press, 1999. 10. Nimri LF, Batchoun R. Prevalence of Cryptosporidium species in elementary school children. Journal of clinical mi- crobiology, 1994, 32(4):1040–2. 11. Stazzone AM et al. Frequency of Giardia and Cryptosporidium infections in Egyp- tian children as determined by con- ventional and immunofluorescence methods. Pediatric infectious disease journal, 1996, 15(11):1044–6. 12. Abdel-Maboud AI et al. Cryptospori- diosis in Benha; study of some modali- ties in diagnosis and treatment. Journal of the Egyptian Society of Parasitology, 2000, 30(3):717–25. 13. Iqbal J et al. Cryptosporidiosis in Kuwaiti children: seasonality and endemicity. Clinical microbiology and infection, 2001, 7(5):261–6. 14. Robin G et al. Cryptosporidium infection in Bedouin infants assessed by prospec- tive evaluation of anticryptosporidial antibodies and stool examination. American journal of epidemiology, 2001, 153(2):194–201. 15. Leach CT et al. Prevalence of Crypto- sporidium parvum infection in children along the Texas–Mexico border and as- sociated risk factors. American journal of tropical medicine and hygiene, 2000, 62(5):656–1. 16. Cha JY et al. High prevalence and sea- sonality of cryptosporidiosis in a small rural village occupied predominantly by aged people in the Republic of Korea. American journal of tropical medicine and hygiene, 2001, 65:518–22. 17. Ungar BLP. Cryptosporidium. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases, 5th ed. Philadelphia, Churchill Livingstone, 1999:2903–15. 18. Fayer R, Speer SA, Dubey JP. The gen- eral biology of Cryptosporidium. In: Fayer R, ed. Cryptosporidium and cryptospo- ridiosis. Boca Raton, Florida, CRC Press, 1997:1–41. 19. Weber R et al. Threshold of detection of Cryptosporidium oocysts in human stool specimens: evidence for low sensitivity of current diagnostic methods. Journal of clinical microbiology, 1991, 29(7):1323– 7. 20. Garcia LS, Brewer TC, and Bruckner DA. Fluorescence detection of Cryptospo- ridium oocysts in human fecal speci- mens by using monoclonal antibodies. Journal of clinical microbiology, 1987, 25(1):119–21. 21. Xiao L, Herd RP. Quantitation of Giardia cysts and Cryptosporidium oocysts in fe- cal sample by direct immunofluores- cence assay. Journal of clinical microbiology, 1993, 31(11):2944–6. 22. Alles AJ et al. Prospective comparison of direct immunofluorescence and conven- tional staining methods for detection of Giardia and Cryptosporidium spp. in hu- man fecal specimens. Journal of clinical microbiology, 1995, 33(6):1632–4. 23. Korich DJ et al. Effects of ozone, chlorine and monochloromine on Crypto- sporidium parvum oocyst viability. Ap- plied and environmental microbiology, 1990, 56:1423–8. 24. Casemore DP, Wright SE, Coop RL. Cryptosporidiosis—human and animal epidemiology. In: Fayer R, ed. Cryptospo- ridium and cryptosporidiosis. Boca Raton, Florida, CRC Press, 1997. 05 Cryptosporidiosis in children.pmd 8/18/2005, 11:18 AM501 502 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Handicap among children in Saudi Arabia: prevalence, distribution, type, determinants and related factors ABSTRACT We determined the prevalence, distribution and determinants of handicap among children in Saudi Arabia. A field survey was carried out from 1417 to 1420 AH (1997–2000 AD) of 60 630 children under 16 years selected from all regions of the country. Information was collected by questionnaire for all children and those with a handicap, or suspected of having a handicap, were referred for confirmatory diagnosis. Of the total sample, 3838 (6.33%) were recorded as handicapped. The region with the highest proportion of handicapped children was Jazan (9.90%); Riyadh had the lowest (4.36%). Motor disability was the common- est kind of handicap (3.0% of the total sample), followed by learning disability (1.8%). The highest proportion of disability was found among children with handicapped parents, those whose mothers were older at the time of their birth and those whose mothers had not had medical care and necessary vaccination during pregnancy. *M.B. Al-Hazmy,1 B. Al Sweilan2 and N.B. Al-Moussa3 1Department of Medical Biochemistry, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia. 2Red Crescent Society, Riyadh, Saudi Arabia. 3Special Education, Ministry of Health, Riyadh, Saudi Arabia. Received: 25/02/03; accepted: 23/02/04 Le handicap chez l’enfant en Arabie saoudite : prévalence, répartition, type, déterminants et facteurs associés RÉSUMÉ Cette étude a déterminé la prévalence, la répartition et les déterminants du handicap chez l’enfant en Arabie saoudite. Une enquête sur le terrain a été réalisée de 1417 à 1420 de l’Hégire (1997-2000) auprès de 60 630 enfants de moins de 16 ans sélectionnés dans toutes les régions du pays. Des informations ont été recueillies à l’aide d’un questionnaire pour tous les enfants, et ceux ayant un handicap ou suspectés d’avoir un handicap ont été adressés à un laboratoire pour diagnostic de confirmation. Dans l’échantillon total, 3838 enfants (6,33 %) ont été recensés comme handicapés. La région ayant le plus fort pourcentage d’enfants handicapés était Jazan (9,90 %) ; Riyad avait le plus faible pourcentage (4,36 %). Le handicap moteur était le type d’handicap le plus courant (3,0 % de l’échantillon total), suivi par les troubles de l’apprentissage (1,8 %). Le pourcentage d’incapacités le plus élevé a été constaté chez les enfants de parents handicapés, chez ceux dont la mère était plus âgée à leur naissance et ceux dont la mère n’avait pas bénéficié d’une surveillance médicale ni reçu les vaccinations nécessaires pendant la grossesse. 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM502 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 503 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM503 504 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM504 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 505 [7, 6] 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM505 506 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM506 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 507 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM507 508 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM508 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 509 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM509 510 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM510 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 511 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM511 512 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM512 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 513 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM513 514 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM514 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 515 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM515 516 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM516 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 517 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM517 518 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM518 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 519 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM519 520 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM520 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 521 2. WHO Expert Committee on Disability Prevention and Rehabilitation. Geneva, World Health Organization, 1981 (Technical Report Series No. 668):1–39. 3. Hutchison T, Nicoll A. Developmental screening and surveillance. British journal of hospital medicine, 1988, 39(1):22–9. 4. Cochran WG. Sampling techniques, 3rd ed. New York, John Wiley, 1977. 5. Wilson JM, Jungner G. Principles and practice of screening for disease. Geneva, World Health Organization, 1968 (Public Health Papers, No. 34):11. 6. Fleiss JL. Statistical methods for rates and proportions, 2nd ed. New York, John Wiley, 1981. 7. SPSS 6.0 for Windows. Chicago, SPSS Inc., 1995. 8. Schneiderman ED et al. A PC program for computing confidence band for average and individual growth curves. Computers, biology and medicine, 1994, 24(2):119–27. 06 Handicap among children in Saudi Arabia.pmd 8/17/2005, 11:06 AM521 522 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Attitudes of a high-risk group of pregnant Saudi Arabian women to prenatal screening for chromosomal anomalies Z.A. Babay1 1Department of Obstetrics and Gynaecology, King Saud University, King Khaled University Hospital, Riyadh, Saudi Arabia. Received: 30/04/03; accepted: 14/01/04 ABSTRACT The attitude of 550 pregnant Saudi Arabian women aged > 35 years to prenatal screening for chromosomal anomalies was investigated. A total of 336 women (61.1%) accepted the general idea of prenatal screening while 160 (29.1%) did not; 54 women (9.8%) were undecided. There was a high accep- tance of non-invasive methods such as ultrasound (61.3%) and biochemical screening (53.0%) but a low acceptance of invasive methods (34.2%). The main reason for refusal of screening was the unacceptability of termination of pregnancy as a treatment option. There were statistically significant differences between those who accepted the idea of screening and those who did not with regard to their awareness of the availability of prenatal screening, their rejection of pregnancy termination, their doubt of the accuracy of the tests and in their belief that chromosomal abnormalities need no be screened for. Attitudes d’un groupe de femmes enceintes saoudiennes à haut risque vis-à-vis du dépistage prénatal des anomalies chromosomiques RÉSUMÉ On a examiné l’attitude de 550 femmes enceintes saoudiennes âgées de plus de 35 ans vis-à-vis du dépistage prénatal des anomalies chromosomiques. Au total, 336 femmes (61,1 %) acceptaient l’idée générale du dépistage prénatal tandis que 160 (29,1 %) ne l’acceptaient pas ; 54 femmes (9,8 %) étaient indécises. Il y avait une forte acceptation des méthodes noninvasives telles que l’échographie (61,3 %) et le dépistage biochimique (53,0 %) mais une faible acceptation des méthodes invasives (34,2 %). La raison principale du refus du dépistage était l’inacceptabilité de l’interruption de grossesse comme option thérapeu- tique. Il y avait des différences statistiquement significatives entre les femmes qui acceptaient l’idée du dépistage et celles qui ne l’acceptaient pas pour ce qui concerne la connaissance de l’existence du dépistage prénatal, leur rejet de l’interruption de grossesse, leur doute au sujet de l’exactitude des tests et leur opinion concernant le fait que les anomalies chromosomiques ne nécessitent pas de dépistage. 07 Attitudes of a high-risk.pmd 8/18/2005, 11:11 AM522 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 523 Introduction Genetic diseases affect all populations and have been apparent since antiquity. In re- cent years many advances have been made in the field of prenatal screening for chro- mosomal anomalies. Techniques now avail- able for such screening include second trimester biochemical screening (α-feto- protein, β human chorionic gonadotropin (HCG) and unconjugated estrogen), first trimester biochemical screening (pregnan- cy associated plasma protein A (PAPPA), and β HCG), ultrasound fetal nuchal trans- lucency measurement, in addition to the older invasive techniques such as amnio- centesis and chorionic villus sampling. Some of the non-invasive methods have high sensitivity, especially if combined with ultrasound nuchal translucency measure- ment (90% sensitivity and 3.1% false posi- tive rate) [1] in addition to causing no harm to the fetus. The use of these tests has re- sulted in a significant decrease in the preva- lence of children with chromosomal abnormalities [2]. The incidence of Down syndrome in Saudi Arabia is 1.8 per 1000 live births [3], which is similar to the reported incidence in Hawaii but higher than the rest of the Unit- ed States of America (10 per 10 000 live births) [4]. Some modern Islamic opinion and rulings have accepted prenatal diagno- sis and approved severe congenital anoma- lies and malformations per se as a reason for termination of pregnancy before en- soulment (120 days from conception or 134 days from last menstrual period) [5,6]. However, in spite of the availability of these screening tests, there are no reports in liter- ature about their use in Saudi Arabia nor the awareness of Saudi Arabian women of such tests and their attitudes to them. Therefore, this study was carried out to assess the awareness and acceptance of such screening methods among pregnant Saudi Arabian women. Methods King Khalid University Hospital (KKUH) Riyadh, Saudi Arabia is the largest teaching hospital in the central region in Saudi Ara- bia, with an average delivery rate of 4500 babies per month. All pregnant women aged 35 years or older attending the Satur- day afternoon antental clinic at KKUH be- tween October 2002 and January 2003 were included in the study and were admin- istered a questionnaire devised by the au- thor. The questionnaire was conducted verbally and it included information on age, parity, personal or family history of a child with chromosomal anomalies, awareness of the availability of prenatal screening for such conditions and their acceptance of such screening in the next pregnancy, in addition to reasons for non-acceptance. None of the women refused to participate. Statistical analysis was done using SPSS, version 10. The Student t-test was used to compare between variables and a P-value of ≤ 0.01 was considered significant. Results A total of 1680 pregnant women attended the antental clinic during the study period. Of those, 550 (32.7%) women were aged 35 years or older and were included in the study. The mean age and standard deviation (SD) was 37 (2.34) years (range 35–44 years) and mean parity was 4 (3.23) (range 1–7). In all, 284 women (51.6%) knew about the availability of prenatal screening, 28 women (5.1%) had a positive family history of a child with chromosomal anom- alies and 13 women (2.4%) had a history of giving birth to an affected child. A total of 07 Attitudes of a high-risk.pmd 8/18/2005, 11:11 AM523 524 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 336 women (61.1%) accepted the general idea of prenatal screening in the next preg- nancy while 160 women (29.1%) did not and 54 women (9.8%) could not decide (Table 1). Among the women who accept- ed the idea of screening, 53.0% accepted the idea of biochemical screening, 61.3% accepted the idea of ultrasound screening and 34.2% accepted the idea of invasive procedures such as amniocentesis and chorionic villus sampling. Further questioning of the women who did not accept the idea of screening showed that 76% did not accept termina- tion of pregnancy as an option in the event of an abnormal result, 22% did not accept screening in general as they doubted the accuracy of the tests, 19% did not believe that they would have an abnormal child and 6% did not believe chromosomal anoma- lies were an abnormality that should be screened for (Table 2). Table 3 shows a comparison between those who accepted the idea of screening in pregnancy versus those who did not. There was a statistically significant difference be- tween the 2 groups in their awareness of the availability of prenatal screening (57.7% versus 42.1%) (P = 0.0005), in their rejection of pregnancy termination (65.5% versus 92.5%) (P = 0.001), in their doubt of the accuracy of the tests (8.9% versus 42.5%) (P = 0.001) and in their belief that chromosomal abnormalities were not an abnormality that should be screened for (0.3% versus 15.0%) (P = 0.001). There was no significant difference in acceptance or rejection of prenatal screening between those who had a posi- tive family history of a child with chromo- somal anomalies, those who had positive personal history of having a child with chromosomal anomalies, and those who believed that they would not have a child with chromosomal anomalies. A comparison was made between the women who had positive family history of a child with a chromosomal anomaly, those with a positive personal history of having a child with a chromosomal anomaly, and those who did not have any such history (Table 4). There was a statistically signifi- cant difference between the 3 groups in acceptance of termination of pregnancy (75.0%, 69.2% and 76.2% respectively) (P = 0.001), in the belief in the possibility Table 1 Characteristics of the study sample Charactersitic No. (n = 550) % Had a positive personal history of a child with chromosomal anomaly 13 2.4 Had a positive family history of a child with chromosomal anomaly 28 5.1 Was aware of the availability of prenatal screening 284 51.6 Found screening: Acceptable 336 61.1 Unacceptable 160 29.1 Undecided 54 9.8 Table 2 Reasons for finding prenatal screening unacceptable Reason % Did not accept termination of pregnancy as an option 76 Doubted the accuracy of the tests 22 Did not believe that they would have a child with chromosomal anomalies 19 Did not believe chromosomal abnormality was an abnormality that should be screened for 6 07 Attitudes of a high-risk.pmd 8/18/2005, 11:11 AM524 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 525 of delivering a child with chromosomal anomalies (64.3%, 84.6% and 14.9% respectively) (P = 0.001), in the accep- tance of chromosomal anomalies as an ab- normality that should be screened for (7.1%, 38.5% and 5.1% respectively) (P = 0.001), in the acceptance of bio- chemical screening during pregnancy (71.4%, 53.8% and 29.7% respectively) (P = 0.001), in the acceptance of ultra- sound screening during pregnancy (71.4%, 61.5% and 25.5% respectively) (P = 0.001), and in the acceptance of an inva- sive investigation (25.0%, 100.0%, 43.4% respectively) (P = 0.001). Discussion The old adage that prevention is better than cure applies as much to genetic as to ac- quired diseases. Primary prevention of ab- normal genotypes would need to act prior to conception. Prenatal diagnosis with se- lective termination (secondary prevention) alters the birth frequency of the condition but is really only a holding measure pending the development of primary prevention of genetic disease. Currently the only primary prevention available is pre-implantation genetic diagnosis which requires in vitro Table 3 Comparison of women who accepted the idea of prenatal screening for chromosomal abnormalities and those who did not Variable Accepted Did not accept Odds 95% CI P-value screening screening/was ratio (n = 336) undecided (n = 214) No. % No. % Had a positive family history of a child with chromosomal anomaly 20 6.9 8 3.7 1.63 0.67–4.11 0.3407 Had a positive personal history of a child with chromosomal anomaly 8 2.4 5 2.3 1.02 0.29–4.02 0.7992 Was aware of the availability of prenatal screening 194 57.7 90 42.1 1.88 1.31–2.70 0.0005** Did not accept termination of pregnancy as an option 220 65.5 198 92.5 0.15 0.08–0.28 0.001** Doubted the accuracy of prenatal screening tests 30 8.9 91 42.5 0.13 0.08–0.22 0.001** Did not believe that they would have a child with chromosomal anomalies 56 16.7 49 22.9 0.67 0.43–1.06 0.0889 Did not believe chromosomal anomaly was an abnormality that should be screened for 1 0.3 32 15.0 0.02 0.0–0.1 0.001** **Statistically significant at P ≤ 0.01. CI = confidence interval. 07 Attitudes of a high-risk.pmd 8/18/2005, 11:11 AM525 526 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 fertilization and this is not suitable as a screening test. The principle for any test to be used for screening populations is that it should be sensitive, relatively specific and harmless. In addition, the disorder screened for should be of appreciable frequency and early diagnosis should be an advantage. In our study almost two-thirds (61.1%) of the women questioned accept- ed the idea of screening. Of those accept- ing the idea of screening, all accepted ultrasound screening, probably because it is part of the antenatal care in Saudi Arabia and is therefore familiar to them and does Table 4 Comparison of the women with a positive family history, those with a positive personal history and those with no history of a child with a chromosomal anomaly Variable Positive family Positive personal No history P-value history (n = 28) history (n = 13) (n = 509) No. % No. % No. % Accepted the idea of prenatal screening 20 71.4 8 61.5 308 60.5 0.263 Was aware of the availability prenatal screening 15 53.6 10 76.9 259 50.9 0.0639 Did not accept termination of pregnancy as an option 21 75.0 9 69.2 388 76.2 0.0019** Doubted the accuracy of prenatal screening tests 5 17.9 3 23.1 113 22.2 0.86 Did not believe that they would have a child with chromosomal anomalies 18 64.3 11 84.6 76 14.9 0.001** Did not believe chromosomal anomaly was an abnormality that should be screened for 2 7.1 5 38.56 26 5.1 0.001** Accepted the idea of biochemical screening 20 71.4 7 53.8 151 29.7 0.001** Accepted the idea of ultrasound screening 20 71.4 8 61.5 130 25.5 0.001** Accepted the idea of invasive screening (aminocentesis and chorionic villus sampling 7 25.0 13 100.0 221 43.4 0.001** **Statistically significant at P ≤ 0.01. not carry any risk of abortion. The accep- tance rate for biochemical screening was lower (53.0%). This rate is similar to the reported acceptance rate in other parts of the world [7,8]. The acceptance rate of invasive procedures was much lower (34.2%) probably because as it carries the risk of abortion. On the other hand, 29.1% of the women did not accept the idea of screening; the main reason was that they did not accept termination of pregnancy as a treatment option. Factors such as socioeconomic struc- ture, education and religion affect the 07 Attitudes of a high-risk.pmd 8/18/2005, 11:11 AM526 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 527 acceptability of prenatal diagnosis. These factors are very important in Saudi Arabia as all Saudi Arabians are Muslims and high parity is a characteristic feature of the community. At the same time, the physi- cian’s attitude towards such tests is impor- tant as they share the same religious background. Public awareness of the risks and diffi- culties facing a child with chromosomal anomalies and the effect on their future health and living is of great importance for acceptance of prenatal screening. In our study 19% of the women believed that they would not have a child with chromosomal anomalies although, because of their age (> 35 years), this was a high-risk popula- tion for certain such conditions. In addi- tion, the difference between those who accepted screening and those who did not was statistically significant in regards to their awareness of the availability of prena- tal screening and in their belief in the accuracy of the tests (Table 3), which reflects a lack of health knowledge. From this study we conclude that com- bined biochemical screening and ultra- sound nuchal translucency are the most acceptable prenatal genetic screening tests for Saudi Arabian women bearing in mind the religious and social background. Prena- tal diagnosis of such anomalies is important for both the parents and physicians even if termination is not undertaken. Physicians should be encouraged to offer these test and to give appropriate counseling as this high-risk group constituted 32.7% of the women attending the antental clinic. Public awareness should also be raised about the issues of genetic abnormalities and prenatal screening until suitable primary prevention is available. References 1. Benn PA et al. Combined second trimes- ter biochemical and ultrasound screen- ing for Down syndrome. Obstetrics and gynecology, 2002, 100(6):1168–76. 2. Cheffins T et al. The impact of maternal serum screening on the birth prevalence of Down syndrome and the use of am- niocentesis and chorionic villus sam- pling in south Australia. British journal of obstetrics and gynaecology, 2000, 107(12):1453–9. 3. Niazi MA et al. Down’s syndrome in Saudi Arabia: incidence and cytogenet- ics. Human heredity, 1995, 45(2):65–9. 4. Forrester MB, Merz RD. Epidemiology of Down syndrome (trisomy 21) in Hawaii, 1986–97. Teratology, 2002, 65(5):207– 12. 5. Ghanem I. [Abortion as a necessity]. Al Faisal medical journal, 1984, 9:6–15 [in Arabic]. 6. [Regarding termination of pregnancy for congenital abnormality (No. 4)]. Twelfth Session of the Moslem World League Conference of Jurists, Mecca 10–17 February 1990 [In Arabic]. 7. DeGraaf IM et al. Women’s preference in Down syndrome screening. Prenatal di- agnosis, 2002, 22(7):624–9. 8. Lam YH et al. Acceptability of serum screening as an alternative to cytoge- netic diagnosis of Down syndrome among women 35 years or older in Hong Kong. Prenatal diagnosis, 2000, 20(6): 487–90. 07 Attitudes of a high-risk.pmd 8/18/2005, 11:11 AM527 528 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Validity of vision screening by school nurses in seven regions of Oman R. Khandekar,1 S. Al Harby,1 T. Abdulmajeed,1 S.A. Helmi2 and I.S. Shuaili3 1Eye and Ear Health Care Department; 2School Health Department, Directorate General of Health Affairs; 3Department of Noncommunicable Diseases, Ministry of Health, Muscat, Oman. Received: 23/06/03; accepted: 20/10/03 ABSTRACT We tested the validity of vision screening in schools in 7 regions of Oman in 2003. Two research- ers tested 1719 randomly selected students in 4 school grades using the Snellen E acuity test. Trained school nurses had previously screened 182 233 students. The visual status recorded in the 2 screenings was compared. Sensitivity of screening by nurses was 68.34% (95% CI: 67.30–69.38) and specificity 99.23% (95% CI: 99.19–99.27). The positive predictive value was 85.42% (95% CI: 84.63–86.21) and negative predictive value was 97.93% (95% CI: 97.87–98.00). The sensitivity of the vision test was signifi- cantly higher in females, older students and in North Sharqiya region. In general, the vision screening of school students in Oman has satisfactory validity. Periodic training of nurses and supervision of the screen- ing procedures could improve its sensitivity. Underlying causes of the high numbers of false negative cases should be further investigated. Validité du dépistage visuel réalisé par des infirmières scolaires dans sept régions d’Oman RÉSUMÉ Nous avons testé la validité du dépistage visuel dans des écoles de sept régions d’Oman en 2003. Deux chercheurs ont testé 1719 élèves choisis de manière aléatoire dans quatre classes à l’aide du test de Snellen (test du E). Des infirmières scolaires formées avaient examiné auparavant 182 233 élèves. Le bilan visuel noté lors des deux examens a été comparé. La sensibilité de l’examen visuel réalisé par les infirmières était de 68,34 % (IC 95 % : 67,30-69,38) et la spécificité de 99,23 % (IC 95 % : 99,19-99,27). La valeur prédictive positive était de 85,42 % (IC 95 % : 84,63-86,21) et la valeur prédictive négative était de 97,93 % (IC 95 % : 97,87-98,00). La sensibilité du test de vision était significativement plus élevée chez les filles, chez les élèves plus âgés et dans la région septentrionale de Sharqiya. De manière générale, le dépistage visuel des écoliers et écolières à Oman avait une validité satisfaisante. La formation périodique des infirmières et le contrôle des procédures d’examen pourraient améliorer sa sensibilité. Les causes sous-jacentes du nombre élevé de cas faux négatifs devraient faire l’objet d’études approfondies. 08 Validity of vision.pmd 8/17/2005, 11:06 AM528 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 529 Introduction Despite the widespread acceptance of vi- sion screening programmes as a means of detecting ocular disorders in children, there has been little formal assessment of their validity and reliability [1]. This is more challenging as different methods are used for vision screening, e.g. the Snellen letter acuity and Modified Clinical Technique vi- sion screening kits, the Random Dot E ste- reogram and the hand-held autorefractor [2]. A study to assess the predictive ability of school screening programmes suggest- ed the need for a detailed prospective study to review predictability of both test-positive and test-negative findings [3]. In our study, the validity of the school vision screening programme was evaluated using specificity and sensitivity parameters. First level screening was performed by trained nurses and was compared with screening by practising optometrists. Validating vision screening by estimating the number of false negatives was also done [4]. In Oman, the eye health care pro- gramme is aimed at the early detection of common and blinding eye diseases. Hence, trained nurses conduct vision screening an- nually, targeting students in 4 grades in all schools in Oman. Refractionists in each re- gion recheck the students shortlisted with defective vision, refract them in schools and prescribe visual aids [5]. In 2002, the number of students with defective vision referred by nurses and subsequently found to be normal was high for 1st primary stu- dents but lower for 1st secondary students [6]. Rapid turnover of the health staff in- volved in this activity has raised serious doubts concerning the quality of the screening procedures. The programme therefore evaluated the validity of vision screening using sensitivity and specificity parameters, reviewed the predictability of vision screening for detection of refractive error and recommended steps to further strengthen the vision screening activities. Methods We carried out a cross-sectional agreement study on 182 233 students in 7 regions of Oman during school year 2002–2003. The study population was from 4 school grades: 1st primary (6–7 years), 4th prima- ry (9–10 years), 1st preparatory (12–13 years) and 1st secondary (16–17 years). The list of schools in each region and the number of students in each grade were provided by the Ministry of Education. The visual status of a randomly selected sample was examined by the study investigators. The visual status of the same students that had been noted by the school nurses during school year 2002–2003 was recovered from school health records. Hypothesis: the vision screening done by school health staff matched the super- visor’s screening in 90% or more of students. Null hypothesis: the vision screening done by school health staff does not match the supervisor’s screening in 90% or more of the students. The study aimed to achieve a goal of 90% power of the study and 95% signifi- cance level among a study population which ranged from 15 000 to 45 000 per region. With an acceptable error of 7%, the sample required was 137. To compensate for the clustering effect of students in se- lected schools and to cover loss of data, the sample was multiplied by a factor of 1.8. Thus, the minimum sample in each region was 250. The list of schools was used to random- ly select 4–6 schools in each region. Since the proportion of male and female students is almost equal, equal numbers of boys’ and girls’ schools were selected. In each 08 Validity of vision.pmd 8/17/2005, 11:06 AM529 530 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 school, 1 class from each grade was ran- domly selected. If the class had less than 50 students, an additional sample was en- rolled from another randomly selected class of the same grade. The aim was to enrol and examine 50 students in all 4 grades in 1 region and give an equal oppor- tunity to all students of that grade in the school to participate in the study. The field staff comprised 2 national eye health care supervisors who had at least 5 years of experience of vision screening. The vision testing procedure and meth- od of response were explained to all students. Each student then was called ac- cording to his or her serial number. The Snellen distant vision E chart was placed 6 metres away from the student. The vision of the right eye was tested first followed by the left and the results immediately noted on a standard form. Personal details of the students such as age, sex, area of residence and visual status of each eye with and with- out visual aids were collected. History of check-ups by an optician or ophthalmolo- gist was obtained from students who had defective vision. The school nurse had tested vision 3 months prior to the study and the visual status of each student had been recorded in the student’s health booklet. These records were referred to after the vision testing was completed by the supervisors. Definitions: if vision screening in 1 eye was found to have no more than 1 line dif- ference in the 2 screenings, it was defined as being in agreement. If vision screening in 1 eye differed by more than 1 line in the 2 screenings, the vision screening of that stu- dent was defined as being in disagreement. The disagreement was further graded ac- cording to the difference in visual status. Sensitivity was defined as ability of vision screening by the nurse to correctly identify the students with defective vision. Speci- ficity was defined as ability of vision screening by the nurse to correctly identify the students without defective vision. Posi- tive predictive value was defined as ability of vision screening to correctly predict cases of defective vision among students with suspected defective vision. Negative predictive value was defined as ability of the test to correctly predict students with- out defective vision among those declared to have normal vision. The data was computed using EpiData. Univariate analysis was conducted using SPSS, version 11. Agreement and disagree- ment rates per student were calculated. The sensitivity, specificity, false positives, false negatives, positive predictive and neg- ative predictive values of the vision screen- ing were estimated. The rates of validity parameters were projected for the study population. They were also adjusted by sex, school grade and region using indirect standardization. The determinants of these parameters by sex, school grade and region of residence were also evaluated. The fre- quencies, percentage proportions, odds ra- tios and 95% confidence intervals were estimated to validate the results. To ensure a high and uniform quality of the study, a standardization workshop was conducted for the field staff. A pilot study was carried out in schools not selected for the study; on the basis of the pilot study, the methodology, data collection form and data entry format were revised. Field staff having at least 5 years experience in vision screening and supervision work were selected for the study. The study was supervised by the study investigators at various stages. During the pilot study, inter-observer variation was evaluated and was found to be minimal. The supervisors’ skills in vision screening were also com- pared to those of optometrists and were found to match. 08 Validity of vision.pmd 8/17/2005, 11:06 AM530 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 531 The authorities in the Department of School Health, Ministry of Health and Min- istry of Education were approached and their consent was obtained for the study. Verbal consent of school principals was also taken. The results of the study were used to improve the vision screening of students. The results were also distributed to regional health authorities and health managers of related health programmes. Due to logistic problems, the study could not be conducted in Dhofar, Musun- dam and Al Wousta regions of Oman. Hence, the result of the study should be ex- trapolated to the whole of Oman with cau- tion. There was a gap of around 3 months between the vision screening done by the nurse and that done by the supervisors. It is assumed that vision status between the 2 screenings had not changed in most of the students. However, a marginal increase in refractive error or progress in pathology causing further deterioration of visual sta- tus in a limited number of cases cannot be ruled out. Results The profile of the study population and the sample we examined is given in Table 1. The total study population comprised 182 233 students in 4 school grades in 7 regions of Oman during the school year 2002– 2003. We enrolled a sample of 1720 stu- dents as participants in our study. One student did not complete the vision testing as he had to leave the school. Of the 1719 students examined, 861 (50.1%) were male and 858 (49.9%) were female. The sample was evenly distributed between the 4 grades and the 7 health regions. The pro- portion of the study population and the sample differed by region so adjusted rates should be used for comparison. The vision of 1599 students (93.0%) was 6/6 in both eyes in both screenings. In 74 (4.30%) students, vision was impaired in at least 1 eye. In 13 (0.76%) students, the screening by the nurse suggested im- paired vision but screening by the supervi- sor showed 6/6 vision. In 33 (1.92%) students the screening by the nurse sug- gested either 6/6 or 6/9 vision, but on re- screening by a supervisor, these students were found to have a higher grade of de- fective vision. Based on these findings, we calculated validity parameters for the sam- ple and for the study population as a whole. For the statistical validation, 95% confi- dence intervals were also estimated (Table 2). The validity parameters of vision screening by sex are given in Table 3. The specificity of screening was high for both sexes. However, the sensitivity of vision Table 1 Profile of the study population and the sample Variable Study population Sample (N = 182 233) (n = 1719) No. % No. % Sex Male 94 276 51.7 861 50.1 Female 87 957 48.3 858 49.9 School grade 1st primary 40 437 22.2 415 24.1 4th primary 48 396 26.6 416 24.2 1st preparatory 51 043 28.0 479 27.9 1st secondary 42 357 23.2 409 23.8 Region Muscat 34 056 18.7 250 14.5 Dhakhiliya 29 101 16.0 237 13.8 North Sharqiya 14 542 8.0 255 14.8 South Sharqiya 15 750 8.6 228 13.3 North Batinah 45 280 24.8 235 13.7 South Batinah 26 621 14.6 259 15.1 Dhahirah 16 883 9.3 255 14.8 08 Validity of vision.pmd 8/17/2005, 11:06 AM531 532 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 screening was significantly higher in fe- male than in male students. The agreement and disagreement rates for 1st primary and 4th primary were de- termined and compared to those for 1st preparatory and 1st secondary students (Table 4). The screening of students in higher grades by school nurses had signifi- cantly higher specificity than that for pri- mary students. Table 2 Parameters of validity Parameter No. Crude Adjusted 95% CI OR OR True positives 74 4.30 4.24 3.79–4.69 False positives 13 93.02 93.07 92.95–93.19 False negatives 33 0.76 0.72 0.26–1.18 True negatives 1599 1.92 1.96 1.51–2.41 % % Sensitivity 69.16 68.34 67.30–69.38 Specificity 99.19 99.23 99.19–99.27 Positive predictive value 85.06 85.42 84.63–86.21 Negative predictive value 97.98 97.93 97.87–98.00 Rates are adjusted for sex, school grade and region. The false positive rate was 13/1719 × 100 = 0.76%. The false negative rate was 33/1719 × 100 = 1.92%. OR = odds ratio; CI = confidence interval. Table 3 Validity of vision screening by sex Variable Males (n = 861) Females (n = 858) No. % No. % True positives 32 4.0 42 4.5 False positives 2 0.3 11 1.2 False negatives 18 2.2 15 1.7 True negatives 809 93.5 790 92.6 % (95% CI) % (95% CI) Sensitivity 64.87 (63.35–66.39) 72.09 (70.68–73.49) Specificity 99.73 (99.69–99.76) 98.69 (98.62–98.77) Positive predictive value 94.02 (93.29–94.75) 78.46 (77.32–79.60) Negative predictive value 97.72 (97.62–97.81) 98.17 (98.08–98.26) Rates are adjusted for school grade and region. CI = confidence interval. 08 Validity of vision.pmd 8/17/2005, 11:06 AM532 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 533 The validity parameters (adjusted for sex and school grade) for each region were compared (Table 5). Sensitivity ranged from 57.29% in Dhahirah to 80.08% in North Sharqiya. Discussion After 10 years of annual vision screening in schools, a review was needed. Our study tested the validity of vision screening. On the basis of our results, the programme would be able to strengthen the strategy for reducing eye strain in schoolchildren. Thus, the study was crucial for the eye care programme. Since the sample was evenly distributed in all regions and the number of school stu- dents varied in different regions and grades, the study results were adjusted be- fore outcomes of variants were compared. This also helped to minimize the confound- ing effects of school grade, sex, region and other related confounders on the validity. The cooperation of students could be the effect modifiers in such a study [7]. Proper explanation of the procedures along with help from teachers ensured the full cooperation of all participants. The vision screening done by the nurses had a specificity of 99.23%. Thus, vision screening by nurses could accurately iden- tify students who did not have vision de- fects. The test had 68.34% sensitivity. Thus, the vision screening procedures missed a substantial proportion of students with defective vision. In a study in New York State in the Unit- ed States of America (USA), using a vision screening battery, the Snellen test was 100% specific but it missed 75.5% of the children found to have vision problems when given a complete visual examination [8]. Although the methodology is different in the 2 studies, our study had a higher rate of specificity and a relatively low sensitivi- ty. The World Health Organization has rec- ommended that vision screening should Table 4 Validity of vision screening by school grade Variable 1st & 4th primary Preparatory and (n = 831) secondary (n = 888) No. % No. % True positives 14 1.67 60 6.68 False positives 4 0.53 9 0.91 False negatives 11 1.36 22 2.54 True negatives 802 96.43 797 89.87 % (95% CI) % (95% CI) Sensitivity 55.08 (52.55–57.61) 72.49 (71.39–73.60) Specificity 99.45 (99.40–99.50) 99.00 (98.93–99.07) Positive predictive value 75.87 (73.97–77.76) 88.06 (87.30–88.81) Negative predictive value 98.61 (98.53–98.68) 97.26 (97.15–97.36) Rates are adjusted for sex and region. CI = confidence interval. 08 Validity of vision.pmd 8/17/2005, 11:06 AM533 534 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 have at least 80% specificity and sensitivity for it to be cost-effective (A. Choudhury, unpublished data, 2003). Vision screening of 652 elementary stu- dents by lay volunteers was compared to that of optometrists in the USA. The Modi- fied Clinical Technique was used in this study. It showed 5.5% false positives and 4.3% false negatives [9]. Our study had a very low number of false positives (0.76%) and false negatives (1.92%). Considering a difference of 1 line as normal in our study could be a lenient criterion resulting in these low rates. There is no evidence to suggest that a more complex protocol would improve the detection of ocular disorders in screening. Rather, a more effective implementation of the current screening procedure gives bet- ter results [1]. In our study, simple vision testing methods were used and still had val- id outcomes. This is in agreement with the observations of earlier studies [1,9]. In view of the shortage of qualified opti- cians, it would be impossible to screen the large number of children in the present school population. Wong found that fol- lowing an educational programme and col- laboration with optometrists, nurses were able to correctly refer a high percentage of children [10]. Therefore, first level screen- ing should be conducted by nurses or other school staff trained in such procedures. Oman has adopted a similar model of using simple vision screening tools, annual train- ing of nurses and active supervision by op- ticians. This has resulted in a reasonable quality of screening. Countries with limited resources should focus on strengthening vision screening procedures using similar models and strategies instead of investing in costly equipment and using complicated screening methods. Bailey compared vision screening pro- cedures done by optometric students with those done by licensed opticians using the Modified Clinical Technique. They were found to have less satisfactory validity. It was proposed that the limited experience of the first level vision screeners was mainly responsible for the low predictive ability of this test [3]. The staff involved in our study had been trained in vision screening fre- quently. This could have accounted for the high validity in our study. Vision screening of schoolchildren in many states of the USA has suggested that even if different procedures and criteria are used, school screening may show a false positive rate of 30% or more [11,12]. In Table 5 Validity of vision screening by region Region Specificity Sensitivity Positive predictive Negative predictive (%) (%) value (%) value (%) Muscat 67.64 98.92 84.21 97.30 Dhakhiliya 75.84 99.19 84.23 98.55 North Sharqiya 80.08 97.83 73.22 98.51 South Sharqiya 67.38 98.52 74.00 97.97 North Batinah 62.71 98.72 75.25 97.71 South Batinah 74.78 99.98 99.61 98.29 Dhahirah 57.29 99.97 99.09 97.53 Rates are adjusted for sex and school grade. 08 Validity of vision.pmd 8/17/2005, 11:06 AM534 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 535 our study, the rate for false positives and false negatives was less than 2%. The low rate of refractive error and the high quality of vision screening in our study could ac- count for these observations. The vision screening carried out by nurses could accurately predict the pres- ence of refractive error in almost 70% of the students with this problem. The num- ber of students declared as having normal vision by a nurse after vision screening was almost 98% accurate. This high rate could be due to the large number of students in our study sample who did not have defec- tive vision. Refractive errors, which often become manifest during school age, rarely carry any serious prognostic implications. Ex- perts disagree on whether an uncorrected refractive error that would be detected by screening has any adverse effects on aca- demic performance in school-age children [13,14]. Hence, the 1.92% asymptomatic refractive error cases that were missed in schools might be of minimal importance. The sensitivity of vision screening in our study was significantly higher for fe- male than for male students. Differences in the attitudes of male and female students to cooperating with female nurses and male supervisors could be responsible for this observation. Refractive error may be marginal in children of primary-school age compared to students in preparatory and secondary grades. Difference in prevalence in these 2 groups of students and differential under- standing of vision screening procedures may have resulted in high specificity in stu- dents of higher grades. Differences in the training of the nurses as well as in the quality of vision screening by different nurses could account for the regional variation in the validity. Vision screening by nurses and second level screening performed by school re- fractionists in Oman is similar to the model proposed in the USA [15]. This would cer- tainly reduce unnecessary referrals to the ophthalmologist. Vision screening in schools by trained nurses in a large part of Oman has very high validity. However, false negative cases observed in this study could be further re- duced through vigilant screening. Further operational research is needed to determine yield and efficiency for the low rate of re- fractive error cases in 1st primary grade. Recommendations Vision screening in schools is an important strategy in many countries to detect and manage defective vision in the early stages. The use of primary staff for first level screening needs to be validity tested. In Oman, screening sensitivity was 68.3% and specificity 99.2.% The large number of false negative cases compromised the qual- ity of vision screening. The underlying causes of low sensitivity should be identi- fied and addressed. Further training and periodic supervision of vision screening by nurses could improve the validity of the vi- sion test. The sensitivity of vision screen- ing in primary school and validity was lower than in preparatory and secondary students. It could be improved through training and more thorough screening Vision screening of school students in Oman has satisfactory validity. Its low sen- sitivity needs to be improved. Periodic training of nurses and supervision of the screening procedures could improve the quality of vision screening. Because of the low yield, vision screening of primary- school students should perhaps be discon- 08 Validity of vision.pmd 8/17/2005, 11:06 AM535 536 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 tinued and replaced by preschool vision screening. Determinants of low sensitivity such as being male and of young age, as well as regional variation, should be further investigated to strengthen the quality of screening. References 1. Macfarlane DJ, Fitzgerald WJ, Stark DJ. Assessment of the Queensland School Health Service vision screening pro- gramme. Australian and New Zealand journal of ophthalmology, 1987, 15(3): 175–80. 2. Hammond RS, Schmidt PP. A Random Dot E stereogram for the vision screen- ing of children. Archives of ophthalmol- ogy, 1986, 104(1):54–60. 3. Bailey RN. Assessing the predictive abil- ity of the test-positive findings of an elementary school vision screening. Op- tometry and vision science, 1998, 75(9): 682–91. 4. Robinson B et al. Measurement of the validity of a preschool vision screening program. American journal of public health, 1999, 89(2):193–8. 5. Eye health care manual, 1st ed. Muscat, Oman, Ministry of Health and United Na- tions Children’s Fund, 1995:55–7. 6. Annual health report year 2002. Muscat, Oman, Ministry of Health, 2003:1–41. 7. Elimination of avoidable visual disability due to refractive errors. Geneva, World Health Organization, 2000 (WHO/PBL/ 00.79). 8. Lieberman S et al. Validation study of the New York State Optometric Association (NYSOA) vision screening battery. American journal of optometry and phy- siological optics, 1985, 62(3):165–8. 9. Wick B, O’Neal M, Ricker P. Comparison of vision screening by lay and profes- sional personnel. American journal of optometry and physiological optics, 1976, 53(9 Pt 1):474–8. 10. Wong SG. Comparison of vision screen- ing performed by optometrists and nurses. American journal of optometry and physiological optics, 1978, 55(6): 384–9. 11. Appelboom TM. A history of vision screening. Journal of school health, 1985, 55(4):138–41. 12. Romano PE. Summary and conclusions. Symposium on preschool/school vision and eye screening: current techniques and future trends. American orthoptic journal, 1988, 38:73–80. 13. Halveston EM et al. Visual function and academic performance. American jour- nal of ophthalmology, 1985, 99(3):346– 55. 14. Rosner J, Rosner J. Comparison of vi- sual characteristics in children with and without learning difficulties. American journal of optometry and physiological optics, 1987, 64(7):531–3. 15. Donaldson LA et al. Pediatric community vision screening with combined optom- etric and orthoptic care: a 64-month review. Ophthalmic and physiological optics, 2002, 22(1):26–31. 08 Validity of vision.pmd 8/17/2005, 11:06 AM536 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 537 Schoolteachers’ knowledge of common health problems in Bahrain F.A. Alnasir1 and J.H. Skerman2 1Department of Family and Community Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Bahrain. 2Department of Anaesthesia and Intensive Care, College of Medicine and Medical Sciences, Arabian Gulf University and Salmaniya Medical Complex, Bahrain. Received: 01/07/03; accepted: 29/10/03 ABSTRACT Schoolteacher could be a useful source of health information for students but that they them- selves would have to possess adequate and accurate knowledge of health issues. We assessed Bahraini schoolteachers’ knowledge of some common health problems using a pre-tested, structured questionnaire which requested information on schools, teachers’ demographic data, and knowledge about 5 common health problems in Bahrain: bronchial asthma, sickle-cell anaemia, hypertension, diabetes mellitus and the dangers of smoking. We analysed the data on 1140 respondents from a random selection of teachers in all schools in Bahrain. The schoolteachers scored only around 50% on average for knowledge about common health problems which indicates a need to educate schoolteachers about health in order to improve their knowledge and their capability to disseminate health knowledge and information to students. Connaissance des problèmes de santé courants par les enseignants scolaires à Bahreïn RÉSUMÉ Les enseignants scolaires pourraient représenter une source utile d’information sur la santé pour les élèves mais il devraient eux-mêmes posséder des connaissances suffisantes et exactes sur les ques- tions de santé. Nous avons évalué les connaissances des enseignants scolaires Bahreïnites concernant des problèmes de santé courants à l’aide d’un questionnaire structuré, testé au préalable, qui cherchait à recueillir des informations sur les écoles, des données démographiques concernant les enseignants et la connaissance de cinq problèmes de santé courants à Bahreïn : l’asthme bronchique, la drépanocytose, l’hypertension, le diabète sucré et les dangers du tabagisme. Nous avons analysé les données de 1140 répondants dans une sélection aléatoire d’enseignants de toutes les écoles de Bahreïn. Les ensei- gnants n’ont obtenu qu’un score d’environ 50 % en moyenne pour les connaissances concernant ces problèmes de santé courants, ce qui indique une nécessité d’éduquer les enseignants en matière de santé afin d’améliorer leurs connaissances et leur capacité à diffuser des connaissances et des informations sur la santé aux élèves. 09 Schoolteachers knowledge.pmd 8/17/2005, 11:06 AM537 538 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Introduction Schoolteachers form a group with great potential for influencing the health knowl- edge and attitudes of students and other population groups. Schoolteachers’ per- ceptions of health, their attitudes and prac- tices, and their knowledge of common health problems could be essential factors in optimizing their roles as health educators in society. Many adult behaviour patterns and atti- tudes develop in early childhood. In addi- tion there is a growing acceptance of the need for health education at primary school age. For example, it has been found that various interventions such as improving teachers’ awareness of cancer education issues and providing appropriate cancer ed- ucation resources might increase the level of primary school-based cancer education [1]. Schoolteachers are expected to be role models so that students can emulate and adopt their behaviour and attitudes. In Sweden, the majority of school pupils thought that schoolteachers were the best sources of information for sexually trans- mitted infections and sexuality [2]. School- teachers are also considered the major source of information for their students and would appear to be suitable as health educators [3]. In Australia, teachers and the clergy have been identified as “gate- keepers” who might serve as a first line of assistance for distressed young people [4]. Since current emphasis in health educa- tion is on prevention of serious illness through lifestyles that promote wholeness, teachers are well placed professionally to carry out health education at school [5,6]. Teachers’ education is considered a major factor in the effective implementation of comprehensive school health [7]. Atti- tudes, behaviour and general knowledge are disseminated to the students from the teachers, either deliberately or uncon- sciously. In order to raise students’ health knowledge and improve their attitudes to- ward health, they should be placed in an appropriate environment that is based on 3 main determining factors: teachers, school and society (including home). School and health professionals should continue to advocate school-wide policies and programmes that support both stu- dents and teachers if the goal of an inte- grated healthy school environment is to be realized [8]. Ministries of education and health should organize seminars on health education [9]. Educational health packages could be developed with collaboration be- tween teachers who have an understanding of the principles of curriculum design and health professionals who are fully aware of health problems [10]. Development efforts by teachers, including training and ongoing reinforcement to increase their sense of preparedness, have significant effects in the classroom [11]. In Nigeria, most teach- ers felt that health education was important and should be an integral part of the curri- culum [12]. Multicultural attitudes and knowledge on the part of teachers changed in a positive direction when candidates at- tended a teacher preparation programme [13]. It is reported that the formation of a population’s healthy lifestyle, which is one of the main tasks of Soviet medicine, can be accomplished with the help of school health education teams [14]. It has been documented, however, that in Bahrain school health education is not included in the curriculum [15]. Few states in the United States of America include health ed- ucation in their state tests, and elementary school teachers often do not feel it is an important subject and therefore spend in- sufficient time on health instruction in the classroom [16]. 09 Schoolteachers knowledge.pmd 8/17/2005, 11:06 AM538 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 539 It was our goal to study teachers’ awareness about common health problems in Bahrain. We hypothesized that the teach- ers were well informed about these prob- lems and hence would be able to disseminate information to others, specifi- cally students. Methods Information was collected about the schools in Bahrain and permission for con- ducting the study was obtained from the Ministry of Education, who sent out an in- formation circular to all schools in the country. The study was carried out during 1997–1998. The target population was all Bahraini teachers of all disciplines in 49 randomly selected schools. Schools in the 5 geographic regions of Bahrain (Muharraq, Manama, Northern area, Central area and Western area) were selected for this study. The total number of schools in these areas is 152, with a total of 3360 teachers. A random sample of 49 schools was selected. Stratified random sampling was done, giving appropriate rep- resentation to the 5 regions, and taking into account the number of Bahraini teachers in each school, the type of school, and the lo- cality. All 1248 Bahraini teachers in those schools were included in the study. The study tool for this investigation was a questionnaire. Based on a comprehensive review of the literature, a 4-item survey was designed. Items addressed each of the following areas: information about the school, teachers’ demographic characteris- tics, teachers’ health perceptions, and health knowledge. The questionnaire was adapted to the local language and designed in a simple way to make it easy for the se- lected teachers to read and complete. The face value and content validity of the ques- tionnaire were tested by distributing it to doctors in various specialties and obtaining their feedback. It was also tested for re- peatability by sending it again to the same doctors after a 1-week lapse. A pilot study was done to test the various areas of the questionnaire. The health information portion of the questionnaire was aimed at collecting infor- mation about the teachers’ health status and their experiences of illness. Five common health problems in Bahrain (asthma, sickle- cell anaemia, hypertension, diabetes melli- tus and the dangers of smoking) were chosen because of their high prevalence among Bahrainis. The teachers were asked questions (a total of 48: 8 questions for the smoking problem and 10 for each of the others) related to signs, symptoms and complications of those problems. Some untrue information for each problem was included to test the teachers’ knowledge. The teachers were asked to give their re- sponse to the pre-set questions by writing “Yes” (agree), “No” (do not agree) or “Do not know” to the answer. Each blank space was considered a missing value (i.e. teach- ers did not respond to it). After analysing the responses, a score of 1 was given for the correct answer and 0 for other answers (wrong, missing or “Do not know” answers). No questions inquiring about whether the teachers had received any formal train- ing or special education about common health problems were included. The head teacher of each school was given complete information on the study, either by telephone or through direct con- tact. The questionnaires were delivered to the teachers in the selected schools in the morning and collected at the end of the same day or after a maximum of 2 days. An accompanying letter was written to the teachers giving them information on the study, its aims, how to complete the ques- tionnaire and requesting their cooperation. 09 Schoolteachers knowledge.pmd 8/17/2005, 11:06 AM539 540 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Data were analysed using SPSS. Results were cross-tabulated and chi-squared cal- culated. The knowledge portions of the data were scored and assessed as percent- age scores. Results Of the 1254 teachers included in the sam- ple, 1140 (91%) responded and 114 (9%) did not. Efforts were made to obtain the questionnaire from the non-respondents, but without success. The general charac- teristics of these non-respondents, such as age, sex and type of school, were investi- gated and were not found to differ from those of the respondents. There were 679 (60%) female respondents and 461 (40%) male. Age range was 20–58 years (mean 32.7 years, median 32 years, standard devi- ation [SD] 6.17). Only 15% of the teachers stated they were above 40 years of age. Of the 220 teachers who did not wish to dis- close their ages (19%), the majority (94%) were female. Of the responding teachers, 78% were married, 20% were single and 2% were either divorced or widowed. There were 774 teachers who were mar- ried and had children (range 1–16 children, mean 3). More male teachers than female teachers had children (65% compared to 35%). Of the 1091 who responded to the question related to the teachers’ level of ed- ucation, 19% had only high school educa- tion and 81% had higher education, which includes a Diploma or Bachelor’s degree. Teachers in primary and intermediate schools were younger (≤ 32 years) (P < 0.01) and more of them had degres than secondary school teachers. More females than males had higher education. Of the to- tal, 29% taught science subjects, including mathematics, and 71% taught arts sub- jects. There were 1068 responses (94%) to the question about the duration of occupa- tion. Duration ranged from 1 year to 35 years (mean 12.3 years, SD 7.3). Only 6% of the teachers were smokers, of whom the majority (94%) were male, while 4% were ex-smokers. Regarding alcohol con- sumption, since it is not usual in an Islamic country, not all who drink admit to it, and the others may find the question offensive. Of the 98% who responded to this ques- tion, only 14 (1%), all of whom were male, admitted to drinking alcohol. Some 40% of the teachers were the heads of the house- hold, and 35% said they shared that re- sponsibility. Table 1 shows the teachers’ responses to questions on their own health and health- related attitudes. The health status of the teachers was satisfactory as only 16% had any acute illness during the past 6 months. The total scores for each teacher, which represented correct answers, ranged between 0 and 41 (mean 21.9, me- dian 24, SD 9.3). Only 1 teacher obtained the highest score, but there were 39 teach- ers (3%) who scored 0, i.e. no knowledge at all. Table 2 shows the scores for each health problem. The total scores for knowl- edge, after categorizing into 2 groups (group 1 = ≤ 24, group 2 = > 24) according to the median, were studied in relation to all other variables in the study (Table 3). There were a large number of missing values on the topics of sickle-cell anaemia and asth- ma, while there were no missing values on knowledge related to hypertension, diabe- tes mellitus or the dangers of smoking. A higher percentage of females than males were teaching science, 23% com- pared with 16% (chi-squared 7.225, P < 0.5). More of the younger teachers (≤ 32 years) were teaching science subjects (46%), while more of the older teachers (> 32 years) were teaching arts subjects (77%) (chi-squared 20.81, P < 0.001). 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM540 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 541 In general, teachers who had no chron- ic illness had better health knowledge for each category of health knowledge (chi- squared 15.8, P < 0.001). Of the 93% of teachers who had not had any recent ill- ness, 88% perceived their general health as satisfactory (chi-squared 67.1, P < 0.001). With regard to the dangers of smoking, surprisingly, it was found that there was no relationship between the smoking habit and knowledge about smoking (P < 0.9). How- ever knowledge about smoking increased as the number of years of occupation in- creased (chi-squared 11.673, P < 0.001). Table 1 Health and health-related attitudes of teachers Variable Yes No Did not respond No. % No. % No. % Suffered from any acute illness during the past 6 months 179 16 936 82 25 2 Any chronic illness 344 30 759 67 37 3 Family illness 322 28 785 69 33 3 Doing exercise 191 17 862 76 87 8 Hospital admissionsa 137 12 963 85 40 4 Good Unsatisfactory No knowledge Teachers’ perception of their general healthb 930 82 100 9 68 6 Perception of health services in Bahrain 762 67 265 23 113 10 aMore females (72%) than males (28%) reported having been admitted to hospital. b42 (4%) teachers did not respond. Table 2 Teachers’ scores on knowledge of five common health problems in Bahrain Health problem Respondents No. of Score SD (n = 1140) questions No. % Range Mean Median Sickle-cell anaemia 1053 92 10 0–10 4.88 5 1.980 Smoking 1067 94 8 0–8 5.28 6 1.852 Asthma 1029 90 10 0–10 5.16 5 2.185 Hypertension 969 85 10 0–10 3.00 3 1.899 Diabetes mellitus 1064 93 10 0–10 5.34 6 2.133 SD = standard deviation. 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM541 542 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Table 4 shows some characteristics that were found to have a significant relation- ship with teachers having adequate knowl- edge (≥ mean) about diabetes mellitus. Knowledge of other health problems was found not to be related to the teachers’ characteristics. There was no relationship between suf- fering from chronic illness and knowledge about asthma, sickle-cell anaemia or the Table 3 Correlation of some characteristics of teachers to better knowledge of five common health problems in Bahrain Characteristic Better knowledge P-value Duration of occupation as a teacher Fewer years > more years < 0.05 Type of school Primary + intermediate > secondary < 0.02 Sex Female > male < 0.001 Marital status Married > single < 0.02 Teaching discipline Science > arts < 0.02 Recent illness No recent illness > having recent illness < 0.05 Chronic illness No chronic illness > having chronic illness < 0.001 Family size Smaller family size > larger family size < 0.01 Table 4 Relationship between characteristics of teachers and having adequate (≥ mean) knowledge about diabetes Characteristic Teachers with P-value χ2 adequate knowledge, % Sex Male 90 < 0.001 33.927 Female 77 Discipline taught Science 90 < 0.05 4.505 Art 84 Family illness Yes 89 < 0.05 5.240 No 83 Perception of own health Satisfactory 84 < 0.05 3.897 Unsatisfactory 93 Drinking alcohol Yes 76 < 0.002 5.040 No 85 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM542 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 543 dangers of smoking. There was a signifi- cant relationship between suffering from chronic illness and knowledge about diabe- tes mellitus (chi-squared 9.2, P < 0.02) and knowledge about hypertension (chi- squared 6.4, P < 0.001) Discussion The majority of the teachers who partici- pated in this study were young adults, and most had a university degree, either a Di- ploma or Bachelor degree. Most of the teachers were female, and we found they had better health knowledge than the males. A study done in the United States of Amer- ica indicated that students’ attitudes im- proved if their teachers were more educated and older. It was reported that the students’ perception and attitude regarding adolescent homosexuality varied with the teacher’s sex, age, educational level and teaching status [17]. The overall knowledge of the school- teachers was found to be average in the ar- eas related to sickle-cell anaemia, asthma and diabetes mellitus. While it was poor (< mean) in the area of hypertension, they had a good (≥ mean) knowledge of the dan- gers of smoking. Considering that the prev- alence of these problems is high in Bahrain and the surrounding areas (3%–5% for sickle-cell anaemia, 25% for diabetes melli- tus, 5% for bronchial asthma and approxi- mately 15% for hypertension) [18], it is alarming that schoolteachers are not more aware of the problems. It is not surprising therefore if students lack information about such problems. Teachers who had personal experience of illness, i.e. chronic or acute illness, ei- ther at the time of the study or earlier in life, or who had a family member with a signif- icant illness, knew more in the areas of dia- betes mellitus and hypertension. Both of these are chronic conditions and are very common in our community. This could ex- plain why teachers were more informed in these 2 areas than the other areas There was no relationship between teachers’ perceptions regarding their own health or the health services in Bahrain and their knowledge of common health prob- lems. This finding was supported by re- sults of another study which found that teachers’ health beliefs are not linked to whether teachers teach health generally [19]. Surprisingly, primary and intermediate school teachers had better knowledge than secondary school teachers. This could be explained by the fact that they may be younger and more of them have university degrees. Such findings regarding knowl- edge about common diseases are supported by studies in other parts of the world. A study in Brazil found that in areas where helminthic diseases are known to have been present for a long time, teachers and pupils still had little information on them, nor were they aware of the mechanism of transmission [20]. Another barrier to quality health instruc- tion is when little or no in-service training is available for teachers. Several conditions are necessary for the development of learn- ing opportunities allowing teachers free- dom to develop new understandings of teaching and learning. Poor knowledge of health can be attributed to the fact that health education is not a priority at many schools, and can also be related to the fact that health education questions are usually absent from end of year examinations [16]. Most teachers in our study were self- taught with regard to health education as there is no formal training, and relied pri- marily on traditional teacher-centred in- struction methods. In order to deliver effective health education in schools, 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM543 544 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 teachers require a substantial body of knowledge and a variety of skills [21,22]. The type of training programme offered usually has a marked influence on the length and type of programme they offer to their students [23]. Our findings are in agreement with those of several other reports which indi- cated that teachers’ health knowledge is deficient and this may ultimately affect their ability either to deliver health educa- tion or to manage acute health problems in school. In one study it was found that the majority of teachers encounter child abuse among their students although they did not receive sufficient education on how to ad- dress it [24]. In another study it was reported that teachers needed more knowl- edge regarding head lice and were signifi- cantly more knowledgeable as teaching experience increased [25]. In an Indian study about sex education, pupils in one school were reassessed after a health talk and distribution of a handout. Despite hav- ing had no formal sex education, most re- spondents were reasonably well informed about the transmission of HIV. Media teachers and health workers were quoted as the main sources of knowledge [26]. In a Canadian study on the effectiveness of school-based sexual health education, it was found that it depended in part on the preparation of the teachers [24]. The deliv- ery of consistently high quality sexual health education in schools requires that all teachers of sexual health education are ade- quately prepared and acquire a substantial body of knowledge. Conclusion We found that there was a deficiency in teachers’ health knowledge and therefore there is a need to educate schoolteachers about health, particularly about health prob- lems prevailing in the society. There should be regular pre-service and in-service train- ing regarding such problems. Health and education ministries in Bahrain should or- ganize joint seminars for schoolteachers on health education to improve their level of health awareness. This would help teachers to develop health education packages in collaboration with the curriculum designers and health professionals to tackle current knowledge about health-related problems. References 1. Carey P et al. Cancer education and the primary school teacher in England and Wales. Journal of cancer education, 1995, 10(1):48–52. 2. Persson E, Sandstrom B, Jarlbro G. Sources of information, experiences and opinions on sexuality, contraception and STD protection among young Swedish students. Advances in contraception, 1992, 8(1):41–9. 3. McGovern M, Barry MM. Death educa- tion: knowledge, attitudes and perspec- tives of Irish parents and teachers. Death studies, 2000, 24(4):325–33. 4. Leane W, Shute R. Youth suicide: the knowledge and attitudes of Australian teachers and clergy. Suicide and life- threatening behaviour, 1998, 28(2):165– 73. 5. Mull, SS. The role of the health educator in development of self-esteem. Journal of health education, 1991, 22:349–51. 6. Masvidal RM et al. La educación sani- taria en la escuela [Health education in school]. Atención primaria 1995, 15(6): 369–70, 372. 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM544 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 545 7. Wood DN. Teacher credential candi- dates’ perceptions of the need for pre-service training in comprehensive health education. Paper presented at the annual meeting of the American School Health Association, Milwaukee, Wiscon- sin, 1995. 8. Kubik MY et al. Food-related beliefs, eat- ing behavior, and classroom food prac- tices of middle school teachers. Journal of school health, 2002, 72(8):339–45. 9. Brook U. Teachers’ attitudes towards AIDS: an explorative study in Israel. Pa- tient education and counseling, 1994, 24(3):337–40. 10. Henry RL et al. Integrated health and education input in the development of educational resources about asthma for schools. Journal of paediatric and child health, 1994, 30(6):492–6. 11. Hausman AJ, Ruzek SB. Implementation of comprehensive school health educa- tion in elementary schools: focus on teacher concerns. Journal of school health, 1995, 65(3):81–6. 12. Fabiyi AK, Blumenthal DS. Health edu- cation in Nigerian secondary schools. Journal of community health, 1991, 16(3):151–8. 13. Capella-Santana N. Voices of teacher candidates: positive changes in multicultural attitudes and knowledge. Journal of educational research, 2003, 96(3):182–92. 14. Tsurikov VT, Gavriushenko VV. Iz opyta organizatsii smotra-konkursa shkol’nykh sanprosvetagitbrigad. [Expe- rience in organizing competition of school health education teams]. Sovetskoe zdravookhranenie, 1991, (5): 54–6. 15. Roemer R. Legislative action to combat the world tobacco epidemic, 2nd ed. Geneva, World Health Organization, 1993:210. 16. Telljohann SK et al. Effects of an inser- vice workshop on the health teaching self-efficacy of elementary school teach- ers. Journal of school health, 1996, 66(7):261–5. 17. Telljohann SK et al. Teaching about sexual orientation by secondary health teachers. Journal of school health, 1995, 65(1):18–22. 18. Health Information Directorate. Health statistics report – 2003. Bahrain, Ministry of Health, 2003. 19. Carey P et al. Is health locus of control related to health education activity? Psy- chological reports, 1995, 76(3 pt 2): 1389–90. 20. Dos Santos MG et al. Educacao em saúde em escolas públicas de 1 grau da periferia de Belo Horizonte, MG, Brasil. II - Conhecimentos, opinioes e pre- valencia de helmintiases entre alunos e professors. [Health education in 1st grade public schools at the periphery of Belo Horizonte, Brazil. II. Knowledge, opinion and prevalence of helminthiasis among students and teachers]. Revista do Instituto de Medicina Tropical de São Paulo, 1993, 35(6):573–9. 21. Gingiss PL, Basen-Engquist K. HIV edu- cation practices and training needs of middle school and high school teachers. Journal of school health, 1994, 64(7): 285–90. 22. McKay A, Barrett M. Pre-service sexual health education training of elementary, secondary, and physical health educa- tion teachers in Canadian faculties of education. Canadian journal of human sexuality, 1999, 8(2):91–101. 23. Sequier A, Demarteau M, Pereira M. L’analyse des représentations: un moyen d’évaluer la formation des enseignants en éducation pour la santé. [Representational analysis: a means to 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM545 546 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 evaluate teacher training in health edu- cation]. Promotion & education, 1994, 1(3):14–8. 24. Abrahams N, Casey K, Daro D. Teachers’ knowledge, attitudes and beliefs about child abuse and its prevention. Child abuse and neglect, 1992, 16(2):229–38. 25. Kirchofer GM, Price JH, Telljohann SK. Primary grade teachers’ knowledge and perceptions of head lice. Journal of school health, 2001, 71(9):448–52. 26. Agrawal KH et al. Knowledge of and atti- tudes to HIV/AIDS of senior secondary school pupils and trainee teachers in Udupi District, Karanataka, India. Annals of tropical paediatrics, 1999, 19(2):143– 9. Note from the Editor We would like to inform our readers that the next issue of EMHJ (Volume 10 No. 6) will be a Special Issue on Nutrition. 09 Schoolteachers knowledge.pmd 8/17/2005, 11:07 AM546 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 547 Comparison of prostaglandin E2 tablets or Foley catheter for labour induction in grand multiparas M.I. Al-Taani1 1Department of Obstetrics and Gynaecology, Queen Alia Military Hospital, Royal Medical Services, Amman, Jordan. Received: 04/05/03; accepted: 23/10/03 ABSTRACT The efficacy, safety and outcome of prostaglandin (PG)E2 was compared with Foley catheter for labour induction in grand multiparous women. At a hospital in Jordan, 147 women with Bishop score ≤ 5 were randomized to receive 3 mg PGE2 vaginal tablets (n = 75) or 50 mL intracervical Foley catheter (n = 72). The change in Bishop score was significantly higher in the PGE2 group than the catheter group, and time from induction to delivery was significantly shorter in the PGE2 group. Significantly more women needed oxytocin for labour augmentation in the catheter than the PGE2 group and fetal distress was significantly more frequent. For grand multiparas, PGE2 vaginal tablets may be preferable for ripening the cervix as well as for labour induction. Comparaison des ovules de prostaglandine E2 et de la sonde de Foley pour le déclenchement du travail chez des grandes multipares RÉSUMÉ L’efficacité, l’innocuité et l’effet de la prostaglandine (PG) E2 ont été comparés avec la sonde de Foley pour le déclenchement du travail chez des grandes multipares. Dans un hôpital en Jordanie, 147 femmes dont le score de Bishop était inférieur ou égal à 5 ont été randomisées pour recevoir des ovules vaginaux de PGE2 de 3 mg (n = 75) ou une sonde de Foley intracervicale de 50 mL (n = 72). La modification du score de Bishop était significativement plus importante dans le groupe de la PGE2 que dans le groupe de la sonde, et le temps entre le début du travail et l’accouchement était significativement plus court dans le groupe de la PGE2. Un nombre significativement plus important de femmes a eu besoin d’ocytocine pour augmenter le travail dans le groupe de la sonde que dans le groupe de la PGE2 et la souffrance foetale était significativement plus fréquente. Chez les grandes multipares, les ovules vaginaux de PGE2 peuvent être préférables pour la maturation cervicale ainsi que pour l’induction du travail. 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM547 548 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Introduction The process of cervical ripening usually commences before labour begins; the cer- vix undergoes significant biochemical changes over a period lasting from 12 hours to 6–8 weeks [1]. It is believed to be controlled by certain hormones (in particu- lar prostaglandin E2) that play a role in trig- gering uterine contractile activity [2]. So the state of the cervix has been suggested to be the most important factor in predict- ing the success rate of labour induction [3– 5]. Calder et al. reported an increasing ma- ternal and neonatal morbidity when labour induction begins with a Bishop score ≤ 3 [6]. Trofatter in 1992 reported a decrease in induction failure when using a variety of methods to ripen the cervix [7]. The use of prostaglandins for cervical ripening admin- istered by any route has been reported to improve the rate of vaginal delivery and de- crease the rate of caesarean section and in- strument deliveries [8]. In addition, the use of a cervical catheter has been shown ef- fective for cervical priming and leads to a favourable outcome [9]. Grand multiparity is considered a risk factor for maternal and neonatal morbidity. However, the subject is still under debate, with several authors reporting conflicting results as to whether a pregnancy is high risk or not because of its associated medi- cal and obstetric complications [10–13]. Labour induction using prostaglandins in this high parity group has been viewed as a stressful and potentially dangerous proce- dure. Other reports on the use of prosta- glandins in grand multiparas contradict this notion and have yielded a safe and effective method of labour induction [14–16]. Grand multiparity is common in Jordan. The total number of deliveries conducted in Queen Alia Military Hospital during the study period (12 months) was 3684 and 1547 (42%) of these were to grand multip- arous women. The number of inductions of labour conducted was 590 (16%). It is therefore important to study the efficacy, safety and outcome of vaginal prostaglan- din (PG)E2 tablet compared with intracer- vical Foley catheter insertion for induction of labour in this high parity group. Methods This prospective randomized study was carried out at Queen Alia Military Hospital, Amman, Jordan. Between September 2001 and August 2002, 147 grand multiparous women who had a clinically unfavourable cervix and indications for labour induction were recruited for the study. Patients were eligible for inclusion if they had a singleton pregnancy at term, vertex presentation, in- tact membranes, reassuring fetal heart tracings and Bishop score ≤ 5. Women with previous caesarean section, ruptured membranes, contraindications for vaginal birth, suspected cephalopelvic dispropor- tion or unexplained antepartum haemor- rhage were excluded. After written informed consent was ob- tained, patients were randomized to one of the 2 methods, using a random number ta- ble. For the first method, 75 women were given PGE2 3 mg vaginal tablet, inserted in the posterior vaginal fornix. This was re- peated at 6-hour intervals, if needed. For the second method, 72 women were given a size 18 Foley catheter, inserted intracervi- cally in order to pass the internal os using a sterile speculum technique. This was inflat- ed with 50 mL distilled water and taped to the inner side of the thigh to produce a small traction. For all women, vital signs were record- ed on admission and blood was drawn for 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM548 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 549 complete blood count and cross-matching. General and systemic examinations fol- lowed by pelvic examination were per- formed. A fetal heart rate tracing was obtained upon admission and after the initi- ation of the induction method for a mini- mum time of 45 minutes. Abdominal and cervical examinations were performed at 4–6 hour intervals to diagnose the start of labour and to measure Bishop score chang- es, unless these were indicated at earlier times. Amniotomy was performed within 1–2 hours of the diagnosis of labour or as soon as clinically feasible. The progress of labour was monitored every 2 hours. Labour abnormalities were defined by Friedman’s criteria [16]. For these cases, oxytocin infusion was started for augmentation of labour, administered in the manner outlined by O’Driscoll and Meagher [17]. Intrapartum continuous fe- tal heart rate monitoring was performed. The primary outcome measures were the route of delivery and the time required from beginning of the induction method to delivery. The secondary outcome measures were the change in Bishop score, intrapar- tum complications or the need for oxytocin for labour augmentation. Comparison of continuous variables was made with Student t-test. Categorical variables were compared using the chi- squared or Fisher exact test. P < 0.05 was considered to indicate a significant differ- ence. Results There were no significant differences in presenting characteristics between the 2 study groups (Table 1) and both groups had similar indications for labour induction (Table 2). Postdates and pre-eclampsia were the most frequent indications in both groups. The frequency of postdate preg- nancies was significantly higher in the cather group than the PGE2 group (P = 0.029). As shown in Table 3, the change in Bishop score was statistically significantly higher in the PGE2 group than the Foley catheter group (mean 3.95 ± SD 2.20 ver- sus 3.10 ± 1.10) (P < 0.01). Significantly more women in the catheter group (49%) needed oxytocin for labour augmentation than in the PGE2 group (20%) (P < 0.001). The time from initiation of the induction method to delivery was significantly short- er in the PGE2 group compared with the catheter group (16.5 ± 2.2 versus 20.5 ± 3.9 hours) (P < 0.01). Of women that were randomized to use PGE2, 61% delivered within 16 hours after initiation of induction compared with 42% of those randomized to use the Foley catheter. This was a statis- tically significant difference (P < 0.01). There were 21 women who delivered after 24 hours in the catheter group, compared with 5 women in the PGE2 group. This dif- ference was highly statistically significant (P < 0.001). Table 1 Presenting characteristics of grand multiparas treated with Foley catheter or prostaglandin E2 (PGE2) vaginal tablet for induction of labour Characteristic Catheter PGE2 group P- group (n = 72) (n = 75) value Maternal age (years) 27.7 (5.5) 27.1 (5.7) 0.438 Gestational age (weeks) 39.4 (1.9) 39.5 (1.7) 0.721 Parity (No.) 7.7 (2.1) 7.4 (1.9) 0.176 Initial Bishop score 2.56 (1.40) 2.61 (1.30) 0.873 Values are shown as mean (standard deviation). n = number of patients. 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM549 550 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Table 2 Indications for induction of labour in grand multiparas treated with Foley catheter or prostaglandin E2 (PGE2) vaginal tablet for induction of labour Indication Catheter group PGE2 group P-value (n = 72) (n = 75) No. % No. % Postdates 29 40 23 31 0.029 Pre-eclampsia 20 28 24 32 0.164 Diabetes 8 11 12 16 0.118 Suspected IUGR 10 14 11 15 0.693 Suspected macrosomia 5 7 5 7 0.999 IUGR = intrauterine growth restriction. n = number of patients. Table 3 Labour and delivery outcomes of grand multiparas treated with Foley catheter or prostaglandin E2 (PGE2) vaginal tablet for induction of labour Outcome Catheter group PGE2 group P-value (n = 72) (n = 75) No. % No. % Change in Bishop score Mean (SD) 3.10 (1.10) 3.95 (2.20) < 0.01 Oxytocin required 35 49 15 20 < 0.001 Time from induction to delivery < 16 hours 30 42 46 61 < 0.01 16–24 hours 21 29 24 32 0.228 > 24 hours 21 29 5 7 < 0.001 Mean (SD) 20.5 (3.9) 16.5 (2.2) < 0.01 Intrapartum complications Fetal distress 11 15 6 8 0.01 Pyrexia 0 0 1 1 0.105 Failure to progress 6 8 7 9 0.617 Haemorrhage 3 4 5 7 0.91 Delivery type Spontaneous vaginal 52 72 57 76 0.166 Forceps 3 4 2 3 0.581 Vacuum 5 7 6 8 0.611 Caesarean section 12 17 10 13 0.147 SD = standard deviation. n = number of patients. 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM550 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 551 There were no significant differences between the groups in intrapartum compli- cations or in type of delivery but the fre- quency of fetal distress was significantly higher in the catheter group than the PGH2 group (P = 0.01) (Table 3). In addition, there were no statistically significant diffe- rences in fetal outcomes (Apgar scores at 5 minutes, birth weight, admissions to the neonatal intensive care unit or meconium aspiration) between the 2 groups (Table 4). No more than 2 × 3 mg PGE2 vaginal tab- lets were needed to achieve a clinically fea- sible cervix for amniotomy. No woman needed a blood transfusion. All women and their babies were discharged home in good condition. Discussion This study demonstrates that cervical rip- ening as well as labour induction in grand multiparas is safe using either PGE2 or Fo- ley catheter. Both methods were effective, but use of PGE2 3 mg vaginal tablets ap- peared to be superior to the intracervical insertion of a Foley catheter, in view of the higher change in Bishop score, shorter in- terval from initiation to delivery and less need of oxytocin for labour augmentation. The current study agrees with other re- ports regarding the use and safety of PGE2 vaginal tablets for labour induction in grand multiparas [14,18,19]. These findings contradict Sciscione et al. [9] who used PGE2 intracervical gel compared with intracervical insertion of Foley catheter; however this gel is not readily available in our hospital. It is well known that some factors might affect the safety, absorption and efficacy of PGE2, such as the vehicle, oily lubrication, humid- ity and possibly vaginal pH [20,21]. The difference in results may be attributed to the type of PGE2 used, as the main effect of PGE2 gel is cervical ripening and its con- tractile effect is considered to be small [22,23]. The most hazardous major complica- tion of labour induction in grand multiparas is rupture of the uterus. Suggested risk fac- tors for uteruine rupture include multipari- ty, oxytocin use and the state of the cervix. The present study revealed no major com- plications. Comparison of intrapartum complications between groups showed no Table 4 Fetal outcomes of grand multiparas treated with Foley catheter or prostaglandin E2 (PGE2) vaginal tablet for induction of labour Outcome Catheter group PGE2 group P-value (n = 72) (n = 75) No. % No. % Mean (SD) birth weight (g) 3503 (575) 3452 (530) 0.319 Apgar score < 6 at 5 min 5 6.9 3 4.0 0.094 Admission to NICU 6 8.3 5 6.7 0.259 Meconium present 13 18.1 15 20.0 0.293 NICU = neonatal intensive care unit. SD = standard deviation. n = number of patients. 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM551 552 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 significant differences except for fetal dis- tress which was significantly higher in the catheter group. Oxytocin was needed for labour augmentation in 48.6% and 20.0% of the Foley and PGE2 groups, respectively. Outcome of labour and delivery compared favourably well in both groups. This dem- onstrates an equivalent safety of both methods, a finding that has been confirmed by others [14,24]. Furthermore, labour induction in grand multiparas with previous caesarean section has been reported to be safe, so too is the use of oxytocin when there is no contrain- dication for repeating the caesarean section [25,26]. However, in the current study there were no cases of previous caesarean section. This might eliminate grand multi- parity as a risk factor in the genesis of rup- ture of the uterus and in the increasing incidence of intrapartum complications as other studies indicate [12,13,27]. In the view of these findings, it can be concluded that cervical priming as well as labour induction in grand multiparous women is safe and effective when using ei- ther PGE2 tablets or Foley catheter, togeth- er with the use of oxytocin if needed for labour augmentation, but in the absence of any contraindications to induction. The use of PGE2 3 mg vaginal tablets is preferred to the intracervical Foley catheter. References 1. Steiner AL, Creasy RK. Methods of cervi- cal ripening. Clinical obstetrics and gy- necology, 1983, 26:37–46. 2. Garfield RE. Cellular and molecular bases for dystocia. Clinical obstetrics and gynecology, 1987, 30:3–18. 3. Garrett WJ. Prognostic signs of surgical induction of labour. Medical journal of Australia, 1960, 49:29. 4. Bishop EH. Pelvic scoring for elective in- duction. Obstetrics and gynecology, 1964, 24:266–8. 5. Anderson AM, Turnbull AC. Relationship between the length of gestation and cer- vical dilatation, uterine contractility and other factors during pregnancy. Ameri- can journal of obstetrics and gynecol- ogy, 1969, 105:1207–14. 6. Calder AA, Embrey MP, Tait T. Ripening of the cervix with extra-amniotic prostag- landin E 2 in viscous gel before induction of labour. British journal of obstetrics and gynaecology, 1977, 84:264–8. 7. Trofatter KF. Cervical ripening. Clinical obstetrics and gynecology, 1992, 35: 476–85. 8. Keirse MJ N. Prostaglandins in prein- duction cervical ripening. Meta-analysis of worldwide clinical experience. Jour- nal of reproductive medicine, 1993, 38 (1 suppl.):89–100. 9. Sciscione AC et al. A prospective ran- domized comparison of Foley catheter insertion versus intracervical prostag- landin E 2 gel for preinduction cervical ripening. American journal of obstetrics and gynecology, 1999, 180(1 Pt 1):55– 60. 10. Mwambingu FT, Al-Meshari AA, Akiel A. The problem of grandmultiparity in cur- rent obstetric practice. International jour- nal of gynaecology and obstetrics, 1988, 26(3):355–9. 11. Evaldson GR. The grandmultipara in modern obstetrics. Gynecologic and ob- stetric investigation, 1990, 30(4):217– 23. 12. Babinszki A et al. Perinatal outcome in grand and great-grand multiparity: ef- fects of parity on obstetric risk factors. American journal of obstetrics and gyne- cology, 1999, 181(3):669–74. 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM552 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 553 13. Goldman GA et al. The grandmultipara. European journal of obstetrics, gynecol- ogy, and reproductive biology, 1995, 61(2):105–9. 14. Abou el-Leil LA, Nasrat AA, Fayed HM. Prostaglandin E2 vaginal pessaries in the grandmultipara with an unripe cer- vix, a comparison of different parity groups. International journal of gynaeco- logy and obstetrics, 1993, 40(2):119–22. 15. Yamani TY, Rouzi AA. Induction of labor with vaginal prostaglandin-E2 in grand multiparous women. International jour- nal of gynaecology and obstetrics, 1998, 62(3):255–9. 16. Friedman EA. The labour curve. Clinics in perinatology, 1981, 8(1):15–25. 17. O’Driscoll K, Meagher D. Active manage- ment of labour. The Dublin experience, 2nd ed. London, Baillière Tindall, 1986. 18. Sobande AA, Al-Bar HM, Archibong EI. A comparison of spontaneous labor with induced vaginal tablets prostaglandin E2 in grand multiparae. Saudi medical journal, 2001, 22(8):698–701. 19. Yamani TY, Rouzi AA. Induction of labor with vaginal prostaglandin-E2 in grand multiparous women with one previous cesarean section. International journal of gynaecology and obstetrics, 1999, 65(3):251–3. 20. Lyrenas S, Clason I, Ulmsten U. In vivo controlled release of PGE2 from a vagi- nal insert (0.8 mm, 10 mg) during induc- tion of labour. British journal of obstetrics and gynaecology, 2001, 108(2):169–78. 21. Ramsey PS et al. Effect of vaginal pH on efficacy of the dinoprostone gel for cervi- cal ripening/labor induction. American journal of obstetrics and gynecology, 2002, 186(4):843–6. 22. Seeras RC. Induction of labor utilizing vaginal vs. intracervical prostaglandin E2. International journal of gynaecology and obstetrics, 1995, 48(2):163–7. 23. Nuutila M, Kajanoja P. Local administra- tion of prostaglandin E2 for cervical ripening and labor induction: the appro- priate route and dose. Acta obstetricia et gynecologica scandinavica, 1996, 75(2): 135–8. 24. St Onge RD, Connors GT. Preinduction cervical ripening: a comparison of intrac- ervical prostaglandin E2 gel versus the Foley catheter. American journal of ob- stetrics and gynecology, 1995, 172(2 Pt 1):687–90. 25. Abu-Heija AT, Ali AM. Induction of labor in grand multiparous women and previ- ous cesarean section: is it safe? Gyneco- logic and obstetric investigation, 2002, 53(2):121–4. 26. Ben-Aroya Z et al. Oxytocin use in grand- multiparous patients: safety and compli- cations. Journal of maternal–fetal medi- cine, 2001, 10(5):328–31. 27. Toohey JS et al. The “dangerous multi- para”: fact or fiction? American journal of obstetrics and gynecology, 1995, 172(2 Pt 1):683–6. 10 Comparison of prostaglandin E2.pmd 8/17/2005, 11:07 AM553 554 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Low-dose quinine for treatment of chloroquine-resistant falciparum malaria in Sudanese pregnant women I. Adam,1 M.H. Ibrahim,1 I.A. A/elbasit 2 and M.I. Elbashir 2 1New Halfa Hospital, New Halfa, Sudan. 2Faculty of Medicine, University of Khartoum, Khartoum, Sudan. Received: 14/07/03; accepted: 28/10/03 ABSTRACT Pregnant Sudanese women who presented at a hospital in eastern Sudan with chloroquine- resistant falciparum malaria were randomly allocated to one of two quinine regimens: low-dose (10 mg/kg 2 times/day) (18 patients) or standard (10 mg/kg 3 times/day) (24 patients). Treatment was for 7 days and follow-up for 28 days. Significantly fewer patients in the low-dose group reported vomiting and abdominal pain than the standard regimen group. Hypoglycaemia, preterm labour and recrudescence were slightly but not significantly higher in patients in the standard group than low-dose group. There were no significant differenc- es between the groups in the mean time from admission to remission of fever and parasite clearance. We tentatively advocate the use of quinine 2 times/day to reduce side-effects and improve compliance. Quinine à faible dose pour le traitement du paludisme à falciparum chloroquino-résistant chez des femmes enceintes soudanaises RÉSUMÉ Des femmes enceintes soudanaises atteintes de paludisme à falciparum chloroquino-résistant qui ont consulté dans un hôpital du Soudan oriental ont été réparties de manière aléatoire entre les deux schémas thérapeutiques de quinine suivants : faible dose, 10 mg/kg 2 fois/jour (18 patientes), ou standard, 10 mg/kg 3 fois/jour (24 patientes). Le traitement durait 7 jours et le suivi 28 jours. Un nombre significative- ment moindre de patientes dans le groupe du traitement à faible dose a signalé des vomissements et des douleurs abdominales par rapport aux patientes recevant le traitement standard. L’hypoglycémie, le travail prématuré et la recrudescence étaient légèrement, mais non significativement, plus élevés chez les pa- tientes du groupe du traitement standard que dans le groupe du traitement à faible dose. Il n’y avait aucune différence significative entre les deux groupes pour ce qui est du temps moyen entre l’admission, la rémis- sion de la fièvre et l’élimination du parasite. Nous recommandons provisoirement l’utilisation de la quinine deux fois par jour pour réduire les effets secondaires et améliorer l’observance du traitement. 11 Low-dose quinine.pmd 8/17/2005, 11:07 AM554 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 555 Introduction In Sudan, falciparum malaria has been re- ported to cause a number of adverse mater- nal and fetal outcomes, such as maternal anaemia, low birth weight, preterm labour and perinatal mortality [1–6]. It is the lead- ing cause of maternal mortality [5,6]. The treatment of falciparum infection remains the main means available to limit the impact of malaria on pregnancy [7]. The spread of chloroquine and sulfadox- ine–pyrimethamine resistance in Sudan [8– 10] necessitates the use of alternative drugs for the treatment of falciparum infections, such as quinine which is the second most prescribed antimalarial drug in Sudan [11]. Quinine is the treatment of choice for se- vere and chloroquine-resistant falciparum malaria. The standard dose of quinine is 10 mg/ kg, 3 times per day for 7 days [12]. This dose has been reduced effectively in chil- dren without impairing its efficacy, and with marked improvement in compliance with drug use [13]. The side-effects of qui- nine treatment that can lead to poor compli- ance are tinnitus, nausea, vomiting, diarrhoea, hypoglycaemia and acute hyper- sensitivity. Physicians in central and east- ern Sudan are now also giving quinine to pregnant women 2 times daily rather than 3 times, with apparently good outcomes. The present study was carried out to verify the efficacy and safety of this ongoing clinical practice. Methods We performed a prospective clinical trial in New Halfa Hospital in eastern Sudan from the period November 2002 to March 2003. After verbal consent, all pregnant women presenting with failure of chloroquine ther- apy for the treatment of falciparum malaria were successively enrolled to the study. Those with one or more manifestations of severe falciparum malaria were excluded [14]. For both groups, quinine (Laboratoires Renaudin, France) was given under strict supervision, first by intravenous infusion in 5% dextrose solution over 2–4 hours, and when the patient could tolerate it, therapy was continued orally in the form of tablets. For this phase of the study, patients were randomized into 2 treatment groups: qui- nine 10 mg/kg 2 times/day for 7 days (BD group) and quinine 10 mg/kg 3 times/day for 7 days (TDS group). A detailed record was made for each patient, including: personal data, medical and obstetric history, physical examination and use of antimalarials in the 3 weeks be- fore entry to the study. During the follow- up, all patients were asked daily about the expected side-effects of quinine (tinnitus, vomiting and abdominal pain). Axillary tem- perature was recorded every 8 hours until it fell to normal (37.5 °C), and then daily until day 7. All patients were kept in the hospital for at least 7 days and then followed up weekly in the antenatal clinic for 28 days. Laboratory investigations Using finger prick blood samples, thick and thin blood smears were prepared from each patient in both groups, stained with Giemsa (pH 7.0, diluted in phosphate-buffered sa- line) and counted against 200 white blood cells assuming that the number of cells is 6000/mm3 of blood. Thin blood films, fixed in methanol and Giemsa-stained were made when the parasite species was doubtful. The blood films were repeated every 8 hours until 2 consecutive films were nega- tive, then daily until day 7 and then on days 14, 21 and 28. Haemoglobin concentration and capillary blood glucose level were de- termined on presentation. Capillary blood 11 Low-dose quinine.pmd 8/17/2005, 11:07 AM555 556 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 glucose was estimated 2 hours after admin- istration of the drug. All patients were resident in the same area during the follow-up period. There- fore, the possibility of re-infection or re- crudescence could not be ruled out. Three spots of blood were taken on filter paper initially and later if parasites reappeared mi- croscopically during the follow-up period. Primers from 3 polymorphic Plasmodium falciparum antigens; merozoite surface protein-1 and 2 (MSP-1 and MSP-2) and glutamate-rich protein (GLURP) were used in polymerase chain reaction analysis (PCR) to differentiate between true recru- descence and re-infection as described pre- viously [15]. Evaluation criteria The efficacy and side-effects of the 2 regi- mens of quinine were assessed according to parasite clearance time, fever clearance time, occurrence of side-effects (tinnitus, vomiting, abdominal pain and hypoglycae- mia) and recrudescence. Parasite clearance time was defined as the time between start of treatment until 2 consecutive negative blood smears were obtained. Fever remis- sion time was defined as the time between admission and achievement of normal body temperature. Statistics Data was entered into the computer using SPSS/PC batching for data analysis. Simple frequency distribution cross-tabulation, de- scriptive statistics, mean, t-test and chi- squared with probability ≤ 0.05 was used for testing the hypotheses. Ethics Informed consent was obtained from the women who participated in the study. Ethi- cal clearance for the study was obtained from the Faculty Research Board, Faculty of Medicine, University of Khartoum and the National Ethical Committee at the Sudanese Federal Ministry of Health. Results Sixty-five pregnant women presented to New Halfa hospital with manifestations of chloroquine-resistant falciparum malaria during the study period. After confirmation of the infection, 14 patients were excluded from the study because they had severe manifestations of the disease. Initially, 25 patients were enrolled in the BD group, and 26 patients in the TDS group. However, 7/ 25 of the BD and 2/26 of the TDS group (P = 0.05) were excluded from the follow-up and evaluation as they chose to leave hospi- tal and continue the treatment at home after the first or the second dose of quinine. Table 1 shows the major characteristics of the remaining women on presentation. There were no significant differences be- tween the 2 groups in age, parity, weight, temperature, haemoglobin level, parasite count and random blood glucose level at presentation. A slightly higher proportion of women in the BD group presented with vomiting than the TDS group—4/18 (22.2%) versus 3/24 (12.5%)—but this was not statistical- ly significant. On day 1, vomiting was re- corded in more BD patients; 7/18 (38.9%) versus 4/24 (16.7%) but this was not sta- tistically significant (P > 0.05). On day 2, significantly fewer patients in the BD than the TDS suffered from vomiting; 29/18 (50.0%) versus 9/24 (79.2%) (P < 0.05). Tinnitus was reported slightly less fre- quently by patients who received quinine BD, than in those who received it TDS; 12/ 18 (66.7%) versus 19/24 (79.2%) (P > 0.05). Significantly fewer patients reported abdominal pain in the BD group than in the 11 Low-dose quinine.pmd 8/17/2005, 11:07 AM556 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 557 TDS group, 1/18 (5.6%) versus 7/24 (29.2%) (P = 0.05). Some of the TDS group developed hypoglycaemia; 4/24 (16.7%), but this was not recorded in any patient in the BD group (0/18); this differ- ence was not significant (P > 0.05). While none of the patients in the BD de- livered prematurely (< 37 weeks), 2/24 (8.3%) patients in the TDS group delivered prematurely at 29 and 30 weeks gestational age and their babies died immediately (P > 0.05). True recrudescence was confirmed by parasite genotyping on days 21 and 28 in 2/ 18 (11.1%) patients among the BD group. They were successfully treated with sulfadoxine–pyrimethamine. There was no detectable parasitaemia during follow-up in the TDS group, but this difference was not significant (P > 0.5). The mean (SD) parasite clearance time was lower in the BD than in the TDS group, but this did not reach the level of significance: 27.2 (12.9) versus 33.7 (12.7) hours. Discussion This is the first study of the efficacy of low-dose quinine in the treatment of chlo- roquine-resistant falciparum malaria during pregnancy in an area of high chloroquine resistance in eastern Sudan [8]. The study showed that significantly more patients chose to continue the quinine treatment at home in the BD than in the TDS group and this may reflect the sim- plicity of this regimen. Moreover, quinine side-effects were reported more frequently Table 1 Characteristics on admission and outcomes of treatment for pregnant women treated with quinine 10 mg/kg 2 times/day (BD) or 10 mg/kg 3 times/day (TDS) Variable BD regimen TDS regimen P-value (n = 18) (n = 24) Mean SD Mean SD On admission Age (years) 25.2 6.0 25.5 6.9 0.4 Parity (No.) 2.6 1.9 2.6 2.2 0.3 Weight (kg) 59.3 15.9 52.2 9.3 0.09 Gestational age (weeks) 26.1 9.9 26.1 8.9 0.4 Axillary temperature (°C) 38.1 0.9 37.8 1.0 0.8 Haemoglobin level (g/L) 89.0 5.6 86.0 9.0 0.08 Parasite count (rings/µL) 5837 8361 4207 12325 0.6 Random blood sugar level (mg/dL) 117.6 30.1 106.5 25.7 0.9 Treatment outcomes Fever remission timea (hours) 25.5 12.1 21.0 16.9 0.13 Parasite clearance timeb (hours) 27.7 12.9 33.7 12.7 0.63 aFever remission time was defined as the time between admission and achievement of normal body temperature (37.5 °C). bTime from admission and start of treatment until 2 consecutive negative blood smears were obtained. SD = standard deviation. 11 Low-dose quinine.pmd 8/17/2005, 11:07 AM557 558 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 in the TDS group than in the BD group; sig- nificantly more patients suffered from vomiting and abdominal pain in the TDS group than in the BD group. Although these side-effects were more frequent in the TDS than in the BD group, they might be considered a subjective assessment of these 2 regimens of quinine. Nevertheless, even objective side-effects were more fre- quent in the TDS than in the BD group. For example, hypoglycaemia was seen in more of the patients in the TDS group than the BD group (16.7% versus 0%) although the different not significant. However, hy- poglycaemia was reported in around 50% of pregnant women at one stage or another of severe falciparum malaria treated with quinine 3 times/day for 7 days [16], there- fore, hypoglycaemia may be dose related. In a recent study, a low dose of quinine was used in children in a community-based study but hypoglycaemia was not assessed [13]. Two patients in the TDS group deliv- ered prematurely and their babies died im- mediately, but there was no premature delivery in the BD group. In a previous study where we were testing the efficacy of quinine 3 times/day in the treatment of severe falciparum malaria during pregnan- cy in central Sudan, 3/33 (9%) patients de- livered prematurely, and only 1 patient delivered during quinine therapy [4]. This comparison should be viewed with caution because in the previous study we used qui- nine for severe illness, while such patients were excluded in the present study. How- ever, no preterm labour was reported by McGready et al. in 1998 [17]. Malaria can cause abortion and preterm labour as well, and in central Sudan it was found to be the leading cause of low birth weight as a result of preterm labour [3]. However, the oxyto- cic effect of quinine on the pregnant uterus cannot be excluded totally. Previously, qui- nine was used as a labour-inducing agent but in high doses [18]. The parasite clearance time was shorter but not significantly so in the BD group than in the TDS group. However, 2 patients (11.1%) in the BD group showed true para- site recrudescence during the follow-up, compared with none of the patient in the TDS group. This difference was not statis- tically significant and it should be viewed with caution as it might be due to quinine resistance in this area of Sudan. Previously, we have observed quinine resistance by in vivo testing and it has been confirmed by in vitro testing in a nearby area [8,19]. We have previously shown 6% quinine resis- tance or re-infection during pregnancy in central Sudan [4]. In conclusion, quinine in a low-dose regimen of 2 times/day causes fewer sub- jective side-effects and therefore is likely to improve patient compliance than the stan- dard 3 times/day regimen. It also has a lower risk of hypoglycaemia (which is im- portant in the outpatient setting) and of pre- term labour. Its disadvantage is the higher probability of recrudescence, which is im- portant in the light of emerging resistance in Africa, where the drug is still the first line for the treatment of severe falciparum ma- laria. However, there is an urgent need to test and apply other alternative drugs, espe- cially sulfadoxine–pyrimethamine combi- nation, which is free of side-effects such as hypoglycaemia and preterm labour. References 1. Ahmed SM et al. Malaria parasitemia during delivery. Saudi medical journal, 2001, 23:684–8. 2. Taha TE et al. Levels and determinants of perinatal mortality in Central Sudan. In- 11 Low-dose quinine.pmd 8/17/2005, 11:07 AM558 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 559 ternational journal of gynaecology and obstetrics, 1994, 45:109–15. 3. Taha TE et al. Malaria and low birth weight in central Sudan. American jour- nal of epidemiology, 1993, 138:318–25. 4. Adam et al. Quinine therapy in severe Plasmodium falciparum malaria during pregnancy in Sudan. Eastern Medi- terranean health journal, 2004, 10(1/2): 159–66. 5. Maternal mortality in Sudan. Inter-re- gional meeting on the prevention of maternal mortality, Geneva 11–15 No- vember, 1985. Geneva, World Health Organization, 1985 (Unpublished docu- ment FHE/PMM/85.95). 6. Dafallah SE, El-Agib FH, Bushra GO. Maternal mortality in a teaching hospital in Sudan. Saudi medical journal, 2003, 24:369–73. 7. Dolan G et al. Bed nets for the prevention of malaria and anaemia in pregnancy. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1993; 87:620–6. 8. Adam I et al. In the Sudan: chloroquine resistance is worsening and quinine re- sistance is emerging. Sudan medical journal, 2001, 39:1–5. 9. Elkheir HK et al. Efficacy of sulphadoxine and pyrimethamine, doxycycline and their combination in the treatment of chloroquine resistant falciparum ma- laria. Saudi medical journal, 2001, 228: 690–3. 10. Adam I et al. Efficacy of sulfadoxine-py- rimethamine in the treatment of uncom- plicated Plasmodium falciparum malaria in a small sample of Sudanese children. Eastern Mediterranean health journal, 2004, 10(3):309–14. 11. Yousif MA, Adeel AA. Antimalarial pre- scribing pattern in Gezira State: precepts and practice. Eastern Mediterranean health journal, 2000, 6:939–47. 12. World Health Organization, Division of Control of Tropical Diseases. Severe and complicated malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1990, 84(suppl.2):1–65. 13. Kofoed PE et al. Treatment of Plasmo- dium falciparum malaria with quinine in Guinea-Bissau: one daily dose is suffi- cient. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2002, 96:185–8. 14. World Health Organization, Comm- unicable Diseases Cluster. Severe falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2000, 94(suppl.1):S1–90. 15. Brockman A et al. Application of genetics marker to the identification of recrudes- cent P. falciparum infection on the North- Western border of Thailand. American journal of tropical medicine and hy- giene, 1999, 60:14–21. 16. Looareesuwan S et al. Quinine and se- vere falciparum malaria in late preg- nancy. Lancet, 1985, 2:4–8. 17. 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, 92:643–53. 18. Mukherjee S, Bhose LN. Induction of labour and abortion with quinine infu- sion in intrauterine fetal deaths. Ameri- can journal of obstetrics and gyneco- logy, 1968, 101:853–4. 19. Khalil IF. Sensitivity of chloroquine resis- tant Plasmodium falciparum to fansimef, mefloquine and halofantrine in Gadaref, eastern Sudan [MSc thesis]. Khartoum, Sudan, University of Khartoum, 1995. 11 Low-dose quinine.pmd 8/17/2005, 11:07 AM559 560 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Quinine for chloroquine-resistant falciparum malaria in pregnant Sudanese women in the first trimester I. Adam1, H.M. Idris1 and M.I. Elbashir 2 1New Halfa Hospital, New Halfa, Sudan. 2Faculty of Medicine, University of Khartoum, Khartoum, Sudan. Received: 14/07/03; accepted: 28/10/03 ABSTRACT A prospective clinical study in eastern Sudan described the efficacy and toxicity of quinine in early pregnancy in mothers with chloroquine-resistant falciparum malaria. Twenty-six pregnant Sudanese women in their first trimester (mean gestational age 8.5 weeks) were given quinine 10 mg/kg 3 times per day for 7 days and followed up every 2 weeks until delivery. One patient aborted (3.8%) and 2 patients (7.7%) experienced threatened abortion but delivered term babies. Recrudescence or re-infection was observed on day 21 in 1 patient. One baby died aged 6 months. There were no detectable congenital malformations, no auditory or visual defects or any other neurological deficits in the remaining infants at birth or 1 year later. Quinine may be safe in the first trimester of pregnancy. La quinine pour le paludisme à falciparum chloroquino-résistant chez des femmes enceintes soudanaises durant le premier trimestre de la grossesse RÉSUMÉ Une étude clinique prospective au Soudan oriental a décrit l’efficacité et la toxicité de la quinine au début de la grossesse chez des mères atteintes de paludisme à falciparum résistant à la chloroquine. On a administré de la quinine à raison de 10 mg/kg trois fois par jour pendant 7 jours à vingt-six femmes enceintes soudanaises durant le premier trimestre de la grossesse (âge gestationnel moyen de 8,5 semaines) et celles-ci ont été suivies toutes les 2 semaines jusqu’à l’accouchement. Une patiente a avorté (3,8 %) et 2 patientes (7,7 %) ont débuté une menace d’avortement mais ont mis au monde leur bébé à terme. Une recrudescence ou une réinfection a été observée au 21e jour chez une patiente. Un bébé est décédé à l’âge de six mois. Il n’y avait aucune malformation congénitale décelable, aucun handicap visuel ou auditif ou autre déficit neurologique chez les autres enfants à la naissance ou un an plus tard. La quinine peut être con- sidérée comme sans danger durant le premier trimestre de la grossesse. 12 Quinine for chloroquine.pmd 8/17/2005, 11:07 AM560 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 561 Introduction Malaria is a major health problem in tropical countries especially sub-Saharan Africa, where about 90% of clinical cases occur. There are nearly 500 million clinical cases of malaria worldwide each year and 1.1 to 2.7 million people die annually [1]. In areas where malaria transmission is seasonal, as in eastern Sudan, there is low transmission and hence low immunity. In Sudan, preg- nant women are particularly vulnerable to falciparum malaria; the disease has adverse effects on pregnancy, affecting all parities [2,3], and all manifestations are seen in- cluding cerebral malaria and haemoglobin- uria [4]. In central Sudan, falciparum malaria was found to be the leading cause of low birth weight, maternal anaemia and maternal and perinatal mortality [5–7]. Plasmodium falciparum isolates from eastern Sudan show the highest levels of antimalarial drug resistance in the country with a rate of chloroquine resistance among isolates of 76% [8,9]. This situation necessitates the use of alternative antima- larial drugs for the treatment of falciparum malaria. Quinine the drug of choice for se- vere falciparum malaria in Sudan. Worldwide, very few studies have been made on the safety of quinine therapy dur- ing early pregnancy [10,11]. Quinine has long been believed to induce abortion and labour [12]; however, malaria itself can also lead to abortion, while quinine, by low- ering fever, may in fact be helpful [13]. This is important as the treatment of chloroquine-resistant falciparum malaria in pregnancy is complicated by the poor safe- ty of other drugs, as both artemether and sulphadoxine-pyrimethamine are reported to cause fetal resorption when given in ear- ly pregnancy [14,15]. In the light of the emerging multi-drug resistance in malaria-endemic areas, we de- scribe here the efficacy and toxic effects of quinine on a small group of women with chloroquine-resistant malaria in early preg- nancy and its outcome on the infants at 1- year follow-up. Methods Patients The study was carried in New Halfa Hospi- tal, eastern Sudan, between October 2000 and November 2002. The study group were all pregnant women in their first tri- mester of pregnancy with symptoms of falciparum malaria and failure to respond to chloroquine. Patients presenting with vagi- nal bleeding were excluded. The women were asked specifically about symptoms suggestive of malaria (fever, headache, sweating, joint pain and vomiting). Physical examination was performed and all infor- mation was kept in case report format. Investigations Peripheral capillary blood smears were pre- pared, stained with Giemsa and examined under oil immersion for parasites. Parasites and leukocytes were counted in the same fields until 200 leukocytes were counted; parasites densities were estimated using an assumed leukocyte count of 6000 leuko- cytes/µL blood. Baseline investigations (haemoglobin, urea, creatinine, albumin and bilirubin levels) were also performed. Ultrasound was performed initially to confirm the pregnancy, gestational age and viability of the fetus, and repeated every 4– 6 weeks for placental localization and to exclude congenital malformations. Treatment and follow-up The women were treated with quinine (Laboratoires Renaudin, France) at a dose of 30 mg salt/kg/day for 7 days. It was giv- en at first by intravenous infusion in 5% dextrose solution over 2–4 hours, and 12 Quinine for chloroquine.pmd 8/17/2005, 11:07 AM561 562 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 when the patient could tolerate it, therapy was continued orally in the form of tablets. The patients were discharged after completing the full dose of quinine on day 8, then seen on days 14, 21, 28, and every 2 weeks in the antenatal clinic until deliv- ery. In the clinic they were examined by the obstetrician for weight, pallor, temperature, pulse, blood pressure, fundal level, fetal heart sounds and oedema. At every visit the patient’s haemoglobin was estimated and blood films for malaria were taken. The obstetrician supervised all hospital deliver- ies and kept close links with those who de- cided to deliver at home. A paediatrician examined all the infants at birth for congenital malformations and made all necessary anthropometric mea- surements. Infants, both hospital- and home-delivered, were followed up to 1 year of age by the same paediatrician. Definitions Chloroquine-resistance was defined as the detection of P. falciparum malaria parasites in peripheral blood after a complete course of chloroquine. Abortion was defined as expulsion of a dead fetus before 28 weeks of gestation. Premature labour was delivery after 28 weeks and before 37 weeks of gestation. Perinatal death was death of the baby from 28 weeks in utero until the age of 1 week post-delivery. Analysis Data were analysed using SPSS/PC. Simple frequency distributions, percentages, means and standard deviations were calcu- lated. Ethics The study received ethical clearance from the Faculty Research Board at the Faculty of Medicine, University of Khartoum and the Federal Ministry of Health. Written con- sent for participation in the study was ob- tained from the patients and their husbands. Results Out of 28 patients, 26 pregnant Sudanese women in their first trimester were given quinine to treat falciparum malaria after failure of chloroquine treatment. Two pa- tients were excluded because they present- ed with vaginal bleeding. Fever, nausea, vomiting, headache, giddiness and insom- nia were the major presenting symptoms. Table 1 shows the main clinical and bio- chemical data at the time of presentation. During quinine treatment, 1 patient (2.8%) developed vaginal bleeding and ab- dominal pain. After the third dose of qui- nine, the cervix was found to be open, implying inevitable abortion, and evacua- tion was carried out. Two more patients (7.7%) developed slight vaginal bleeding, i.e. threatened abortion, during quinine Table 1 Major clinical and laboratory findings on admission in 26 pregnant women with chloroquine-resistant malaria Parameter Mean SD Age (years) 26.2 3.5 Parity (No.) 2.8 2.6 Gestational age (weeks) 8.5 0.9 Weight (kg) 65.8 4.6 Temperature (°C) 38.2 0.6 Haemoglobin (g/dL) 9.2 1.3 Parasite count (rings/µL)a 5856 1652 Blood glucose (mg/dL) 123.6 12.9 Blood urea (mg/dL) 27.3 3.6 Serum bilirubin (mg/dL) 1.09 0.12 aGeometric mean. SD = standard deviation. 12 Quinine for chloroquine.pmd 8/17/2005, 11:07 AM562 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 563 therapy on day 2 and 3 respectively, but their pregnancies continued until the deliv- ery of term babies. All patients had negative blood films on day 7. However, 1 patient presented on day 21 with recurrence of malaria symptoms and the blood film was positive for falci- parum malaria parasites. She was readmit- ted at the 10th week of gestation and given artemether intramuscularly, 80 mg initially followed by 80 mg after 12 hours and then daily for 4 days. She was discharged after completing the treatment with full recovery and was followed up closely until delivery. Just under half the patients (12/26, 46.2%) delivered in the hospital, the rest (14/26, 53.8%) delivered at home. The mean (SD) birth weight of babies whose mothers delivered at hospital was 2.9 (0.4) kg. One of the babies died at home at the age of 6 months due to unexplained febrile illness. There were no detectable congenital malformations and no auditory, visual or other neurological deficits in the remaining infants at birth or 1 year later. Discussion Pregnant women are more susceptible to malaria infection which can lead to many adverse effects on the pregnancy such as abortion, premature labour and maternal anaemia [3]. The World Health Organiza- tion recommends that pregnant women with demonstrable malaria illness should receive prompt treatment with effective and safe antimalarial drugs [16]. This situa- tion is limited by the safety profile of anti- malarial drugs themselves [14,15] and the spread of chloroquine-resistant strains of P. falciparum. In this study, 1 patient showed reap- pearance of the parasite on day 21, which might due to re-infection or parasite resis- tance to quinine therapy. In Sudan, resis- tance to chloroquine has been recorded in almost every region of the country and even quinine resistance has been shown by in vivo and in vitro tests in the area of the study and in a nearby area [8,17]. We have previously observed that quinine failed to treat 2/33 (6%) of pregnant women in cen- tral Sudan [4]. This phenomenon warrants more investigations since quinine is still the first line of treatment for severe falciparum malaria in Africa. One patient aborted and 2 patients threatened to abort but their pregnancies continued until term. This agrees with McGready and colleagues’ report of qui- nine in early pregnancy [11], where the rate of abortion was not different from the pop- ulation in our community. In a recent com- munity-based study of risk factors for anaemia in our area, around 50% of women gave a history of previous abortion [18]. We have previously observed that no pa- tient aborted among 33 patients treated with quinine for severe falciparum malaria in central Sudan [4]. However, in that study 3 patients delivered prematurely, 1 of them during the quinine therapy. In another 2 studies there was no effect of quinine on the rate of abortion or preterm labour [19,20]. In the latter studies the patients presented later in pregnancy (the gestation- al age was > 20 weeks) and this might ex- plain the rate of abortion (1/26, 3.8%) in the present study where quinine was used in early pregnancy. There are difficulties in interpreting the findings of abortion, be- cause malaria itself is a known cause of abortion especially during epidemics [21]. Certainly in our study, 2 out of 28 malaria patients presented with vaginal bleeding and their pregnancies aborted before qui- nine was started (these women were ex- cluded from the study). Quinine has long ago been reported to induce abortion and 12 Quinine for chloroquine.pmd 8/17/2005, 11:07 AM563 564 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 labour [12] and we believe that this has been influential in limiting the use of quinine during pregnancy. The situation remained so until in 1985 it was declared that malaria and its fever were responsible for abortion, while quinine, by lowering temperature, may in fact decrease the amplitude of uter- ine contractions as confirmed by fetal monitoring [13]. In our study, we found no hearing or visual defects and no congenital or devel- opmental abnormalities in the infants after 1 year. This confirms another recent study [11]. However, deafness and hypoplasia of the optic nerve have been described in chil- dren born after unsuccessful attempts to induce abortion in women taking quinine overdoses [22]. These were retrospective reports and the exact numbers of patients were not known. In conclusion, our study and that of McGready and colleagues [11] suggests that quinine could be used safely as a cost- effective therapy during the first trimester of pregnancy. Acknowledgements The authors thank the women who partici- pated in the study, Mrs Asma Abd Elwakeil, Mr Abdalla Ahmed Hafazalla for technical assistance, and the staff of New Halfa Hos- pital for support and cooperation. References 1. WHO expert committee on malaria: twen- tieth report. Geneva, World Health Orga- nization, 2000 (WHO Technical Report Series No. 892). 2. Brabin BJ et al. A study of the conse- quences of malaria infection in pregnant women and their infants Parassitologia, 1993, 35(suppl.):9–11. 3. Nosten F et al. Malaria during pregnancy in an area of unstable endemicity. Trans- actions of the Royal Society of Tropical Medicine and Hygiene, 1991, 85:424–9. 4. Adam I al. Quinine therapy in severe Plasmodium falciparum malaria during pregnancy in Sudan. Eastern Mediterra- nean health journal, 2004, 10(1/2):159– 66. 5. Taha Tel T, Gray RH, Mohamedani AA. Malaria and low birth weight in central Sudan. American journal of epidemiol- ogy, 1993, 138:318–25. 6. Ahmed SM et al. Malaria parasitemia during delivery. Saudi medical journal. 2001, 23:684–8. 7. Taha TE et al. Levels and determinants of perinatal mortality in central Sudan. In- ternational journal of gyneacology and obstetrics, 1994, 45:109–15. 8. Adam I et al. In the Sudan: chloroquine resistance is worsening and quinine re- sistance is emerging. Sudan medical journal, 2001, 39:5–11. 9. Babiker HA et al. Genetic diversity of Plasmodium falciparum in a village in Eastern Sudan. 2. Drug resistance, mo- lecular karyotypes and the mdr1 geno- type of recent isolates. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1991, 85:578–83. 10. Heinonen OP, Slone D, Shapiro S. Birth defects and drugs in pregnancy. Little- ton, Massachusetts, Publishing Sci- ences Group, 1977. 11. McGready R et al. The effects of quinine and chloroquine antimalarial treatment in the first trimester of pregnancy. Trans- actions of the Royal Society of Tropical Medicine and Hygiene, 2002, 96:180–4. 12 Quinine for chloroquine.pmd 8/17/2005, 11:07 AM564 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 565 12. Mukherjee S, Bhose LN. Induction of labour and abortion with quinine infu- sion in intrauterine fetal deaths. Ameri- can journal of obstetrics and gyneco- logy, 1968, 101:853–4. 13. Looareesuwan S et al. Quinine and se- vere falciparum malaria in late preg- nancy. Lancet, 1985, 2:4–8. 14. Briggs GC, Freeman RK, Yaffe SJ, eds. Drugs in pregnancy and lactation, 2nd ed. Baltimore, William and Wilkins, 1986: 537–53. 15. Uche-Nwachi EO, Caxton-Martins AE. Sulfadoxine–pyrimethamine embryopa- thy in Wistar rats. Kaibogaku zasshi, 1998, 73:135–9. 16. WHO expert committee on malaria: eigh- teenth report. Geneva, World Health Or- ganization, 1986:57–78 (WHO Technical Report Series, No. 735). 17. Khalil IF. Sensitivity of chloroquine resis- tant Plasmodium falciparum to fansimef, mefloquine and halofantrine in Gadaref, eastern Sudan [MSc thesis]. Khartoum, Sudan, University of Khartoum, 1995. 18. Adam I et al. Anemia in pregnant Suda- nese women: community based study. Saudi medical journal, 2004, 25:447–8. 19. McGready R et al. Quinine and meflo- quine in the treatment of multidrug-re- sistant Plasmodium falciparum malaria in pregnancy. Annals of tropical medi- cine and parasitology, 1998, 92:643–53. 20. 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, 94:689–93. 21. Menon R. Pregnancy and malaria. Medi- cal journal of Malaysia, 1972, 27:115–9. 22. Studies on the toxicity of qinghaosu and its derivatives. China Cooperative Re- search Group on qinghaosu and its de- rivatives as antimalarials. Journal of traditional Chinese medicine, 1982, 2: 31–8. 12 Quinine for chloroquine.pmd 8/17/2005, 11:07 AM565 566 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Impact of the national protocol for malaria treatment on prescribing patterns in Gezira state, Sudan M.E. Ahmed1 and M.A. Yousif 2 1Department of Community Medicine, Faculty of Medicine; 2Faculty of Pharmacy, University of Gezira, Gezira, Sudan. Received: 08/08/02; accepted: 18/08/03 ABSTRACT A cross-sectional study to assess the impact of the national protocol for malaria treatment was conducted in a town in Gezira state, central Sudan, in 2001. Most of the 165 doctors and medical assistants interviewed (80.0%) had not been trained in the protocol and many (57.5%) were still using their own protocols. Analysis of 410 prescriptions showed chloroquine was the most common antimalarial drug used (69.5% of prescriptions). Compared with a study before implementation of the protocol, more prescriptions met the protocol standards for correct chloroquine dose, whereas regimens for administration of intrave- nous quinine were still inadequate. The study showed a lack of continuous supervision, training and follow- up in the protocol guidelines and negative attitudes of hospital specialists towards the protocol. Impact du protocole national de traitement du paludisme sur les modes de prescription dans l’État de Gezira (Soudan) RÉSUMÉ Une étude transversale a été réalisée dans une ville de l’État de Gezira (Soudan central) en 2001 afin d’évaluer l’impact du protocole national pour le traitement du paludisme. La plupart des 165 médecins et auxiliaires médicaux interrogés (80,0 %) n’avaient pas été formés à l’utilisation du protocole et beaucoup (57,5 %) utilisaient toujours leur propre protocole. L’analyse de 410 ordonnances a montré que la chloroquine était l’antipaludique le plus couramment utilisé (69,5 % des ordonnances). Par rapport à une étude effectuée avant l’application du protocole, un plus grand nombre d’ordonnances se conformaient aux normes du protocole concernant la dose correcte de chloroquine, alors que les schémas d’administration de quinine par voie intraveineuse demeuraient inappropriés. L’étude a montré un manque de supervision continue, de formation et de suivi pour les directives du protocole et des attitudes négatives des spécialistes hospitaliers vis-à-vis du protocole. 13 Impact of the national.pmd 8/17/2005, 11:07 AM566 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 567 Introduction Sudan has contributed to and endorsed the World Health Organization (WHO) global strategy for malaria control and ‘Roll back malaria’. It has been observed that, unless diagnosed and treated promptly, patients with malaria deteriorate rapidly and the out- come is grave; hence plans to formulate a national protocol for the treatment of ma- laria were a priority in Sudan [1]. The na- tional protocol is a set of recommendations and regulations concerning antimalarial drugs and their utilization in a country. It defines the national malaria control policy and forms part of the national drug policy, which expresses and prioritizes the medium- to long-term goals set by the gov- ernment for the pharmaceutical sector. The national drug policy is both a commitment to a goal and a guide for action, identifying the main strategies for attaining them, and providing a framework within which the activities of the pharmaceutical sector can be coordinated [2]. The idea of formulating an antimalarial drug policy was encouraged in Sudan through a coordinated effort between the Directorate of Malaria, the Federal Ministry of Health and WHO. A preliminary work- shop of consultants was held in the Faculty of Medicine, University of Gezira, in April 1998, followed by a national committee in June 1998, which finalized the policy under evaluation [1]. A study of antimalarial drug prescribing patterns was carried out in Wad Medani town in Gezira state before the implementa- tion of the protocol in 1999 [3]. The study showed poor standards of prescribing of antimalarial drugs, in terms of over- prescribing of chloroquine tablets and in- correct regimens for intravenous adminis- tration of quinine. The same study revealed that most of the medical practitioners tend- ed to follow their own regimens to treat malaria infection. The present study is the first attempt to measure the influence of the national proto- col on prescribing patterns in the same area. It is important to make an evaluation of knowledge, attitudes and practices of health providers towards the national pro- tocol, so that unintended consequences or constraints can be identified and successful interventions and strategies reinforced. Methods This cross-sectional study was carried out in Wad Medani, a town situated in Gezira state in central Sudan. The study was con- ducted in October, the month in which a normal rise of malaria infection is annually observed. The research process consisted of 3 steps. The first step was an interview with the state director of the malaria control pro- gramme. In the second step, we contacted all 181 doctors and medical assistants (from both public and private sectors) who were providing medical services in the town; 165 were available for interview. Questions were asked to assess their knowledge, attitudes and practices relating to the national protocol. In the third step, a sample of 6 pharmacies was selected using stratified random sampling from 3 strata. Over 3 consecutive days, 410 prescriptions from both general practitioners and hospital outpatients departments were collected and a pre-tested checklist was filled in to assess their conformity to the protocol standards of drug dosage, frequency of administra- tion, etc. Standard treatment regimens at that time according to the Malaria Administra- tion Department of the Federal Ministry of Health were as follows. 13 Impact of the national.pmd 8/17/2005, 11:07 AM567 568 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 • First line treament for simple malaria: chloroquine oral 25 mg/kg over 3 days. For chloroquine injection of adults: 1 ampoule (200 mg base) followed by 1 ampoule after 6 hours then 2 times per day (12 hours apart) for a total of 7 in- jections. For chloroquine injection of children: 2.5–3.5 mg/kg. • Second line treatment: pyrimethamine- sulfadoxine, 25/500 mg. For adults: 3 tablets at once. For children: according to weight. • Third line treatment: mefloquine or qui- nine. The data were tabulated and analysed using SPSS. Results Interview with state director The interview with the state director of the malaria control programme revealed that 6 training courses had been conducted for 145 doctors and medical assistants over a 2-year period. The 3-day training sessions, which were run at 2 different centres, cov- ered the epidemiology, clinical picture and treatment of malaria according to the na- tional protocol guidelines. The protocol guidelines had been distributed to all health workers after training, but neither continu- ous supervision nor surveys to assess the implementation of the protocol had been carried out by the malaria control pro- gramme. Interviews with health workers Overall, the majority of the 165 health workers interviewed (132, 80.0%) report- ed that they had not received training about the national protocol guidelines. None of the 58 house officers or 25 consultants had been trained. No training had been received by 88.8% of hospital registrars, 64.0% of medical assistants or 52.0% of general practitioners. A significant difference was observed in the training status among dif- ferent categories of health worker (Table 1). With regard to the level of awareness of the protocol, around two-thirds of the health workers (107, 64.8%) were aware of the guidelines. Hospital house officers had the lowest level of awareness (37.9%). The difference was significant across dif- ferent categories of health worker (Table 1). Regarding the availability of the guide- lines, only 5 health workers (3.0%) report- ed having it in their clinic at the time of the study. Adherence to the protocol was checked by asking the health workers what regi- mens they used for the treatment of simple malaria and complicated malaria compared to the standard regimens recommended by the Malaria Administration at the Ministry of Health. Despite the relatively high rate of awareness, just over half of the interviewed health workers (95, 57.5%) showed no ad- herence to the protocol, with a significant difference between the different categories (Table 1). When asked about reasons for not adhering to the protocol guidelines, one-third of health workers mentioned lack of awareness of them (Table 2). Among the senior hospital staff, however, it was due to negative attitudes towards the protocol, since 72.0% of consultants and 100% of registrars claimed that the protocol was in- effective. Some health workers (11.5%) said that they did not adhere to the guide- lines in order to satisfy patients. When evaluating the impact of the train- ing on the adherence to the protocol guide- lines a significant difference was observed. The 33 trained staff were more likely to adhere to the protocol (60.6% adhering) than the 132 untrained staff (only 37.9% adhering) (χ2 = 4.691, P < 0.05). 13 Impact of the national.pmd 8/17/2005, 11:07 AM568 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 569 Table 1 Training in, awareness of and adherence to the guidelines of the Sudan national protocol of malaria treatment according to type of health worker Variable Medical GPs House Registrars Consultants Total assistants (n = 48) officers (n = 9) (n = 25) (n = 165) (n = 25) (n = 58) No. % No. % No. % No. % No. % No. % Trained about guidelines 9 36.0 23 48.0 0 0 1 11.2 0 0 33 20.0 Not trained about guidelines 16 64.0 25 52.0 58 100.0 8 88.8 25 100.0 132 80.0 χ2 = 48.58, P < 0.01 Aware of protocol 18 72.0 36 75.0 22 37.9 9 100.0 22 88.0 107 64.8 Not aware of protocol 7 28.0 12 25.0 36 62.1 0 0 3 12.0 58 35.2 χ2 = 31.92, P < 0.01 Adhering to protocol 10 40.0 30 62.5 19 32.8 4 44.4 7 28.0 70 42.4 Not adhering to protocol 15 60.0 18 37.5 39 67.2 5 55.6 18 72.0 95 57.5 χ2 = 12.34, P = 0.015 n = total number of respondents. GPs = general practitioners. Table 2 Reasons given by the health workers for not adhering to the guidelines of the national protocol of malaria treatment (those adhering gave hypothetical answers) Variable Medical GPs House Registrars Consultants Total assistants (n = 48) officers (n = 9) (n = 25) (n = 165) (n = 25) (n = 58) No. % No. % No. % No. % No. % No. % Lack of awareness of protocol 10 40.0 16 33.3 30 51.7 0 0 0 0 56 33.9 Believe protocol ineffective 5 20.0 24 50.0 19 32.8 9 100.0 18 72.0 75 45.5 Better patient satisfaction 4 16.0 8 16.7 7 12.1 0 0 0 0 19 11.5 Others 6 24.0 0 0 2 3.4 0 0 7 28.0 15 9.1 n = total number of respondents. GPs = general practitioners. 13 Impact of the national.pmd 8/17/2005, 11:07 AM569 570 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Prescription analysis Out of 410 prescriptions, 128 were for an- timalarial drugs (31.2%). Most (91) were written by general practitioners, 11 by medical assistants, and 26 by consultants. Overall, 102 (79.7%) of antimalarial drug prescriptions were judged to be adequate in terms of correct dosage according to the protocol. No significant difference was observed between different specialties regarding correct dosage; 80.2% of pre- scriptions from GPs followed the protocol, 72.2% from medical assistants and 80.8% from consultants. Chloroquine was the most commonly prescribed antimalarial drug (89 prescrip- tions, 69.5%), followed by quinine (22, 17.2%), pyrimethamine-sulfadoxine (13, 10.2%), artemether (2, 1.6%), halofantrine (1, 0.8%) and primaquine (1, 0.8%). The proportion of antimalarial drug pre- scriptions that correctly complied with the protocol recommendations showed that in- tramuscular quinine was the formulation most often prescribed incorrectly (4 out of 9 prescriptions, 30.8%). One-fifth of pre- scriptions (5 out of 25, 19.2%) for chloro- quine oral tablets were incorrect, generally for more than the recommended 10 tablets. Conversely, many prescriptions for intra- venous chloroquine prescribed too few ampoules (15 out of 56 prescriptions, 26.8%), as many doctors were still follow- ing the former recommendations for 5 am- poules instead of 7 ampoules in the 1999 protocol guidelines. The poor compliance with protocol guidelines for quinine oral tablets (2 out 8 prescriptions incorrect, 25.0%) was mostly due to dispensing too few tablets. Discussion The implementation of a national drug poli- cy faces several constraints, such as the logistics of distribution, the large number and variety of people and institutions in- volved and the rising cost of treatment [4]. Appropriate planning is therefore essential for successful implementation. In this study, some constraints and problems were highlighted which reflect on the implemen- tation of the protocol for national malaria control in Sudan. The study has revealed the impact of training on adherence to the protocol guide- lines, which highlights the importance of continuous in-service training. Although the house officers constituted the majority of health providers, they were not targeted in the training process. This was obvious from the level of non-adherence to the pro- tocol. It might be necessary to introduce the protocol in the pre-service training. The great majority of health workers did not have the protocol guidelines in their clinic at the time of the study, reflecting a lack of continuous supervision and follow- up of the protocol. Lack of awareness was an important reason for the non-adherence in the major- ity of the health workers and this can be mostly attributed to the rapid turnover of health workers. Patient satisfaction was another reason for non-adherence to the protocol by some categories of health worker, suggesting that education of the community about the malaria treatment protocol would also be of value. Although awareness of the protocol was high among consultants, they were not adhering well to the protocol. Poor atti- tudes of senior staff are a concern as they may be an influence on junior staff, espe- cially house officers being trained. The consultants justified their non-compliance in the belief that the protocol was not ef- fective due to the appearance of chloro- quine-resistant malaria in the area. The resistance to chloroquine has been studied 13 Impact of the national.pmd 8/17/2005, 11:07 AM570 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 571 in Sudan by Abdel-Hamid et al., who con- cluded that chloroquine-resistant malaria was more than 25% in 4 sentinel posts [5]. Another recent study in the same area in the year 2000 revealed that 38% of Plasmodi- um falciparum were resistant to chloro- quine [S.A. Faragalla, unpublished report, 2002]. Thus, monitoring and updating of the protocol is highly necessary. The study revealed that the majority of prescriptions (70.0%) were written by general practitioners, thus highlighting the importance of targeting them in future in- terventions. This is the routine practice in the Sudan malaria control programme, ac- cording to the director of the programme; however the continuous turnover of gener- al practitioners has had a negative impact on the effectiveness of training. The rate of prescriptions for antimalari- al drugs as a proportion of all prescriptions in this study (31.2%) was similar to the na- tional figure (30.0%) [6]. Chloroquine was the most commonly prescribed antimalarial drug (69.5%), as in the previous study (52.2%) [3]. Warrel observed that despite the extensive spread of P. falciparum resis- tant strains, chloroquine is still the most widely used antimalarial drug in the world [7] as it is readily available and compara- tively cheap [8]. Two antimalarial drugs re- cently launched in Sudan, artemether and halofantrine, appeared on prescriptions in this study although they should be reserved for complicated malaria cases (which are treated as hospital inpatients) as recom- mended by the protocol. The proportion of antimalarial drug pre- scriptions that were compliant with the protocol (79.7%) reflects a marked im- provement compared with the study before the implementation of the protocol (33.3%) [3]. However, regimens for administration of intravenous quinine were still inadequate in 30% of cases and this should be stressed in future interventions. We recommend the following: monitor- ing and updating of the protocol; introduc- ing the protocol guidelines in pre-service training; and thorough distribution of the protocol guidelines to health workers, with close follow-up and supervision. Acknowledgements Thanks are due to Professor Ali Ahmed Idris, Department of Community, Faculty of Medicine, University of Gezira for his invaluable assistance. We also thank the Batch 18 pharmacy students at the University of Gezira who contributed to data collection. References 1. Department of Quality Assurance of Di- agnosis and Treatment. National pro- tocol for the treatment of malaria. Khartoum, Sudan, National Malaria Ad- ministration, 2001. 2. WHO policy perspectives on medicines. How to develop and implement a na- tional drug policy. Geneva, World Health Organization, 2003 (WHO/EDM/2002.5). 3. Yousif MA, Adeel AA. Antimalarial pre- scribing patterns in Gezira State: pre- cepts and practices. Eastern Medi- terranean health journal, 2000, 6(5): 939–47. 4. Antimalarial drug polices: data require- ments, treatment of uncomplicated ma- laria and management of malaria in pregnancy. Report of an informal consul- tation. Geneva, 14–18 March 1994. Geneva, World Health Organization, 1994 (WHO/MAL/94.1070). 13 Impact of the national.pmd 8/17/2005, 11:07 AM571 572 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 5. Abdel-Hameed AA, El-Jak IE, Faragalla IA. Sentinel posts for monitoring thera- peutic efficacy of antimalarial drugs against Plasmodium falciparum infec- tions in the Sudan. African journal of medical sciences, 2001, 30(suppl.):1–5. 6. Malaria Administration Unit. Report on malaria therapy. Khartoum, Sudan, Fed- eral Ministry of Health, 1998. 7. Warrel DA. Treatment and prevention of malaria. In: Gilles HM, Warrel DA, eds. Bruce-Chwatt’s essential malariology, 3rd ed. London, Arnold, 1993:164–95. 8. Adome RO, Whyte SR. Hardon A. Popu- lar pills: community drug use in Uganda. Amsterdam, Het Spinhuis, 1996. Funds and technical support are available: however, malaria is still a serious challenge in the Region Dr Hussein Gezairy, WHO Regional Director for the Eastern Mediterra- nean, called upon governments and the private sector in the most countries affected by malaria to ensure that safe and effective drugs are made affordable and accessible to patients, and that the implementation of available vector control tools is through intersectoral action for health – including community-based initia- tives and outreach health services. The Regional Director pointed out that malaria is still a serious prob- lem in the Eastern Mediterranean Region, with more than 15 million estimated cases every year and five of the worst-affected countries in the world, namely Afghanistan, Djibouti, Somalia, Sudan and Yemen. The Region still faces a serious malaria challenge to which the Regional Office is responding in many ways. Source: WHO/EMRO Press release No. 7 22 May 2004 13 Impact of the national.pmd 8/17/2005, 11:07 AM572 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 573 Larvicidal activity of a neem tree extract (Neemarin) against mosquito larvae in the Islamic Republic of Iran H. Vatandoost1 and V.M. Vaziri1 1School of Public Health and Institute of Health Research, Tehran University of Medical Science, Tehran, Islamic Republic of Iran. Received: 22/10/02; accepted: 18/08/03 ABSTRACT An insecticide containing azadirachtin, a neem tree (Azadirachta indica) extract, was tested against mosquito larvae in the Islamic Republic of Iran under laboratory and field conditions. LC50 and LC90 values for Neemarin were 0.35 and 1.81 mg/L for Anopheles stephensi, the main local malaria vector, and 0.69 and 3.18 mg/L for Culex quinquefasciatus. The mortality in the pupal stage was significantly higher than the other stages. In field trials, using recommended dosages of 1 and 2 L/hectare, mortality of Anopheles spp. larvae was also higher than Culex spp. Prevention of adult emerged and pupal mortality was the main activity of this compound. The maximum time of efficacy was 7 days at the highest concentration (2 L/hectare). Activité larvicide d’un extrait du margousier (Neemarin) contre les larves de moustiques en Répu- blique islamique d’Iran RÉSUMÉ Un insecticide contenant de l’azadirachtine, un extrait du margousier (Azadirachta indica), a été testé en laboratoire et sur le terrain pour la lutte contre les larves de moustiques en République islamique d’Iran. Les valeurs CL50 et CL90 pour le Neemarin étaient de 0,35 et 1,81 mg/L pour Anopheles stephensi, le principal vecteur local du paludisme, et 0,69 et 3,18 mg/L pour Culex quinquefasciatus. La mortalité au stade nymphe était significativement plus élevée qu’aux autres stades. Dans les essais sur le terrain, en utilisant les dosages recommandés de 1 et 2 L/hectare, la mortalité des larves d’Anopheles spp. était également plus élevée que pour Culex spp. La prévention de l’éclosion imaginale et la mortalité des nymphes constituaient la principale activité de ce composé. Le temps d’efficacité maximum était de sept jours à la concentration la plus élevée (2 L/hectare). 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:07 AM573 574 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Introduction Malaria is the most important problem of developing countries. According to the lat- est report, it kills between 1.5–2.7 million people every year [1]. Malaria has always been considered as the most important vec- tor-borne disease in the Islamic Republic of Iran due to its socioeconomic effects on the population [2]. Since the discovery of the insecticide dichloro-diphenyl-trichloroethane (DDT) before the Second World War, the wide- spread use of synthetic insecticides for the control of pests as well as human disease vectors has led to concerns about their tox- icity and environmental impact [3]. Be- cause of this, the search for new environmentally safe, target-specific insec- ticides is active throughout the world. To find new modes of action and to develop active agents based on natural plant prod- ucts, efforts are being made to isolate, screen and develop phytochemicals pos- sessing pesticidal activity. These categories of pesticides are known as biopesticides [3]. The neem tree (Azadirachta indica) is a member of the mahogany family (Melia- cea) that is native to India and Burma, but it was introduced to other countries in the late 19th century [4]. Six species in the family Meliacea have been studied for pes- ticidal properties in different parts of the world. They are Azadirachta indica Juss, A. excelsa Jack, A. siamens Valeton, Melia azadirachta L., M. toosendan Sieb. and Zucc. and M. volkensii Gurke [3]. Howev- er, the most promising phytochemical pes- ticides studied in recent years are those based on extracts of Az. indica [3]. Various neem products have been re- searched extensively for their phytochem- istry and exploitation in pest control programmes [3]. A number of bioactive components have been isolated from vari- ous parts of the neem tree. These chemical compounds have different designations, among which azadirachtin A is the major component. In addition to azadirachtin, a number of other active ingredients have also been isolated and identified from dif- ferent parts of the neem tree, such as salan- nin, meliantriol and nimbin [3,4]. Two new triterpenoids (22,23-dihydronimocinol and des-furano-6-alpha-hydroxyazadiradione) were isolated from a methanolic extract of the fresh leaves of Az. indica along with a known meliacin, 7-alpha-senecioyl-(7- deacetyl)-23-O-methylnimocinolide [5]. Neem components show multiple ef- fects against different insects such as mosquitoes, flies, triatomine bugs, cock- roaches, fleas, lice and ticks [3,4]. The ef- fect of neem on the activity of insects has been neglected up to now, possibly because it does not rapidly lead to mortality. Howev- er, affected insects cannot survive adverse environmental conditions in the same way as normal, healthy individuals; for example insects with reduced activity (reduced sight, jumping, crawling and flying ability) may be caught more easily by natural pred- ators. Because of the variety of compo- nents and different mechanisms of action, insect resistance to neem compounds seems likely to be low [8–10]. The repellent activity of neem oil solu- tions in coconut oil against populations of mosquitoes consisting mainly of Mansonia spp. in Gambella, western Ethiopia, was demonstrated by Hadis et al. [6]. The aim of the present study was to evaluate the ef- ficacy and durability of a neem extract against the main mosquito species in the southern part of the Islamic Republic of Iran. 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:07 AM574 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 575 Methods Laboratory and field trials were carried out using an azadirachtin-rich product, Neemarin 0.15% (Biotech International Limited, New Delhi, India). The formula- tion consists of active ingredient (0.15% w/w), inert material (1.35% w/w) and pro- pylene glycol (98.5% w/w). Laboratory tests Larvae of laboratory-reared strains of Anopheles stephensi and Culex quinquefas- ciatus (originally from the Bandar-e-Abass city area) were tested with different con- centrations of Neemarin at the late 3rd in- star and early 4th instar stages in a room at 25 °C ± 1 °C in autumn and winter 1999, according to WHO methods [11]. The strains are susceptible to different insecti- cides such as DDT, organophosphates, carbamates and pyrethroids. Preliminary testing was carried out to establish suitable concentrations. Selected stock solutions of Neemarin after preliminary tests were as follows: 0.0586, 0.117, 0.234, 0.469, 0.938, 1.875, and 3.750 mg/L. Lower loga- rithmic concentrations of Neemarin were diluted by adding the required volume of al- cohol solvent to the main stock of Neemar- in. At each concentration, 200 mosquitoes representing individuals of 25 larvae were tested on 4 occasions. Each test run con- sisted of 74 mL water, 1 mL of Neemarin stock solution (by use of sampler) and then 25 larvae in 25 mL water were added, so that the final volume was 100 mL. In con- trol runs, 1 mL alcohol was added instead of Neemarin. Mortality counts were made every 24 hours after exposure until the test was ter- minated (when all the adults had emerged). In the analysis, both dead and moribund larvae were considered as dead, and the numbers alive at different stages (larvae, pupae, adults) were scored separately. The percentage mortality in the treated larvae was corrected relative to the controls using Abbotts formula [11]. The data were sub- jected to probit regression analysis accord- ing to Finney [12]. Goodness of fit of the points to a straight line was tested by chi- squared analysis. Field trials Field trials were carried out in artificial ponds (100 × 30 × 50 cm) in Jadas, Kazer- oun, in the south-eastern part of the Islamic Republic of Iran in summer 2000, accord- ing to the method of Mulla and WHO rec- ommendations [11,13]. The ponds were constructed separately, without vegetation and were exposed to sunlight. Replicate ponds were created for each treatment: 2 control ponds and 4 treatment ponds. In the treatment ponds, Neemarin was sprayed on the water surface using a manual sprayer at 2 different concentra- tions (1 L/hectare and 2 L/hectare), as rec- ommended by other researchers [9,14]. The number of larvae in the artificial ponds before and after the application of Neemarin (up to 10 days) were counted using a standard dipper. The frequency of Anopheles and Culex spp. larvae were counted using the method of Mulla with a cubic metal frame incorporated into the net for keeping and counting larvae in artificial ponds [13]. The larvae were identified according to the national identification key described by Shahgudian [15]. Results Laboratory tests Using probit regression analysis software, regression lines were plotted for the dose– 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:07 AM575 576 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 response to Neemarin treatment of labora- tory strains of An. stephensi and Cx. quin- quefasciatus larvae (Figures 1 and 2). For An. stephensi the LC50 (lethal concentration to cause 50% mortality in the population) was measured as 0.35 mg/L and the LC90 (lethal concentration to cause 90% mortali- ty in the population) was 1.81 mg/L. For Cx. quinquefasciatus the LC50 was 0.69 mg/L and LC90 was 3.18 mg/L respectively (Table 1). Thus, An. stephensi larvae need- ed a significantly lower concentration of Neemarin than Cx. quinquefasciatus to cause the same mortality (P < 0.05). The mortality among the pupal stages was greater than other stages (P < 0.05). For example, among 400 larvae of Anophe- les species tested at the highest concentra- tion, the mortality rate of larvae, pupae and adults were 15.8%, 79.8% and 40.3% re- spectively. Similar data were obtained for other concentrations and for Culex species. Inhibition of adult emerged larvae through mortality of pupae was the main action of Neemarin. Field trials In the field trials in artificial ponds, the dis- tribution of species identified during the first run of the test were An. stephensi (29%), An. fluviatilis (27%), An. dthali (13%), An. superpictus (6%) and Culex spp. (25%) for 500 mosquito larvae. Dur- ing the second run of the test the species were as follows: An. stephensi (26%), An. dthali (22%), An. superpictus (13%) and Culex spp. (38%) for 450 mosquito larvae. Tables 2 and 3 show the mortality rates of Anopheles and Culex spp. at different stages (larvae, pupae, adult), comparing controls with 2 different concentrations of Neemarin treatment (combining the 2 repli- cate runs). The main indicator of treatment response was the percentage inhibition of emerged adults. The inhibitory effect of Neemarin declined over the 3 days of treat- ment. For Anopheles species, inhibition of emerged adults fell from 33% and 56% at 1 L/hectare and 2 L/hectare after 1 day to 5% and 20% respectively after 3 days. For Culex species, inhibition of emerged adults fell from 30% and 46% at 1 L/hectare and 2 Figure 1 Probit regression line for response of Anopheles stephensi larvae to Neemarin treatment in laboratory tests Figure 2 Probit regression line for response of Culex quinquefasciatus larvae to Neemarin treatment in laboratory tests 50% mortality 50% mortality 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:08 AM576 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 577 L/hectare after 1 day to 1% and 21% re- spectively after 3 days. The frequency of larvae in the artificial ponds were different before and after application and increased after 7 days in all replicates, that shows maximum time of efficacy and inhibition of emerged adults at 7 days after application did not show a significant difference (P < 0.05).The maximum time of efficacy was 7 days at the 2 L/hectare concentration (P < 0.05). The durability of the product depended on the dosage applied (P < 0.05). As in the laboratory tests, pupal mortal- ity was higher than the other stages for Anopheles (Table 2) and Culex spp. (Table 3). A lower concentration of Neemarin was needed for Anopheles spp. larvae than for Culex spp. to cause the same mortality (P < 0.05). Table 1 Probit regression line parameters of response of Anopheles stephensi and Culex quinquefasciatus to Neemarin treatment in laboratory tests Mosquito Intercept Slope (SE) LC50 95% CI LC90 95% CI χ2 (df) P-value species (mg/L) (mg/L) An. stephensi 1.31 1.78 (0.07) 0.35 0.18–0.37 1.81 0.96–2.05 26.70 (4) < 0.0001 Cx. quinquefasciatus 0.85 1.91 (0.06) 0.69 0.36–0.74 3.18 1.68–3.38 29.08 (5) < 0.0001 SE = standard error. LC 50 = lethal concentration to cause 50% mortality in population. LC90 = lethal concentration to cause 90% mortality in population. CI = confidence interval. χ2 (df) = heterogeneity about the regression line (degrees of freedom). Table 2 Mortality of Anopheles spp. at different stages in artificial ponds, comparing controls with 2 different concentrations of Neemarin Time after Larvae Mortality rate Survival Inhibitiona treatment tested Larvae Pupae Adults Total rate (SE) No. % % % % % % 1 day Controls 93 7 8 3 18 82 1 L/hectare 130 18 22 5 45 55 33 (4.1) 2 L/hectare 272 24 29 11 64 36 56 (2.9) 2 days Controls 90 9 6 3 18 82 1 L/hectare 160 10 18 3 31 69 16 (3.6) 2 L/hectare 337 14 27 10 51 49 40 (2.7) 3 days Controls 105 12 14 5 18 82 1 L/hectare 200 6 9 2 17 78 5 (2.6) 2 L/hectare 310 11 18 5 34 66 20 (2.6) aPercentage inhibition of adult emerged larvae comparing treatment with controls. SE = standard error. 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:08 AM577 578 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 The findings of the present study were compared with other researchers’ results using different neem extract formulations (Neemazal, ANSKE, AZT-VR-K-E and MTB) on Aedes aegypti mosquitoes. The EC50 for above formulations (molar con- centration of product which produces 50% of the maximum possible response) were 8.4, 78.2, 18.1 and 5.9 ppm respectively (Table 4). Discussion Neem products are capable of producing multiple effects on a number of insect spe- cies, such as anti-feeding effects, growth regulation, fecundity suppression and ster- ilization, oviposition repellency or attracta- ncy and changes in biological fitness [3]. In some cases, neem has repellent ef- fects. For example, the percentage protec- tion against sand fly bites provided by neem oil was significantly higher than N,N-diet- hyphenylacetamide (DEPA) when applied at 1% and 2% concentrations [16,17]. Neem extracts have been shown to have repellent activity against Mansonia spp. mosquitoes in Gambella, western Ethiopia [5]. Studies on the anti-feeding activity of the neem extracts showed that crops treat- ed with an aqueous suspension of neem seeds were protected from attack by lo- custs. Host plant selection is mainly gov- erned by the responses of the insect’s gustatory and olfactory sensilla. Since aza- dirachtin is non-volatile, the specificity and responsiveness of receptors on the insect’s taste neurons are likely to be critically im- portant in this process. The effects of neem products on the reproduction of insects have been known since 1975 and reproduction reduction ef- fects have been found in Caelifera, Table 3 Mortality of Culex spp. at different stages in artificial ponds, comparing controls with 2 different concentrations of Neemarin Time after Larvae Mortality rate Survival Inhibitiona treatment tested Larvae Pupae Adults Total rate (SE) No. % % % % % % 1 day Controls 61 7 4 2 13 87 1 L/hectare 50 14 22 3 39 61 30 (4.2) 2 L/hectare 75 16 26 11 53 47 46 (5.3) 2 days Controls 45 5 5 7 17 83 1 L/hectare 60 5 15 1 21 79 5 (4.3) 2 L/hectare 90 8 20 6 34 66 20 (4.2) 3 days Controls 54 6 7 0.4 13 87 1 L/hectare 51 5 8 1 14 86 1 (3.6) 2 L/hectare 110 8 18 5 31 69 21 (3.8) aPercentage inhibition of adult emerged larvae comparing treatment with controls. SE = standard error. 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:08 AM578 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 579 Table 4 Comparison of effectiveness of different neem formulations in laboratory tests on mosquito species Mosquito species Neem EC50 Reference formulation (ppm) Aedes aegypti Neemazal 8.4 [11] Ae. aegypti ANSKE 78.2 [11] Ae. aegypti AZT-VR-K-E 18.1 [11] Ae. aegypti MTB 5.9 [11] Anopheles stephensi Neemark 0.05 [6] Culex quinquefasciatus Neemark 0.22 [6] An. stephensi Neemarin 0.18 Present study Cx. quinquefasciatus Neemarin 0.36 Present study Neemazal (Trifolio-M GmbH, Lahnau, Germany) 10 g/L azadirachtin. ANSKE = aqueous neem seed kernel extract. AZT-VR-K-E = enriched and formulated neem seed kernel extract. MTB = neem seed extract. Neemarin (Biotech International Limited, New Delhi, India) 0.15% azadirachtin. EC50 = molar concentration of product which produces 50% of the maximum possible response. Heteroptera, Homoptera, Hymenoptera, Lepidoptera and Diptera [3,9]. A large num- ber of abortions (dead-born larvae) in the tsetse flies Glossina morsitans morsitans and Glossina pallidipes after treatment of pregnant females with neem oil and the aza- dirachtin-enriched neem seed kernel ex- tract AZT-VR-K were found. In mosquitoes, compounds extracted from Az. indica showed mortality for fourth instar larvae of An. stephensi, with LC50 values of 60 and 43 ppm, respectively [4]. This compares with the LC50 and LC90 in our study of 0.36 and 1.81 ppm for An. stephensi and 0.69 and 3.18 ppm for Cx. quinquefasciatus respectively using a com- mercial preparation of neem extract, Neemarin. Our results were comparable with findings from other researchers as shown in Table 4. The variation in LC50 is due to mosquito species, formulation, cli- mate and method of application. In order to compare the larvicidal effect of Neemarin with WHO-recommended lar- vicides (malathion, fenitrothion, temephos, chlorpyrifos), the regression lines were compared. This showed that the toxicity of Neemarin is less than other chemicals and the LC50 and LC90 of Neemarin on laborato- ry strains of An. stephensi were to some extent similar to temephos [1]. Neem extracts act like insect growth regulators, so the mortality at different stages were considered. Mortality of the pupae stage was significantly higher than the larvae and adult stages. In addition, the mortality of Cx. quinquefasciatus was sig- nificantly lower than An. stephensi. We conclude that Neemarin, at the rec- ommended concentrations in field studies of 1 and 2 L/hectare, significantly reduces the frequency of larvae and the estimated residual effect is 7 days. 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:08 AM579 580 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Acknowledgements We would like to thank all of the staff mem- bers of the Medical Entomology Depart- ment and Giahpezeshk Limited for their kind collaboration. References 1. Report of the fourth meeting of the global collaboration for development of pesti- cides for public health. Geneva 24–25 June, 2004. Geneva, World Health Orga- nization, 2004 (WHO/CDS/WHOPES / GCDPP/2004.8). 2. Zaim M. Malaria control in Iran, present and future. Journal of the American Mos- quito Control Association, 1987, 3:392– 6. 3. Mulla MS, Su T. Activity and biological effects of Neem products against arthropods of medical and veterinary im- portance. Journal of the American Mos- quito Control Association, 1999, 15(2): 133–52. 4. Ruskin FR. Neem: a tree for solving glo- bal problems. Washington DC, National Academy Press, 1992. 5. Siddiqui BS et al. Two new triterpenoids from Azadirachta indica and their insec- ticidal activity. Journal of natural prod- ucts, 2002, 65(8):1216–8. 6. Hadis M et al. Field trials on the repellent activity of four plant product against mainly Mansonia population in western Ethiopia. Phytotherapy research, 2003, 17(3):202–5. 7. Sharma SK, Sharma VP. Field studies on the mosquito repellent action of neem oil. Southeast Asian journal of tropical medicine and public health, 1995, 26(1): 180–2. 8. Sharma VP, Dhiman RC. Neem oil as a sandfly (Diptera: Psycodidae) repellent. Journal of the American Mosquito Con- trol Association, 1993, 9:364–6. 9. Dhar R et al. Effect of volatiles from neem and other natural products on gono- trophic cycle and oviposition of Anoph- eles stephensi and An. culicifacies (Diptera:Culicidae). Journal of medical entomology, 1996, 33:195–201. 10. Rao DR, Reuben R. Evaluation of neem cake power and neem cake coated urea as mosquito larvicides in rice fields. In: Uren MF, Block J, Manderson LH, eds. Arbovirus research in Australia. Pro- ceedings of the Fifth Symposium 28 Au- gust to 1 September 1989. Brisbane, Australia, CSIRO Tropical Animal Sci- ence, 1989:138–42. 11. Instructions for determining the suscepti- bility or resistance of mosquito larvae to insect development inhibitors. Geneva, World Health Organization, 1981 (WHO/ VBC/81.812). 12. Finney DJ. Probit analysis, 3rd ed. New York, Cambridge University Press, 1971. 13. Mulla M.S. Insect growth regulators for the control of mosquito pests and dis- ease vectors. Chinese journal of ento- mology, 1991, 6:81–91. 14. Boschitz C, Grunewald J. The effect of NeemAzal on Aedes aegypti (Diptera: Culicidae). Applied parasitology, 1994, 35(4):251–6. 15. Shahgudian ER. A key to the Anophe- lines of Iran. Acta medica Iranica, 1960, 3(3):38–48. 16. Srinivasan R, Kalyanasundaram M. Re- lative efficacy of DEPA and neem oil for repellent activity against Phlebotomus papatasi, the vector of leishmaniasis. 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:08 AM580 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 581 Journal of communicable diseases, 2001, 33(3):180–4. 17. Parida MM et al. Inhibitory potential of neem (Azadirachta indica Juss) leaves on dengue virus type-2 replication. Jour- nal of ethnopharmacology, 2002, 79(2): 273–8. Malaria control in the Eastern Mediterranean Region Significant progress was made in 2003 with the development of appropriate technical guidelines for the improvement of key strate- gies for the control of malaria and other vector-borne diseases. These included the regional strategic framework for integrated vec- tor management, guidelines on monitoring insecticide resistance, regional guidelines on the management of public health pesticides, including country profiles, and guidelines on malaria microscopy and quality assurance. The WHO publications Instructions for treat- ment and use of insecticide-treated mosquito nets and Basic ma- laria microscopy were translated into Arabic. National strategic plans on use of insecticide-treated nets were finalized for Afghanistan, Djibouti, Saudi Arabia, Sudan and Yemen. A regional network for monitoring vector resistance was initiated and country-level part- nership was fostered at the annual meeting of national malaria pro- gramme managers held in Lahore, Pakistan in June 2003. Source: The Work of WHO in the Eastern Mediterranean Region. Annual Report of the Regional Director 1 January–31 December 2003 Available at: http://www.emro.who.int/rd/AnnualReports/2003/index.htm 14 Larvicidal activity of a neem.pmd 8/17/2005, 11:08 AM581 582 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Characteristics of districts in Pakistan with persistent transmission of wild poliovirus, 2000–2001 S.A. Lowther,1 T. Mir,2 M.K. Bile,2 R. Abdul Hafiz3 and A.W. Mounts2 1World Health Organization, Polio Eradication Initiative, Islamabad, Pakistan (Consultant, 2001). 2World Health Organization, Islamabad, Pakistan. 3National Institutes of Health, Expanded Programme on Immunization, Islamabad, Pakistan, Received: 31/03/03; accepted: 14/01/04 ABSTRACT We sought to identify factors associated with being a reservoir district for wild poliovirus in Pakistan. Differences between reservoir and non-reservoir districts were identified using acute flaccid paralysis surveillance data, population census statistics and data from a survey of district health officials (DHOs). Of the 11 poliovirus reservoir districts identified, population density was significantly higher (median 550 persons/km2) than the non- reservoirs (median 175 persons/km2). DHOs from reservoir districts more often reported that planning was affected by refugees and they had more frequent DHO transfers compared with non-reservoir districts. Multivariate analysis confirmed that reservoirs more often had high population density and frequent DHO transfers. Assessment of district- level and management characteristics can supplement surveillance methods to further improve health programmes. Caractéristiques des districts où la transmission du poliovirus sauvage continue au Pakistan, 2000-2001 RÉSUMÉ Nous avons cherché à identifier les facteurs qui font qu’un district est une zone de réservoir du poliovirus sauvage au Pakistan. Les différences entre les districts qui sont ou non une zone de réservoir ont été identifiées en utilisant les données de la surveillance de la paralysie flasque aiguë, les statistiques du recensement de la population et des données tirées d’une enquête des responsables sanitaires de district. Dans les 11 districts identifiés comme étant une zone de réservoir du poliovirus, la densité de population était significativement plus élevée (médiane de 550 personnes/km2) que dans les districts qui ne sont pas des zones de réservoir (médiane de 175 personnes/km2). Les responsables sanitaires des districts qui sont des zones de réservoir signalaient plus souvent que la planification était affectée par les réfugiés et étaient plus fréquemment transférés par rapport aux districts qui ne sont pas une zone de réservoir. L’analyse multivariée a confirmé que les zones de réservoir avaient plus souvent une forte densité de population et dans ces zones, les transferts de responsables sanitaires de district étaient plus fréquents. L’évaluation des caractéristiques de la gestion et au niveau du district peut compléter les méthodes de surveillance traditionnelles pour améliorer davantage les programmes de santé. 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM582 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 583 Introduction Global poliomyelitis incidence has de- creased 99% since the World Health As- sembly agreed to instigate the Poliomyelitis Eradication Initiative in 1988 [1]. Pakistan began poliomyelitis eradication activities in 1994 and has had considerable success [2]. These activities are conducted with the on- going World Health Organization (WHO) Expanded Programme on Immunization (EPI), which seeks to vaccinate children against poliomyelitis, measles, diphtheria, pertussis, tuberculosis, tetanus, and hepati- tis B. Numerous national immunization days (NIDs) have resulted in a considerable de- cline and localization of cases in Pakistan [2]. However, despite these efforts, several areas in Pakistan appear to be reservoirs where wild poliovirus circulation persists throughout the year, repeatedly reintroduc- ing infection to nearby susceptible popula- tions during the higher transmission season. Presumably a certain threshold of susceptible population would be required to sustain virus circulation in these districts; however, other factors such as effective management of health resources may also be important. In Pakistan, the administrative tiers of the health system include the federal, pro- vincial and district levels. The federal of- fice is responsible for national health policy decisions, vaccine procurement and distri- bution of resources to provinces. Provin- cial health offices are responsible for the administration of health programmes throughout the province, distribution of vaccines and supplies to districts, and su- pervision and monitoring of district-level activities. Programme implementation, dai- ly management and control of resources are performed at the district level by dis- trict health officers (DHOs) (or by agency surgeons in the case of federally adminis- tered tribal agencies). In 2000 there were 122 districts-level administrative areas (in- cluding 7 tribal agencies). Areas with continued transmission of wild poliovirus have been examined and identified through ongoing active surveil- lance [1]. However, no published studies have taken an ecologic approach to exam- ining district-level management character- istics that may affect the success of the administrative area in poliomyelitis eradica- tion. Using acute flaccid paralysis (AFP) surveillance data, we sought to describe the characteristics of districts where there ap- peared to be persistent wild poliovirus transmission in Pakistan. This study exam- ines the relationship between several char- acteristics of districts, district health management and the presence of a poliovi- rus reservoir to identify specific factors that might be modified to improve the ef- fectiveness of poliomyelitis eradication in Pakistan. Methods On February 28, 2001 a national confer- ence on poliomyelitis eradication was held in Islamabad, Pakistan. All 122 DHOs and agency surgeons were asked to attend. (For this study, the designation “DHO” will include both district health officers and agency surgeons.) DHOs were asked to complete a self-administered survey to col- lect demographic information such as age, sex, educational achievements, training and years of experience. Information on their district health system that might affect health programme planning, such as data on population migration (e.g. refugees or drought-related movement) was collected. The survey was also used as a forum to express opinions (e.g. describe specific 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM583 584 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 weaknesses or gaps in their district in per- sonnel or supplies). Surveys were later mailed to those DHOs that either did not at- tend the conference or did not complete the survey at the time of the conference. Be- cause of its nature as a feedback mecha- nism, the survey was neither anonymous nor confidential, and respondents were in- formed that the information they provided would be examined to give feedback and assess programme planning with specific regard to their district. AFP surveillance data reported from 2000 through 2001 were analysed to identi- fy districts with persistent and low trans- mission season wild poliovirus circulation. Adequacy of surveillance data was as- sessed using standard surveillance indica- tors, i.e. rates of non-poliomyelitis AFP (1 case per 100 000 population expected), 60- day case follow-up (expected to be done on all cases), and adequate stool collection (greater than 80% of all stool specimens collected met the requirements of 2 stool specimens per case collected at least 24 hours apart, within 14 days of the onset of paralysis, and arriving in the laboratory with intact reverse cold chain and suffi- cient quantity for analysis). Data on popu- lation size, area size and population density were obtained from the Population Census Bureau [3]. Analysis Reservoir districts were defined as those districts with wild poliovirus isolated dur- ing 5 out of 8 quarters of the years 2000 and 2001 and with virus isolated during low transmission season (December through March) at least one of the years 2000 and 2001. Several continuous variables were re- coded for assessment. For example, be- cause of its broad range among districts, population density was transformed to a logarithmic scale [i.e. ln (population densi- ty)] and was categorized into 2 levels: high density, defined as ln (population density) > 7.0 and low density, defined as ln (popula- tion density) ≤ 7.0. The number of DHOs transferred in the past 5 years was also cat- egorized into 2 levels: frequent transfers (more than 4 per 5 years) and less frequent transfers (4 or fewer per 5 years). Univari- ate analysis was performed using Epi-Info software where differences were examined between poliovirus reservoir districts and non-reservoir districts. The Kruskal–Wallis test was used to compare district-level characteristics whose values were coded as continuous with exact P-values report- ed. Odds ratios (OR) and exact 95% confi- dence intervals (95% CI) were used to compare characteristics coded as categori- cal. Any factors found to be significantly associated with being a reservoir district from univariate analysis were included in multivariate analysis using SAS (Cary, North Carolina, United States of America) statistical software. For all statistical tests a P-level of 0.05 was used as significant. Results Reservoirs for wild poliovirus Fifty-nine districts had poliovirus isolated in 2000 and 34 in 2001; 11 administrative districts met our definition of reservoir dis- trict. These included Quetta district in Balochistan province; Bannu and Peshawar districts in North-west Frontier Province, Faisalabad district in Punjab province; and Hyderabad, Jacobabad, and Karachi dis- tricts in Sindh province (Figure 1). Karachi included 5 administrative districts of Kara- chi Central, Karachi South, Karachi East, Karachi West and Karachi Malir. As can be 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM584 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 585 seen from Figure 1, the districts were not clustered together geographically which ar- gues against a single large poliovirus reser- voir. Surveillance indicators for 2000 from reservoir districts (rates of non-polio AFP, 60-day follow-up and adequate stool col- lection) were not significantly different from non-reservoir districts, and met the worldwide standards for such indicators of adequate surveillance (Table 1). Population density was higher among reservoir dis- tricts compared with non-reservoir dis- tricts (median = 550.7 versus 175.9 persons per square km, P = 0.001). Characteristics of DHOs In all, 101 DHOs responded to the survey (21 never responded) from all provinces of Pakistan. There were no differences in the DHO response rate by reservoir district status, AFP surveillance characteristics, geographic location/province, or popula- tion density. The median age of respon- dents was 50 years (range 40–60 years) and all DHOs were male. All DHOs were physicians (MBBS) and 46% had a public health degree or diploma; 10% reported re- ceiving management training in the past 3 years. In addition, 97% reported having as- signed a specific person to be responsible for EPI. As regards the complications of health programme planning, 90% of DHOs reported seasonal migration as a complica- tion, 51% cited refugees 36% cited drought-related migration, 11% cited no- mads or gypsies, 4% cited other complica- tions including tribal clashes, border or line-of-control conflict, or smuggling routes. About 16% reported having a pri- vate practice. Prior experience as a DHO was reported by 49% of respondents with a median of 6 years of experience (range 0– 27 years). In the past 5 years, 59% of Figure 1 Districts identified from acute flaccid paralysis surveillance to have persistent wild poliovirus transmission in Pakistan during 2000–2001 (defined as districts with wild poliovirus isolated during 5 out of 8 quarters of the years 2000 and 2001 and with the virus isolated during low transmission season (December–March) in at least 1 of the years) 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM585 586 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Table 1 Characteristics among districts and district health officials comparing wild poliovirus reservoir districts to non-reservoir districts, Pakistan, 2000–2001 Characteristics Reservoir Non-reservoir Statistical analysis district district Continuous variables Median Median Kruskal– P-valuea Wallis Surveillance indicators No. poliomyelitis cases 2001 3.5 0.0 32.70 0.000 Non-poliomyelitis AFP rate (1.00 expected) 1.95 1.42 2.75 0.097 Non-poliomyelitis enterovirus rate (0.10 expected) 0.15 0.17 0.16 0.690 Percentage with 60-day follow-up 100 100 0.25 0.617 Percentage with adequate stool collection 74 71 0.02 0.892 District-level characteristics Population density (persons per km2) 550.7 175.9 13.1 0.001 Area size (km2) 2268 5286 6.80 0.009 Population size 1 724 915 805 235 6.99 0.008 Total district health officers in last 5 years 5 3 7.73 0.005 Categorical variables No. % No. % Odds 95% CIa ratio District-level characteristics Log (population density) > 7.0 3 33 1 1 45.5 4.1–506.2 Log (population density) ≤ 7.0 6 67 91 99 1 – 5 to 8 district health officers per 5 years 6 67 20 22 7.2 1.7–31.4 ≤ 5 district health officers per 5 years 3 33 72 88 1 – District health officer characteristics Respondents 9/11 82 101/111 91 0.98 0.2–9.5 Previous experience as district health officer 6/9 67 42/93 45 2.38 0.6–10.1 Has private practice 0/9 0 16/96 17 Undef – Has public health degree 2/9 22 44/94 47 0.3 0.1–1.6 Specific person assigned to manage EPI 9/9 100 89/92 97 Undef – Had management training in last 5 years 0/9 0 10/91 11 Undef – Reports drought affects district 3/9 33 31/89 35 0.92 0.2–3.9 Reports refugees affect district 8/9 89 43/91 47 8.74 1.1–72.8 Reports seasonal migration affects district 8/9 89 89/92 97 0.88 0.10–7.8 aExact P-value and 95% confidence intervals (CI) are given. A P-level of 0.05 and 95% CI excluding 1.0 was considered statistically significant. AFP = acute flaccid paralysis. EPI = Expanded Programme on Immunization. 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM586 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 587 DHOs reported 2 or 3 transfers, with 20% reporting zero or 1 transfer and 21% re- porting 4 to 7 transfers. In univariate analysis, several differenc- es were identified between reservoir and non-reservoir districts (Table 1) among characteristics of DHOs and districts. There was no difference in DHO response rate between reservoir and non-reservoir districts (82% versus 92% respectively, P = 0.97). DHOs from reservoir districts were more likely to report that problems in health programme planning were affected by refugees (OR = 8.74, P = 0.02) but were equally likely as non-reservoir DHOs to report that problems in planning were affected by factors such as drought or sea- sonal movement. DHOs from reservoir and non-reservoir districts did not differ by ed- ucational status, additional public health training, or years of experience. DHOs re- ported that reservoir districts had signifi- cantly more DHOs in the last 5 years compared with non-reservoir districts (me- dian = 5 versus 3 DHOs, P = 0.005). Multivariate analysis included 2 district- level characteristics (population density and frequency of DHO transfers) and 1 DHO characteristic (reporting that refu- gees affected health programme planning). This analysis indicated that reservoir dis- tricts were more likely to be those among districts of high population density [ln(population density) > 7.0] (adjusted aOR = 28.1, 95% CI: 2.2–361.0) and dis- tricts with frequent DHO transfers (> 4 DHO transfers in the last 5 years) (aOR = 5.1, 95% CI: 1.03–25.5). However, after controlling for population density and fre- quency of DHO transfers, DHOs reporting that refugees affected programme planning was no longer significantly associated with reservoir district status. Discussion This analysis describes characteristics of districts and their DHOs in Pakistan with persistent transmission of wild poliovirus, and considers the effect of management and administration on the outcomes of a disease eradication programme. Our data showed that districts with less frequent change of managers were less likely to be poliovirus reservoirs than those with fre- quent turnover, indicating that consistency of management may improve the outcome of poliomyelitis eradication activities in a given district. Other characteristics of the DHO, such as previous experience as a DHO, management training or total years of experience, were not associated with poliovirus reservoir status. DHOs in the Pakistan health care system are the primary managers of all national public health pro- grammes and are key individuals responsi- ble for a programme’s success. Some examples of the responsibilities of DHOs in regard to poliomyelitis eradication planning include: supervising and monitoring of dis- trict logistical and personnel planning, dis- bursement of financial resources and communication with local authorities for involvement. Our analysis also demonstrated that res- ervoir districts were more likely to be among districts with the highest population density. This finding is consistent with evi- dence that urban areas with increased pop- ulation density are high-risk poliovirus reservoirs [4]. In addition, our analysis il- lustrates the process of identifying reser- voir districts based on natural seasonality of the virus in Pakistan. We believe this method helped improve the effectiveness of immunization campaigns by allowing the concentration of resources in areas needing 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM587 588 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 additional support; it continues to be an im- portant step in the final stages of poliomy- elitis eradication. Our data also suggest that the presence of a substantial refugee population may af- fect the success of poliomyelitis eradica- tion at the district level. This is consistent with supplementary individual-level epide- miological data collected during 2001 which indicated that Afghan refugees were at higher risk of poliomyelitis in Pakistan [2]. The additional population may burden a health programmes’ allocation of resources as well as increase virus transmission be- cause of a raised population density. Con- tinued attention to identifying high-risk groups will be invaluable as has been illus- trated in outbreak situations [5,6]. Previous studies have shown why indi- vidual children were under-vaccinated thereby creating reservoirs for wild poliovi- rus [7,8]. However our study is the first to examine risk factors for district and man- agement characteristics of these reser- voirs. In Pakistan during 1994, children missed during NIDs were also those more likely to have been unvaccinated or partial- ly-immunized through routine immuniza- tion services [9]. Elsewhere, risk factors for children missed during NIDs included failure to be reached by methods of social mobilization, increased distance to NID site [10], lower parental literacy or educational status [2], and age 0–6 months [11]. All polio vaccination campaigns in Pakistan have been house-to-house since 1998 [12] because they have been found to be more complete in coverage and cost-effective. While the house-to-house strategy is shown consistently to improve coverage, published studies to describe reasons why children are missed during house-to-house coverage are lacking. House-to-house im- munization campaigns are a massive under- taking which involve considerable planning and more complex logistics on multiple ad- ministrative levels. It is therefore conceiv- able that quality and consistency of programme administration and manage- ment may play a greater role in the suc- cessful outcomes of eradication activities. Our assessment makes no attempt to explain all the reasons for the continued transmission of poliovirus in Pakistan. In the recent past, poliomyelitis cases in Paki- stan have been un- or under-vaccinated through routine immunization [8]. Routine immunization coverage data could not be validated for the time period of study for every district, and complete, validated countrywide district-specific NID cover- age estimations were not available. The relationship between population density, management turnover rate and po- liovirus reservoir may be complex. While a certain population density is necessary to sustain poliovirus circulation, it may also be that densely populated areas, particularly urban areas, may be more desirable posts resulting in more frequent transfer of staff. Alternatively, DHOs in densely populated urban areas may have more difficulties in meeting expected performance standards. Other factors, such as a district literacy rates, socioeconomic status, or per capita health programme funding, may help to de- scribe areas having barriers to successful health programme outcomes. Because of its exploratory nature, our questionnaire did not capture specific reasons for DHO transfer. However, our analysis did identify DHO transfer to be associated with district reservoir status with no association found among factors such as total years of expe- rience, previous experience as a DHO, and training or certification in management. Further assessment of district management may be warranted, both in performance expectations and achievements. 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM588 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 589 This analysis identifies a management factor that may have an impact on the suc- cess of a high-priority disease eradication programme. Our data suggest that decreas- ing the frequency of transfers in district management may improve the quality of programme implementation. As a result of this study, the United Nations Children’s Fund (UNICEF) and WHO have now placed district support teams, comprised of individuals with varying skills, to work di- rectly under the district managers and sup- port all poliomyelitis- and EPI-related activities. These teams receive technical supervision from international and national consultants from the 2 United Nations agencies who are assigned to high-risk dis- tricts for periods of up to 1 year and pro- vide additional programme support and continuity. During both 2002 and 2003 Pakistan conducted 4 rounds of NIDs and 4 rounds of sub-NIDs, which are targeted at areas with factors (such as those described in our analysis) that indicate a high risk for continuing virus transmission [13]. In addi- tion, Pakistan introduced wide- scale inde- pendent monitoring of coverage through third-party survey companies to improve the quality of supplementary immunization activities by immediately identifying and vaccinating children initially missed during NIDs. In conclusion, our analysis has identi- fied DHO transfer rate and population density as important determinants of polio- myelitis eradication success. These aspects are now being addressed along with other critical factors to improve efforts to stop transmission of wild poliovirus. We beleive that the findings described in our paper have implications beyond poliomyelitis eradication and should be considered in other disease control programmes. Acknowledgements We would like to thank Mr Abid Sheik for his administrative assistance in survey col- lection, and Alex and Samantha Rowe for their critical review of the manuscript. References 1. Progress toward global eradication of poliomyelitis, 2001. Morbidity and mor- tality weekly report, 2002, 51:253–6. 2. Progress toward poliomyelitis eradica- tion—Pakistan and Afghanistan, Janu- ary 2000–April 2002. Morbidity and mor- tality weekly report, 51(24):523–4. 3. 1998 census report of Pakistan. Islamabad, Population Census Organi- zation, Statistics Division, Government of Pakistan, 1999. 4. Hull HF et al. Paralytic poliomyelitis: sea- soned strategies, disappearing disease. Lancet, 1994, 343:1331–7. 5. Aylward RB et al. Unimmunized gypsy populations and implications for eradi- cation of poliomyelitis in Europe. Journal of infectious diseases, 1997, 175 (suppl. 1):S86–8. 6. Reichler MR et al. Outbreak of paralytic poliomyelitis in a highly immunized population in Jordan. Journal of infec- tious diseases, 1997, 175(suppl. 1): S62–70. 7. Hennessey KA et al. Widespread para- lytic poliomyelitis in Pakistan: a case- control study to determine risk factors and implications for poliomyelitis eradi- 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM589 590 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 cation. Journal of infectious diseases, 2000, 182(1):6–11. 8. Hennessey KA et al. Widespread para- lytic poliomyelitis in Pakistan: a case– control study to determine risk factors and implications for poliomyelitis eradi- cation. Journal of infectious diseases, 2000, 182(1):6–11. 9. Reichler MR et al. Evaluation of oral po- liovirus vaccine delivery during the 1994 national immunization days in Pakistan. Journal of infectious diseases, 1997, 175(suppl. 1):S205–9. 10. Reichler MR et al. Cluster survey evalua- tion of coverage and risk factors for fail- ure to be immunized during the 1995 national immunization days in Egypt. In- ternational journal of epidemiology, 1998, 27(6):1083–9. 11. Singh B et al. Pulse polio immunization in Delhi—1995–96: a survey. Indian journal of pediatrics, 1997, 64(1):57–64. 12. Linkins RW et al. Evaluation of house-to- house versus fixed-site oral poliovirus vaccine delivery strategies in a mass im- munization campaign in Egypt. Bulletin of the World Health Organization, 1995, 73(5):589–95. 13. Progress toward poliomyelitis eradica- tion—Afghanistan and Pakistan, Janu- ary 2002–May 2003. Morbidity and mortality weekly report, 2003, 52(29): 683–5. Poliomyelitis eradication in the Eastern Mediterranean Region Rapid and significant progress towards the eradication of poliomy- elitis is continuing in all countries of the Eastern Mediterranean Re- gion. Poliovirus transmission has been interrupted in 17 countries of the Region for more than 3 years. Comprehensive information about the poliomyelitis eradication programme in the Eastern Medi- terranean Region can be found at: http://www.emro.who.int/polio/ 15 Characteristics of districts.pmd 8/17/2005, 11:08 AM590 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 591 Characterization of Leishmania infection in rodents from endemic areas of the Islamic Republic of Iran M. Mohebali,1 E. Javadian,1 M.R. Yaghoobi-Ershadi,1 A.A. Akhavan,1 H. Hajjaran1 and M.R. Abaei1 1School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. Received: 14/04/03; accepted: 26/10/03 ABSTRACT Between 1991–2000, Leishmania species were isolated and characterized by isoenzyme and molecular analysis from rodents caught in various parts of the Islamic Republic of Iran. In areas endemic for cutaneous leishmaniasis, parasites were observed by direct microscopy in smears from 18.6% of 566 specimens. L. major was isolated from 4 species: Rhombomys opimus, Meriones libycus, Tatera indica and Mer. hurrianae. L. turanica was isolated from R. opimus for the first time in this country. In endemic areas of visceral leishmaniasis, parasites were observed in liver and spleen from 13.7% of 504 rodents. Two species were positive on culture; promastigotes isolated from Mer. persicus were characterized as L. donovani zymodeme LON50 and from Mesocricetus auratus as L. infantum LON49. Caractérisation de l’infection à Leishmania chez des rongeurs des zones endémiques de la Répu- blique islamique d’Iran. RÉSUMÉ Entre 1991 et 2000, des espèces de Leishmania ont été isolées et caractérisées par isoenzymes et analyse moléculaire chez des rongeurs capturés dans diverses parties de la République islamique d’Iran. Dans les zones d’endémie de la leishmaniose cutanée, des parasites ont été observés par microscopie directe dans des frottis provenant de 18,6 % des 566 échantillons. L. major a été isolé chez quatre espèces : Rhombomys opimus, Meriones libycus, Tatera indica et Mer. hurrianae. L. turanica a été isolé chez R. opimus pour la première fois dans ce pays. Dans les zones d’endémie de la leishmaniose viscérale, des parasites ont été observés dans le foie et la rate de 13,7 % des 504 rongeurs. Deux espèces ont donné des cultures positives ; les promastigotes isolés chez Mer. persicus ont été caractérisés comme zymodème LON50 de L. donovani et ceux isolés chez Mesocricetus auratus comme LON49 de L. infantum. 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM591 592 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Introduction Leishmaniasis is an important health problem in the Islamic Republic of Iran. There are sev- eral foci of zoonotic cutaneous leishmaniasis (CL) in the north, east and south of the coun- try [1–6]. Zoonotic CL is essentially a disease of gerbils, transmitted by Phlebotomus pap- atasi and P. cocausicus and other species of sand fly that breed in gerbil burrows [7]. The human disease is secondary to the infection of gerbils and is seen only in places where the infected gerbils live [8]. Three different epi- demiological types of zoonotic CL have been observed in this country and 4 species of ro- dents (Gerbillidae) are the principal animal reservoir hosts in all foci [9]. Visceral leishmaniasis (VL), or kala-azar, is also seen sporadically all over the Islamic Republic of Iran and is of the Mediterranean type. Wild and domestic carnivores are the main animal reservoirs [10–12], but rodents have been reported as reservoirs in the Mesh- kin-Shar district [13]. Sand flies of the genus Phlebotomus are the most likely vector of VL in the endemic areas [10]. The study of Leishmania infection in rodents in the Islamic Republic of Iran started in 1953 in the north-east of the country [8] but, while it was extended to other parts of the country, the isolation and characterization of the parasites has not been investigated in these areas. In this study, we report the isolation and charac- terization of Leishmania species infection from a number of species of rodents that were trapped alive in different parts of the Islamic Republic of Iran in the last decade. Methods Study area The investigation was conducted over a period of 10 years from 1991 to 2000 in endemic foci of zoonotic CL and VL in the Islamic Republic of Iran (Figure 1). Collection and examination of rodents The study sites were determined by reports from local health authorities of outbreaks of human CL and VL infection. The active colonies of rodents were identified and the rodents were trapped alive in various parts of these areas. Specimens were collected from the colonies of gerbils located about 1–1.5 km around villages where CL or VL were endemic. Around 20–30 live traps were used each week and rodents were caught in all seasons. The genus and spe- cies of the rodents were determined by external characteristics: colour, body mea- surements, ears, tail, feet, teeth and crani- um [14,15]. Isolation of parasites from the caught rodents For detecting CL infection, 2 impression smears were taken from the ears of each rodent [13,16]. For detecting VL parasites, 2 impression smears from the spleen and liver of each rodent were prepared. The smears were fixed in methanol, stained by standard Giemsa methods and examined for parasites by light microscope at high magnification (× 1000). The samples from infected rodents were cultured in Novy–MacNeal–Nicolle (NNN) culture and liver infusion broth tryptose (LIT) and RPMI 1640 medium (Gibco Life Technologies, New York, USA) containing 10% heat-inactivated fetal calf serum. The cultures were checked for promastigotes twice a week for a period of 6 weeks. Leishmania species were characterized by random amplified polymorphic DNA– polymerase chain reaction (RAPD–PCR) 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM592 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 593 analysis [17,18] at the Medical Faculty, Shiraz University of Medical Sciences and the School of Pubic Health, Tehran Univer- sity of Medical Sciences and by isoenzyme analysis at the London School of Hygiene and Tropical Medicine, United Kingdom, and the Faculty of Medicine, University of Montpellier, France. Characterization of isolated parasites For the RAPD–PCR analysis, DNA was extracted from the promastigotes, cultured at 20 °C in RPMI1640 medium (10 000 parasites per 10 mL) and washed with Locke’s solution. The pellet was resus- pended in 100 µL lysis buffer. The lysate was extracted once with equal volumes of 1:1 (v/v) phenol:chloroform and once with 24:1 (v/v) chloroform isoamylalcohol and precipitated by ethanol. The DNA was re- suspended in the specified materials and amplification were done in a mixture con- taining 20 mmol/L (NH4)2(SO4), 75 mmol/L Tris-HCl, pH.9, 0.01% (w/v) Tween 20, 2 mmol/L MgCl2, 200 µmol/L deoxynulcleo- tide triposphate, 1 mmol/L primer and 1 unit of Taq polymerase. Then 1 µL of DNA (20 ng/µL) was added by centrifugation through the mineral oil overlay and the re- action was carried out in a thermocycler (Genius, Techne Ltd, United Kingdom) programmed for 1 cycle of 2 min at 94 °C, followed by 30 cycles of 30 s at tempera- tures of 94 °C, 1 min at 36 °C and 2 min at 72 °C. Aliquots from each reaction (12 µL) were run on 1.5% agarose gel and visual- ized under ultraviolet light with ethidium Figure 1 Areas endemic for zoonotic cutaneous leishmaniasis (ZCL) and visceral leishmaniasis (VL) where rodents were collected for the study aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa aaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa aaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaa aaaa aaaa aaaa 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM593 594 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 bromide. The primers used in this study were as follows: • AB1-07 GGT GAC GCA G • 327. ATA CGG CGT C • 329. GCG AAC CTC C • 333. GAA TGC GAC G • 335. TGG ACC ACC C For the isoenzyme characterization, af- ter mass production of promastigotes, samples were cultured in monophasic me- dia with 10% to 20% fetal calf serum, washed with phosphate-buffered saline at 4 °C with centrifugation at 2500–3000 × g for 20 min 3 times and freeze-thawed in liq- uid nitrogen several times, followed by electrophoresis on polyacrylamide gel. In this technique 12 enzymes were used: pyruvate kinase (PK), superoxide dismu- tase (SOD), phosphoglucomutase (PGM), peptidase D (PEPD), alanine aminotrans- ferase (ALT), aspartate aminotransferase (AST), nucleoside hydrolase (NH), glu- cose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphate isomerase (GPI), esterase (ES), methanol dehydrogenase (MDH) and mannose-6-phosphate iso- merase (MPI) [19]. Results Areas endemic for cutaneous leishmaniasis Altogether, 566 rodents (Gerbillidae) were trapped alive in several CL-endemic areas throughout the Islamic Republic of Iran from 1991 to 2000. Leishmania parasites were observed in cutaneous smears from 105 (18.6%) of the rodents by direct high magnification microscopy examination (Table 1). L. major was isolated from Rhombomys opimus, Meriones libycus, Tatera indica and Mer. hurrianae and characterized by isoenzyme analysis and molecular proce- dures (RAPD–PCR). All of the Leishmania species and strains were similar to Leish- mania species that had been isolated from human infection in the same areas. L. tu- ranica was isolated from an infected R. opimus for the first time in this country. R. opimus was the principal reservoir host of zoonotic CL in the north-eastern (Minoo Dasht) district where 85.2% of iso- lates tested positive (Table 1). It was also prominent in the central parts of the coun- try (Badrood, Ardakan and Sabzevar dis- tricts). Mer. libycus was found in 35.1% of isolates in the south-west (Fars province) and 25.0% in the central area. T. indica was the main reservoir host in foci of the south-west (14.3%) and south (Dashti and Dashtestan districts) of the country (4.5% of isolates tested positive). In the south- east of the country (including southern parts of Baluchistan, Dashtyari, Konarak and Chabahar areas) the main animal reser- voir was Mer. hurrianae (17.9% of iso- lates). Areas endemic for visceral leishmaniasis A further 504 rodents (Gerbillidae, Crice- tidae) were caught during 1994 to 2000 in 2 areas endemic for VL: Meshkin-Shahr dis- trict (north-west) and Dashti and Dash- testan districts (south). Leishmania para- sites were seen in livers and spleens of 69 (13.7%) of these rodents by microscopy (Table 2). Leishmania spp. were isolated from 2 specimens of Mer. persicus and 1 specimen of Mesocricetus auratus in culture media (Table 2). Although parasites were ob- served in a few specimens of Cricetulus migratorius, none were positive on culture. Using isoenzyme techniques the promastig- otes isolated from Mer. persicus were char- acterized as L. donovani zymodeme 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM594 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 595 Table 1 Leishmania species isolates from rodents caught in areas of the Islamic Republic of Iran endemic for cutaneuos leishmaniasis (1991–2000) Location of capture/ No. Positive on Leishmania rodent species tested microscopy species No. % identified North-east (Minoo Dasht district) Rhombomys opimus 27 23 85.2 L. major Meriones libycus 1 0 0 – South (Dashti and Dashtestan district) Tatera indica 133 6 4.5 L. major Meriones crassus 48 0 0 – Rattus rattus 3 0 0 – Nesokia indica 3 0 0 – Mus musculus 5 0 0 – South-east (Baluchestan) Meriones hurrianae 28 5 17.9 L. major Tatera indica 27 1 3.7 – Rattus rattus 3 0 0 – Rattus norvegicus 4 0 0 – Mus musculus 5 0 0 – Nesokia indica 2 0 0 – Funambulus pennanti 1 0 0 – West (Mehran district) Tatera indica 22 2 9.1 L. major Nesokia indica 8 0 0 _ Central (Badrood district) Meriones libycus 36 9 25.0 L. major Rhombomys opimus 25 8 32.0 L. major South-west (Fars province) Meriones libycus 97 34 35.1 L. major Tatera indica 21 3 14.3 – Central (Ardakan district) Rhombomys opimus 26 3 11.5 L. major Meriones libycus 19 3 15.8 – Central (Sabzevar district) Rhombomys opimus 22 8 36.4 L. major and L. turanica Total 566 105 18.6 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM595 596 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 LON50 and those from Mes. auratus were identified as L. infantum LON49. Discussion Both CL and VL are endemic in the Islamic Republic of Iran. Mucosal leishmaniasis is usually an extension of the cutaneous form, except for 3 cases of lesions of the palate for which the causative organisms are un- known [20]. The cutaneous form of leishmaniasis is seen in 2 forms: anthroponotic and zoonot- ic. Anthroponotic CL is endemic in many large- and medium-size cities, as well as villages in the suburbs of these foci. The main reservoir host of CL is man, although the lesions have been observed on dogs in Tehran, Mashad, Shiraz and Kerman [9]. Zoonotic CL is endemic in many foci in the north, east and south of the country [9]. This is essentially a disease of gerbils, transmitted by sand flies that live and breed in the gerbil burrows. The human disease is secondary to the infection of gerbils and is seen only in places where the infected ger- bils live. Our results show that R. opimus (great gerbil) is the principal reservoir host of zoonotic CL in the central and north-east parts of the country. Mer. libycus (Libyan jird) was also found to be infected and can act as a secondary reservoir host in the ab- sence of R. opimus. Of course, in some areas from the centre and south of the country, gerbils have become the primary reservoir of zoonotic CL due to ecological changes [21]. Other foci are in Turkemen- Sahara, Lotfabad and Sarakhs, that is the border with Turkemenistan Republic, Es- farayen in Khorasan, Bakran in Semnan, Abarkuh in Yazd, Neiriz and Estahban in Fars provinces. Natural Leishmania spp. infection of R. opimus is found in Abardej of Varamin near Tehran but far from human residences and Leishmania species have not yet been determined [9,22]. T. indica (Indian jird) is the main reser- voir host of zoonotic CL in foci of the south-west and south of the country. Table 2 Leishmania species isolates from rodents caught in areas of the Islamic Republic of Iran endemic for visceral leishmaniasis (1994–2000) Location of capture/ No. Positive on Positive on Leishmania species rodent species tested microscopy culture media and zymodemes identified No. % No. % Meshkin-Shahr Cricetulus migratorius 15 2 13.3 0 0 – Mesocricetus auratus 2 1 50.0 1 50.0 L. infantum LON49 Meriones persicus 394 66 16.8 2 0.5 L. donovani LON50 Mus musculus 7 0 0 0 0 – Allactaga spp. 1 0 0 0 0 – Dashti and Dashtestan district Tatera indica 85 0 0 0 0 – Total 504 69 13.7 3 0.6 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM596 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 597 These areas include the Iran–Iraq borders from Sumar to the Gulf, all the provinces of Khuzestan and some parts of Ilam, Bushehr and Hormozegan [1,11,23]. In foci of the south-east of the country, the main animal reservoir is Mer. hurrianae (Indian desert jird). These areas include the southern parts of Baluchistan, Dashtyari, Konarak and Chabahar areas. This type of zoonotic CL is similar to the foci of the dis- ease reported from Rajasthan in India [4,7,9]. The visceral form of leishmaniasis is seen in sporadic form all over the Islamic Republic of Iran and is endemic in Ardebil and east Azerbaijan provinces in the north- west, and in Fars and Bushehr in the south. Wild and domestic dogs are the main reser- voir hosts of VL [12]. In this study, amastigotes were observed in 13.7% of the rodents on microscopic examination of the smears prepared from internal organs. L. donovani LON-50 was isolated from 2 specimens of Mer. persicus (Persian jird). It seems to transmit from infected rodents to humans in these endemic areas. L. in- fantum LON-49 was isolated from 1 spec- imen of Mes. auratus (golden hamster). This species of Leishmania is zoonotic and had been previously isolated from humans [10] and dogs in the Meshkin-Shahr area [12], and also from dogs and foxes in the Dashti district of Bushehr province [11]. L. infantum had been isolated from Rattus rat- tus (black rat) in Italy and Iraq [24]. In one study, Mer. persicus was reported to be nat- urally infected with Leishmania spp. in east Azerbaijan, in the north-west of the Islamic Republic of Iran. In the smears prepared from the cutaneous lesion of this gerbil, considerable numbers of amastigotes were seen. However, microscopic examination of the smears prepared from the internal organs and blood of this rodent did not show any amastigotes [25]. In the other study that was carried out in the Semes- kandeh area of Mazanderan province in the north of the Islamic Republic of Iran, Leishmania spp. infection was reported in internal organs of R. rattus but Leishmania parasites were not isolated from them (Gholami, personal communication). In conclusion, this study has shown that rodents harbour Leishmania spp. in- fection and may therefore have a role in transmission of leishmaniasis to humans, particularly to children. Further ecological and biological studies of rodents and sand flies are necessary in endemic foci of zoonotic VL from the Islamic Republic of Iran until the exact role of the rodents as animal reservoirs is clarified completely. Acknowledgements We are very grateful to the field staff of the provincial health department of Isfahan, Golestan, Bushehr, Baluchistan, Ilam, Fars and Yazd provinces. The authors would like to thank Dr D. Evans and Dr S. Mazlumi from the London School of Hygiene and Tropical Medicine; Dr J.P. Dedet from Montpellier, France, for isoenzyme charac- terization of the Leishmania isolates; and Dr K.P. Chang from Chicago University, USA, and student Kayako for performing PCR-RFLP. Thanks are also due to Dr Y. Hamzavi and Dr H. Kathiri for field activi- ties. This investigation was supported by the School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences. 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM597 598 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 References 1. Javadian E et al. Reservoir host of cuta- neous leishmaniasis in Iran [Abstract]. Proceedings of the XIIth International Congress of Tropical Medicine and Ma- laria. Amsterdam, The Netherlands, 18– 23 September, 1988. 2. Nadim A, Seyedi-Rashti MA, Mesghali A. Epidemiology of cutaneous leishmania- sis in Turkemen Sahara, Iran. Journal of tropical medicine and hygiene, 1968, 71:238–9. 3. Nadim A, Seyedi-Rashti MA. A brief re- view of the epidemiology of various types of leishmaniasis in Iran. Acta medica iranica, 1971, XIV:99–106. 4. Seyedi-Rashti MA et al. Cutaneous leishmaniasis in Baluchistan, Iran [Ab- stract and Poster]. Proceedings of the XI International Congress of Tropical Medi- cine and Malaria. Calgary, Canada, 16– 22 September, 1984. 5. Yaghoobi-Ershadi MR et al. Epidemiol- ogy study in a new focus of cutaneous leishmaniasis due to Leishmania major in Ardestan town, Central Iran. Acta tropica, 2002, 79:115–21. 6. Hamzavi Y et al. Epidemiological studies of cutaneous leishmaniasis (human in- fection, animal reservoirs) in Dashti and Dashtestan districts, Bushehr province. Iranian public health, 2000, 29(1–4): 177–91. 7. Control of the leishmaniases. Report of a WHO Expert Committee. Geneva, World Health Organization, 1990:1–158 (WHO Technical Report Series, No. 793). 8. Nadim A, Faghih M. 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Rodents: another group of animal reservoir hosts of vis- ceral leishmaniasis in Meshkin-Shahr district, the Islamic Republic of Iran. East- ern Mediterranean health journal, 1998, 4(2):376–8. 14. Ziaei H. A field guide for identifying of Ira- nian desert mammalians, 1st ed. Tehran, Iran, Iranian Environment Orga- nization, 1996:129–87. 15. Boitani L, Bartoli S. Macdonald encyclo- pedia of mammals. London, Macdonald & Co., 1980. 16. Edrissian GH, Zovein Z, Nadim A. A simple technique for preparation of smears from the ear of Rhombomys opimus for the detection of leishmanial infection. Transactions of the Royal Soci- ety of Tropical Medicine and Hygiene, 1982, 76:706–7. 17. Noyes HA, Belli AA, Maingon R. Ap- praisal of various RAPD–PCR primers 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM598 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 599 for Leishmania identification. American journal of tropical medicine and hy- giene, 1996, 55(1):98–105. 18. Motazedian H, Noyes H, Maingon R. Leishmania and sauroleishmania: the use of random amplified polymorphic DNA for identification of parasites from vertebrates and invertebrates. Experi- mental parasitology, 1996, 83:150–4. 19. Evans DB. Handbook on isolation, char- acterization and cryopreservation of Leishmania. UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. Geneva, World Health Organization, 1989:14– 32. 20. Yaghoobi MR et al. Mucosal leishmania- sis: report of three cases. Archives of Ira- nian medicine, 2001, 4(3):138–40. 21. Yaghoobi-Ershadi MR, Akhavan AA, Mohebali M. Meriones libycus and Rhombomys opimus (Rodentia: Ger- billidae) are the main reservoir hosts in a new focus of zoontic cutaneous leishma- niasis in Iran. Transactions of the Royal Society of Tropical Medicine and Hy- giene, 1996, 90(5):503–4. 22. Seyedi-Rashti MA et al. A new focus of zoonotic cutaneous leishmaniasis near Tehran, Iran. Proceedings of the VIIth In- ternational Congress of Parasitology, Paris, France, 20–24 August. Bulletin de la Societe Francaise de Parasitology, 1990, (suppl.)2:1145. 23. Javadian E et al. Confirmation of Tatera indica (Rodentia:Gerbillidae) as the main reservoir host of zoonotic cutane- ous leishmaniasis in the west of Iran. Ira- nian journal of public health, 1998, 27(1–2):55–60. 24. Desjeux P. Information of epidemio- logy and control of the leishmaniases by country or territory. Geneva, World Health Organization, 1991 (WHO/ LEISH/91.30). 25. Edrissian GH, Ghorbani M, Tahvildar- Bidruni G. Meriones persicus, another probable reservoir of zoonotic cutane- ous leishmaniasis in Iran. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1975, 69(5–6):517–9. 16 Characterization of Leishmania.pmd 8/17/2005, 11:08 AM599 600 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Smoking in Oman: prevalence and characteristics of smokers A.A. Al Riyami1 and M. Afifi1 1Department of Research and Studies, Ministry of Health, Muscat, Oman. Received: 07/01/03; accepted: 20/10/03 ABSTRACT We carried out a cross-sectional survey to study the prevalence and the characteristics of current and former smoking among Omani adults. Crude prevalence of current smoking was 7.0% (males 13.4%, females 0.5%); 2.3% were former smokers. The overall highest prevalence of current smoking (11.1%) was observed in those 40–49 years (18.7% of males, 0.9% of females). Older age (≥ 40 years), higher educational level and larger family size were protective against smoking. Mean age for starting smoking was 18.7 years for males and 24.3 years for females. Although smoking prevalence is low in Oman, prevention should be addressed in health education programmes, with the emphasis on heightening aware- ness in adolescents. Government action, e.g. tobacco taxation, clean air laws and bans on advertising, is also recommended. Le tabagisme à Oman : prévalence et caractéristiques des fumeurs RÉSUMÉ Nous avons réalisé une enquête transversale pour étudier la prévalence et les caractéristiques des fumeurs actuels et des anciens fumeurs parmi les Omanais adultes. La prévalence brute du tabagisme actuel était de 7,0 % (hommes : 13,4 %, femmes : 0,5 %) ; 2,3 % étaient des anciens fumeurs. La préva- lence globale du tabagisme actuel la plus élevée (11,1 %) était observée chez les personnes de 40 à 49 ans (18,7 % d’hommes, 0,9 % de femmes). Un âge plus avancé (≥ 40 ans), un niveau d’études plus élevé et une famille de plus grande taille représentaient une protection contre le tabagisme. L’entrée dans le tabagisme avait lieu à un âge moyen de 18,7 ans chez les hommes et 24,3 ans chez les femmes. Bien que la prévalence du tabagisme soit faible à Oman, la prévention devrait être envisagée dans le cadre des programmes d’éducation sanitaire, en mettant l’accent sur la sensibilisation chez les adolescents. Une action des pou- voirs publics, par exemple par les taxes sur le tabac, les lois sur la pureté de l’air et l’interdiction de la publicité, est également recommandée. 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM600 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 601 Introduction Worldwide, it is estimated that tobacco causes about 8.8% of deaths (4.9 million) and 4.1% of disability adjusted life years (59.1 million). Attributable mortality is greater in males (13.3%) than in females (3.8%) [1]. Tobacco use is a growing health concern in the developing world, particularly in places where disposable in- come is increasing [2]. Smoking preva- lence has increased in adolescents since 1991 even though there has been a decline in the overall prevalence of smoking in many industrialized countries [3]. According to the most recent estimate by the World Health Organization, 4.9 mil- lion people worldwide died in 2000 as a re- sult of their addiction to nicotine, about half of them prematurely [1]. Developing coun- tries already account for half of all deaths attributable to tobacco. The proportion will rise to 7 out of 10 by 2025 because smok- ing prevalence has been increasing in many low-income and middle-income countries while it is falling in richer countries, espe- cially among men [4]. Lam et al. concluded that among middle aged men the proportion of deaths caused by smoking was more than twice as great in Hong Kong in 1998 as in mainland China 10 years earlier [5]. Another study on smoking and mortality from tuberculosis and other diseases in In- dia showed that the death rates from medi- cal causes of ever-smokers were double those of never smokers [6]. In Saudi Ara- bia, Al Khadra found that smoking was the main risk factor for having acute myocar- dial infarction at a young age (< 45 years), followed by low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and diabetes [7]. Oman and other oil-producing countries in the Middle East have experienced rapid economic, sociodemographic and epidemi- ological transitions over the past 3 decades. The sociocultural and economic patterns of the Omani population do not typically cor- respond to either the Western community or to the developing countries in Asia. This is why data on smoking in Oman would be valuable and therefore why we conducted our study. The aim of the study was to estimate prevalence of smoking among adults of both sexes aged 20 years and above, to study the characteristics of current smok- ers, to identify the age of starting smoking, reasons for smoking and factors related to smoking cessation in a community-based survey as a part of the Omani National Health Survey, 2000. Methods Sample The sample for the survey was selected to be representative of the nation as a whole. The survey adopted a multi-stage, stratified probability-sampling design. In the first stage, all 10 regions of Oman were selected and the sample was distributed according to proportional allocation of the population in each. In each region, 1 or more wilayat (districts) were randomly chosen accord- ing to the size of the population. The num- ber of wilayat selected was 16 out of a total of 59 (27%). Then, each wilayat was strat- ified into 2 strata; the first stratum was the wilayat centre, covering the urban area and the second stratum was the villages or re- mote areas, the rural areas. The urban:rural ratio was 2:1, which is similar to the ratio in the 1993 national census [8]. The second stage was the random se- lection of the population sampling units in each stratum. These population sampling units were the census units which were used during the 1993 population census. 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM601 602 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 The third stage was the selection of house- holds from these population sampling units. Maps of the selected population sampling units were updated and a complete listing of all Omani households in each unit was made to obtain the sampling frame, then households were systematically randomly selected. All individuals aged 20 years and above in the selected household were invit- ed to participate in the survey. The total number of households selected was 1968 with a total of 7011 people fulfilling the se- lection criteria. The prevalence of the least expected disorder of the lifestyle risk fac- tors studied (smoking rate among female adults, 0.2%) was used to calculate the sample size of the survey. The response rate varied, according to the type of mea- surement or completed laboratory investi- gation, from 83% (for fasting blood sugar) to 91.5% (for blood pressure measure- ment). Questionnaire and measurements The questionnaire covered demographic and socioeconomic data (age, sex, marital status, educational status, work status, family size and place of residence) and in- cluded questions related to current smok- ing, age of starting smoking, number of cigarettes smoked per day, type of tobacco product smoked, reasons for smoking, his- tory of temporarily quitting smoking for a year or more, being a former smoker and the number of years of smoking cessation and reasons for smoking cessation. Mea- surements of blood pressure, weight, height, waist circumference and hip cir- cumference were registered in the ques- tionnaire. World Health Organization proce- dures were used for taking the measure- ments [9]. The questionnaire also included items for the laboratory investigations for fasting blood sugar and serum cholesterol. Specimen collection and analysis The survey was carried out by 25 teams. Each consisted of a nurse to take the mea- surements, a laboratory technician to draw the blood samples, a health educator to in- terview the subjects, a health inspector to transport the samples to the laboratory and a field supervisor (statistician) to supervise and review the questionnaires during field operations. They were all trained on the methodology of the survey for 2 weeks. The eligible members of the selected households were asked to start fasting 1–2 hours before midnight the night before they were due a visit by the survey team. The following morning at 07.00 the participants were interviewed, measurements were tak- en, and venous fasting blood samples were collected. Fasting blood samples for glu- cose were collected in sodium fluoride po- tassium oxalate tubes, labelled and transferred immediately with laboratory forms to the laboratory in the wilayat hos- pital in coldboxes. Samples were then im- mediately centrifuged, the plasma was separated and fasting plasma glucose was determined by a glucose oxidase method on the same day using the Hitachi 911 auto- mated clinical chemistry analyser (Boe- hringer Mannheim, Germany) [10]. The same manufacturer supplied the reagents. The samples for estimation of cholesterol were collected in tubes containing lithium heparin anticoagulants and transferred to the laboratory in the same way. Estimation of serum cholesterol was done by enzy- matic colorimetric method using the Hita- chi 911 automated clinical chemistry ana- lyser [11]. Diagnostic criteria The World Health Organization criteria (1999) for diagnosis of hypertension, hy- percholesterolaemia, anthropometric mea- 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM602 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 603 surement and glucose intolerance were used [12]. Prevalence of hypertension was esti- mated by adding the number of people self- reporting systolic or diastolic hypertension (whether their blood pressure was normal or not at the screening time) and the num- ber of people with mean of 2 readings ≥ 140 mmHg systolic blood pressure or ≥ 90 mmHg diastolic phase 5 blood pres- sure i.e. either isolated systolic or diastolic hypertension. Blood pressure was taken in a sitting position at 5-minute intervals; the average of these readings was calculated to the nearest 5 mmHg. High total cholesterol was defined as ≥ 5.2 mmol/L or ≥ 200 mg/dL. Participants were considered under- weight if their body mass index (BMI) was < 18.5 kg/m2, normal if their BMI was 18.5–24.9 kg/m2, overweight if their BMI was 25.0–29.9 kg/m2, obese if their BMI was 30.0–39.9 kg/m2, morbid obese if their BMI was ≥ 40.0 kg/m2. Abnormal waist:hip ratio [waist circum- ference (m)/hip circumference (m)] (cen- tral obesity) was defined as ≥ 0.85 for females and ≥ 0.95 for males. Impaired fasting glucose (IFG) was defined as fasting blood glucose 6.1–6.9 mmol/L. Diabetes prevalence was estimated by adding the number of people selfreporting diabetes and the number of people with fast- ing blood glucose ≥ 7.0 mmol/L. The total number of participants with IFG was the sum of those with IFG and those with dia- betes. Pilot study A pretest was carried out to test the house- holds and the individual questionnaires and forms to obtain information about opera- tional and organizational procedures and to get an indication of the general response to physical examination and specimen collec- tion. A total of 120 households were se- lected from different areas in Muscat gov- ernorate. All the survey questionnaires and forms were interpolated and were revised by experts. Measurements and specimens were also taken. The questionnaires and forms and some organizational procedures were adjusted after the debriefing session for interviewers and supervisors. The problems, performance rates and general receptivity to the survey were analysed and discussed. Data processing and analysis Data entry was done using Epi-Info, ver- sion 6. The preparation of the data file was completed by July 2000. Respondents were defined as current smokers if they were smoking at the time of the survey and had smoked more than 100 cigarettes in their lifetime; they were defined as former smokers if they had smoked more than 100 cigarettes in their lifetime but no longer smoked; and they were defined as never smokers if they had never smoked or had smoked less than 100 cigarettes in their lifetime. Analysis of the data was done using SPSS, version 5.0. Data were given as counts, means and percentages. Likelihood chi-squared test examined the distribution of data while group means were compared using analysis of variance. Logistic regres- sion was conducted to test the most impor- tant independent associated factors (age, level of education, marital status, family size, residence, work status, hypertension, total IFG, hypercholesterolaemia, obesity or central obesity) with the dependent or the outcome variable (current smoking) with and the adjusted odds ratio (OR) was calculated for these factors. Logistic re- gression determines the independence of the associations observed in bivariate anal- ysis by controlling for potential confound- 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM603 604 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 ing variables. The OR shows the change in the odds of the dependent variable when the independent changes from 0 to 1. P < 0.05 was considered statistically signifi- cant. Results A total of 7011 respondents aged 20 years and over [mean age 38 years, standard de- viation (SD) 15.2] participated in the study, 3506 of them males (50% of the sample, mean age 38.4 years, SD = 16.7) and 3505 females (mean age 37.6 years, SD = 15.6). Overall, 7.0% of the respondents were classified as current smokers, 2.3% as former smokers and 90.7% as never smok- ers. The majority of current smokers smoked cigarettes (82.9%), 6.4% smoked shisha (water pipe), 7.9% smoked gadou (gouza, a differently shaped pipe that uses different tobacco and a more direct burning method), 7.7% smoked a pipe, and 4.5% used other tobacco products e.g. chewing tobacco. Current smokers constituted 13.4% of males; 4.6% were former smokers and 82.1% were never smokers. Only 0.5% of females were current smokers, 0.1% were former smokers and 90.4% were never smokers. Of current smokers, 16.7% had a history of smoking cessation for 1 year or more then returned to smoking; 41.8% of them stopped smoking for only 1 year. Table 1 shows the number of current smokers according to age group, marital status, education level, etc. In males and in the overall sample, smoking prevalence was highest in the age group 40–49 years, with 18.7% of males, 1.0% of females, and 11.1% overall in this age group (χ2 test sig- nificant at P < 0.05). For the whole sample, the prevalence of smoking was also significantly associated with marital status, education level, work status and family size. For males, the same pattern was shown except for work status (χ2 test significant at P < 0.05). For fe- males, smoking was only associated with age and education level (Fisher exact test significant at P < 0.05). Smoking was not significantly associated with total IFG for the overall sample, males or females, whereas it was significantly associated with hypertension for all 3 groups. We found no association between smoking and hypercholesterolaemia, obesity or central obesity in the overall sample or the male sub-sample. Using multiple logistic regression, age, level of education, marital status and family size were the strongest determinants of current smoking for males (Table 2). The test was not done for the female group due to the very low prevalence. The majority of male smokers (58.7%) started smoking before the age of 20 years, while among females the highest percent- age (31.6%) started smoking at a later age (20–29 years) (Table 3). The mean age of starting smoking was 18.7 years for males and 24.3 years for females and the differ- ence was significant at P < 0.05 by analysis of variance test (data not shown). Of the current male smokers, 49.7% smoked 10 cigarettes or fewer per day, 38.0% smoked 11–20 cigarettes per day (Table 4), while former smokers smoked fewer cigarettes: 62.3% smoked 1–10 cig- arettes per day. The same pattern was no- ticed for the overall sample. Of the current smokers, 46.0% said that the reason for smoking was out of habit, while 21.5% of them said smoking helped them to relax. In addition, 13.4% of the sample smoked because their friends smoked and 11.5% looked on smoking as leisure (data not shown in tables). 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM604 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 605 Table 1 Prevalence of smoking in males and females for some demographic and health characteristics Characteristic Males (n = 3506) Females (n = 3505) Total (n = 7011) n No. % n No. % n No. % Age group (years) 20–29 1454 167 11.5 1431 2 0.1 2885 169 5.9 30–39 674 118 17.5 789 5 0.6 1463 123 8.4 40–49 465 87 18.7 344 3 0.9 809 90 11.1 50–59 391 57 14.6 552 4 0.7 943 61 6.5 60–64 189 14 7.4 136 3 2.2 325 17 5.2 ≥ 65 329 26 7.9 249 2 0.8 578 28 4.8 Marital status Married 2327 337 14.5 2336 14 0.6 4663 351 7.5 Single, divorced, widowed 1168 131 11.2 1156 5 0.4 2324 136 5.9 Education level Illiterate/preparatory school 2492 413 16.6 2658 19 0.7 5150 432 8.4 Secondary and above 964 52 5.4 789 0 0.0 1753 52 3.0 Work status Working 2348 327 13.9 429 0 0.0 2777 327 11.8 Not working 1141 140 12.3 3044 18 0.6 4185 158 3.8 Residence Urban 2592 343 13.2 2548 17 0.7 5140 360 7.0 Rural 910 126 13.8 953 2 0.2 1863 128 6.9 Family size ≤ 10 members 1818 286 15.7 1870 12 0.6 3688 298 8.1 > 10 members 1684 183 10.9 1631 7 0.4 3315 190 5.7 Total IFG Normal 2340 317 13.5 2441 13 0.5 4781 330 6.9 TIFG 531 76 14.3 471 6 1.3 1002 82 8.2 Blood pressure Normal 1975 252 12.8 2312 7 0.3 4287 259 6.0 Hypertension 1079 168 15.6 1042 12 1.2 2121 180 8.5 Cholesterol Normal 1747 240 13.7 1726 10 0.6 3473 250 7.2 Hypercholesterolaemia 1171 157 13.4 1201 9 0.8 2372 166 7.0 Obesity No 1654 253 15.3 1694 10 0.6 3348 263 7.9 Yes 1417 171 12.1 1659 9 0.5 3076 180 5.9 Central obesity No 1947 258 13.3 1179 8 0.7 3126 266 8.5 Yes 896 122 13.6 2145 11 0.5 3041 133 4.4 Some categories do not sum to the total sample due to missing data. TIFG = total impaired fasting glucose. 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM605 606 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Of the current smokers, 17.12% had a history of temporarily stopping smoking for 1 year or more. Of these, 40.7% had stopped for 1 year, 45.1% for 2–5 years and 14.2% for more than 5 years then re- turned to smoking. As regards former smokers, 21.1% stopped smoking for cur- ative reasons, 33.6% because in the nega- tive effects of smoking and 27.5% realized that there was no benefit in smoking. About 7% of the former smokers had ceased smoking for 1 year, 31.5% for 2–5 years, 24.2% for 6–10 years and the rest for more than 10 years. There was no significant as- sociation between the reason for smoking cessation and the number of years of smoking cessation. (χ2 = 0.01, P = 0.9) (data not shown in tables). Discussion There are few published data on the epide- miology of smoking in Gulf countries, in- cluding Oman. Comparable data on the prevalence of smoking are not widely avail- able and are often inaccurate, especially when age-specific data are required. More importantly, current prevalence of smoking is a poor proxy for the cumulative hazards of smoking, which depend on several fac- tors, including the age at which smoking began, duration of smoking, number of cigarettes smoked per day, degree of inha- lation, and cigarette characteristics such as tar and nicotine content or type of filter [1]. Smoking is related to substantially in- creased risk of mortality from lung cancer, upper aerodigestive cancer, several other cancers, heart disease, stroke, chronic res- piratory disease and a range of other medi- cal conditions. As a result, in populations where smoking has been common for many decades, tobacco use accounts for a considerable proportion of mortality, as il- lustrated by estimates of smoking- attributable deaths in industrialized coun- tries [5,13]. In 1995, the Oman Family Health Sur- vey revealed that an estimated 6.7% of those aged 15 years or over were current Table 2 Multiple logistic regression for variables significantly associated with current smoking among males Variable OR 95% CI P Age group (years) 20–39a ≥ 40 0.61 0.47–0.79 < 0.01 Education level Illiterate/preparatory schoola Secondary and above 0.26 0.18–0.38 < 0.01 Family size < 10 membersa ≥ 10 members 0.6 0.48–0.77 < 0.01 Marital status Marrieda Single, divorced, widowed 0.73 0.55–0.97 0.03 OR = odds ratio. CI = confidence interval. aReference category. Table 3 Age when started smoking for current and former smokers among males, females and overall sample Age at starting Males Females Total smoking No. % No. % No. % (years) ≤ 10 32 5.6 1 5.3 33 5.6 11–14 81 14.3 3 15.8 84 14.3 15–19 221 38.8 4 21.1 225 38.3 20–29 195 34.3 6 31.6 201 34.2 30–39 31 5.4 3 15.8 34 5.8 ≥ 40 9 1.6 2 10.5 11 1.9 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM606 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 607 smokers, 13.2% for males and 0.2% for the female respondents (A.J.M. Sulaiman, A. Al Riyami, S. Farid, unpublished data, 1995). The results of the 1995 survey were only descriptive in nature and there was, therefore, a need to study the epidemiology and correlates of smoking. The smoking rate in our study did not show any signifi- cant rise compared to 1995. The preva- lence of smoking in Oman is lower than that in other Gulf or Asian countries. In Kuwait, smoking rate was 38.1% among physicians [14], 30% among male students [15], 37% among married men and 0.5% among married women [16]. In Saudi Ara- bia, the 1994 smoking rate was 40.0% for males and 8.2% for females [17]. In Bahr- ain, in a study conducted in the year 2000, the prevalence of smoking was high for both sexes: 32.1% among men and 20.7% among women aged 30–79 years [18]. In China, the rate was much higher for males, 66.6%, whereas it was low, 1.7%, among females [19]. Women in Oman as well as other devel- oping countries tend to have lower rates of smoking than men [20, A.J.M. Sulaiman, A. Al Riyami, S. Farid, unpublished data, 1995]. They also start smoking later than men and smoke fewer cigarettes. This is mainly the result of sociocultural, religious or economic factors. In some societies, it may be considered improper or indecent for females to be seen smoking in public; in addition there may be religious or economic arguments against it. Smoking rates were significantly lower in people having a higher educational level (secondary and above) using bivariate and multivariate analysis. The same results were found by Memon et al. in Kuwait [20]. In contrast, Saeed, Khoja and Khan in Saudi Arabia found that smoking rates were significantly higher among literate than illit- erate people, which could be explained by smoking being popular in higher social classes as it could denote prestige [17]. Older age was a protective factor against smoking; the majority of the current and former smokers in our study, almost 55%, began smoking in adolescence. For this reason, a major effort should be directed towards implementing health education for children and adolescents. Anti-tobacco ed- ucation should be included as an integral part of the curriculum in schools. Table 4 Number of cigarettes smoked per day for former and current smokers No. Males Females Total cigarettes Current Former Current Former Current Former per day smokers smokers smokers smokers smokers smokers No. % No. % No. % No. % No. % No. % ≤ 10 217 49.7 94 62.3 10 62.5 2 66.7 227 50.1 96 62.3 11–20 166 38.0 44 29.1 5 31.3 1 33.3 171 37.8 45 29.2 21–30 33 7.6 6 4.0 1 6.3 0 0.0 34 7.5 6 3.9 31–40 21 4.8 4 2.6 0 0.0 0 0.0 21 4.6 4 2.6 > 40 0 0.0 3 2.0 0 0.0 0 0.0 0 0.0 3 1.9 Mean (SD) 13.8 (9.3) 11.8 (10.3) 10.2 (8.5) 9.7 (9.1) 13.7 (9.3) 11.8 (10.3) SD = standard deviation. 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM607 608 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Conclusion and recommendations Although the study revealed lower rates of smoking in Oman in comparison with other Gulf countries, anti-tobacco programmes should be vigorously implemented to pre- vent the health consequences of smoking. Tobacco is not cultivated or produced in Oman. A pack of 20 imported cigarettes costs around US$ 1, and the war against tobacco is not easy. Children and adoles- cents should be targeted, and reasons for smoking cessation and the diseases associ- ated with smoking should be taken into consideration in planning a health education programme. Because some of the issues concerning tobacco control may be beyond the domain of national policies and legislation, tobacco control policies are not being implemented worldwide at a rate that current scientific knowledge about the dangers of toba- cco warrants. International collaboration should be aimed for in order to share policy and programme information and implement tobacco control strategies. Government action in the form of tobacco taxation; clean indoor air laws in public places through legislation and enforcement; com- prehensive bans on advertising of tobacco through legislation; dissemination of infor- mation through health warning labels, counter-advertising and various consumer information packages; and nicotine re- placement therapy targeting current smok- ers aged 20–60 years are recommended. The benefits of reduction in tobacco use now, although taking longer to materialize than those resulting from reduction of some other risks, are great and long lasting. This is seen in the estimated tens of mil- lions of healthy life years to be saved by 2010 and 2020 as a result of preventing and reducing tobacco use [1]. References 1. The world health report 2002: reducing risks, promoting healthy life. Geneva, World Health Organization, 2002. 2. World Bank. World development report 1993: investing in health. New York, Ox- ford University Press, 1993. 3. Wechsler H et al. Increased levels of cigarette use among college students: a cause for national concern. Journal of the American Medical Association, 1998, 280(19):1673–8. 4. de Beyer J, Brigden LW, eds. Tobacco control policy: strategies, success, and setbacks. Washington, World Bank and Research for International Tobacco Con- trol, 2003:1. 5. Lam TH et al. Mortality and smoking in Hong Kong: a case–control study of all adult deaths in 1998. British medical journal, 2001, 323(7309):361–7. 6. Gajalakshmi V et al. Smoking and mor- tality from tuberculosis and other dis- eases in India: retrospective study of 43 000 adult male deaths and 35 000 controls. Lancet, 2003, 362(9383):507– 15. 7. Al Khadra AH. Clinical profile of young patients with acute myocardial infarction in Saudi Arabia. International journal of cardiology, 2003, 91(1):9–13. 8. Facts and figures: Special issue on devel- opment efforts 1970–2000. Muscat, Oman, Ministry of National Economy, Information and Publication Centre, 2000: 4. 9. King H, Minjoot-Pereira G. Diabetes and noncommunicable disease risk factor 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM608 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 609 surveys: a field guide. Geneva, World Health Organization, 1999. 10. Kadish AH, Hall DA. A new method for the continuous monitoring of blood glucose by measurement of dissolved oxygen. Clinical chemistry, 1965, 11(9): 869–75. 11. Allain CC et al. Enzymatic determination of total serum cholesterol. Clinical chem- istry, 1974, 20(4):470–5. 12. Definition, diagnosis and classification of diabetes mellitus and its complica- tions. Report of a WHO consultation. Part 1: Diagnosis and classification of diabe- tes mellitus. Geneva, World Health Orga- nization, 1999 (WHO/NCD/NCS/99.2). 13. Boyle P. Cancer, cigarette smoking and premature death in Europe: a review including the Recommendations of Eu- ropean Cancer Experts Consensus Meeting, Helsinki, October 1996. Lung cancer, 1997, 17(1):1–60. 14. Bener A, Gomes J, Anderson JA. Smok- ing habits among physicians in two Gulf countries. Journal of the Royal Society of Health, 1993, 113(6):298–301. 15. Moody PM, Al Bustan A, Al Shatti A. Cigarette smoking habits among Kuwait University male students pre- and post- invasion periods. Journal of the Kuwait Medical Association, 1996, 28(3): 274–8. 16. Radovanovic Z, Shah N, Behbehani J. Prevalence of smoking among currently married Kuwaiti males and females. Eu- ropean journal of epidemiology, 1999, 15(4):349–54. 17. Saeed AA, Khoja TA, Khan SB. Smoking behaviour and attitude among adult Saudi nationals in Riyadh City, Saudi Arabia. Tobacco control, 1996, 5(3):215– 9. 18. Hamadeh RR, Musaiger AO. Life style patterns in smokers and non-smokers in the state of Bahrain. Nicotine and to- bacco research, 2000, 2(1):65–9. 19. Gong YL et al. Cigarette smoking in China. Prevalence, characteristics and attitudes in Minhang district. Journal of the American Medical Association, 1995, 274(15):1232–4. 20. Memon A et al. Epidemiology of smoking among Kuwaiti adults: prevalence, char- acteristics, and attitudes. Bulletin of the World Health Organization, 2000, 78(11):1306–15. 17 Smoking in Oman.pmd 8/17/2005, 11:08 AM609 610 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Some risk factors for hypertension in the United Arab Emirates S. Sabri,1 A. Bener,2 V. Eapen,1 M.S.O. Abu Zeid,3 A.M. Al-Mazrouei 4 and J. Singh5 1Department of Psychiatry, Faculty of Medicine and Health Science, UAE University, United Arab Emirates. 2Department of Medical Statistics and Epidemiology, Hamad Medical Corporation and School of Epidemiology and Health Sciences, University of Manchester, United Kingdom. 3Primary Health Care Clinic, Oud Al Thoba, Ministry of Health, Al-Ain, United Arab Emirates. 4Khalifa Hospital, Abu Dhabi Health Authority, Abu Dhabi, United Arab Emirates. 5Department of Biological Sciences, University of Central Lancashire, United Kingdom. Received: 22/06/03; accepted: 23/12/03 ABSTRACT A case–control study evaluated the relationship between hypertension and socioeconomic and lifestyle factors in Al-Ain city. The survey included 426 hypertensive adults aged 20–65 years attending urban and semi-urban clinics and a randomly selected sample of 436 normotensive controls. Hypertension among cases was higher for men, age 40–49 years, non-UAE nationals, urban living, currently married, having children, illiterate, administrative/professional job, living in traditional house and low income. There were significant differences between cases and controls with regard to obesity, raised cholesterol level, low physical activity and family history of heart disease, kidney disease or diabetes. Multivariate logistic regres- sion analysis revealed that obesity, medium/high income, history of diabetes, low physical activity and having 3+ children were significantly associated with hypertension. Certains facteurs de risque d’hypertension aux Émirats arabes unis RÉSUMÉ Une étude cas-témoins a évalué la relation entre l’hypertension et des facteurs socio- économiques et liés au mode de vie dans la ville d’Al-Ain. L’étude comprenait 426 adultes hypertendus âgés de 20 à 65 ans qui consultaient dans des dispensaires urbains et semi-urbains et un échantillon, sélectionné de manière aléatoire, de 436 témoins normotendus. L’hypertension parmi les cas était plus élevée chez les hommes, âgés de 40 à 49 ans, non ressortissants des Émirats arabes unis, vivant en milieu urbain, mariés au moment de l’étude, ayant des enfants, analphabètes, occupant un emploi administratif/professionnel, vivant en maison traditionnelle et ayant un faible revenu. Il y avait des différences significatives entre les cas et les témoins concernant l’obésité, un taux de cholestérol élevé, une activité physique faible et des antécé- dents familiaux de maladie cardiaque, de maladie rénale ou de diabète. L’analyse de régression logistique multivariée a révélé que l’obésité, un revenu moyen/élevé, des antécédents de diabète, une activité phy- sique faible et le fait d’avoir plus de trois enfants étaient significativement associés à l’hypertension. 18 Some risk factors.pmd 8/17/2005, 11:08 AM610 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 611 Introduction The United Arab Emirates (UAE), like other developing countries, has undergone rapid changes during the past 2 decades [1]. The discovery of oil in the middle of the last century has contributed to significant so- cial change, and UAE, along with other Gulf Arab states, have experienced a rapid transition in its socioeconomic status. Peo- ple in UAE now enjoy a high standard of living and substantial improvements in their living conditions. There has been a dramat- ic rise in the national economy, expressed in terms of per capita income. In 2001, the gross domestic product (GDP) per capita were estimated as US$ 22 800. The infant mortality rate has decreased from 10.5 per 1000 live births in 1981 to 6.6 in 2000 and life expectancy has increased from 68 years in 1977 to 75 years in 2000 (Ministry of Health, Annual Report, 1980–2000) [2]. Rapid economic growth in UAE has, however, brought about marked changes both in lifestyle and in patterns of health and disease. With the greater availability of housekeepers, cars, televisions and sophis- ticated household appliances, the lifestyle of the people of UAE has become more sedentary, and watching television and eat- ing snack foods are the main leisure-time activities. Hypertension has become one of the leading public health problems. Hypertension is a major contributor to atherosclerosis-induced cardiovascular disease [3,4]. The prevalence is higher in men than in women below the age of 35 years but by the age of 65 years the preva- lence is higher in women [5]. In elderly women, it is the single most important risk factor for cardiovascular disease [6]. Data available from several Eastern Mediterranean countries indicate that hy- pertension is emerging as an important cause of morbidity and mortality. Epidemi- ological surveys on hypertension report a prevalence of 20% to 26% in the adult pop- ulation [7]. In some urban areas high blood pressure may affect up to 30% of the adult population [8]. The prevalence of hyper- tension appears to be lower in rural than in urban areas [9–11]. Other risk factors, such as obesity, dyslipidaemia, diabetes and smoking, are also higher among hyperten- sive than normotensive people [12]. There is also a significant association between hypertension and diabetes mellitus in the UAE [3,4,13]. There have been no systematic studies in the UAE population of the relationship between health and socioeconomic factors such as income or demographic factors in- cluding education and occupation. Since each community has its own common and unique socioeconomic determinants for cardiovascular diseases, particularly hyper- tension, it is important to study these vari- ables in different populations. In the UAE it is believed that the effect of education and occupation on health are much weaker than in the Western European countries due to differences in the educational system and the influence of the industrial economy in Europe. The present study in the city of Al-Ain, UAE, compared hypertensive patients at- tending primary health care clinics with non-hypertensive controls. The aim was to investigate the importance of socioeco- nomic status and lifestyle habits in relation to hypertension. Methods This was a matched case–control study to determine the relationship between hyper- tension and demographic, socioeconomic and lifestyle factors. The survey was con- ducted from October 2001 to July 2002. 18 Some risk factors.pmd 8/17/2005, 11:08 AM611 612 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Sampling procedure A multi-stage stratified cluster sampling de- sign was developed using the administra- tive divisions of the Al-Ain city medical health district which have approximately equal numbers of inhabitants. In order to secure a representative sample of the study population, sampling was stratified with proportional allocation according to stra- tum size from urban and semi-urban areas. The sample size was determined on the a priori assumption that the prevalence of hypertension in the UAE would be more or less similar to the 20% rate observed in the pilot study. Assuming the prevalence of hy- pertension to be 20% and allowing for an error of 5% at the 1% level of significance (Type 1 error) a sample size of 500 cases and 500 matched controls would be re- quired. Of the total 22 primary health care clinics in Al-Ain medical health district, 8 clinics were selected randomly (7 from ur- ban and 1 from semi-urban areas). Selection of participants The study population was identified by re- cruiting consecutive hypertensive patients aged 20–65 years attending any of the clin- ics for follow-up examination or any other cause during a specified period of time. The researcher visited each clinic in a rota- tion of 2–3 weeks and reviewed the medi- cal records of the first 20 hypertensive patients attending any of the specified pri- mary health centres until the target sample was reached. The exclusion criteria were non-Arab national, any severe chronic dis- ease, age less than 20 and more than 65 years. To select the control group, for every hypertensive case a matching pair who was non-hypertensive and met the same inclu- sion criteria were recruited from the same clinic. The control group subjects were identified from the visitors escorting the patients to the health care centre or those attending for any other reason. Cases and controls were matched for age, sex and nationality. Before conducting the inter- view, the investigator reviewed the medical file of the controls (history and examina- tion) to ensure they were suitable for the inclusion criteria of the research, in partic- ular to check that they were free of any se- vere chronic diseases. Data collection Patients were checked by the general prac- titioner to see whether they met the inclu- sion criteria of the study and whether they had any family history of severe chronic diseases. The recruited patients were given a brief explanation about the study and were instructed to give their consent to participate in the study. They were asked by either the principal investigator or the nurse to fill out the questionnaire. Qualified nurses measured the blood pressure, height, and weight of the participants. The survey was based on standardized interviews performed by trained health pro- fessionals and nurses. Informed consent was obtained from each person who agreed to enter the study. The participants were interviewed about their age, sex, na- tionality, educational level, occupation, place of living (urban or semi-urban), life- style habits, previous family history of hy- pertension, diabetes or kidney problems and current use of medication for hyper- tension and diabetes. Blood pressure was measured and height and weight were mea- sured using standardized methods with participants wearing light clothes without shoes. Information on cholesterol level was collected from the patient’s medical record. Blood pressure measurement was car- ried out by practising nurses who were trained for 1 week on the use of the sphyg- momanometer and how to measure blood 18 Some risk factors.pmd 8/17/2005, 11:08 AM612 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 613 pressure with patients in the sitting posi- tion. It was measured from the right upper arm, with a random zero sphygmomanom- eter with a 14 cm cuff, after the partici- pants had rested for 10 minutes and was recorded to the nearest mmHg. Systolic pressure was recorded at the appearance of sounds (first Korotkoff sounds) and dias- tolic pressure was recorded at the disap- pearance of sounds (fifth Korotkoff sounds). The mean value obtained from 3 readings was used in the analysis. Questionnaire The questionnaire and criteria for hyperten- sion were designed to meet the objectives of this study. A translated Arabic version of the questionnaire was revised by the bilin- gual physician (M.S.O.A-Z) and translated back by a bilingual co-investigator, unac- quainted with the original English version. Both translators met and made the neces- sary corrections, modifications and re- wording after considering the minor differences and discrepancies that had oc- curred. In a pilot study as a part of the process of validation, the first 20 patients were asked about the clarity and appropriateness of items on the questionnaire. Minor changes were made in the questionnaire taking into account their feedback. In addition to the questionnaire, a re- view was made of the medical files of all participants recruited. Definitions Hypertension was defined according to World Health Organization (WHO) stan- dardized criteria [14] as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and/ or the use of antihypertensive medication [14]. Control participants were those with systolic blood pressure < 140 mmHg or di- astolic < 90 mmHg and not currently taking antihypertensive medication. BMI was calculated as the weight in ki- lograms (1 kg subtracted to allow for clothing) divided by height squared in meters. Subjects were classified into 3 cat- egories: acceptable weight (BMI < 25 kg/ m2); overweight (BMI 25–29.9 kg/m2); and obese (BMI 30+ kg/m2) [15]. Smoking behaviour was classified as: current smoker (regularly smoked at least 1 cigarette per day), ex-smoker (given up smoking for at least 6 months) and non- smoker (never smoked regularly). High cholesterol was a total cholesterol level > 230 mg/dL, low-density lipoprotein (LDL) cholesterol level > 130 mg/dL or triglyceride level 200–400 mg/dL. Alcohol consumption was defined as: never drank, current drinker or ex-drinker. No data were obtained on alcohol con- sumption among women because it is un- common among females and due to the difficulty in gathering information on this subject in this conservative Muslim com- munity. Physical activity was classified as fol- lows: sedentary and relatively inactive (not practising sports or practising < 1 hour/ week); relatively active (practising sports for 1–3 hours a week); or highly active (practising sports for > 3 hours a week). Healthy eating was assessed by record- ing the number of times per week that fruit and vegetables were consumed. Analysis The data were analysed using SPSS, ver- sion 11. Student t-test was used to find the difference between means of systolic and diastolic blood pressure among hyperten- sive and non-hypertensive patients. Mann– Whitney test was used for non-parametric distribution. The chi-squared test was used 18 Some risk factors.pmd 8/17/2005, 11:09 AM613 614 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 for comparison of frequencies between hy- pertensive and non-hypertensive people and the frequency of other associated so- cioeconomic and lifestyle factors. Logistic regression analysis was used to adjust for potential confounders and to order the im- portance of risk factors (determinants) for hypertension. Logistic regression results were expressed as odds ratios (OR) and 95% confidence interval (CI) along with P values (derived from likelihood ratios sta- tistics which have a chi-squared distribu- tion). The level P < 0.05 was the cut-off value for significance. Results Of the 500 patients with hypertension re- cruited, 64 did not participate in the study and thus 436 cases and 436 matched non- hypertensive controls were included in the final analysis (87.2% response rate for completion of the study). Among hypertensive patients, the mean and standard deviation (SD) of blood pres- sure [systolic 141.9 (17.1) mmHg/diastolic 92.7 (9.8) mmHg] was significantly higher than for controls [systolic 116.8 (8.7) mmHg/ diastolic 75.7 (6.2) mmHg] (P < 0.0001). Among the hypertensive patients, the categories with the highest rates of hyper- tension were: men (55.3%), age group 40– 49 years (39.7%), non-UAE nationals (52%), urban living (93.3%), currently married (86.7%), having children (93.6%), illiterate (33.7%), administrative/profes- sional job (40.7%), living in mud-brick or traditional house (56.9%) and low income (< 5000 dirhams per month) (34.1%) (Ta- ble 1). Table 1 compares the sociodemograph- ic characteristics of hypertensive patients and normotensive controls. There were statistically significant differences between cases and controls in the percentage of participants having 3 or more children (P = 0.034), administrative/professional occu- pation (P < 0.037), (low/medium income (5000–9999 dh) (P < 0.001) and obesity (BMI > 30 kg/m2) (P < 0.001). Table 2 compares the lifestyle habits of cases and controls. Significantly more pa- tients with hypertension than controls were current smokers (P = 0.047), consumed alcohol (P < 0.03) and had a low level of physical activity (P = 0.007). Table 3 shows a comparison of the medical conditions of hypertensive patients and non-hypertensive control participants. Significantly more patients with hyperten- sion than controls had raised cholesterol levels (P < 0.001) or a family history of heart disease (P < 0.001), kidney disease (P < 0.033) or diabetes (P < 0.001). A stepwise logistic regression analysis was used to adjust for potential confound- ers and order the importance of risk factors (determinants) for hypertension status (0 for non-hypertensive and 1 hypertensive) (Table 4). The logistic regression model was adjusted for age, sex, nationality and marital status. As can be seen from this ta- ble, factors associated with hypertension were: obesity (BMI > 30 kg/m2) (P < 0.0001), medium/high income (5000+ dh) (P < 0.001), family history of diabetes (P < 0.001), no physical activity (P = 0.003) and a high number of children (3+) (P = 0.026). Discussion Hypertension is the most common of the cardiovascular diseases and is one of the most powerful contributors to cardiovas- cular morbidity and mortality especially from strokes and congestive heart failure [16–18]. In the present study, hypertension was found to be associated with poor 18 Some risk factors.pmd 8/17/2005, 11:09 AM614 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 615 Table 1 Socioeconomic characteristics of clinic attenders with hypertension and non- hypertensive controls in Al-Ain city, United Arab Emirates (UAE) Variable Cases Controls Odds 95% CI P-value (n = 436) (n = 436) ratio No. % No. % Sex Female 195 44.7 217 50.2 1.00 Male 241 55.3 219 49.8 0.903 0.79–1.03 0.154 Age (years) < 40 98 22.4 134 31.1 1.00 40–49 173 39.7 172 39.9 0.73 0.51–1.03 0.062 50–59 93 21.3 74 17.2 0.80 0.54–1.18 0.239 60+ 72 16.5 51 11.8 0.89 0.54–1.47 0.628 Nationality UAE 209 48.0 207 47.7 1.00 Other Arab 226 52.0 227 52.3 1.014 0.77–1.32 0.946 Area Urban 402 93.3 375 86.4 1.00 Semi-urban 29 6.7 59 13.6 1.30 0.87–1.87 0.242 Marital status (current) Married 372 86.7 359 83.9 1.00 Single 57 13.3 69 16.1 1.25 0.84–1.87 0.242 No. of children < 3 101 23.3 123 29.1 1.00 3+ 304 70.2 265 62.8 0.72 0.52–0.99 0.034 Not married 28 6.5 34 8.1 1.39 0.80–2.44 0.216 Educational level Illiterate 145 33.7 126 29.2 1.00 Elementary/preparatory 103 24.0 86 20.0 0.96 0.65–1.42 0.833 Secondary 44 10.2 40 9.3 1.09 0.63–1.88 0.746 College/university 138 32.1 179 41.5 1.43 0.86–2.38 0.148 Occupation type Not working 50 11.6 45 10.3 1.00 Unskilled/semi-skilled labourer 62 14.3 46 10.6 0.82 0.46–1.49 0.495 Administrative/ professional 176 40.7 206 47.5 1.58 1.00–2.48 0.037 Housewife 144 33.3 137 31.6 0.81 0.59–1.12 0.188 Type of residence Villa 92 21.3 94 21.8 1.00 Traditional mud-brick/ prefabricated 245 56.9 244 56.3 0.97 0.69–1.39 0.882 Apartment 94 21.8 95 21.9 1.01 0.72–1.44 0.931 18 Some risk factors.pmd 8/17/2005, 11:09 AM615 616 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Table 2 Comparison lifestyle habits of clinic attenders with hypertension and non- hypertensive controls in Al-Ain city, United Arab Emirates Variable Cases Controls Odds 95% CI P-value (n = 436) (n = 436) ratio No. % No. % Tobacco smoking Never 292 68.4 344 79.8 1.00 Current smoker 55 12.9 42 9.7 0.65 0.41–1.02 0.047 Ex-smoker 80 18.7 45 10.4 0.74 0.41–1.31 0.270 Alcohol consumption Never 402 94.1 413 97.2 1.00 Current/ex-drinker 25 5.9 12 2.8 0.47 0.22–0.99 0.030 Physical activity Yesa 188 43.1 229 52.5 1.00 No 248 56.9 207 47.5 0.72 0.52–0.89 0.007 Vegetable consumption 3+ times /week 366 87.4 359 85.4 1.00 < 3 times /week 53 12.6 61 14.6 1.17 0.78–1.78 0.428 Fruit consumption 3+ times /week 341 81.6 342 81.8 1.00 < 3 times /week 77 18.4 76 18.2 0.98 0.68–1.42 0.928 n = total number of participants (data were missing in some categories). CI = confidence interval. aIf subject practised sport more than 1 hour per week. Table 1 Socioeconomic characteristics of clinic attenders with hypertension and non-hypertensive controls in Al-Ain city, United Arab Emirates (UAE) (concluded) Variable Cases Controls Odds 95% CI P-value (n = 436) (n = 436) ratio No. % No. % Monthly income (dh)a < 5000 138 34.1 98 25.1 1.00 5000–9999 140 34.6 176 45.1 1.77 1.24–2.53 < 0.001 10 000–14 999 57 14.1 60 15.4 0.84 0.54–1.31 0.413 15 000+ 80 17.3 56 14.4 0.66 0.39–1.13 0.108 BMI (kg/m2) Acceptable (< 25) 99 25.1 163 40.9 1.00 Overweight (25–29.9) 132 33.5 150 37.6 0.69 0.48–0.99 0.035 Obese (30+) 163 41.4 86 21.6 0.46 0.32–0.67 < 0.001 aUS$ 1 = 3.68 dirhams. n = total number of participants (data were missing in some categories). CI = confidence interval. BMI = body mass index. 18 Some risk factors.pmd 8/17/2005, 11:09 AM616 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 617 Table 4 Stepwise logistic regression analysis for hypertension and associated socioeconomic and family history characteristics of clinic attenders with hypertension and non- hypertensive controls in Al-Ain city, United Arab Emirates Independent variable Odds ratio 95% CI P-value BMI (< 30 kg/m2 = 0, 30+ kg/m2 = 1) 4.29 2.76–6.66 0.0001 Incomea (< 5000 dh = 0, 5000+ dh = 1) 2.69 1.76–4.10 0.001 Family history of diabetes (no = 0, yes = 1) 2.58 1.69–3.74 0.001 Physical activity (yes = 0, no = 1) 1.80 1.20–3.69 0.003 No. of children (< 3 = 0, 3+ = 1) 1.67 1.23–2.11 0.026 aUS$ 1 = 3.68 dirhams. CI = confidence interval. BMI = body mass index. Table 3 Comparison of medical condition of clinic attenders with hypertension and non-hypertensive controls in Al-Ain city, United Arab Emirates Variable Cases Controls Odds 95% CI P-value (n = 436) (n = 436) ratio No. % No. % Cholesterol level Normal 149 34.6 128 29.5 1.00 Higher than normal 140 32.5 12 2.8 0.10 0.05–0.19 < 0.001 Not measured 142 32.9 294 67.7 – – Family history of diabetes No 345 80.4 399 93.7 1.00 Yes 84 19.6 27 6.3 0.28 0.17–0.45 < 0.001 Family history of heart disease No 352 82.1 415 98.1 1.00 Yes 77 17.9 8 1.9 0.09 0.04–0.19 < 0.001 Family history of kidney problems No 404 94.8 411 97.6 1.00 Yes 22 5.2 10 2.4 0.45 0.19–1.00 0.033 n = total number of participants (data were missing in some categories). CI = confidence interval. 18 Some risk factors.pmd 8/17/2005, 11:09 AM617 618 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 health status as indicated by raised choles- terol levels and a family history of heart dis- ease, renal disease or diabetes. The present study confirms the hypoth- esis of an association between hyperten- sion and poorer socioeconomic factors and more sedentary lifestyle. We found a posi- tive association between hypertension and physical inactivity, smoking and obesity. These finding are similar to those of Jo- hansson and colleagues in a study carried out in Sweden [19]. This has implications for preventive strategies, because smoking behaviour, body fatness and physical activ- ity have been shown to be major candidates for possible early interventions [20]. Perhaps the common link to hyperten- sion for all these sociodemographic factors is physical inactivity. If this were the case, it would suggest a number of potentially modifiable factors that could be targeted for intervention. A study in Finland has shown that the mean intensity of leisure time physical activity had a positive dose– response relationship with level of educa- tion and income [21]. It was also shown that married or engaged men, those less educated, on lower incomes and unem- ployed or retired had a shorter duration of conditioning physical activity especially in urban areas than others [21]. The authors of the study concluded that physical activi- ty protects against poor health irrespective of high BMI and smoking. Our finding that more expatriates than UAE nationals had hypertension is in keep- ing with previous findings of a Swedish study [22], which found that foreign-born individuals had a higher risk for poor health than Swedes after adjustment for sociode- mographic and lifestyle factors. In conclusion, the present study sup- ports the importance of socioeconomic factors, lifestyle habits and family history in shaping risk for hypertension in UAE and indicates a need for more effective preven- tion programmes for control of hyperten- sion in this fast developing Arab country. References 1. Bener A, Gomes J, Hamouda MFB. Hy- pertension among workers occupation- ally exposed to hydrocarbons and organic solvents. Journal of environ- mental science and health, Part-A, 1996, 31:291–303. 2. Annual report. Preventive medicine in 20 years. Abu Dhabi, United Arab Emirates, Ministry of Health, 2000:1–270. 3. Bener A et al. Acanthosis nigricans, hyperinsulinaemia and risk factors for cardiovascular disease. Eastern Medi- terranean health journal, 2000, 6:416– 24. 4. Corrao JM et al. Coronary heart disease risk factors in women. Cardiology, 1990, 77(suppl. 2):8–24. 5. Rowland M, Roberts J. Blood pressure levels and hypertension in persons aged 6–74 years: United States, 1976– 1980. National Health and Nutrition Examination Survey 1. Hyattsville, Mary- land, US Department of Health and Hu- man Services, 1982. 6. Sarraf-Zadegan N et al. Prevalence of hypertension and associated risk factors in Isfahan, Islamic Republic of Iran. East- ern Mediterranean health journal, 1999, 5:992–1001. 7. Alwan A. Prevention and management of hypertension. Alexandria, World Health Organization, Regional Office for the Eastern Mediterranean, 1996 (WHO EMRO Technical Publication, No. 23). 18 Some risk factors.pmd 8/17/2005, 11:09 AM618 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 619 8. Alwan A. Prevention and control of car- diovascular diseases. Alexandria, World Health Organization, Regional Office for the Eastern Mediterranean, 1995 (WHO EMRO Technical Publication, No. 22). 9. Sarraf-Zadegan N, Amini-Nik S. Blood pressure pattern in urban and rural ar- eas in Isfahan, Iran. Journal of human hypertension, 1997,11:425–8. 10. Sayeed MA et al. Prevalence of hyper- tension in Bangladesh: effect of socio- economic risk factor on difference between rural and urban community. Bangladesh Medical Research Council bulletin, 2002, 28:7–18. 11. Faruqui A. Heart disease in South Asia: experiences in Pakistan. In: Hurst JW, ed. Clinical essays on the heart. Volume 2. New York, McGraw–Hill, 1983. 12. Laurenzi M et al. Multiple risk factors in hypertension: results from the Gubbio study. Journal of hypertension, supple- ment, 1990, 8:S7–12. 13. Bener A et al. Association between blood levels of lead blood pressure and risk of diabetes and heart disease in workers. International archives of occu- pational and environmental health, 2001, 74(5):375–8. 14. World Health Organization/International Society of Hypertension. Guidelines for the management of hypertension. Jour- nal of hypertension, 1999, 17:151–82. 15. Bray GA. Definition, measurement and classification of the syndrome of obesity. International journal of obesity, 1978, 2:99–112. 16. Kannel WB, Thom TJ. Declining cardio- vascular mortality. Circulation, 1984, 70:331–6. 17. MacMahon S et al. Blood pressure, stroke and coronary heart disease. Part 1, Prolonged differences in blood pres- sure: prospective observational studies corrected for the regression dilution bias. Lancet, 1990, 335:765–74. 18. National Center for Health Statistics. An- nual summary of births, marriages, di- vorces and deaths, United States, 1989. Monthly vital statistics report, 1990:38(13). 19. Johansson SE, Sundquist J. Change in lifestyle factors and their influence on health status and all-cause mortality. In- ternational journal of epidemiology, 1999, 28(6):1073–80. 20. Twisk JW, Kemper HC, van Mechelen W. Tracking of activity and fitness and the relationship with cardiovascular disease risk factors. Medicine and science in sports and exercise, 2000, 32(8):1455– 61. 21. Lakka TA, Kauhanen J, Salonen JT. Con- ditioning leisure time physical activity and cardiorespiratory fitness in socio- demographic groups of middle-ages men in eastern Finland. International journal of epidemiology, 1996, 25(1): 86–93. 22. Sundquist J. Living conditions and health. A population-based study of la- bour migrants and Latin American refu- gees in Sweden and those who were repatriated. Scandinavian journal of pri- mary health care, supplement, 1995, 13(2):128–34. 18 Some risk factors.pmd 8/17/2005, 11:09 AM619 620 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Diabetic nephropathy as a cause of end-stage renal disease in Egypt: a six-year study A. Afifi,1 M. El Setouhy,2 M. El Sharkawy,1 M. Ali,1 H. Ahmed,1 O. El-Menshawy3 and W. Masoud4 1Department of Internal Medicine and Nephrology; 2Department of Public Health and Occupational Medicine, Ain Shams University, Cairo, Egypt. 3Department of Internal Medicine and Nephrology, Al Minya University, Egypt. 4Department of Nephrology, Ahmed Maher Teaching Hospital, Cairo, Egypt. Received: 09/06/03; accepted: 26/10/03 ABSTRACT The prevalence of diabetic nephropathy as a cause of end-stage renal disease (ESRD) in Egypt has been examined in small cross-sectional studies, with conflicting results. The need for a large-scale study prompted us to perform this 6-year multiple cross-sectional study. A sample of ESRD patients enrolled in the Egyptian renal data system was evaluated during the period 1996–2001 for the prevalence of diabetic nephropathy. Prevalence gradually increased from 8.9% in 1996, to 14.5% in 2001. The mean age of patients with diabetic nephropathy was significantly higher than that of patients with ESRD from other causes. Mortality was also significantly higher in diabetic patients with ESRD. La néphropathie diabétique comme cause de l’insuffisance rénale terminale en Égypte : étude sur six ans RÉSUMÉ La prévalence de la néphropathie diabétique comme cause de l’insuffisance rénale terminale en Égypte a été examinée dans de petites études transversales, donnant des résultats contradictoires. Le besoin d’une étude à grande échelle nous a incités à réaliser une étude transversale multiple sur six ans. Un échantillon de patients souffrant d’insuffisance rénale terminale enregistrés dans le système égyptien de données rénales a fait l’objet d’une évaluation pendant la période 1996-2001 pour la prévalence des né- phropathies diabétiques. La prévalence a augmenté progressivement, passant de 8,9 % en 1996 à 14,5 % en 2001. L’âge moyen des patients souffrant de néphropathie diabétique était significativement plus élevé que celui des patients souffrant d’insuffisance rénale terminale due à d’autres causes. La mortalité était aussi significativement plus élevée chez les diabétiques ayant une insuffisance rénale terminale. 19 Diabetic nephropathy.pmd 8/18/2005, 11:12 AM620 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 621 Introduction Egypt, a developing country in North Afri- ca, had a population of approximately 68 million in 2001. The estimated number of dialysis patients in Egypt in that year was 25 518 [1] Diabetic nephropathy is rapidly becom- ing the leading cause of end-stage renal disease (ESRD), particularly in the industri- alized countries of the world [2]. Ethnic and racial origin play an important role, resulting in increased prevalence rates of diabetic nephropathy in certain regions [3]. In many studies from Western Europ- ean countries as well as many other regions of the world, diabetic nephropathy has been reported as the main cause of ESRD. Variable incidence and prevalence rates have been reported in Eastern Europe. Ta- ble 1 gives a summary of reported preva- lence of this condition in a number of countries. Data from 12 countries in the Asian Pacific region, including Australia and New Zealand, showed an increase in both incidence and prevalence between 1998 and 2000 [4]. The prevalence of diabetic nephropathy as a cause of ESRD in Egypt has previously been examined in 2 small cross-sectional studies with conflicting results [22,23]. Other reports on prevalence of diabetic nephropathy also produced the following widely divergent figures: 8.4% [11], 13.7% [24], 20.1% [12] and 8.9% [25]. These marked differences in the reported preva- lence rates may reflect the effect of urban- ization. The need for a large-scale study has prompted us to carry out this 6-year, multi- ple, cross-sectional study. The aim of our study was to critically evaluate the preva- lence of diabetic nephropathy as a cause of ESRD in Egypt. Methods A sample of patients with ESRD enrolled in the Egyptian renal data system was evaluat- ed during the period 1996–2001 for the Table 1 Reported prevalence of diabetic nephropathy as a cause of renal disease for various parts of the world Location End-stage renal disease Prevalence of diabetic Reference nephropathy (%) No. United States of America ~ 50 5 Western Europe Leading cause 6 Japan Leading cause 7 France Leading cause 8 Germany 21 9 Norway 10% of the incident RRT population 10 Egypt 8.4 11 Egypt 20.1 12 Primary renal disease Yugoslavia 7 13 Czech Republic 25.0 14 Slovakia 17.9 14 Poland 10.3 15 South America 16.0 16 Puerto Rico 51.2 16 Asian Pacific region including Australia and New Zealand 17.3 4 China 4.7 17 Taiwan 24.8 18 Saudi Arabia 27.9 19 Tunisia 11.4 20 Kuwait 21.2 21 RRT = renal replacement therapy. 19 Diabetic nephropathy.pmd 8/18/2005, 11:12 AM621 622 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 prevalence of diabetic nephropathy. Centre and patient questionnaires were sent to all identified dialysis centres (370 centres). All responding centres and all patients reported from these centres were included in the study. The number of patients evaluated was 4905 in 1996, 3013 in 1997, 1754 in 1998, 1616 in 1999, 2150 in 2000 and 3172 in 2001. Requested data included number of patients, age, sex, renal biopsy results, cause of ESRD, and cause of death. Criteria used for diagnosing diabetic nephropathy included: • long duration of diabetes before onset of chronic renal failure (usually more than 10 years) • normal sized kidneys by ultrasound • presence of diabetic retinopathy by fun- dus examination • absence of haematuria or red blood cell casts in urine • proteinuria still present when the patient has already started dialysis. The data collected were processed us- ing an IBM-compatible PC and SPSS, ver- sion 6.1 for statistical analysis. Results The prevalence of diabetic nephropathy among ESRD patients in Egypt increased from 8.9% in 1996 to 14.5% in 2001 (Fig- ure 1). The main causes of ESRD in Egypt oth- er than diabetic nephropathy included hypertensive kidney disease, chronic glom- erulonephritis, undetermined etiology, reflux and chronic pyelonephritis, schisto- somal obstructive uropathy and schistoso- mal nephritis (Table 2). The mean age of patients with diabetic nephropathy was higher than that of pa- tients having other causes of ESRD in the years we studied (Table 3). Mortality among diabetic patients with ESRD was higher than in patients with ESRD from other causes (Figure 2). Discussion The prevalence of diabetes in adults world- wide was estimated to be 4.0% in 1995 and is predicted to rise to 5.4% by the year 2025. It is higher in industrialized than in developing countries. The number of adults with diabetes in the world is forecast to rise from 135 million in 1995 to 300 million in the year 2025. Most of this increase will occur in developing countries [26]. A series of surveys of diabetes mellitus have been performed in Egypt using World Health Organization criteria for diagnosis and classification. Average prevalence for people above the age of 10 years was 4.3%, with distinct geographical differen- ces: 5.7% in urban areas, 4.1% in rural ag- ricultural areas, and 1.5% in rural desert areas. In some remote villages, diabetes was almost completely absent [22]. A more recent study in Egypt revealed that the prevalence of diabetes in rural areas was Figure 1 Prevalence of diabetic nephropathy among Egyptian patients with end-stage renal disease, 1996–2001 19 Diabetic nephropathy.pmd 8/18/2005, 11:12 AM622 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 623 4.9%, increasing to 13.5% in lower socio- economic urban areas and 20% in higher socioeconomic urban areas [23]. Diabetic nephropathy is the commonest cause of ESRD in industrialized countries [26]. All countries with registries have re- ported a massive increase in the incidence and prevalence in their dialysis population. Table 3 Mean age of diabetic nephropathy patients and patients with end-stage renal disease (ESRD) from other causes Year Diabetic Other causes P-value nephropathy of ESRD Mean age SD Mean age SD (years) (years) 1996 55.7 9.9 44.6 14.1 > 0.001 1997 54.9 11.4 44.9 16.8 > 0.001 1998 54.2 15.1 45.2 15.3 > 0.001 1999 56.6 11.6 45.4 15.3 > 0.001 2000 56.1 10.9 45.2 15.5 > 0.001 2001 56.5 29.2 46.1 16.1 > 0.001 SD = standard deviation. Figure 2 Cause of mortality among diabetic and non-diabetic Egyptian patients with end-stage renal disease This increase is caused by an actual in- crease in prevalence of diabetes, increasing age of the dialysis population and better survival rates for patients with diabetes, thus allowing more time for diabetic nephr- opathy to develop [2]. In Egypt, the estimated prevalence of ESRD increased from 225 per million pop- 19 Diabetic nephropathy.pmd 8/18/2005, 11:12 AM623 624 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Ta bl e 3 M ai n c au se s o f e n d -s ta g e re n al d is ea se in E g yp t o th er th an d ia b et ic n ep h ro p at hy Ye ar M ai n c au se s o f e n d -s ta g e re n al d is ea se 19 96 H yp er te ns io n: C hr on ic U nd et er m in ed C hr on ic O bs tr uc tiv e D ia be tic S ch is to so m al 28 .0 % gl om er ul on ep hr iti s: 16 .2 % py el on ep hr iti s: ur op at hy : ne ph ro pa th y: ob st ru ct iv e 16 .6 % 14 .6 % 9. 3% 8. 9% ur op at hy : 6 .0 % 19 97 H yp er te ns io n: C hr on ic U nd et er m in ed : C hr on ic D ia be tic S ch is to so m al O bs tr uc tiv e 19 .6 % gl om er ul on ep hr iti s: 12 .5 % py el on ep hr iti s: ne ph ro pa th y: ob st ru ct iv e ur op at hy : 13 .2 % 10 .4 % 8. 5% ur op at hy : 7 .6 % 7. 5% 19 98 U nd et er m in ed : H yp er te ns io n: C hr on ic O bs tr uc tiv e D ia be tic S ch is to so m al C hr on ic 22 .1 % 21 .0 % gl om er ul on ep hr iti s: ur op at hy : ne ph ro pa th y: ob st ru ct iv e py el on ep hr iti s: 11 .0 % 9. 5% 9. 1% ur op at hy : 6 .7 % 5. 5% 19 99 H yp er te ns io n: U nd et er m in ed : C hr on ic O bs tr uc tiv e C hr on ic D ia be tic A du lt 23 .6 % 18 .4 % gl om er ul on ep hr iti s: ur op at hy : py el on ep hr iti s: ne ph ro pa th y: po ly cy st ic : 13 .9 % 9. 2% 7. 8% 7. 1% 4. 3% 20 00 H yp er te ns io n: U nd et er m in ed : C hr on ic D ia be tic C hr on ic O bs tr uc tiv e S ch is to so m al 23 .5 % 21 .8 % gl om er ul on ep hr iti s: ne ph ro pa th y: py el on ep hr iti s: ur op at hy : ob st ru ct iv e 12 .4 % 10 .5 % 7. 4% 6. 0% ur op at hy : 4 .0 % 20 01 H yp er te ns io n: D ia be tic C hr on ic U nd et er m in ed : C hr on ic O bs tr uc tiv e S ch is to so m al 22 .1 % ne ph ro pa th y: gl om er ul on ep hr iti s: 12 .1 % py el on ep hr iti s: ur op at hy : ob st ru ct iv e 14 .5 % 12 .4 % 5. 6% 5. 1% ur op at hy : 4 .4 % 19 Diabetic nephropathy.pmd 8/18/2005, 11:12 AM624 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 625 ulation in 1996 [25] to 375 per million in 2001 [1]. We found that the prevalence of diabetic nephropathy as a cause of ESRD increased from 8.9% of patients in 1996 to 14.5% in 2001. The mean age of diabetic nephropathy patients was higher than that of patients with ESRD due to other causes for the years studied. Mortality among diabetic patients with ESRD in Egypt is higher than mortality for all other causes of ESRD which is probably related to the well known cardiovascular complications of diabetes (Figure 2). Conclusions Diabetic nephropathy is the commonest cause of ESRD in the industrialized coun- tries. In Egypt, there is a slower increase in the prevalence of ESRD due to diabetic nephropathy, probably because of the high- er incidence of infections causing glo- merulonephritis, delayed referral to neph- rologists and increased mortality among di- abetic patients due to cardiovascular disease and strokes before ESRD can de- velop. References 1. Afifi A. Sixth annual report of the Egyp- tian Society of Nephrology. Paper pre- sented at the 22nd Congress of the Egyptian Society of Nephrology, 4–8 February 2003, Sharm El Sheikh, Egypt. 2. Ritz E et al. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. American journal of kidney disease, 1999, 34(5): 795–808. 3. Earle KK et al. Variation in the progres- sion of diabetic nephropathy according to racial origin. Nephrology, dialysis, transplantation, 2001, 16(2):286–290. 4. Lee G. End-stage renal disease in the Asian-Pacific region. Seminars in neph- rology, 2003, 23(1):107–14 5. US Renal Data System. USRDS 2002 annual data report. Bethesda, Maryland, National Institutes of Health, National In- stitute of Diabetes and Digestive and Kidney Diseases, 2002. 6. Jager K, Van Dijk P. 2002 ERA-EDTA reg- istry annual report, XXXIX ERA-EDTA congress. Copenhagen, Denmark, Euro- pean Renal Association, 2002. 7. Hollenberg NK. Higher incidence of dia- betic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Ja- pan. Current hypertension reports, 2001, 3(3):177. 8. Halimi S et al. Huge progression of dia- betes prevalence and incidence among dialysed patients in mainland France and overseas French territories. A sec- ond national survey six years apart. (UREMIDIAB 2 study). Diabetes and me- tabolism, 1999, 25(6):507–12. 9. Frei U, Schober-Halstenberg HJ. Annual report of the German renal registry 1998. QuaSi-Niere task group for quality assur- ance in renal replacement therapy. Nephrology, dialysis, transplantation, 1999, 14(5):1085–90. 10. Bergrem H, Leivestad T. Diabetic nephr- opathy and end-stage renal failure: the Norwegian story. Advances in renal re- placement therapy, 2001, 8(1):4–12. 11. El-Sharkawi M. Changing pattern of eti- ology of chronic renal failure among dialysis patients [thesis]. Cairo, Ain Shams University, 1996. 12. Ahmed T. Clinical and laboratory fea- tures of patients with chronic renal failure at the start of dialysis [thesis]. Cairo, Ain Shams University, 1991. 13. Djukanovic L et al. Epidemiology of end- stage renal disease and current status of 19 Diabetic nephropathy.pmd 8/18/2005, 11:13 AM625 626 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 hemodialysis in Yugoslavia. Interna- tional journal of artificial organs, 2002, 25(9):852–9. 14. Rutkowski B et al. Evolution of renal re- placement therapy in Central and East- ern Europe 7 years after political and economical liberation. Nephrology, di- alysis, transplantation, 1998, 13(4):860– 4. 15. Rutkowski B et al. Renal replacement therapy in an era of socioeconomic changes–report from the Polish Registry. Nephrology, dialysis, transplantation, 1997, 12(6):1105–8. 16. Mazzuchi N et al. Latin American registry of dialysis and renal transplantation: 1993 Annual dialysis data report. Neph- rology, dialysis, transplantation, 1997, 12(12):2521–7. 17. Li L. End-stage renal disease in China. Kidney international, 1996, 49(1):287– 301. 18. Yang WC et al. The impact of diabetes on economic costs in dialysis patients: ex- periences in Taiwan. Diabetes research and clinical practice, 2001, 54(suppl. 1):S47–54. 19. Al-Khader AA. Impact of diabetes in re- nal diseases in Saudi Arabia. Nephrol- ogy, dialysis, transplantation, 2001, 16(11):2132–5. 20. Ben Abdallah. Report of dialysis registry in Tunisia. Paper presented at the 21st Congress of the Egyptian Society of Nephrology, 15–20 February 2002, Cairo, Egypt. 21. El-Reshaid K et al. End-stage renal dis- ease and renal replacement therapy in Kuwait–epidemiological profile over the past 4½ years. Nephrology, dialysis, transplantation, 1994, 9(5):532–8. 22. Arab M. Diabetes mellitus in Egypt. World health statistics quarterly, 1992, 45(4): 334–7. 23. Harman WH et al. Diabetes mellitus in Egypt: risk factors and prevalence. Dia- betic medicine, 1995, 12(12):1126–31. 24. Ibrahim T. Etiology of chronic renal failure among a sample of Egyptian population [thesis]. Cairo, Ain Shams University, 1998. 25. Afifi A, Karim MA. Renal replacement therapy in Egypt: first annual report of the Egyptian Society of Nephrology, 1996. Eastern Mediterranean health journal, 1999, 5(5):1023–9. 26. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: preva- lence, numerical estimates, and pro- jections. Diabetes care, 1998, 21(9): 1414–31. 19 Diabetic nephropathy.pmd 8/18/2005, 11:13 AM626 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 627 Antiphospholipid syndrome and retinal vein occlusion in adults R.M. Maaroufi,1,3 R. Hamdi,2 N. Jmili,3 M. Ghorbal,2 F. Bel Hadj Hamida 2 and T. Mahjoub3 1Higher Institute of Biotechnology, Monastir, Tunisia. 2Department of Ophthalmology, Farhat Hached University Hospital, Sousse, Tunisia. 3Haematology and Autoimmune Diseases Unit, Faculty of Pharmacy, University of Monastir, Tunisia. Received: 29/04/03; accepted: 23/12/03 ABSTRACT Antiphospholipid antibodies may play an important role in the pathogenesis of retinal vascular occlusions; therefore, we investigated the prevalence among 33 patients with retinal vein and artery occlu- sions and 80 controls. Prevalence was 33% and 5% respectively. Ophthalmic examination and fluorescein angiography showed that occlusions were due to ischaemic events. The 11 patients were diagnosed with antiphospholipid syndrome: 9 patients were treated successfully with laser photocoagulation and anticoag- ulant and anti-aggregant therapy. Two patients with antiphospholipid antibodies associated with resistance to activated protein C had unfavourable outcomes. Our results suggest a correlation between antiphospholipid syndrome and retinal vein occlusions; we recommend a systematic search for antiphospholipid antibodies in occlusions of unexplained origin and laser photocoagulation treatment and long-term oral anticoagulant and anti-aggregant therapy. Le syndrome des antiphospholipides et l’occlusion veineuse rétinienne chez l’adulte RÉSUMÉ Les antiphospholipides peuvent jouer un rôle important dans la pathogenèse des occlusions vasculaires rétiniennes ; nous avons donc étudié la prévalence chez 33 patients atteints d’occlusions veineuses et artérielles rétiniennes et 80 témoins. La prévalence s’élevait à 33 % et 5 % respectivement. L’examen ophtalmologique et l’angiographie fluorescéinique ont montré que les occlusions étaient dues à des événements ischémiques. Le syndrome des antiphospholipides a été diagnostiqué chez 11 patients : neuf patients ont été traités avec succès par photocoagulation au laser associant un traitement anticoagulant et antiagrégant. Deux patients présentant des anticorps antiphospholipides associés à une résistance à la protéine C activée ont eu une issue défavorable. Nos résultats semblent indiquer une corrélation entre le syndrome des antiphospholipides et les occlusions veineuses rétiniennes ; nous recommandons une re- cherche systématique des anticorps antiphospholipides dans les occlusions d’origine inexpliquée et un traitement par photocoagulation au laser et un traitement anticoagulant et antiagrégant de longue durée. 20 Antiphospholipid syndrome.pmd 8/17/2005, 11:09 AM627 628 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Introduction Antiphospholipid antibodies are a heteroge- neous family of antibodies directed to plas- ma protein co-factors bound to anionic phospholipids. The clinical relevance of an- tiphospholipid antibodies derives from the association with venous and arterial throm- bosis, recurrent abortions and thrombocy- topenia [1]. Antiphospholipid antibodies include lupus anticoagulant and anticardio- lipin antibodies [2,3]. This association has been termed the antiphospholipid syndrome (APS), which may occur alone (primary APS) or in the setting of an underlying dis- ease, mainly systemic lupus erythematosus (SLE) [4–7]. Hypercoagulable states, including a va- riety of disorders such as reduced levels of antithrombin, protein C, protein S or pres- ence of antiphospholipid antibodies, are common in patients with retinal vein occlu- sions and may contribute to the etiology of the disease [8]. In particular, retinal vascular occlusions in patients with primary APS, i.e. with an- tiphospholipid antibodies but with no other conventional risk factors, result from thrombus formation in either the retinal vein, artery or both [9–12]. We investigated the prevalence of an- tiphospholipid antibodies in a group of 33 patients with retinal vein occlusion and in 80 normal controls. Whether antiphospho- lipid antibodies included lupus anticoagu- lant, anticardiolipin antibodies or both was also investigated. This study aimed to assess the relationship between the occur- rence of antiphospholipid antibodies in pri- mary APS and occlusive retinal vascular events. Methods From January–December 2002, 33 patients (14 men and 19 women, mean age 37 years and age range 22–63 years) with retinal vein (29) or artery (4) occlusions were se- lected from the Department of Ophthalmol- ogy of the Farhat Hached Hospital, Sousse, Tunisia. Exclusion criteria were diabetes, hypertension, hypercholesterolaemia and hypertriglyceridaemia. We used 80 normal controls from among healthy blood donors at the Centre Régional de Transfusion San- guine of Farhat Hached Hospital. Informed consent was obtained from patients and controls prior to their participation in our study. Patients were examined clinically. A questionnaire was administered before pa- tients underwent ophthalmologic examina- tion and retinal flourescein angiography. Biological assays for cholesterol and triglycerides were performed. Antinuclear antibodies were investigated with standard- ized enzyme-linked immunosorbent assay (ELISA). Screening studies for APS included as- says for anticardiolipin antibodies and lupus anticoagulant. Anticardiolipin antibodies (IgG and IgM isotypes) were also deter- mined by ELISA assay (Diagnostica Stago, Asnières, France). Lupus anticoagulant was assayed with clotting techniques. Anti- cardiolipin antibodies and lupus anticoagu- lant were measured 8 weeks later. We also screened for abnormalities in the coagulation process. Activated partial thromboplastin time and kaolin clotting time tests were performed. The levels of protein C and protein S were determined by ELISA assay (Diagnostica Stago, Asnières, France). Antithrombin III level was evalu- ated by colorimetric assay (Asserachrom, Diagnostica Stago, Asnières, France) and levels of factors VIIIc and XI were deter- mined with clotting assays (Diagnostica Stago, Asnières, France). Factor V Leiden was investigated through the evaluation of the activated protein C–sensitivity ratio 20 Antiphospholipid syndrome.pmd 8/17/2005, 11:09 AM628 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 629 (Accelerimat, bioMérieux, Marcy l’Etoile, France). Genetic analysis of factor V Leiden mutation was performed as previ- ously described [13]. Chi-squared test was used to compare the patient and control groups. Results All patients underwent fundus fluorescein angiography and ophthalmologic examina- tion. Almost all suffered from retinal vein occlusions (29 of 33 patients); the occlu- sive events primarily involved the central (9 patients) and the temporal (8 patients) veins. Only 4 patients had artery occlusions (Table 1). The prevalence of antiphospho- lipid antibodies in the study group was 33% (11 of 33 patients) while in the control group it was 5% (4 of 80). This difference was statistically significant (χ2 = 16.29, P < 0.001) . All patients with antiphospholipid anti- bodies had retinal vein occlusions, particu- larly temporal vein occlusions (5 of 11 patients). Only 1 patient with antiphospho- lipid antibodies had a central vein occlu- sion. None of the patients with artery occlusions tested positive for any of the assays. In the study group 2 patients were pos- itive for IgG-anticardiolipin antibodies, 3 patients for IgM-anticardiolipin antibodies and 1 patient for both isotypes IgG and IgM-anticardiolipin antibodies. The 5 re- maining patients were negative for anticar- diolipin antibodies but showed positivity for lupus anticoagulant (Table 1). Two patients had associated protein C resistance. All pa- tients were negative for antinuclear anti- bodies. No deficiency in antithrombin III, protein C or protein S was found. Factors VIII and XI levels were within normal. Discussion The etiology of retinal vein occlusion is still not well understood although thrombosis does occur histologically. Hypercoagulable states seem to be common in patients with retinal vein occlusions [8]. The presence of antiphospholipid antibodies in APS is likely to generate a hypercoagulable state such as to cause thrombosis to occur [1]. It is known that antiphospholipid antibodies im- pair the metabolism of arachidonic acid in endothelial cells and platelets causing the inhibition of prostaglandin I2 (PGI2) pro- duction by endothelial cells and activation of platelets through stimulating thrombox- ane A2 generation [14,15]. Furthermore, antiphospholipid antibodies inhibit protein C and protein S, preventing coagulation fac- tors Va and VIIa from inactivation [16,17]. Among other implications of the antiphos- pholipid antibodies syndrome is an increase in tissular factor release and in plasminogen activator inhibitor level. These implications could make it possible for thrombosis to occur even in veins or arteries, although Table 1 Presence of anticardiolipin antibodies, lupus anticoagulant and factor V Leiden among the 11 retinal vein occlusion patients testing positive for antiphospholipid antibodies Measurand No. Anticardiolipin antibodies 6a IgG 2 IgM 3 IgG and IgM 1 Lupus anticoagulant 5 Associated factor V Leiden 2 Antinuclear antibodies 0 20 Antiphospholipid syndrome.pmd 8/17/2005, 11:09 AM629 630 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 most vascular occlusions (81%) were found to affect venous vessels in a recent study [11]. Elevated levels of anticardiolipin anti- bodies have recently been associated with acute vascular occlusions of the eye al- though their role remains unclear [12,18– 21]. Of 33 patients with retinal vascular occlusions, 11 (33%) were diagnosed with APS. They possibly had primary APS without any underlying immune disorder like lupus erythematosus because each was negative for antinuclear antibodies. None of our patients, however, was investigated for other possible immune disorders. It is note- worthy that 9 of the 11 patients had no oth- er conventional risk for thrombosis, whereas the presence of antiphospholipid antibodies was associated with resistance to activated protein C for the 2 others. The high prevalence of antiphospholipid antibodies in our study indicates that an- tiphospholipid antibodies may play an im- portant role in the pathogenesis of retinal vein occlusions and thus may represent a risk factor of importance in the etiology of the disease. This may also suggest the ne- cessity of screening for antiphospholipid antibodies in such patients. Furthermore, in our study group, the prevalence of an- tiphospholipid antibodies seemed to be re- lated to retinal vein occlusions mainly involving the temporal vein and not to ar- tery vein occlusions. This warrants further investigation. It should be noted that the role of antiphospholipid antibodies in retinal vein occlusion is still controversial. Our re- sults provide more support for such a role of antiphospholipid antibodies in the patho- genesis of this disease. Our results (33% prevalence of an- tiphospholipid antibodies in patients with retinal vascular occlusions) were dissimilar from studies that identified lower preva- lences of 5%, 7.5% and 9% respectively among patients with primary APS [18,9,12]; however, in the two latter stud- ies, these levels could have been 22.5% and 22% if antiphospholipid antibodies were as- sociated with lupus erythematosus, the ele- vation of circulating immune complexes or complement deficiencies respectively [9,12]. Our results nevertheless indicate higher prevalence of antiphospholipid anti- bodies in retinal vein occlusions than the results of these authors. It should be noted that our study is the first of its kind in Tuni- sia and that a cohort study among the Tuni- sian population is needed. In our study, all patients with antiphos- pholipid antibodies except 2 were treated successfully with laser photocoagulation and anticoagulant and anti-aggregant thera- py (acenocoumarol, to get the patient’s in- ternational normalized ratio to 2–4, and lysine acetylsalicylate, 250 mg per day) [22]. The 2 exceptions had associated re- sistance to activated protein C with the presence of antiphospholipid antibodies and experienced unfavourable developments. One had an occlusive event in the second eye and the other became blind even though therapy was provided. In retinal vascular occlusions of unex- plained origin, antiphospholipid antibodies may play an important role in pathogenesis. Detecting these antibodies in the serum of patients with retinal vascular occlusions may help to determine the appropriate treat- ment. The high prevalence of anticardio- lipin antibodies in these patients who are free of conventional risk factors leads us to recommend a systematic search for specif- ic antiphospholipid antibodies for them. This should be part of a treatment combin- ing laser photocoagulation, and long-term anti-aggregant and oral anticoagulant thera- py [19]. 20 Antiphospholipid syndrome.pmd 8/17/2005, 11:09 AM630 Eastern Mediterranean Health Journal, Vol. 10, Nos. 4/5, 2004 631 References 1. De Groot PG, Oosting JD, Derksen RH. Antiphospholipid antibodies: specificity and pathophysiology. Balliere’s clinical haematology, 1993, 6:691–709. 2. Exner T, Triplett DA. Lupus anticoagu- lants: characteristics, methods of la- boratory detection and some clinical associations. In: Harris EN et al., eds. Phospholipid binding antibodies. Boca Raton, Florida, CRC Press, 1991:141– 58. 3. Loizou S et al. Measurement of anticardiolipin antibodies by an en- zyme-linked immunosorbent assay (ELISA): standardization and quanti- tation of results. Clinical and experimen- tal immunology, 1985, 62:738–45. 4. Harris EN et al. Clinical and serological features of the antiphospholipid syn- drome (APS). British journal of rheuma- tology, 1987, 26:19. 5. Alarcon-Segovia D, Sanchez-Guerrero J. Primary antiphospholipid syndrome. Journal of rheumatology, 1989, 16:482– 8. 6. Italian registry of antiphospholipid anti- bodies (IR–APA). Thrombosis and throm- bocytopenia in antiphospholipid syn- drome (idiopathic and secondary to SLE): first report from the Italian registry. Haematologica, 1993, 78:313–8. 7. Khamashta MA. Management of throm- bosis in the antiphospholipid syndrome. Lupus, 1996, 5(5):463–6. 8. Abu El-Asrar AM et al. Hypercoagulable states in patients with retinal vein occlu- sion. Documenta ophthalmologica, 1998, 95(2):133–43. 9. Cobo-Soriano R et al. Antiphospholipid antibodies and retinal thrombosis in pa- tients without risk factors: a prospective case–control study. American journal of ophthalmology, 1999, 128(6):725–32. 10. Coniglio M et al. Antiphospholipid anti- bodies are not an uncommon feature in retinal venous occlusions. Thrombosis research, 1996, 83(2):183–8. 11. Demirci FY et al. Ocular involvement in primary antiphospholipid syndrome. Ocular involvement in primary APS. International ophthalmology, 1998, 22(6):323–9. 12. Cobo Soriano R et al. Trombosis retiniana en pacientes jóvenes. Aspec- tos inmunológicos y clínicos. [Retinal thrombosis in young patients. Immuno- logical and clinical aspects.] Archivos de la Sociedad Española de Oftalmología, 2001, 76(11):641. 13. Ridker PM et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. New England journal of medicine, 1995, 332:912–7. 14. Lellouche F et al. Influence of thrombox- ane/prostacyclin biosynthesis in pa- tients with lupus anticoagulant. Blood, 1991, 78:2894–9. 15. Karmochkine M et al. The effect of sera with antiphospholipid antibodies on en- dothelial cell procoagulant activity is de- pendent upon the charge of the phospholipids against which they are di- rected. Thrombosis research, 1994, 74:435–40. 16. Cariou R et al. Effect of lupus anticoagu- lant on antithrombogenic properties of endothelial cells. Inhibition of thrombo- modulin-dependent protein C activation. Thrombosis and haemostasis, 1988, 60:54–8. 17. Smirnov MD et al. On the role of phos- phatidylethanolamine in the inhibition of protein C activity by antiphospholipid antibodies. Journal of clinical investiga- tion, 1995, 95:309–18. 20 Antiphospholipid syndrome.pmd 8/17/2005, 11:09 AM631 632 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 18. Glacet–Bernard A et al. Antiphospho- lipid antibodies in retinal vascular occlu- sions. A prospective study of 75 patients. Archives of ophthalmology, 1994, 112(6):790–5. 19. Wiechens B et al. Primary antiphos- pholipid antibody syndrome and retinal occlusive vasculopathy. American journal of ophthalmology, 1997, 123(6): 848–50. 20. Ermakova NA et al. Rol’ antifosfo- lipidnykh antitel v okkliuzii sosudov setchatki pri razlichnykh sosudistykh zabolevaniiakh glaza. [Role of anti- phospholipid antibodies in occlusion of retinal vessels in various vascular eye diseases.] Vestnik oftalmologii, 2002, 118(2):29–32. 21. Carbone J et al. Antiphospholipid anti- bodies: a risk factor for occlusive retinal vascular disorders. Comparison with ocular inflammatory diseases. Journal of rheumatology, 2001, 28(11):2437–41. 22. Dunn JP et al. Antiphospholipid antibod- ies and retinal vascular disease. Lupus, 1996, 5(4):313–22. Correction Screening for congenital hypothyroidism in the Islamic Republic of Iran: strategies, obstacles and future perspectives A. Ordookhani, P. Mirmiran, R. Hajipour, M. Hedayati and F. Azizi. Eastern Mediterranean Health Journal, 2002, Vol. 8 Nos 4/5, pages 480–9. The title of the French abstract should read: Dépistage de l’hypothyroïdie congénitale en République islamique d’Iran : stratégies, obstacles et perspectives futures and hypothyroïdie should replace hyperthyroïdie throughout the text of the abstract. 20 Antiphospholipid syndrome.pmd 8/17/2005, 11:09 AM632 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 633 Hyperhomocysteinaemia: risk of retinal vascular occlusion G.H. Yaghoubi,1 F. Madarshahian 2 and M. Mosavi 3 1Department of Ophthalmology, Valiaser Hospital; 2Nursing College, Birjand Medical University, Birjand, Islamic Republic of Iran. 3Department of Ophthalmology, Mashhad University of Medical Science, Mashhad, Islamic Republic of Iran. Received: 09/05/03; accepted: 20/10/03 ABSTRACT To investigate the possible relationship between hyperhomocysteinaemia and retinal vascular occlusion, we measured plasma homocysteine levels in 25 patients with a history of retinal vascular occlu- sion in the previous 2 years and in a control group of 24. The difference in mean plasma homocysteine levels was not statistically significant. All except 5 of the cases had hypertension, diabetes mellitus or hyperlipi- daemia. Most of the patients had branch retinal vein occlusion associated with recent onset of occlusion. Factors such as emotional status and associated systemic disease may play a role in predisposition of retinal vascular occlusion, so more-precise studies are needed to determine the possible risk factors of hyperhomocysteinaemia in retinal vascular occlusion. Hyperhomocystéinémie : risque d’occlusion vasculaire rétinienne RÉSUMÉ Afin d’examiner le lien possible entre l’hyperhomocystéinémie et l’occlusion vasculaire rétinienne, nous avons mesuré les taux d’homocystéine plasmatique chez 25 patients ayant fait une occlusion vascu- laire rétinienne dans les deux années précédentes et dans un groupe témoin de 24 sujets. La différence des taux moyens d’homocystéine plasmatique n’était pas statistiquement significative. Tous les cas sauf cinq avaient une hypertension, un diabète sucré ou une hyperlipidémie. La plupart des patients avaient une occlusion de branche veineuse rétinienne associée à la survenue récente de l’occlusion. Des facteurs tels que l’état émotionnel et une maladie systémique associée peuvent jouer un rôle dans la prédisposition à l’occlusion vasculaire rétinienne. Des études plus précises sont donc nécessaires pour déterminer les facteurs de risque possibles de l’hyperhomocystéinémie dans l’occlusion vasculaire rétinienne. 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM633 634 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Introduction Thrombophilia is an increased tendency to thrombosis which is sustained by an ongo- ing stimulus to thrombogenesis or by a defect in the normal anticoagulant or fibrin- olytic mechanism. Genetic factors are im- portant in thrombophilia since thrombosis can be familial and may be associated with congenital deficiencies of the protein C an- ticoagulant pathway, antithrombin III, hep- arin cofactor II or plasminogen. Although the relationship between hyperhomocys- teinaemia and vascular occlusion is still un- certain, it is of increasing interest that less severe abnormalities of methionine metabo- lism may predispose to the development of premature vascular disease. Endothelial dysfunction is also a factor in the complex changes that occur in vessel walls in hyper- homocysteinaemia [1,2]. Retinal vein oc- clusion is a major cause of retinal vascular disease, second only to diabetic retinopathy [3]. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are the 2 major categories, both having a similar potential for loss of vision owing to complications causing macular oedema and neovascularization [4]. Considering the various uncertainties regarding the many possible risk factors for retinal vascular occlusion, this study was carried out to measure plasma ho- mocysteine levels in patients diagnosed with retinal vascular occlusion and to com- pare the results with those of a control group to determine whether elevated ho- mocysteine level is a risk factor in retinal vascular occlusion. Methods We carried out a retrospective study of 25 out of 31 patients with retinal vein occlu- sion who consecutively attended the eye clinic of Valiasr Hospital, a teaching hospi- tal of Birjand Medical University, from May 2002 to December 2002. Diagnosis of reti- nal vascular occlusion was based on clini- cal findings of ophthalmoscopic exami- nation (well-demarcated haemorrhage and oedema along obstructed retinal vein). In uncertain cases fluorescein angiography was also done. A matched control group of 24 individuals was selected from people at- tending the clinic but who had no signs of retinal vascular occlusion, glaucoma, uvei- tis or intraocular surgery/trauma. All participants completed a checklist consisting of questions covering demo- graphic data, current disease, disease histo- ry, eye trauma and consumption of drugs. Then the fasting plasma homocysteine lev- els of the patients who had agreed to partic- ipate and had given informed consent was measured. Patients were classified into 3 major categories of retinal vascular occlu- sion based on their first episode: CRVO, BRVO (macular or main branch) or central retinal artery occlusion. The cases and controls were matched for age and sex. Fasting blood samples were collected in heparinized tubes from all participants. Af- ter immediate centrifugation, the resultant plasma samples were packed in an icebox and sent to the Pars Laboratory, Tehran to measure plasma homocysteine levels. Analysis of data was done with respect to presence/absence of a systemic condi- tion, sex, age group and mean plasma ho- mocysteine as independent variables and retinal vein occlusion as the dependent vari- able. Results Of the 25 patients with retinal vascular oc- clusion, 14 had BRVO and 10 had CRVO. Central retinal artery occlusion was diag- nosed in a single case. 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM634 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 635 The onset of occlusion in 6 patients oc- curred within the previous 6 months (1–6 months); in the rest, occlusion had oc- curred more than 6 months previously (7– 30 months). The characteristics of all participants, both cases and controls, are shown in Ta- bles 1 and 2. A more detailed comparison of related disease in both cases and controls is shown in Table 3. The mean total plasma ho- mocysteine level was 15.0 (SD, 5.7) µmol/L for patients with retinal vascular occlusion and 13.4 (SD 4.1) µmol/L for the control group (Table 4). The mean level was 13.8 µmol/L in patients with BRVO and 16.5 µmol/L in patients with CRVO. Of the 25 patients, 20 had at least 1 associated disease (diabetes mellitus, hypertension, hyperlipidaemia, asthma) for which they were under treat- ment by their primary care doctor and were taking medication. In the control group, these conditions were present in only 4 of the 24. The independent t-test showed no significant difference between plasma ho- mocysteine levels for cases and controls (P = 0.24). The Mann–Whitney test showed no sig- nificant difference between homocysteine levels in patients with BRVO and those with CRVO (P = 0.33). The Fisher test showed that there was also no significant difference in homocysteine level between hyperten- sive patients with BRVO and those with CRVO (P = 0.67). Visual acuity in all BRVO cases was 1.1 or better in comparison to hand motion per- ception, and 0.1 in CRVO patients. Discussion In this study, we found no significant clini- cal association between hyperhomocys- teinaemia and retinal vascular occlusion, although mean plasma homocysteine levels were higher in patients than in the control group. Most of these patients had at least 1 associated systemic disease. The sample size in our study was small and both the patients and those in the con- trol group were hospital-based subjects. This was a single blind study, in which the results may have been affected by the type of retinal vascular occlusion (most of the cases had BRVO). Our findings are similar to those of Larsson et al., who also report- ed that hyperhomocysteinaemia was not an important factor in the etiology of CRVO [5]. There may be different pathogeneses for the different kinds of retinal vascular occlusion. If there is an association with the location of the vascular obstruction, this finding may be related to increasing plasma homocysteine levels, or more prob- ably to homodynamic change or local vas- cular insult. This was discussed by Cahill et al., who considered CRVO to be associated with similar risk factors to retinal arterial occlusive disease. Local factors such as atherosclerotic retinal arteries compressing the retinal vein at arteriovenous crossings may be more important in the etiology of BRVO [6]. Hyreh et al. recommended that, apart from routine medical evaluation, an exten- sive and expensive workup for systemic disease is unwarranted in the vast majority of patients with retinal vein occlusion [7]. This raises 2 points. First, is vascular oc- clusion pathophysiologically different in different organs? If so, we can consider that the attributing factors must be pro- duced in greater amounts or elevated in larger vessels of the affected organ. Sec- ond, how much time has passed between the occurrence of vascular occlusion and the measurement of the plasma homocys- teine level, because homocysteine levels are affected by many factors (diet, emotional state, etc.). 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM635 636 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Table 1 Characteristics of patients with retinal vascular occlusion Patient Age Sex Eye Type of Associated Addiction Plasma (years) occlusion disease homocysteine (µmol/L) 1 42 Female L BRVO HY None 6.6 2 76 Male R CRVO HY None 25.0 3 68 Male R CRVO HY None 11.9 4 60 Male L CRVO HY None 16.8 5 71 Female L BRVOMB None None 17.9 6 48 Female R CRAO None None 17.4 7 60 Female R BRVO HY, DI None 25.0 8 66 Female L BRVO HY None 18.0 9 56 Female L BRVO HY None 12.4 10 68 Female R CRVO DI None 12.5 11 45 Male L BRVO None None 14.2 12 48 Male L CRVO DI, HCH None 13.0 13 40 Male L BRVOMB HY, HCH None 12.7 14 38 Female R BRVO HY, DI None 14.6 15 56 Female R BRVO HCH None 11.0 16 60 Female R BRVO HY None 15.5 17 60 Female L BRVO HY None 11.5 18 63 Female R BRVO HY, HCH None 12.6 19 63 Male L CRVO AS None 18.0 20 61 Female R BRVO HCH None 10.3 21 65 Female L CRVO None None 9.2 22 70 Male R BRVO HY None 10.5 23 70 Male R CRVO HCH None 27.0 24 80 Male L CRVO None None 10.5 25 80 Male L CRVO HY None 21.0 CRVO = central retinal vein occlusion. BRVO = branch retinal vein occlusion. CRAO = central retinal artery occlusion. MB = macular branch. HY = hypertension. HCH = hypercholesterolaemia. DI = diabetes. AS = asthma. Although our study did not find a signif- icant difference in hyperhomocysteinaemia levels between the case and the control groups, Lahey et al. have reported that hy- percoagulability plays a role in thrombus formation in patients with CRVO who are 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM636 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 637 under 56 years old [8]. They concluded that hypercoagulability may play a part in the pathogenesis of CRVO, but the cause remains multifactorial, and laboratory tests alone cannot determine the cause in most patients. They recommended examining blood pressure, intraocular pressure, com- plete blood count, glucose level and a lipid Table2 Characteristics of participants in the control group Participant Age Sex Associated Addiction Plasma (years) disease homocysteine (µmol/L) 1 79 Male None None 7.0 2 77 Female None None 16.9 3 75 Female None None 11.7 4 25 Female None None 7.1 5 53 Female HY None 13.0 6 61 Female DI None 15.4 7 52 Male None None 21.0 8 57 Male HY None 19.4 9 47 Male None None 9.0 10 65 Female None Smoking 10.2 11 67 Female None None 11.8 12 47 Male None None 17.6 13 47 Female None None 7.3 14 47 Male None None 14.0 15 50 Female None None 11.8 16 51 Female HY None 13.8 17 60 Male None None 17.3 18 65 Female None None 9.9 19 70 Male None None 11.5 20 70 Male None None 12.5 21 74 Male None None 11.5 22 76 Male None None 22.0 23 80 Female None None 16.2 24 85 Male None None 13.8 HY = hypertension. DI = diabetes. panel in all patients with CRVO. When tests for these common risk factors for CRVO are negative, they would consider ordering selected tests in young patients with CRVO to rule out thrombophilia. Furthermore, in 2 other studies the authors describe sclerotic thickening of the central retinal artery that could easily compress the adjacent central 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM637 638 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Table 3 Characteristic of cases with retinal vascular occlusion and participants in the control group Variable Cases (n = 25) Controls (n = 24) % Mean % Mean homocysteine homocysteine (µmol/L) (µmol/L) Male sex 44.0 – 50.0 – Hypertension 56.0 15.3 12.5 15.4 Hyperlipidaemia 24.0 14.4 0.0 – Diabetes mellitus 16.0 16.2 4.2 15.4 Without disease 16.0 13.8 83.3 12.4 Mean age of cases and controls was 60.5 and 61.7 years respectively (P = 0.77). Mean homocysteine level in cases and controls was 15.0 and 13.4 µmol/L respectively (P = 0.24). retinal vein and begin the sequence that leads to thrombus formation. Therefore, hyperhomocysteinaemia may represent a “double hit” in the multifactorial pathogene- sis of CRVO [9,10]. Although many reports suggest hyper- homocysteinaemia is a risk factor for vas- cular occlusion, our study shows that it plays a less important role than systemic risk factors for retinal vascular occlusion. Systemic hypertension was more common in cases than in control subjects. Also, most of the cases had at least 1 systemic disease (e.g. hypertension, diabetes, hyper- lipidaemia). Therefore, hyperhomocystein- aemia may represent a coincidental association in the pathogenesis of retinal vascular occlusion. These paradoxical re- sults not only demand repeating cohort studies with a larger sample size, they also Table 4 Distribution of cases according to type of retinal vascular occlusion Type of No. Diabetes Hyper- Hyper- Mean occlusion mellitus tension lipidaemia homocysteine No. No. No. (µmol/L) CRAO 1 0 0 0 17.4 CRVO 10 2 4 2 16.5 BRVO 14 2 10 4 13.8 Total 25 4 14 6 15.5 CRAO = central retinal artery occlusion. CRVO = central retinal vein occlusion. BRVO = branch retinal vein occlusion. 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM638 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 639 highlight the need to assess the preventive effects of lowering homocysteine levels on the recurrence of retinal vascular occlusion in cases compared to future attacks in con- trol subjects. Acknowledgement We wish to thank our colleague Hydari Be- hroze for his valuable assistance. References 1. Fermo I et al. Prevalence of moderate hyperhomocysteinaemia in a patients with early-onset venous and arterial oc- clusive disease. Annals of internal medi- cine, 1995, 123(10):747–53. 2. Faraci FM. Hyperhomocysteinemia: a million ways to lose control. Arterioscle- rosis, thrombosis, and vascular biology, 2003, 23(3):371–3. 3. Blice JP, Brown GC. Retinal vascular oc- clusive disease. In: Spaide RF ed. Dis- eases of the retina and vitreous. Philadelphia, W.B. Saunders Company, 1999:116. 4. Clarkson JG. Central retinal vein occlu- sion. In: Ryan SJ. Retina. Singapore, CV Mosby, 2001:1368. 5. Larsson J, Hultberg B, Hillarp A. Hyper- homocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion. Acta ophthalmologica scandi- navica, 2000, 78(3):340–3. 6. Cahill M et al. Raised plasma homocys- teine as a risk factor for retinal vascular disease. British journal of ophthalmol- ogy, 2000, 84(2):154–7. 7. Hayreh SS et al. Systemic diseases as- sociated with various types of retinal vein occlusion. American journal of oph- thalmology, 2001, 131(1):61–77. 8. Lahey JM et al. Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmol- ogy, 2002, 109(1):126–31. 9. Vine AK. Hyperhomocysteinemia: a new risk factor for central retinal vein occlu- sion. American journal of ophthalmol- ogy, 2000, 129(5):640–4. 10. Brown BA et al. Homocysteine: a risk fac- tor for retinal venous occlusive disease. Ophthalmology, 2002, 109(2):287–90. 21 Hyperhomocysteinaemia.pmd 8/17/2005, 11:09 AM639 640 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Aspects cytologiques des leucémies aiguës : à propos de 193 cas colligés dans la région centrale de la Tunisie N. Braham Jmili,1 A. Ben Abdelaziz,2 M. Nagara,1 T. Mahjoub,1 H. Ghannem2 et M. Kortas1 1Laboratoire d’Hématologie; 2Service d’Epidémiologie, C.H.U. Farhat Hached, Sousse (Tunisie). Reçu : 13/08/03 ; accepté : 22/01/04 RÉSUMÉ En Tunisie, peu de données concernant les leucémies aiguës sont disponibles en l’absence d’un registre de population. Nous avons étudié les caractéristiques épidémiologiques et cytologiques de 193 patients atteints de leucémie aiguë. Des hémogrammes ont été réalisés et des frottis de sang et de moelle ont été examinés pour chaque patient. L’âge des patients variait de 10 mois à 83 ans avec une prédominance masculine (rapport : 1,27). Concernant le type de leucémie aiguë, 40,4 % avaient une leucémie aiguë lymphoblastique, 51,8 % une leucémie aiguë myéloblastique et 7,8 % étaient des cas difficiles à classer. Dans notre série, 31,6 % des cas de leucémie aiguë s’observaient à un âge de moins de 10 ans et 72 % de ces cas étaient de type lymphoblastique. Une anémie (hémoglobine <11 g/dL) a été observée dans 88,5 % des cas, une thrombopénie (plaquettes <100 000/mm3) dans 80,5 %, une hyperleuco- cytose > 100 000/mm3 dans 14,5 % avec une blastose sanguine dans 92 % des cas. Cytological features of acute leukaemia in the central region of Tunisia ABSTRACT In Tunisia, because of an absence of population registry, data on acute leukaemia are scarce. We studied the epidemiological and cytological characteristic of 193 patients with acute leukaemia. Haemo- grams were carried out and slides for peripheral blood and bone marrow were prepared for each patient. The age range of the patients was 10 months to 83 years with a predominance of males (ratio: 1.27). As regards type of leukaemia, 40.4% had acute lymphoblastic leukaemia, 51.8% had acute myeloblastic leukemia and 7.8% were unclassified. Diagnosis was made at less than 10 years in 31.6% of cases and 72% of these were the lymphoblastic type. Anaemia (Hb < 11 g/dL was found in 85% of cases, thrombocytopenia (plate- lets < 100 000/mm3) in 80.5% and hyperleukocytosis (WBC > 100 000/mm3) in 14.5% of cases with blasts in peripheral blood in 92% of cases. 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM640 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 641 Introduction Les leucémies aiguës (LA) constituent un groupe hétérogène d’affections héma- tologiques clonales caractérisées par une prolifération maligne dans la moelle osseuse d’un clone cellulaire anormal du tissu hématopoïétique et bloqué à un stade précis de différenciation avec expansion de cellules immatures (blastes) qui peuvent être présentes dans le sang périphérique [1,2]. En Europe et aux États-Unis, les LA représentent 80 % des leucémies et environ 35 % des cancers de l’enfant [2,3]. En Tunisie, les leucémies représentent la première hémopathie maligne diagnostiquée et traitée [4]. Dès les premières descriptions, la sous- classification des LA en une série de variétés distinctes s’est imposée du simple fait de leur diversité morphologique. Ces subdivisions ont montré par la suite un intérêt pronostique du fait de leur sensibilité différente aux chimiothérapies [1,5]. Malgré le développement de nouvelles tech- nologies pour la caractérisation des différentes entités de leucémies aiguës dans les applications cliniques [6-8], on continue à utiliser dans beaucoup de pays en déve- loppement les recommandations anciennes de la classification FAB (French-American- British), mise au point en 1976 et basée sur des caractéristiques morphologiques et cy- tochimiques [9]. En Tunisie, en l’absence d’un registre de population, les laboratoires d’anatomo- pathologie et les dossiers hospitaliers constituent les principales sources d’infor- mation sur l’épidémiologie des cancers [10]. Toutefois, peu de données nationales concernant le profil épidémiologique et cytologique des leucémies aiguës sont disponibles. L’objectif de ce travail est de décrire, à travers une série de 193 cas, les caractéris- tiques épidémiologiques et cytologiques du sang périphérique et de la moelle chez les patients atteints de leucémie aiguë dans la région du centre de la Tunisie. Méthodes Il s’agit d’une étude descriptive réalisée au Laboratoire d’Hématologie de l’Hôpital Far- hat Hached de Sousse. Cette étude a con- cerné tous les patients chez lesquels une leucémie aiguë a été diagnostiquée entre le 1er janvier 1998 et le 30 juin 2002. Les échantillons de sang ont été prélevés par ponction veineuse sur des tubes avec EDTA K3 (acide éthylène diamine tétracétique tripotassique). La ponction de la moelle osseuse a été pra- tiquée chez l’adulte au sternum et en épine iliaque postérieure chez l’enfant. L’hémogramme a été déterminé sur « Coulter MAXM ». Les frottis de sang et de moelle ont été colorés au MGG (May- Grünwald-Giemsa) par la méthode automa- tique (HEMATEK-AMES). Pour chaque patient, trois lectures indépendantes des frottis de sang et de moelle ont été assurées et validées par des cytologistes. Le diagnostic de LA a été porté dès qu’il y avait plus de 30 % de blastes dans la moelle osseuse. L’examen de sang a permis d’établir la formule leucocytaire sanguine et a contribué à la classification des LA selon le groupe FAB. La séparation entre les sous-groupes des LA a été basée sur l’appréciation du pourcentage des blastes dans la moelle, le type de blastes et le compte absolu des monocytes sanguins [11]. La sous-classification morphologique des leucémies aiguës lymphoblastiques 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM641 642 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 a été basée sur un système de score uti- lisant les caractères cellulaires suivants : le rapport nucléocytoplasmique, la présence de nucléoles, l’irrégularité du profil nu- cléaire et la présence de grandes cellules [12]. La recherche de l’activité myélope- roxydasique par la technique à la pyronine a été la réaction cytochimique appliquée sur un frottis de moelle dans le cas où l’aspect myéloïde n’était pas évident et elle a été considérée négative si on notait une propor- tion de moins de 3 % de blastes peroxydase positive. Les données répertoriées ont été ensuite informatisées sur le logiciel de traite- ment statistique (SPSS.10) au Service d’Epidémiologie du C.H.U. Farhat Hached de Sousse. Les statistiques descriptives (moyennes, fréquences) ont été utilisées pour résumer les données. Résultats La répartition de 193 cas de LA selon les mois a montré une variation saisonnière avec deux pics : printemps et automne. L’âge des patients variait de 10 mois à 83 ans. Le rapport était de 1,27 en faveur du sexe masculin. Les leucémies aiguës touchaient tous les âges avec une fréquence plus élevée chez l’enfant (Figure 1). L’examen cytologique des frottis de sang et de moelle ont permis d’affirmer le diagnostic des 193 cas de LA et d’en pré- ciser le type cellulaire (Tableau 1) : 40,4 % des cas étudiés étaient de type lymphoblas- tique dont 56,4 % étaient de type L1 et 32,1 % étaient de type L2. La réaction de myéloperoxydase était indispensable dans 36 % des cas, vu l’absence de signe de dif- férenciation cytologique, et il était impossi- ble de classer 7,8 % des frottis examinés. Les leucémies aiguës de type myéloïde Figure 1 Répartition par âge et par sexe de 193 cas de leucémie aiguë colligés dans la région centrale de la Tunisie A : LAL (Leucémie aiguë lymphoblastique) B : LAM (Leucémie aiguë myéloïde) Hommes Femmes Hommes Femmes  ge ( an s)  ge ( an s) 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM642 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 643 représentaient 51,8 % des cas avec une dis- tribution homogène des différents sous- types 1, 2, 3, 4 et 5. Les LAM 6 et 7 étaient plus rares. Le sous-typage était impossible dans 17 % des LAM et 6,6 % des LAL. L’étude de la numération et formule sanguine de ces 193 patients atteints de LA a conclu aux différentes anomalies illus- trées par la figure 2. Elle a montré une blas- tose sanguine dans 92 % des cas. L’anémie a été observée dans 88,5 % des cas avec une thrombopénie dans 80,5 % des cas. Discussion Depuis une vingtaine d’années, la classifi- cation des LA fait appel aux recommanda- tions du groupe FAB. L’intérêt longtemps porté à cette classification tient à sa relative simplicité basée sur une description morphologique simplifiée, après coloration des frottis de sang et de moelle par la mé- thode de May-Grünwald-Giemsa com- plétée par des examens cytochimiques [11], accessible à tous les laboratoires et tenant compte des anomalies cytologiques du sang et de la moelle. Cette approche reste toujours la base du diagnostic des LA en application clinique malgré ses limites. En effet, dans notre étude, le plus souvent le diagnostic des LA est évident. Cependant, des difficultés de classement se sont posées en cas de frottis pauvres ou mal étalés. La ponction est difficile à réali- ser en cas de myélofibrose pouvant gêner l’aspiration de moelle. D’où la nécessité de caractériser la population blastique par d’autres marqueurs immunologiques et cytogénétiques pour affirmer ou même modifier le diagnostic et aussi mieux cibler les indications thérapeutiques initiées [2]. C’est la confrontation de l’examen des frottis sanguins et l’étude des molécules membranaires de surface qui permettra un diagnostic dans les cas difficiles [13,14]. En effet, l’immunophénotypage est indis- pensable pour confirmer le diagnostic des LAL, rechercher une LA biphénotypique et éliminer une LAM indifférenciée (LAM0) [15]. L’intérêt du caryotype dans les leucé- mies aiguës est bien établi. Les anomalies décelées représentent l’un des critères de classement d’une LA [6,16]. De même, la biologie moléculaire a fait aujourd’hui son entrée dans l’évaluation des LA, notam- ment pour la mise en évidence des translo- cations cryptiques et l’analyse des échecs du caryotype et surtout son intérêt majeur Tableau 1 Classification cytologique des 193 cas de leucémie aiguë colligés dans la région centrale de la Tunisie Cas Nbre % LAM 1 100 51, 8 LAM1 12 12,0 LAM2 17 17,0 LAM3 15 15,0 LAM4 16 16,0 LAM5 15 15,0 LAM6 7 7,0 LAM7 1 1,0 LAMDAC2 17 17 LAL3 78 40,4 LAL1 44 56,4 LAL2 25 32,1 LAL3 4 5,1 LALDAC4 5 6,4 LADAC5 15 7,8 Total 193 100 1LAM : leucémie aiguë myéloïde. 2LAMDAC : leucémie aiguë myéloïde difficile à classer. 3LAL : leucémie aiguë lymphoïde. 4LALDAC : leucémie aiguë lymphoïde difficile à classer. 5LADAC : leucémie aiguë difficile à classer. 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM643 644 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 pour l’évaluation de la maladie résiduelle [7]. Ainsi, la classification des LA proposée par l’OMS intègre les données mor- phologiques, immunophénotypiques, géné- tiques et cliniques dans le but de définir des entités biologiquement homogènes et cli- niquement pertinentes [17]. Le classement des leucémies aiguës est basé sur l’appartenance des blastes à une lignée lymphoïde ou myéloïde. Les leucémies aiguës lymphoïdes (LAL) sont divisées en LAL à précurseurs B et LAL à précurseurs T. Les leucémies aiguës myéloïdes (LAM) comprennent 4 grandes catégories [8,17] : • LAM avec anomalies génétiques récur- rentes ; • LAM avec signes de dysplasie touchant plusieurs lignées ; • LAM secondaires à des thérapeu- tiques ; • LAM autres, n’entrant pas dans les catégories précédentes. Toutefois, il faut noter que ces nou- velles techniques sont longues à mettre en œuvre et nécessitent une certaine pratique, ce qui les réserve à des laboratoires spécia- lisés, et devant l’extrême urgence de la maladie, l’examen cytologique du sang et de la moelle reste un moyen rapide qui per- met, dans l’heure qui suit le prélèvement, le diagnostic de la majorité des LA. Les deux variétés L1 et L2 des LAL ne sont pas réellement distinctes par une catégorie particulière de cellules blastiques mais plutôt par des proportions différentes d’éléments cellulaires qu’elles peuvent Figure 2 Anomalies de l’hémogramme chez 193 cas de leucémie aiguë colligés dans la région centrale de la Tunisie. Anémie (hémoglobine < 11 g/dL), thrombopénie (plaquettes < 100 000/mm3), neutropénie (polynucléaires neutrophiles < 1500/mm3) hyperleucocytose (globules blancs > 10 000/mm3), neutropénie sévère (polynucléaires neutrophiles < 1000/mm3), thrombopénie sévère (plaquettes < 20 000/mm3), pancytopénie (anémie, thrombopénie et leucopénie : globules blancs < 4000/mm3) 100 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM644 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 645 avoir en commun [4]. La valeur pronos- tique des formes L2 par rapport aux formes L1 n’a jamais pu être mise en évidence [11]. Cinq pour cent (5 %) des LAL étaient de type L3. Cette forme, distinguée par un critère cytoplasmique très particulier des cellules de Burkitt, doit être considérée à part des LAL classiques. Le type L3 est peu fréquent en France, tant chez l’adulte (9,7 %) que chez l’enfant (4,6 %) [18]. Les LAL de type Burkitt étaient classiquement de pronostic très péjoratif mais l’instau- ration de protocoles de chimiothérapie in- tensive et brève a entraîné un changement de pronostic et une amélioration des chan- ces de guérison. La présence de granulations dans les blastes fait suspecter une origine myélo- blastique. Le diagnostic peut être porté avec certitude sur un très faible pourcen- tage de blastes s’ils renferment un ou des corps d’Auer, témoignant de leur caractère malin [15]. Les caractères cytologiques des LAM ont une valeur pronostique discutée ; des études ont montré que le taux de rémis- sion complète a été plus élevé dans les catégories M1, M2 et M3 que dans les formes M4, M5 et M6, mais ces constata- tions n’ont pas été partagées par d’autres auteurs [19]. La littérature médicale rapporte que les LA de l’enfant, bien que rares en soi, représentent la première cause de cancer pédiatrique (30 %) et surviennent surtout avant 9 ans. En Europe et aux États-Unis, les LAL représentent 75 % à 80 % des leucémies et environ 20 % des cancers de l’enfant de moins de 15 ans [3]. En effet, les LAL touchent de préférence les âges extrêmes avec une distribution bimodale de l’incidence et de la mortalité (<15 ans et > 80 ans). Chez l’adulte, elles sont au con- traire quatre fois plus rares que les LAM (environ 5 % des leucémies) [18]. Dans notre série, 31,6 % des cas de LA s’observent à un âge de moins de 10 ans, et 72 % des cas sont de type lymphoblastique. Cependant, notre série comportait seule- ment 2 cas de LAL chez les patients âgés de plus de 50 ans et nous pensons que cette fréquence pourrait être sous-estimée et que la pathologie serait sous-diagnostiquée dans cette tranche d’âge. En revanche, nos ré- sultats corroborent ce qui est rapporté dans les différentes séries concernant la fré- quence des LAM chez l’adulte. Les LAM étaient quatre fois plus importantes que les LAL dans la tranche 20 à 60 ans, puis la fréquence restait stable jusqu’à un âge supérieur à 80 ans. L’âge est le facteur de pronostic le plus important pour la réussite du traitement d’induction des LAM [20]. Concernant les LAL, chez l’adulte, le risque de rechute ou d’échec primaire s’accroît au-dessus de 35 ans ; la maladie est souvent hyperleuco- cytaire avec une atteinte méningée initiale, et le traitement est plus toxique à cet âge. Chez l’enfant plus grand, le pronostic se dégrade à partir de 10-11 ans pour rejoindre celui de l’adulte à partir de 15 ans. Le pronostic est très défavorable si l’âge est inférieur à 12 mois, et surtout inférieur à 6 mois [2]. Le genre humain a une moindre valeur pronostique. Dans notre série, le rapport a été de 1,27 en faveur du sexe masculin avec une nette prédominance du sexe mas- culin à l’âge adulte. La prédominance mas- culine a été manifeste pour les leucémies aiguës de type lymphoblastique (Figure 1). Le pronostic est plus défavorable pour le sexe masculin dans ce cas (rechute testicu- laire dans 5 % des cas). Contrairement aux LAL, le sexe ne semble pas être un facteur de pronostic dans les LAM. Les leucémies aiguës associent à des degrés variables des signes de prolifération et d’insuffisance médullaire. L’étude de 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM645 646 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 l’hémogramme a montré des cellules blas- tiques dans 92 % des cas mais cela n’a pas été suffisant pour poser le diagnostic [2]. La détermination de la numération et formule sanguine a permis par ailleurs d’apprécier : • le degré de l’anémie : un chiffre normal d’hémoglobine (11,5 % des cas) traduit souvent une forme rapidement évolutive et de plus mauvais pronostic ; • l’intensité de la thrombopénie et le risque hémorragique : on notait une thrombopénie sévère avec un risque d’hémorragie cérébrale dans 35,1 % des cas ; • la leucocytose qui constitue un facteur pronostique majeur. Le pronostic est plus favorable quand la leucocytose est inférieure à 100 000/mm3 [2]. Dans notre série, les LA se présentaient fréquemment sous une forme hyper- leucocytaire (64,5 % des cas). Le chif- fre de globules blancs a été supérieur à 100 000/mm3 dans 14,5 % des cas avec une pancytopénie uniquement dans 10,5 % des 193 cas. • Le degré de la neutropénie absolue prédit le risque infectieux. Nos résultats ont montré une neutropénie dans 78,3 % des cas ; elle a été sévère dans 55,5 % des cas. Des résultats similaires ont été déjà décrits et ont trouvé notam- ment une leucocytose supérieure à 100 000/mm3 dans 5 à 10 % [2]. Conclusion Un hémogramme complet avec une lecture minutieuse des frottis de sang et de moelle complétée par des réactions cytochimiques permettent encore le classement de la plupart des LA. Cependant l’étude d’autres marqueurs cytogénétiques, immunolo- giques et moléculaires est devenue néces- saire pour confirmer le diagnostic des LAL et pour identifier des LA d’aspect atypique. La classification OMS nouvellement proposée utilise une combinaison de l’ensemble de ces approches, prenant en considération leur capacité à définir des en- tités biologiques qui, avec l’âge et les anomalies de l’hémogramme, permettent de définir le schéma thérapeutique et représentent les éléments utiles au pronos- tic [9,17]. Références 1. Hollard D. Les leucémies aiguës. EMC (Paris-France). Sang, 1983, 13015 A20 : 5-1983, 5–13. 2. Hunault-Berger M, Pellier I, Norbert I. Leucémie aiguë lymphoblastique (adulte et enfant). La Revue du Praticien, 1999, 49:441–5. 3. Chan KW. Acute myeloid leukaemia. Acute lymphoblastic leukaemia. Current problems in pediatric and adolescent health care, 2002, 32(2):40–9. 4. Laatiri M, Ennabli S. Lymphomes non hodgkiniens. In : Maalej M, ed. Cancé- rologie pratique. Tunis, Centre de Publi- cation universitaire, 1999: 447–55 5. Flandrin G et al. Classification des leucémies aiguës. EMC (Paris-France), Sang, 13015 A10, 7-1988, 5–10. 6. Charrin C, Mugneret F. Cytogénétique des leucémies aiguës de novo. La Re- vue du Praticien, 1996, 46:37–41. 7. Gabert J. Utilité de la biologie molécu- laire dans le diagnostic des leucémies aiguës et l’évaluation de la maladie résiduelle. La Revue du Praticien, 1996, 46:42–7. 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM646 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 647 8. Paredes-Aguilera R et al. Flowcyto-met- ric analysis of cell-surface and intra cel- lular antigens in the diagnosis of acute leukaemia. American journal of hematol- ogy, 2001, 68(2):69–74. 9. Flandrin G. La nouvelle classification OMS des hémopathies malignes. Hémo- pathies myéloïdes. Hématologie, 2001, 7(2):136–41. 10. Ben abdallah M. Epidémiologie des can- cers en Tunisie. In : Maalej M, ed. Cancérologie pratique. Tunis, Centre de Publication universitaire, 1999:33–7. 11. Imbert M, Jouault H, Tulliez M. Cytologie des leucémies aiguës. La Revue du Praticien, 1996, 46:23–9. 12. Bennet JM et al. The morphological clas- sification of acute lymphoblastic leu- kaemia: concordance among observers and clinical correlation. British journal of haematology, 1981, 47(4):553–61. 13. Feki S et al. Contribution of flow cyto- metry to acute leukaemia classification in Tunisia. Disease markers, 2000, 16: 131–3. 14. Cabrera E et al. Acute myeloid leu- kaemia: clinical and laboratory charac- teristics. Revista modica de Chile, 1999, 125(4):433–7. 15. Imbert M. Place du biologiste dans le diagnostic et le suivi des leucémies aiguës. Revue Française des Labora- toires, 2002, 344:67–70. 16. Bennett JM et al. Hypergranular promy- elocytic leukaemia: correlation between morphology and chromosomal translo- cations including t(15;17) and t(11;17). Leukaemia, 2000, 14(7):1197–200. 17. Valensi F. Classification des leucémies aiguës : nouvelles propositions de l’OMS. Revue Française des Labora- toires, 2002, 344:19–24. 18. Roy P, Coleman MP. Epidémiologie des leucémies aiguës lymphoïdes. Revue d’épidémiologie et de santé publique, 1992, 40:323–34. 19. Reiffers J, Perel Y, David B. Traitement des leucémies aiguës. In : Breton-Gorius J et al., eds. L’hématologie de Bernard Dreyfus. Paris, Flammarion, 1992 :805– 25. 20. Xavier T, Belharbi A. Leucémies aiguës myéloïdes du sujet âgé : Mise au point. Bulletin du cancer, 2002, 2(2):143–54. 22 Aspects cytologiques 1.pmd 8/17/2005, 11:09 AM647 648 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Physicians’ knowledge, attitude and practice towards erectile dysfunction in Saudi Arabia M.F. Abdulmohsen,1 I.S. Abdulrahman,1 A.H. Al-Khadra,1 A.A. Bahnassy,2 S.A. Taha,3 B.A. Kamal3, A.M. Al-Rubaish1 and A.H. Al-Elq1 1Department of Internal Medicine; 2Department of Family and Community Medicine; 3Department of Urology, College of Medicine, King Faisal University, Dammam, Saudi Arabia. Received: 06/05/03; accepted: 19/11/03 ABSTRACT We aimed to test the knowledge, attitude and practice (KAP) of physicians towards erectile dysfunction in the Eastern province of Saudi Arabia. At a scientific meeting about erectile dysfunction, 159 physicians from both government and private sectors answered a 34-item questionnaire in private. The mean total KAP score for the group was below the expected standard of 60%. Male physicians scored significantly higher than females. Urologists scored the highest, followed by andrologists. Surprisingly, phy- sicians with higher qualifications scored lower than those with intermediate qualifications and even less than general practitioners. Those who had practised for ≥ 10 years scored better than those with < 10 years practice. The role of cardiologists in the diagnosis and management of erectile dysfunction is discussed. Connaissances, attitudes et pratiques des médecins concernant le dysfonctionnement érectile en Arabie saoudite RÉSUMÉ Cette étude visait à tester les connaissances, attitudes et pratiques (CAP) des médecins concer- nant le dysfonctionnement érectile dans la province orientale d’Arabie saoudite. Lors d’une réunion scienti- fique sur le dysfonctionnement érectile, 159 médecins du secteur gouvernemental et du secteur privé ont répondu en privé à un questionnaire de 34 items. Le score CAP total moyen pour le groupe était en deçà du niveau escompté de 60 %. Les médecins hommes ont obtenu un score significativement plus élevé que les médecins femmes. Les urologues ont eu les scores les plus élevés, suivis par les andrologues. De manière surprenante, les médecins ayant les qualifications les plus élevées ont eu des scores inférieurs à ceux qui avaient des qualifications intermédiaires et même à ceux des généralistes. Les médecins qui pratiquaient depuis 10 ans ou plus ont eu de meilleurs scores que ceux qui pratiquaient depuis moins de 10 ans. Le rôle joué par les cardiologues dans le diagnostic et la prise en charge du dysfonctionnement érectile est examiné. 23 Physicians knowledge.pmd 8/17/2005, 11:09 AM648 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 649 Introduction Erectile dysfunction is one of the more commonly under-diagnosed medical disor- ders in the world [1]. It is defined as the persistent inability to maintain or to achieve an erection of sufficient rigidity to have sat- isfying sexual activity [2]. Recent estimates from the National Institutes of Health (NIH) in the United States suggest that about 30 million Americans have partial or complete erectile dysfunction [1]. The problem of erectile dysfunction is mainly linked to age, as shown in the Mas- sachusetts Male Aging Study, where 52% of the male study population aged 40–70 years had some degree of erectile dysfunc- tion [3]. Surprisingly, only about 1 in 10 men with erectile dysfunction between 18 and 59 years of age seek medical advice about their problem [4]. In another study, 44% of 500 patients who were consulting their urologists for reasons other than erec- tile dysfunction were found to have a histo- ry of erectile dysfunction but failed to inform their physicians about their prob- lem. The reason given by 74% of them was embarrassment [5]. It is believed that there are 2 major rea- sons for overlooking erectile dysfunction as a major health disorder. First, the major- ity of men with erectile dysfunction do not seek medical advice despite the growing awareness of the available treatment op- tions. The main causes for that are: social as well as religious; concerns about embar- rassment and shame; indifference; and fears about side-effects of treatment. Sec- ondly, the majority of physicians do not ask enough questions to identify men with erectile dysfunction or encourage them to seek treatment [6]. The prevalence of erectile dysfunction in non-insulin dependent Saudi diabetic men from the Mecca region was 81.1% [7]. The risk factors for erectile dysfunc- tion were: age, history of long standing dia- betes for more than 10 years, and poor metabolic control. In another study includ- ing 388 patients with different degrees of erectile dysfunction from Jeddah, Saudi Arabia, the severity of erectile dysfunction was mainly age-related, and physical inac- tivity, alcohol consumption and drug addic- tion were the only independent risk factors after adjusting for age. It has also been found that severe erectile dysfunction was a strong predictor of poor quality of life [8]. Therefore, physicians in general, and cardiologists in particular, should take the initiative to open the discussion about sexu- al activity with their male patients for sev- eral important reasons. First, erectile dysfunction and coronary artery disease share many risk factors such as diabetes mellitus, hypertension, smoking, dyslipi- daemia and ageing. Secondly, it is possible that the same vascular and endothelial changes that take place in the coronary ar- teries are likely to occur in the cavernosal arteries that supply the penile erectile tissue [2,3,9]. The evaluation of erectile function of a male patient may thus open a clinical window to a silent, yet growing coronary, peripheral or cerebrovascular disease and to other undiagnosed medical problems such as hypertension, diabetes mellitus and dyslipidaemia [10–16]. One more aspect of the problem of overlooking erectile dys- function in our opinion is the inappropriate knowledge, attitude and practice (KAP) of physicians towards erectile dysfunction, which may alter their ability to provide their patients with proper advice about the treat- ment options. The objective of this study was to as- sess the KAP of practising physicians to- wards erectile dysfunction in one region of Saudi Arabia. 23 Physicians knowledge.pmd 8/17/2005, 11:09 AM649 650 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Methods Sample This was a cross-sectional study carried out in the Eastern province of Saudi Arabia. The estimated sample size was 200 physi- cians, selected from both the government and private medical sectors in Dammam region (Dammam, Al-Qatif and Al-Khobar). A multistage random sample was used, where physicians were classified into 2 main strata: government and private. Using proportional allocation, a systematic ran- dom sample was used to select the required number of physicians from each stratum. Questionnaire A questionnaire with 36 questions was de- signed to collect information on: demo- graphic and professional data of the recruited physicians (8 items), current knowledge (13 items), attitudes towards erectile dysfunction (8 items) and practices when dealing with a patient suffering from erectile dysfunction (7 items). The questionnaire was designed by the authors and validated by a panel of experts in the field. A pilot study was undertaken on 20 physicians from the university hospital who were excluded from the study popula- tion before choosing the sample. Based on the results of the pilot study, the question- naire was modified. The weighting of each question relating to knowledge, attitude and practice was determined by the research team and experts in epidemiological stud- ies. The total score was 100 marks and the maximum scores for knowledge, attitude and practice questions were 42, 28 and 30 marks respectively. Data collection and analysis The targeted physicians were invited to at- tend a scientific meeting on erectile dys- function at 2 different locations, one for the private and the other for the government hospital doctors. The questionnaires were distributed and answered in a 45-minute private session at the beginning of the scientific meeting. The second part of that scientific meeting was a comprehensive lecture about erectile dys- function including anatomy and patho- physiology, delivered by the principal investigator. The data were entered into the personal computer using SPSS, version 10. Descrip- tive statistics for all variables were performed after scrutinizing the data. Sta- tistical analysis was made using t-test, Mann–Whitney test, analysis of variance and Kruskal–Wallis as appropriate. Results Two hundred (200) physicians were invit- ed to attend the 2 scientific meetings. A to- tal of 192 physicians were able to attend (96%) and out of that number, 159 an- swered the questionnaire, giving a response rate of 82.8%. The number of male physi- cians was much higher than female physi- cians: 151 (95.6%) and 7 (4.4%) respec- tively. One physician failed to mention his/ her sex. The mean and standard deviation (SD) overall KAP score for all the respondents was 55.6 (14.9) (maximum 100), the knowledge score was 19.0 (8.2) (maxi- mum 42), the attitude score was 19.0 (4.5) (maximum 28) and the practice score was 17.3 (5.3) (maximum 30). Table 1 shows the mean total KAP score by sex. The mean overall KAP score for females was significantly lower than that of male physicians (P < 0.001). This was re- flected in significantly lower mean knowl- edge and practice scores for females (P = 0.021 and P = 0.011 respectively). The 23 Physicians knowledge.pmd 8/17/2005, 11:09 AM650 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 651 mean attitude score was also lower for fe- males than males but this difference was not statistically significant. The mean overall KAP score of physi- cians was significantly different by special- ity (Table 1). Urologists scored the highest marks followed by andrologists, psychia- trists, general surgeons, cardiologists, gy- naecologists and other specialties including general practitioners (P < 0.001). The knowledge score of the urologists was the highest, followed by andrologists, then general surgeons, cardiologists, psychia- trists, gynaecologists, and other specialities (P < 0.001). The highest score for attitude was obtained by gynaecologists and the lowest by other specialities, but the differ- ence was not significant (P = 0.087). The score for practice was significantly differ- ent among different specialities (P < 0.001). Urologists scored the highest marks, followed by andrologists, psychia- Table 1 Knowledge, attitude and practice scores for physicians by sex, specialty, qualifications and years of practice Variable No. Mean (SD) Knowledge Attitude Practice Total (max. 42) (max. 28) (max.30) (max. 100) Sex Male 151 19.4 (8.1) 19.0 (4.5) 17.6 (5.2) 58.2 (14.9) Female 7 11.4 (5.6) 17.4 (3.4) 12.5 (3.9) 42.9 (9.6) P = 0.011 P = 0.353 P = 0.013 P = 0.021 Specialty Urologist 14 29.0 (6.2) 19.7 (4.5) 23.6 (2.9) 73.0 (8.9) Andrologist 11 24.3 (10.6) 21.1 (4.0) 21.6 (3.8) 67.0 (14.9) Psychiatrist 7 20.0 (7.3) 20.9 (6.6) 19.3 (3.5) 60.1 (14.1) General surgeon 16 20.7 (8.2) 20.8 (3.4) 16.9 (5.6) 58.9 (15.9) Cardiologist 10 20.4 (8.9) 18.6 (4.9) 18.3 (6.1) 57.3 (18.1) Gynaecologist 6 19.7 (9.9) 21.5 (3.6) 13.2 (6.7) 54.4 (19.2) Other specialty 84 16.9 (6.5) 18.3 (4.2) 16.3 (4.6) 51.8 (11.8) P < 0.001 P = 0.087 P < 0.001 P < 0.001 Qualifications MD or equivalent 31 14.5 (6.3) 17.1 (4.6) 15.0 (4.3) 47.4 (11.7) MSc or equivalent 55 21.0 (8.9) 20.1 (3.9) 18.3 (5.2) 59.5 (15.3) GP with MB BS 66 19.9 (7.7) 19.4 (4.4) 18.1 (5.3) 57.5 (14.2) P < 0.001 P = 0.007 P = 0.008 P < 0.001 Years of practice < 10 52 17.3 (6.8) 18.3 (4.0) 15.9 (4.6) 51.6 (13.0) ≥ 10 97 20.5 (8.6) 19.5 (4.7) 18.4 (5.3) 58.7 (15.1) P = 0.021 P = 0.112 P = 0.005 P = 0.005 GP = general practitioner. SD = standard deviation. aNumber of respondents; responses missing for some categories. 23 Physicians knowledge.pmd 8/17/2005, 11:10 AM651 652 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 trists, cardiologists, general surgeons, oth- er specialities, and the lowest score by gy- naecologists. Table 1 also shows physicians’ KAP to- wards erectile dysfunction in relation to their qualifications. Surprisingly, the physi- cians with highest qualifications, e.g. med- ical doctorate or equivalent, scored the lowest marks [mean knowledge score 14.5 (SD 6.3)] compared with physicians with intermediate qualifications, e.g. master’s degree or equivalent, (21.0, SD = 8.9) or general practitioners (19.9, SD = 7.7) (P < 0.001). There was a similar trend on the attitude and practice sections, with signifi- cant differences among the physicians ac- cording to level of qualifications (P = 0.007 and P = 0.008 respectively). The mean overall KAP score was signif- icantly higher for physicians with 10 or more years practice than those with less than 10 years practice (P = 0.005) (Table 1). The difference between the 2 groups was significant for knowledge and practice (P = 0.021 and P = 0.005 respectively) but not for attitude (P = 0.112). Some examples of responses to individ- ual questions are as follows. Question no. 10 (knowledge question) asked for the proper definition of erectile dysfunction; this was correctly answered by 66.5% of physicians. Question no.12 (attitude ques- tion) inquired about the most common eti- ology of erectile dysfunction; surprisingly, 52.5% of the physicians believe that it is mainly a psychogenic problem. Question no. 23 (practice question) inquired about the actions to be considered in dealing with a patient reporting a new onset of erectile dysfunction; 46.2% believed that such pa- tients should be referred to the urologist, whereas 14.0% did not know the correct answer to this question. Question no. 26 (practice question) dealt with the therapeu- tic modality of choice for treating the ma- jority of cases of erectile dysfunction, and 83.9% of the physicians were able to give the correct answer. Discussion Erectile dysfunction is a major public health problem worldwide, but is commonly un- der-diagnosed [1,2,7,13]. In this study, we aimed to answer the main question: “Do physicians know enough about erectile dysfunction and do they have the right atti- tude and practice towards it?” The study results revealed a high re- sponse rate, with 159 out of 192 meeting attendees (83%) answering the question- naire. The mean overall KAP score for all physicians was below 60% of the total, the known accepted standard for the evalua- tion of both undergraduate and postgradu- ate medical students. The performance of female physicians was significantly lower than the performance of male physicians, despite the assurance of the highest degree of confidentiality. Social and cultural fac- tors may account for the significant gap in both knowledge and interest of the female physicians in this part of the world. Approximately 80% of cases of erectile dysfunction are due to an organic cause, especially atherosclerosis of the cavernosal arteries of the penile tissue, and only 20% of the cases are due to psychiatric and psy- chogenic disorders [1–3]. Therefore, the clinical evaluation and treatment of erectile dysfunction should have a multidisciplinary approach. Fifty per cent (50%) of the members of NIH Consensus Development Panel on Impotence held in 1992 were urol- ogists, 14% were psychiatrists and 35% were representatives of other medical spe- cialities [1]. This misconception that erec- tile dysfunction is under the domain of urologists agrees with our results. Urolo- 23 Physicians knowledge.pmd 8/17/2005, 11:10 AM652 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 653 gists had the highest marks in the total KAP score (73%), followed by andrologists and psychiatrists, as compared with the rest of the specialities who scored lower. Despite the fact that 66.5% of the studied physi- cians were able to define erectile dysfunc- tion correctly, 52.5% still believed that the etiology of this problem is mainly psy- chogenic. Furthermore, 46% of the studied physicians preferred to refer patients pre- senting with new onset erectile dysfunction directly to the urologist, and 60% of them ignored the importance of obtaining a de- tailed medical history, performing a proper physical examination or requesting the nec- essary investigations (such as fasting blood sugar, lipid profile, testosterone, prolactin, luteinizing hormone and follicle-stimulating hormone) [2,9]. The total KAP score of the study popu- lation was strongly affected by the level of qualifications. Unexpectedly, physicians with higher qualifications scored much lower than physicians with intermediate qualifications, and even less than general practitioners. The poor performance of highly qualified physicians may be related to an inappropriate attitude towards erectile dysfunction, whose diagnosis and manage- ment was thought to be mainly under the domain of urologists and/or psychiatrists. Physicians with higher qualifications and who are highly specialized may have little interest in updating their general medical knowledge. However, the duration of phy- sicians’ practice in years was a positive predictor of better performance. Physi- cians who had more than 10 years practice scored significantly higher than those with less than 10 years practice. The increased understanding of the pathogenesis, proper evaluation and accu- rate diagnosis, and the available treatment options of erectile dysfunction, should stimulate health care planners to find ways of improving public awareness and physi- cians’ up-to-date knowledge about this ma- jor medical problem. Conclusion and recommendations The role of physicians, especially cardiolo- gists, is pivotal in the process of evaluation and management of erectile dysfunction. In this study of physicians who have a scien- tific and clinical interest in erectile dysfunc- tion, the overall KAP scores for all physicians were below the expected stan- dard. We recommend that: • Undergraduate curricula and postgradu- ate training programmes should be modified to accommodate and empha- size up-to-date knowledge about early detection, evaluation and management of erectile dysfunction. • The Ministry of Health, through health policy planners, universities and other medical sectors should find the proper approach and plans to improve the gen- eral public awareness regarding the importance of early diagnosis and treat- ment of erectile dysfunction. Acknowledgements We are grateful to Dr Emmanuel Larbi, Consultant Internist/Clinical Pharmacology and Professor of the Department of Inter- nal Medicine, King Faisal University, and King Fahd Hospital of the University for his invaluable effort in reviewing this manu- script, and Mr Ramesh Kumar for his sec- retarial support. 23 Physicians knowledge.pmd 8/17/2005, 11:10 AM653 654 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 1. NIH Consensus Development Panel on Impotence. Journal of the American Medical Association, 1993, 270:83–90. 2. Miller TA. Diagnostic evaluation of erec- tile dysfunction. American family physi- cian, 2000, 61(1):95–104, 109–10. 3. Feldman HA et al. Impotence and its medical and psychological correlates, results of the Massachusetts Male Aging Study. Journal of urology, 1994, 151:54– 61. 4. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: preva- lence and predictors. Journal of the American Medical Association, 1999, 281:537–44. 5. Baldwin KC, Ginsberg PC, Harkaway RC. Underreporting of erectile dysfunc- tion among men with unrelated urologic conditions. Abstract presented at the An- nual Meeting of the American Urological Association, April 29–May 4, 2000, At- lanta, Georgia. 6. Levine LA, Kloner RA. Importance of ask- ing questions about erectile dysfunction. American journal of cardiology, 2000, 86:1210–3. 7. El-Sakka AI, Tayeb KA. Erectile dysfunc- tion risk factors in noninsulin dependent diabetic Saudi patients. Journal of urol- ogy, 2003, 169(3):1043–7. 8. Abolfotouh MA, Al-Helali NS. Effect of erectile dysfunction on quality of life. Eastern Mediterranean health journal, 2001, 7(3):510–8. 9. DeWire DM. Evaluation and treatment of erectile dysfunction. American family physician, 1996, 53:2101–8. 10. Pritzker MR. The penile stress test: a win- dow to the hearts of man. Abstract pre- sented at the 72nd Scientific Session of the American Heart Association, Novem- ber 7–10, 1999, Atlanta, Georgia. 11. Billups K, Friedrich S. Assessment of fast- ing lipid panels and Doppler ultrasound testing in men presenting with erectile dysfunction and no other medical prob- lems. Abstract presented at the Ame- rican Urological Association, April 29– May 4, 2000, Atlanta, Georgia. 12. Cheitlin MD et al. ACC/AHA expert con- sensus document. Use of sildenafil citrate (Viagra) in patients with cardio- vascular disease. Journal of the Ameri- can College of Cardiology, 1999, 33: 273–82. 13. Jackson G. Erectile dysfunction and car- diovascular disease. International jour- nal of clinical practice, 1999, 53:363–8. 14. Jackson G et al. A systematic approach to erectile dysfunction in the cardiovas- cular patient: a consensus statement. In- ternational journal of clinical practice, 1999, 53:445–51. 15. Jackson G. Sexual intercourse and an- gina pectoris. International rehabilitation medicine, 1979, 3:35–7. 16. O’Kane PD, Jackson G. Erectile dysfunc- tion: is there silent obstructive coronary artery disease? International journal of clinical practice, 2001, 55:219–20. References 23 Physicians knowledge.pmd 8/17/2005, 11:10 AM654 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 655 Report SARS: the new challenge to international health and travel medicine S. Venkatesh1 and Z.A. Memish2 1Medical Affairs Division; 2Infection Prevention and Control Program and Infectious Diseases Division, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia. Received: 24/08/03; accepted: 25/01/04 SUMMARY Severe acute respiratory syndrome (SARS), the first severe new infectious disease of this millennium, caused widespread public disruption. By July 2003, 8427 probable SARS cases had been reported from 29 countries with a case fatality rate of 9.6%. The new febrile respiratory illness spread around the world along the routes of international air travel, with outbreaks concentrated in transportation hubs or densely populated areas. The etiologic agent was identified as a novel coronavirus, SARS-CoV. The disease is transmissible person-to-person through direct contact, large droplet contact and indirect contact from fomites and unwashed hands. Saudi Arabia successfully prevented the entry of the disease by imposing travel restrictions, special entry requirements, screening procedures at airports, including temperature checks, and quarantine. Ongoing efforts are aimed at developing case investigation, case management and surveillance protocols for SARS. Introduction In the first half of 2003, the global commu- nity saw the emergence and impact of se- vere acute respiratory syndrome (SARS), the first severe and easily transmissible new infectious disease of the new millenni- um. From Guangdong province of China, the SARS virus spread along international travel routes to 30 countries and became deeply embedded in 6 of them. By 11 July 2003, 8427 probable SARS cases had been reported from 29 countries with 813 deaths [1]. There was widespread public panic, and social stability was jeopardized in some of the hardest hit areas. Economists esti- mated the costs in the Far East alone at US$ 30 billion. The containment of SARS, how- ever, was achieved through the diligent ap- plication of centuries’ old control measures. The most pressing questions now are whether SARS is seasonal and could return in winter, and whether the SARS virus could hide in some animal or environmental reservoir and resurface when conditions again become favourable for spread to humans. Development of the SARS pandemic The first cases of a life-threatening respira- tory disease of unknown cause are now known to have appeared in Guangdong province in China in mid-November 2002 [2]. But it was only on 11 February 2003, that the World Health Organization (WHO) received the first official report of an out- break of atypical pneumonia in the prov- 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM655 656 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 ince, said to have affected 305 persons and caused 5 deaths. An infected medical doc- tor, who had treated patients in his home- town in Guangdong province, carried the SARS infection out of China on 21 Febru- ary 2003 to Hong Kong. Guests and visi- tors to the hotel’s ninth floor where he stayed seeded outbreaks in the hospital sys- tems of Hong Kong, Viet Nam and Sin- gapore days later [2]. Dr Carlo Urbani, a WHO epidemiologist who investigated the Hanoi outbreak, was the first to recognize the condition as a dis- tinct entity. The WHO designated the illness as severe acute respiratory syndrome (SARS) in late February 2003. Consider- able progress was achieved in the following months in understanding its epidemiology and clinical features. A collaborative net- work of scientists from 11 laboratories around the world worked hard and suc- cessfully identified the etiologic agent as a new species of coronavirus, now called SARS-CoV [3–5]. WHO confirmed the Guangdong cases to be consistent with the definition of SARS after its team was per- mitted on 2 April 2003 to visit the province. SARS began spreading along air travel routes, as persons who came in contact with the earliest cases travelled internation- ally. Hanoi, Hong Kong, Singapore and Tor- onto were the initial “hot zones” for SARS, with rapid increases in the number of cas- es, especially in health care workers (who exposed themselves without barrier protec- tion) and their close contacts. Subsequent chains of secondary transmission occurred outside the health care environment. The new disease showed a clear capac- ity to spread around the world along the routes of international air travel. The maxi- mum incubation period, estimated at 10 days, allows spread via air travel between any 2 cities in the world. Mounting evi- dence now points to certain source cases making a special contribution to the rapid spread of SARS infection. An imported hospitalized SARS case infected health care workers and other patients; they infected their close contacts and then the disease moved into the larger community. Epidemi- ological analyses revealed that the out- breaks of greatest concern were concentrated in transportation hubs or densely populated areas. Clinical features and management The Centers for Disease Control and Pre- vention (CDC) defines a “suspected case” of SARS as a person with onset of fever and lower respiratory tract symptoms (temperature > 38 ºC or 100.4 ºF) within 10 days of either travel to an area with docu- mented transmission of SARS or close contact with a person believed to have SARS [6,7]. If a suspected case develops chest radiographic findings of pneumonia, acute respiratory distress syndrome (ARDS) or an unexplained respiratory ill- ness resulting in death, with autopsy find- ings of ARDS without identifiable cause then he/she is reclassified as a “probable case” of SARS. Laboratory findings fur- ther reclassify suspected and probable cas- es into “laboratory positive”, “laboratory negative” or “indeterminate”. Household members or persons caring for or sharing personal items with a SARS patient are considered a “close contact” [6]. The incubation period for the disease varied from 2 to 10 days with a mean and median of 5 and 6 days respectively [8–12]. The classical presentation was of a febrile illness followed in 48–72 hours by dry cough, which progressed rapidly to cause respiratory compromise and hypoxaemia. This necessitated ventilator support in one- 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM656 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 657 quarter of the patients and led to mortality in 20%–45% of cases. The mortality was highest among elderly patients who had other co-morbid conditions [9]. Exposure to a high viral load was another factor sug- gested to explain the mortality from SARS among previously healthy young health care workers. Interestingly, SARS affected relatively few children and appeared milder in this age group [13]. Serological studies have shown that a symptomatic or sub- clinical infection is uncommon. None of the therapeutic modalities tried in different parts of the world (broad-spec- trum antibiotics, steroids, ribavirin, inter- feron, and retinovir/lopinavir) have shown conclusive evidence of curative effect on the disease and no standard regimen has been developed [14]. Current management of the disease therefore is purely supportive and efforts should be focused on appropri- ate infection control measures to prevent its spread. Infection control The epidemiological features of the disease suggest that it is transmissible from per- son-to-person through direct contact, large droplet contact, and through indirect con- tact from fomites and unwashed hands [8]. The virus is present in the respiratory se- cretions of infected patients and has also been found in the urine and faeces, raising the possibility of faecal–oral spread in some situations. It is critical that patients with suspected SARS be identified promptly to institute the isolation precautions needed to prevent the spread of the disease. Triage screening has been recommended, with a questionnaire to identify SARS symptoms and history of possible exposure. Patients suspected of having SARS need to be immediately sepa- rated from other patients, given a mask and evaluated carefully by a health care worker wearing a gown, gloves, and N-95 respira- tor, ideally in a negative pressure room. One way of avoiding the spread of disease in hospitals is to set up a fever triage clinic outside the hospital emergency room, equipped with all necessary contact pre- caution supplies. These clinics were devel- oped in Taiwan and Toronto during the peak of the SARS epidemic. Patients who need to be admitted should be isolated in a negative pressure room in a special isolation ward, with restrictions on visitors and the number of health care workers involved in the patient care. Medi- cal procedures such as bronchoscopy or respiratory nebulization of medications should be avoided. If the number of pa- tients exceeds the hospital’s capacity for negative pressure rooms, then the priority should be to keep patients with SARS pneumonia in isolation negative pressure rooms while maintaining other SARS pa- tients in private rooms. Restricting employees’ access to hospi- tals with SARS patients and identifying the employees who are taking care of SARS patients are critical steps to ensuring that health care workers do not suffer unpro- tected exposure to SARS patients. Staff should be actively monitored for any signs and symptoms of SARS, i.e. new onset upper respiratory tract illness and high tem- perature, for early detection of cases. Health care workers with symptoms should be immediately confined to their homes with daily reporting of symptoms to the employee health department or infec- tion control personnel at the hospital. All personnel involved in aerosol-generating procedures on patients with confirmed SARS should be quarantined for 10 days if 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM657 658 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 adequate precautionary measures were not taken during the procedure. Intensive education of health care workers and family is mandatory. This in- cludes proper infection control precau- tions, which should stress the 2 most likely modes of transmission of SARS: contact and respiratory droplets. Health care work- ers need personal protective equipment ap- propriate for standard, contact and airborne precautions (i.e. hand hygiene, gown, gloves and N-95 respirator) in addi- tion to eye protection, and use of these should be enforced. Household members should be educated about the mode of spread of the disease and proper precau- tions when in contact with the infected per- son by wearing gloves and mask and washing and disinfecting the hands fre- quently. If they develop symptoms, they should call the public health department and arrange to be examined by a qualified per- son. This coordination is crucial to pre- venting the spread of the disease from infected family members to health care workers who may be unaware of the risk of SARS contact. Suspect or possible cases that do not require admission to hospital should be managed as outpatients. These patients should be given clear instructions about hand hygiene practices with frequent hand washing and wearing a surgical mask to cover the mouth for coughing and sneez- ing. In addition, they should not share eat- ing utensils, towels and bedding with family members until washed. These pa- tients should remain at home until 10 days after the resolution of fever, if cough and other respiratory symptoms have resolved or improved. When no respiratory symp- toms or fever are present, family members need not be restricted from going out and carrying out their usual activities including work or school. Global action WHO issued a global alert on 12 March 2003 about cases of severe atypical pneu- monia with unknown etiology that ap- peared to place health workers at high risk. On 15 March 2003, WHO increased the level of the global alert to a rare emergency travel advisory for international travellers, health care professionals, and health au- thorities to the perceived worldwide threat to health from SARS. The Global Outbreak Alert and Response Network (GOARN) teams from WHO provided support at all the main outbreak sites. WHO regarded every country with an international airport, or bordering an area having recent local transmission, as being at potential risk of an outbreak. The lack of vaccine and effective treatment forced health authorities to resort to control tools dating back to the earliest days of empirical microbiology: isolation and quarantine. Countries around the world, guided by WHO, adopted aggressive and unprece- dented measures including travel restric- tions, special entry requirements, screening procedures at airports including tempera- ture checks and quarantine. Other control measures included public information and education to encourage prompt reporting of symptoms, early identification and isola- tion of patients, vigorous contact tracing, and management of close contacts. These succeeded to a large extent in containing the disease. Hospitals, schools, and borders were closed, and several governments advised their citizens not to travel to hard-hit areas. Some airlines decided not to carry passen- ger with a fever of 37.5 °C or above on any of their flights regardless of local govern- ment regulations. Hong Kong adapted an electronic tracking system used in criminal investigations for contact tracing and mon- 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM658 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 659 itoring of compliance with quarantine. Sin- gapore deployed its military forces to assist in contact tracing and to enforce quaran- tines that halted the normal lives of thou- sands of people [7]. The country also banned visitors at public hospitals. On being notified by Singapore, through WHO, Germany removed a physician from Singapore (returning from New York after attending a medical conference who had symptoms suggestive of SARS) along with his 2 accompanying family members from their flight at a stopover in Frankfurt, im- mediately isolated them and placed them under hospital care. This prompt action saved Germany from any further spread. The WHO announced in late June that Hong Kong and Beijing, the 2 most severely affected areas, had interrupted transmis- sion. Toronto and Taiwan followed shortly afterwards. On 5 July 2003, the WHO de- cided [15], on the basis of country surveil- lance reports, that all known person-to- person transmission of SARS-CoV had ceased and the global SARS outbreak was contained as it removed Taiwan from its list of areas with recent local transmission of the disease. The human chains of SARS vi- rus transmission appeared to have been broken everywhere. While the containment was a milestone, nations were cautioned against becoming complacent, and to main- tain vigilance against the re-emergence of the illness that resulted in over 800 deaths worldwide, mostly in China and Hong Kong, and for which there is no simple treatment. Some experts say it could be seasonal. Saudi Arabia Saudi Arabia had a special reason for con- cern. It has a large expatriate working pop- ulation of 5.3 million persons coming from various regions of the world. Around 2 mil- lion international pilgrims from over 140 countries visit Mecca, the focal point of Is- lam, for the annual hajj pilgrimage; a small- er number visit the country throughout the year for the individual and shorter umra pil- grimage. The country also receives a large number of business travellers the year round. Were measures not taken immedi- ately to prevent the entry of SARS, it would spread quickly and wreak havoc. Acting promptly, the Saudi Ministry of Health, on 10 April 2003, banned the entry of people who had visited any of the 5 SARS-stricken South East Asian coun- tries—China, Hong Kong, Taiwan, Sin- gapore and Viet Nam. The ban was enforced to protect both citizens and expa- triates in the country. Saudi Arabian citizens were advised against travelling to SARS af- fected countries. The Saudi missions in China, Singapore, Hong Kong and the Phil- ippines were instructed to stop issuing umra visas indefinitely. Isolation wards were designated in major hospitals in all re- gions to quarantine all suspected cases of SARS and admit confirmed SARS cases. The Sahari hospital, a new tuberculosis hospital in Riyadh, was the designated hos- pital for the Central region. Mass media was used extensively to increase aware- ness of SARS among the population. Customs, passport and health employ- ees at international airports were ordered to put on masks while dealing with flights ar- riving from countries with cases of SARS. All arriving passengers were required to fill in a mandatory health declaration form for immigration clearance. At the same time, the health officers at the airport distributed a health alert card with information about SARS. The card advised persons to con- tact doctors or designated hospitals if they later developed symptoms suggestive of 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM659 660 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 SARS, such as high fever (> 38 °C, > 100.4 °F), dry cough, shortness of breath or breathing difficulties. Health personnel checked all incoming passengers for fever. Within weeks, ther- mal scanners were installed before immi- gration clearance at the 3 international airports at Riyadh, Jeddah and Dammam in Saudi Arabia to identify persons with raised body temperature. This non-intrusive check did not affect passengers, as it did not delay them. Passengers with tempera- ture below 38 °C were allowed to proceed for immigration clearance as normal. Those with body temperature above 38 °C were taken for a secondary temperature check. Where fever was confirmed, the staff asked the passenger a series of health- related questions recommended by the WHO: if they have other symptoms of SARS, such as cough, breathing difficulty or shortness of breath; if they or their fam- ily members have had close contact with any person/s who have been diagnosed with SARS; and if, in the last 10 days, they had travelled to any SARS-affected areas. When SARS was suspected, the passenger was to be referred to the airport health de- partment for follow-up to be kept under observation for 10 days. Saudi Arabian cit- izens and expatriate workers returning from or transiting through SARS-affected countries within the incubation period of SARS, when cleared by checking for fever and symptoms in the airport, were quaran- tined in their homes; staff from the Minis- try of Health visited them daily to check their temperature until the 10th day. The measures were further stepped up on 28 April 2003. The Saudi Ministry of Health set up a special committee in Riyadh with branches throughout the country to coordinate efforts to fight the disease. The Ministry barred entry to nationals of SARS- affected countries as a precautionary mea- sure. All international airlines were notified not to transport any passenger coming to the Kingdom from the SARS-hit countries via a third country unless that passenger had stayed at least 10 days in that third country after departing from the last SARS-stricken station. The Saudi Arabia and 6 other Gulf countries met in Qatar in the first week of May to coordinate their efforts against SARS. The countries agreed to inform each other about SARS cases registered among their citizens or expatriates. The ban on passengers coming to Saudi Arabia from countries affected by SARS was lifted on 8 July 2003 following positive reports from WHO that no new cases had been reported for the past 20 days, includ- ing Canada and China. The Saudi Arabian health authorities, however, continued to monitor the country’s entry points in order to prevent the incursion of any potential SARS-carrier. For the subsequent hajj (at the end of January/beginning of February 2004), plans were made that all pilgrims coming from the earlier SARS endemic countries would not be allowed to enter the country unless there was evidence on his/ her passport that he/she had been outside of the country for a minimum of 10 days immediately prior to arrival in Saudi Arabia. Perspective SARS is a particularly serious threat for public health internationally. It also had far- reaching economic and social consequenc- es. Alerted by WHO, all countries with imported cases, with the exception of provinces in China, were able through rapid case detection, immediate isolation, strict infection control, and vigorous contact tracing to successfully prevent further transmission. 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM660 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 661 The high level of mass media attention focused on SARS and the concerted work of medical professionals, together with WHO’s pragmatic leadership role, helped create widespread awareness of the severi- ty of the infectious disease threat, and unit- ed the global community. Scientists and clinicians in various countries collaborated and pooled expertise and resources to com- bat the shared threat. This helped health authorities to identify imported SARS cases quickly, prevent a SARS outbreak, and thus avoid the devastating consequences seen elsewhere. The SARS experience in coun- tries like Viet Nam and Singapore showed that immediate political commitment at the highest level can prove decisive in combat- ing the spread of the disease. SARS has posed important challenges for medical professionals. There are con- cerns over the future evolution of out- breaks as the virus belongs to a family notorious for its frequent mutations. Ge- nomic studies have shown a remarkable genetic conservation of the virus; there ap- pears little likelihood of mutation to a be- nign infection with attenuated symptoms. With neither herd immunity nor attenuation of the virus, the next epidemic when it oc- curs will have large-scale outbreaks with severe symptoms. Efforts are on to devel- op case investigation, case management and surveillance protocols for SARS in the post-outbreak environment. The major challenges of the disease are its poorly understood epidemiology and pathogenesis, its non-specific and common initial symptoms, the limitations in the avail- able diagnostic tests and the vulnerability of hospital staff, the human resource vital for SARS control [8]. The requirement for in- tensive care for SARS cases is a strain on hospital resources. A rapid diagnostic test needs to be developed urgently for diagnos- ing SARS within days of onset for differen- tiating it from other atypical pneumonias. Research should be intensified to identify the possible animal reservoir. A global data- base on SARS has to be developed and an evidence-based approach used for thera- peutic approaches for SARS treatment [2]. The efforts at combating the threat of SARS have revealed the strengths and weaknesses of national, regional and global capacities to respond to infectious disease threats. Areas for urgent improvement have now been highlighted in the health surveil- lance systems of various countries. These need to be addressed so that countries are adequately prepared when the world is next confronted with SARS or another infec- tious disease pandemic. References 1. Cumulative number of reported cases of severe acute respiratory syndrome (SARS). Geneva, World Health Organi- zation, 2003 (http://www.who.int/csr/ sars/country/2003_07_11/en, accessed 12 January 2005). 2. Severe acute respiratory syndrome (SARS): status of the outbreak and les- sons for the immediate future. Geneva, World Health Organization, 2003. 3. Peiris JSM et al. Coronavirus as a pos- sible cause of severe acute respiratory syndrome. Lancet, 2003, 361:1319–25. 4. Ksiazek TG et al. A novel coronavirus associated with severe acute respiratory syndrome. New England journal of medi- cine, 2003, 348:1953–66. 5. Drosten C et al. Identification of a novel coronavirus in patients with severe 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM661 662 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 acute respiratory syndrome. New En- gland journal of medicine, 2003, 348: 1967–76. 6. Centers for Disease Control and Pre- vention. Updated interim surveillance case definition for severe acute respira- tory syndrome (SARS)—United States, April 29, 2003. Morbidity and mortality weekly report, 2003, 52(17):391–3. 7. Centers for Disease Control and Pre- vention. Severe acute respiratory syn- drome—Singapore, 2003. Morbidity and mortality weekly report, 2003, 52:405– 11. 8. Conly JM, Johnston BL. SARS: a tale of two epidemics. Adult infectious disease notes, 2003, 14(3) (http://www.pulsus. com/Infdis/14_03/conl_ed.htm, acces- sed 12 January 2005). 9. Peiris JS et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumo- nia: a prospective study. Lancet, 2003, 361:1767–72. 10. Poutanen SM et al. Identification of se- vere acute respiratory syndrome in Canada. New England journal of medi- cine, 2003, 348:1995–2005. 11. Hsu LY et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial con- tacts. Emerging infectious diseases, 2003, 9(6):713–7. 12. Booth CM et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. Jour- nal of the American Medical Association, 2003, 289:2801–9. 13. Hon KLE et al. Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet, 2003, 361:1701–13. 14. So LK et al. Development of a standard treatment protocol for severe acute res- piratory syndrome. Lancet, 2003, 361: 1615–7. 15. SARS outbreak contained worldwide. Press release. Geneva, World Health Or- ganization, 2003 (http://www.who.int/ mediacentre/releases/2003/pr56/en ac- cessed 12 January 2005). 24 SARS the new challenge.pmd 8/17/2005, 11:10 AM662 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 663 Review Prevalence of physical inactivity in Saudi Arabia: a brief review H.M. Al-Hazzaa1 1Exercise Physiology Laboratory, King Saud University, Riyadh, Saudi Arabia. Received: 06/06/03; accepted: 23/12/03 SUMMARY Major lifestyle changes in recent years in Saudi Arabia may be leading to physical inactivity and a low level of physical fitness. This paper reviews the current literature about physical inactivity in the Saudi Arabian population and discusses its implications for health. Available data from a small number of studies suggests a high prevalence (43.3%–99.5%) of physical inactivity among Saudi children and adults alike. Furthermore, the proportion of Saudi children and adults who are at risk due to inactivity is much higher than for any other coronary heart disease risk factor. It is recommended that a national policy encouraging activity in daily life be established and more studies are carried out to address physical activity patterns with representative samples of the Saudi Arabian population. Introduction Until recent times, the physical demands of daily life and work in Saudi Arabia were sufficient to maintain a lean body mass and an appropriate level of physical fitness among the population. However, during the past 25 years, rapid developments in stan- dards of living in the Kingdom of Saudi Arabia and increased mechanization have touched all aspects of people’s lives. As a result, great changes in physical activity and eating habits have occurred in our soci- ety and low levels of physical activity and sedentary living are becoming increasingly prevalent among the Saudi population [1– 9]. Moreover, with massive urbanization and increased reliance on computer and telecommunication technology, further re- ductions in physical activity are projected for the coming years. These lifestyle changes that are rapidly occurring in Saudi Arabia (as well as in the rest of the Gulf Cooperation Council coun- tries) have a considerable impact on the health of society. In fact, such lifestyle transformation is thought to be responsible for the epidemic of non-communicable dis- eases, and their complications, in this part of the world [1,10–16]. In addition, the World Health Organization (WHO) has rec- ognized physical inactivity as a major threat to worldwide population health [17]. WHO recommended some possible goals and pri- ority actions aimed at promoting active liv- ing. Included in these actions is the need to assess the level of physical activity among various segments of the population. This paper aims to provide a brief over- view of the published data about the level of physical activity in the Saudi Arabian popu- lation and discuss the implications of phys- ical inactivity on the health of Saudi society. 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM663 664 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Prevalence of physical inactivity among the Saudi Arabian population A MEDLINE search was made for studies published from 1990 onwards, using the words “physical activity and Saudi Arabia” and “physical inactivity and Saudi Arabia”. Seven papers were found, 3 of which were relevant and were included in the review. A manual search of the local medical journals was conducted, which revealed 5 addition- al papers related to physical inactivity in Saudi Arabia. That little research has been published on this important public health issue shows that research into the epidemiology of physical activity in Saudi Arabia and neigh- bouring countries is still in its infancy. No nationally representative population study has been made to describe the patterns of physical activity and energy expenditure of the Saudi people. The available published data on the physical activity profile of Sau- di people come from studies largely con- ducted in urbanized areas and few of these have used large and randomized samples [2–9]. In addition, in some cases, assess- ment of physical activity was not the pri- mary focus of the study [6,8]. Table 1 presents a summary of physical inactivity prevalence among various seg- ments of the Saudi population [1–9]. Seven out of the 8 reported studies used question- naires [3–9], while 1 study involving pre- adolescent boys utilized continuous heart rate monitoring [2]. Across all of the stud- ies shown in Table 1, the total rate of inac- tivity ranged from 43.3% to 99.5%. Only 2 studies included data for both males and females and their findings indicated that fe- males were much less active than males [6,9]. Based on the results of 1 recent study involving adult men living in Riyadh city and using a fairly large and random sample, there appears to be a curvilinear relation- ship between inactivity prevalence and age [5]. As shown in Figure 1, the proportion of inactive men was highest during the middle-age years (30–49 years). In the same study, physical inactivity was shown to be higher among the less educated Saudi males [5]. Furthermore, the most important reasons for being physically inactive among Saudi males were time constraints and lack of facilities, as reported by more than 70% of the respondents [5]. In anoth- er study [9], the prevalence of physical in- activity in males increased from early adulthood (16–30 years) to reach its peak at a later age (46–60 years). Overall, what is striking from the find- ings of these studies is that the prevalence of inactivity among the Saudi population seems to be higher than rates reported in many industrialized countries of Europe and America [18–22]. However, according to the WHO report, 60% of the world pop- ulation is sedentary or not active enough to gain health benefits [17]. As shown also in Table 1, the percent- age of Saudi boys who do not take moder- ate daily physical activity, i.e activity that raises the heart rate to above 139 beats per minute (bpm), for 30 minutes or more was reported to be 57.1% [1,2]. Such a level of moderate intensity physical activity has been recommended as a minimum level of physical activity for children and adoles- cents [18,23–26]. In addition, Saudi boys spend, on average, limited time on activities that raise the heart rate above 159 bpm. This level of vigorous activity is considered necessary for optimal cardiovascular health and fitness in children and adolescents [24– 26]. In addition, according to a recent sur- vey conducted on a sample of adolescent boys in Riyadh city, the rate of inactive ad- olescents (exercising for 1 day or less per 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM664 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 665 Ta bl e 1 P h ys ic al a ct iv it y ra te s in th e S au d i A ra b ia n p o p u la ti o n P o p u la ti o n R eg io n [r ef er en ce ] A ss es sm en t N o . o f A g e (y ea rs ) L ev el o f p h ys ic al a ct iv it y m et h o d su b je ct s M ea n (S D ) R an g e N ev er Ir re g u la r To ta l ac ti ve ac ti vi ty in ac ti ve a % % % C hi ld re n P re -a do le sc en t R iy ad h ci ty [1 ,2 ] C on tin uo us h ea rt 92 9. 6 (1 .5 ) 7– 12 – – 57 .1 b bo ys ra te m on ito rin g A do le sc en ts A do le sc en t b oy s R iy ad h ci ty [3 ] Q ue st io nn ai re c 89 4 15 .7 (1 .8 ) 12 –2 0 – – 48 .4 A du lts C ol le ge m en R iy ad h ci ty [4 ] Q ue st io nn ai re 36 2 21 .9 (2 .1 ) 17 –3 0 45 .8 32 .4 78 .2 A du lt m en R iy ad h ci ty [5 ] Q ue st io nn ai re 13 33 41 .1 (9 .7 ) 19 –6 8 53 .4 27 .5 80 .9 P rim ar y ca re pa tie nt s E as te rn p ro vi nc e [6 ] Q ue st io nn ai re 22 7 M al e 41 .5 (1 1. 2) 43 .3 – – Fe m al e 32 .5 (1 1. 4) 84 .7 – – P rim ar y ca re ph ys ic ia ns R iy ad h ci ty [7 ] 98 42 .0 (6 .5 ) 26 –6 0 21 .5 55 .0 76 .5 A nd ro lo gy a nd ur ol og y pa tie nt s Je dd ah c ity [8 ] Q ue st io nn ai re 38 8 43 .2 (1 2. 5) 20 –8 6 82 .0 – – Lo w la nd er s an d hi gh la nd er s A si r p ro vi nc e [9 ] Q ue st io nn ai re d 90 5 M al e 16 –6 0 27 .5 31 .9 59 .4 Fe m al e 16 –6 0 88 .6 11 .3 99 .5 a T ot al r ep re se nt s bo th n ev er e xe rc is e an d irr eg ul ar p hy si ca l ac tiv ity . b P er ce nt ag e of b oy s no t ta ki ng e xe rc is e su ffi ci en t to r ai se h ea rt r at e > 1 39 b pm f or a t le as t 30 m in ut es p er d ay . c F re qu en cy o f ph ys ic al a ct iv ity ≤ 1 t im e/ w ee k. d U si ng L ip id R es ea rc h C lin ic Q ue st io nn ai re ( in ac tiv e m ea ns t ho se r ep or tin g no s tr en uo us e xe rc is e fo r ≥ 3 tim es p er w ee k) . S D = s ta nd ar d de vi at io n. 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM665 666 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 week) was approximate 50% [3]. The ma- jor determinants of physical activity in Sau- di children and adolescents appear to be cardiorespiratory fitness, obesity, the quali- ty of the physical education programmes, TV viewing and parental influence [27]. From a comparative point of view, it seems that both levels of moderate (heart rate > 139 bpm) and vigorous (> 159 bpm) phys- ical activity of Saudi boys are considerably lower than those levels reported for chil- dren from other countries [19,28,29]. Health implications of physical inactivity in Saudi Arabian society It is now well recognized that physical in- activity and increased sedentary habits rep- resent a risk factor for a number of chronic diseases including coronary heart disease (CHD) and obesity [30,31]. On the other hand, regular physical activity has been shown to reduce the risk of both cardio- vascular disease and all-cause mortality [18,23,30,32]. Furthermore, research on physical activity epidemiology indicates that inactivity appears to be far more im- portant risk factor than was previously es- timated [33,34]. The reason is that there are higher proportions of the population who are inactive and at risk for CHD than those who are at risk for any of the other CHD risk factors [33,34]. Figure 2 illus- trates this point using data from a recent physical activity study conducted on Saudi males [5]. The proportion of Saudi adults who are at risk due to inactivity is much higher than those at risk due to any of the other CHD risk factors, including hyper- tension [13], hypercholesterolaemia [14], obesity [15] and cigarette smoking [35]. Therefore, health promotion strategies aim- ing at decreasing the proportion of inactive Saudi adults should be a priority public health concern. The proportion of Saudi boys who are at risk of CHD due to inactivity relative to other risk factors is similar to that of Saudi adults. Figure 3 clearly shows that the per- centage of Saudi boys who are physically inactive is twice the rate of those with hy- perlipidaemia. Diseases such as CHD and obesity, for which inactivity is a likely risk factor, have their origin in childhood [36,37]. Moreover, CHD risk factors were shown to track from childhood to adult- Figure 1 Prevalence of physical inactivity among Saudi Arabian males by age [5] 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM666 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 667 Figure 2 Risk factors for coronary heart disease among Saudi Arabian males: proportions with physical inactivity [5], high systolic (SBP) and high diastolic (DBP) blood pressure [13], high total cholesterol level (TC) [14], obesity [15] and cigarette smoking [35] Figure 3 Risk factors for coronary heart disease among Saudi Arabian boys: proportions with physical inactivity [1,2], low high-density lipoprotein cholesterol level (HDL-C), high blood pressure (BP), low cardiorespiratory fitness (unfit), obesity (fat > 25% body mass), high low- density lipoprotein cholesterol level (LDL-C), high total cholesterol level (TC) and high triglycerides level (TG) [10] Inactivity 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM667 668 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 hood [38]. Thus, prevention of lifestyle-re- lated disease at an early age is an important public health priority, especially consider- ing the fact that children and adolescents account for more than 50% of the Saudi population. Indeed, a recent statement from the American Heart Association’s Council on Cardiovascular Disease in the Young has recommended that physicians should incorporate physical activity coun- selling into medical practice as a way of promoting physical activity among children and adolescents [39]. Conclusion and Recommendations From this brief review of the current level of physical activity in Saudi Arabia, it can be concluded that the prevalence of physi- cal inactivity among Saudi children, adoles- cents and adults is high. This may be large- ly the result of the recent dramatic changes in the people’s lifestyle. Moreover, the pro- portion of Saudi children and adults who are at-risk due to inactivity is much higher than for any of the other CHD risk factors. It is recommended, therefore, that a nation- al policy encouraging active living and dis- couraging inactivity be established. Such an approach has been recommended previ- ously [12,27]. Health care providers have an important role in promoting physical ac- tivity and fitness among all Saudi people. Finally, national studies addressing physical activity patterns with representative sam- ples of the Saudi population are urgently needed. Such surveillance will provide in- valuable information for public health au- thorities and policy-makers. References 1. Al-Hazzaa HM. Physical activity, fitness and fatness among Saudi children and adolescents: implications for cardiovas- cular health. Saudi medical journal, 2002, 23:144–50. 2. Al-Hazzaa HM, Sulaiman MA. Maximal oxygen uptake and daily physical activ- ity in 7-to-12 year-old boys. Pediatric ex- ercise science, 1993, 5:357–66. 3. Al-Rukban MO. Obesity among Saudi male adolescents in Riyadh, Saudi Arabia. Saudi medical journal, 2003, 24:27–33. 4. Al-Hazzaa HM. Physical activity profile of college male subjects. King Saud Uni- versity journal, 1990, 2:383–96 [in Ara- bic]. 5. Al-Refaee S, Al-Hazzaa HM. Physical activity profile of Saudi males: implica- tions for health. Saudi medical journal, 2001, 22:784–9. 6. Taha AZ, Bella H. Heart disease risk fac- tors: prevalence and knowledge in a pri- mary care setting, Saudi Arabia. East Mediterranean health journal, 1998, 4:293–300. 7. Al-Shahri M, Al-Almaei S. Promotion of physical exercise by primary health care physicians in Riyadh city. Saudi medical journal, 1998, 19:67–9. 8. Al-Helali NS, Abolfotouh MA, Ghanem HM. Pattern of erectile dysfunction in Jeddah city. Saudi medical journal, 2001, 22:34–8. 9. Khalid M. The association between strenuous physical activity and obesity in high and low altitude populations in southern Saudi Arabia. International journal of obesity and related metabolic disorders, 1995, 19:776–80. 10. Al-Hazzaa H et al. Prevalence of coro- nary artery disease risk factors in Saudi 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM668 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 669 children. Journal of the Saudi Heart As- sociation, 1993, 5:126–33. 11. Al-Hazzaa H et al. Cardiorespiratory fit- ness, physical activity patterns, and se- lected coronary artery disease risk factors in preadolescent boys. Interna- tional journal of sports medicine, 1994, 15:267–72. 12. Alwan A. Noncommunicable diseases: a major challenge to public health in the Region. Eastern Mediterranean health journal, 1997, 3:6–16. 13. Al-Nozha M, Ali M, Osman A. Arterial hy- pertension in Saudi Arabia. Annals of Saudi medicine, 1997, 17:170–4. 14. Al-Nuaim A et al. Prevalence of hyperc- holesterolemia in Saudi Arabia, epide- miological study. International journal of cardiology, 1996, 19:41–9. 15. Al-Nuaim AR et al. High prevalence of overweight and obesity in Saudi Arabia. International journal of obesity and related metabolic disorders, 1996, 20: 547–52. 16. El-Hazmi M et al. Diabetes mellitus and impaired glucose tolerance in Saudi Arabia. Annals of Saudi medicine, 1996, 4:381–5. 17. Annual global Move for Health initiative: a concept paper. Geneva, World Health Organization, 2003 (WHO/NMH/PAH/ 03.1) 18. US Department of Health and Human Services. Physical activity and health: a report of the Surgeon General. Atlanta, Georgia, Centers for Disease Control and Prevention (CDC), National Cen- ters for Chronic Disease Prevention and Health Promotion, 1996 (http:// www.cdc.gov/nccdphp/sgr/sgr.htm, ac- cessed 26 December 2004). 19. US Department of Health and Human Services. Healthy people 2010: under- standing and improving health, 2nd ed. Washington, DC, US Government Printing Office, 2000 (http://www. h e a l t h y p e o p l e . g o v / D o c u m e n t / tableofcontents.htm, accessed 26 De- cember 2004). 20. Crespo CJ et al. Prevalence of physical inactivity and its relation to social class in US adults: results from the Third National Health and Nutrition Examination Sur- vey, 1988–1994. Medicine and science in sports and exercise, 1999, 31:1821– 7. 21. Caspersen CJ, Merritt RK. Physical ac- tivity trends among 26 states, 1986– 1990. Medicine and science in sports and exercise, 1995, 27:713–20. 22. Caspersen C, Merritt R, Stephens T. In- ternational physical activity patterns: a methodological perspective. In: Dish- man R, ed. Advances in exercise ad- herence. Champaign, Illinois, Human Kinetics, 1994:73–110. 23. National Institutes of Health. NIH con- sensus development panel on physical activity and cardiovascular health. Jour- nal of the American Medical Association, 1996, 276:241–6. 24. American College of Sports Medicine. ACSM’s guidelines for exercise testing and prescription. Baltimore, Williams and Wilkins, 2000. 25. Cavill N, Biddle S, Sallis J. Health en- hancing physical activity for young people: statement of the United Kingdom expert consensus conference. Pediatric exercise science, 2001, 13:12–25. 26. Sallis J, Patrick K. Physical activity guidelines for adolescents: consensus statement. Pediatric exercise science, 1994, 6:302–14. 27. Al-Hazzaa H. Patterns of physical activity among Saudi children, adolescents and adults with special reference to health. In: Musaiger A, Miladi S, eds. Nutrition 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM669 670 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 and physical activity in the Arab coun- tries of the Near East. Manama, Bahrain Centre for Studies and Research, 2000: 109–27. 28. Armstrong N, Bray S. Physical activity patterns defined by continuous heart rate monitoring. Archives of disease in childhood, 1991, 66:245–7. 29. Sallo M, Silla R. Physical activity with moderate to vigorous intensity in pre- school and first grade schoolchildren. Pediatric exercise science, 1997, 9:44– 54. 30. Leon A, ed. Physical activity and cardio- vascular health. A national consensus. Champaign, Illinois, Human Kinetics, 1997. 31. Bijnen FC, Caspersen CJ, Mostard WL. Physical inactivity as a risk factor for coronary heart disease: a WHO and In- ternational Society and Federation of Cardiology position statement. Bulletin of the World Health Organization, 1994, 72(1):1–4. 32. Blair SN et al. Physical fitness and all- cause mortality: a prospective study of healthy men and women. Journal of the American Medical Association, 1989, 262:2395–401. 33. Caspersen CJ. Physical activity epide- miology: concepts, methods and appli- cations to exercise science. Exercise and sport sciences reviews, 1989, 17: 423–73. 34. Powell K. Population attributable risk of physical inactivity. In: Leon A, ed. Physi- cal activity and cardiovascular health. A national consensus. Champaign, Illinois: Human Kinetics, 1997:40–7. 35. Jarallah JS et al. Prevalence and deter- minants of smoking in three regions of Saudi Arabia. Tobacco control, 1999, 8:53–6. 36. Berenson G et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. New England journal of medicine, 1998, 338(23):1650–6. 37. McGill HC Jr et al. Association of coro- nary heart disease risk factors with microscopic qualities of coronary ath- erosclerosis in youth. Circulation, 2000, 102:374–9. 38. Webber LS et al. Tracking of serum lipids and lipoproteins from childhood to adult- hood. The Bogalusa Heart Study. Ameri- can journal of epidemiology, 1991, 133: 884–99. 39. Williams C et al. Cardiovascular health in childhood. A statement for health pro- fessionals from the committee on athero- sclerosis, hypertension, and obesity in the young (AHOY) of the council on car- diovascular disease in the young, Ameri- can Heart Association. Circulation, 2002, 106:143–60. 25 Prevalence of physical.pmd 8/17/2005, 11:10 AM670 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 671 Report Frequency of the CCR5-delta 32 chemokine receptor gene mutation in the Lebanese population W. Karam,1 R. Jurjus,2 N. Khoury,3 H. Khansa,3 C. Assad,4 P. Zalloua5 and A. Jurjus2 1Faculty of Public Health, Balamand University, Beirut, Lebanon. 2Faculty of Medicine, American University of Beirut, Beirut, Lebanon. 3Faculty of Public Health, Lebanese University, Beirut, Lebanon. 4Division of Medical Sciences and Public Health, Lebanese Council for Scientific Research, Beirut, Lebanon. 5Chronic Care Centre, Hazmieh, Lebanon. Received: 14/05/03; accepted: 14/09/03 SUMMARY A direct correlation between HIV infection and mutation in the chemokine receptor (CCR5) gene has been established. However, such correlation has never been investigated in Lebanon. We report the frequency of the CCR5-delta 32 mutation in a random sample of 209 healthy, HIV-1 seronegative Lebanese aged 19–68. Overall, 4.8% were heterozygous for the mutation. Homozygosity was absent from our sample. The frequency for the CCR5-delta 32 allele was 2.5%. Distribution of the mutation was unaffected by sex, age, religion or educational level. The frequency in the Lebanese population is consistent with that in the origin of the mutation in northern Europe. This could be attributed to a gene flow into the Middle East from northern Europe. Introduction According to a World Health Organization report, 42 million people were living with HIV/AIDS worldwide in 2002; 92% were adults, 46% women, and 8% children un- der the age of 15. This resulted in 3.1 mil- lion deaths in 2002. In North Africa and the Middle East alone, 550 000 people are cur- rently living with HIV/AIDS [1]. In Leba- non, the cumulative number of reported HIV/AIDS cases reached 987 by the end of 2002, while the estimated number could be as much as 3000 [2]. It has been established that infection by HIV-1 is influenced by a mutation in the chemokine receptor (CCR5) gene [3,4]. The product of the CCR5 gene encodes a CC-type seven-transmembrane G-protein- coupled chemokine receptor that binds RANTES, MIP-1alpha and MIP-1beta, and has been shown to mediate entry of M- tropic HIV-1 strains into target cells [5–7]. CCR5 also serves as an entry co-receptor for primary human immunodeficiency vi- rus strains that infect monocytes and mac- rophages [7–9]. The CCR5 gene is located on chromosome 3p21.3. Individuals resis- tant to repeated exposure to the virus have been shown to be homozygous for a 32 bp deletion in the CCR5 gene [5,6]. Heterozy- gosity for the mutation is associated with a slower progression to AIDS following HIV- 1 infection with a typical delay of 2–4 years [4,6,10]. The 32 bp deletion in the gene causes a frame shift at amino acid 185, 26 Frequency of the CCR5-delta.pmd 8/17/2005, 11:10 AM671 672 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 which results in a stop codon and prema- ture truncation within the third extracellular domain. Analysis of the infectability of cells of 3 different genotypes by Liu et al. dem- onstrated that HIV-1 replicated in wild-type homozygous cells but failed to replicate in homozygous delta-32 cells, whereas repli- cation of the virus in cells heterozygous for the mutation proceeded at an intermediate rate [5]. In this study we report the frequency of the CCR5-delta 32 mutation in the Lebanese population. Methods The participants were selected from Leba- nese adults attending the blood bank of a major teaching hospital in Beirut, Lebanon over a 6-month period between July and December 2001. Sample size was 220. Participants were healthy, HIV-1 seronega- tive, of both sexes, and ages ranged from 19 to 68 years. Palestinian, Syrian, and Ar- menian donors were not included in the study. None of the blood samples collected tested positive for HIV. In addition, the do- nated blood was further screened for anti- body titres and potential pathogens before being considered suitable for donation. Ev- ery third qualified donor was included in the study; people who donated blood at night or on Sundays, however, were ex- cluded. The donors were not inconve- nienced in any way. An anonymous questionnaire was completed for each par- ticipant. The questionnaire included ques- tions relating to marital status, number of sex partners, practice of safe sex, drug use, history of blood or blood products transfusion, and whether the participant had previously been tested for HIV. Institu- tional ethical clearance and informed con- sent of the blood donors were obtained. We followed the Helsinki Declaration (1964, amended in 1975 and 1983) of the World Medical Association. About 2 mL of donated peripheral venous blood was collected from each par- ticipant. The GFX genomic blood DNA pu- rification kit (Amersham Pharmacia Biotech Europe GmbH, Freiburg, Germa- ny) was used to extract genomic DNA from white blood cells following the lysis of red blood cells. DNA was eluted in 100 µL molecular biology grade water and stored at –20 °C. DNA concentrations were determined spectrophotometrically. Polymerase chain reaction was per- formed following the methods of Martin- son et al. [11]. Briefly, 100 ng of genomic DNA was denatured at 94 °C for 10 min- utes, following which it was subjected to 30 cycles of denaturation, annealing and extension. The last cycle was followed by an incubation at 72 °C for 10 minutes. The reaction mixture of 50 µL contained, 50 mmol KCl, 10 mmol Tris-HCl, pH 8.3, 800 µmol dNTPs, 100 µg/mL gelatin, 10 pmoles of each of the CCR5-specific for- ward and reverse primers, and 1.5 units of Taq polymerase enzyme (GibcoBRL Life Technologies GmbH, Karlsruhe, Germa- ny). Electrophoresis was performed in Tris-Borate EDTA running buffer and poly- merase chain reaction products were de- tected in 2% agarose containing 1 µg/mL ethidium bromide, and visualized by transil- lumination with ultraviolet light [11]. Cross contamination was avoided by using pipette-tips fitted with aerosol barrier filters, and frequent decontamination of work surfaces with short ultra-violet light irradiation and diluted bleach. Carry-over contamination was prevented by physically separating the extraction, amplification and detection areas. Both deleted and normal PCR products were extracted from agarose gels using the PCR product clean-up kit from (Roche 26 Frequency of the CCR5-delta.pmd 8/17/2005, 11:10 AM672 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 673 Molecular Biochemicals GmbH, Man- nheim, Germany) and dideoxytermination cycle sequencing (Applied Biosystems, Foster City, California,) of normal and de- leted polymerase chain reaction products was performed to confirm the identities of amplicons and to determine the exact na- ture and location of the deletion along the CCR5 gene. Eleven samples did not yield amplifiable DNA, consequently, the effective number of donors included in the study was 209. Statistical analysis was performed and individual parameters were tested for sig- nificance by analysis of variance. Results Overall, 4.8% of the people we studied were heterozygous for the mutation; ho- mozygosity was not found. The frequency for the CCR5-delta 32 allele was 2.5%. Distribution of the mutation was unaffect- ed by sex (P = 0.21), age (P = 0.41), or education level (P = 0.62), and was similar among the religious groups that we exa- mined (P = 0.43) (Table 1). The sequen- cing of the polymerase chain reaction products purified from agarose gels con- firmed their identity with that of the CCR5 gene (GenBank X91492). Also, the nature and location of the deletion identified by se- quencing of the deleted polymerase chain reaction products were identical to that re- ported by Liu et al. [5]. Discussion A north to south gradient in the delta 32 al- lele frequency has been reported across Europe, with the highest allele frequencies in the Finnish and other populations living around the Baltic Sea (10%–20% heterozy- gous; 1% homozygous), and the lowest in Sardinia and Greece, where the frequency drops to almost zero [11–13]. The mutation is also seen at very low frequencies in pop- ulations from Saudi Arabia, Syrian Arab Republic, Islamic Republic of Iran, Tuni- sia, Morocco, Cyprus (Greek), India, Paki- stan and Asia. It is virtually absent in native populations from sub-Saharan Africa and Oceania [11–15]. Based on the demograph- ic distribution, it is believed that the muta- tion arose in northern Europe in response to selective pressures such an infection epi- demic. Our results are consistent with re- ports in the medical literature: we detected the mutated allele in our study population at Table 1 Distribution of CCR5 genotype in healthy HIV-1 seronegative Lebanese adults (n = 209) Variable No. with No. with P- CCR5/CCR5 CCR5/CCR5- valuea delta 32 Total 199 (95.2%) 10 (4.8%) Sex M 112 6 0.21 F 87 4 Age (years) Range 19–68 20–60 0.41 ≤ 40 125 5 > 40 32 3 Unknown 42 2 Ethnicity Christian 119 8 0.43 Muslim 40 2 Unknown 40 0 Education University 84 5 0.62 High school 63 3 Technical 31 2 Other 21 0 aAll P-values were > 0.05, indicating no significant effect of age, sex, education or ethinicity in this case on the mutation frequency. 26 Frequency of the CCR5-delta.pmd 8/17/2005, 11:10 AM673 674 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 a frequency of 2.5%, which is close to what is being reported in the Syrian Arab Republic (1.4%), Islamic Republic of Iran (2.4%), Tunisia (1%), Morocco (1.5%) and Cyprus (2.8%) [15]. The frequency in the Lebanese popula- tion is consistent with the location of the origin of the mutation in northern Europe. This could be attributed to a gene flow into the Middle East from northern Europe. In addition, frequencies of the deletion gradu- ally decrease as the distance from Europe becomes greater and it is virtually absent in Asia, the Far East, Oceania and South Afri- ca. We therefore propose that, in addition to the gradient seen in Europe, a gradient outside Europe also exists for the mutation across the Middle East region and into Asia, the Far East and Oceania and across Eu- rope into Africa. This is in accord with a single point of origin for the mutation locat- ed in northern Europe, where the highest frequencies for the deletion have been re- ported. Acknowledgement The authors would like to acknowledge the support of the Lebanese Scientific Re- search Council for funding the study. References 1. AIDS epidemic update. Geneva, World Health Organization, 2002. 2. National AIDS program annual report 2002. Beirut, Lebanon, Ministry of Public Health, 2002. 3. Huang Y et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nature medicine, 1996, 2(11):1240–3. 4. Fowke KR et al. Resistance to HIV-1 in- fection among persistently seronegative prostitutes in Nairobi, Kenya. Lancet, 1996, 348(9038):1347–51. 5. Liu R et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell, 1996, 86(3):367– 77. 6. Dean M et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia growth and develop- ment study, Multicenter AIDS cohort study, Multicenter hemophilia cohort study, San Francisco City cohort, ALIVE study. Science, 1996, 274(5290): 1856–62. 7. Dragic T et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature, 1996, 381(6584): 667–73. 8. Alkhatib G et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fu- sion cofactor for macrophage-tropic HIV- 1. Science, 1996, 272(5270):1955–8. 9. Zhao SF et al. Chemokine receptors and the molecular basis for human immuno- deficiency virus type 1 entry into periph- eral hematopoietic stem cells and their progeny. Journal of infectious diseases, 1998, 178(6):1623–34. 10. Michael NL et al. The role of viral pheno- type and CCR-5 gene defects in HIV-1 transmission and disease progression. Nature medicine, 1997, 3(3):338–40. 11. Martinson JJ et al. Global distribution of the CCR5 gene 32-basepair deletion. Nature genetics, 1997, 16(1):100–3. 12. Libert F et al. The deltaccr5 mutation con- ferring protection against HIV-1 in Cau- casian populations has a single and recent origin in Northeastern Europe. Human molecular genetics, 1998, 7(3): 399–406. 26 Frequency of the CCR5-delta.pmd 8/17/2005, 11:10 AM674 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 675 13. Magierowska M et al. Distribution of the CCR5 gene 32 base pair deletion and SDF1-3´ A variant in healthy individuals from different populations. Immunoge- netics, 1998, 48(6):417–9. 14. Szalai C et al. High frequency of the CCR5 deletion allele in Gypsies living in Hungary. Immunology letters, 1998, 63(1):57–8. 15. Lu Y et al. Genotype and allele frequency of a 32-base pair deletion mutation in the CCR5 gene in various ethnic groups: absence of mutation among Asians and Pacific Islanders. International journal of infectious diseases, 1999, 3(4):186–91. Genetics in developing countries 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). Source: WHO Fact sheet: genetics and health Available at: http://www.who.int/genomics/en/E_hgn-_final.pdf 26 Frequency of the CCR5-delta.pmd 8/17/2005, 11:10 AM675 676 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Report Evaluation of cervical smears at King Hussein Medical Centre, Jordan, over three and a half years S.R. Malkawi,1 R.M. Abu Hazeem,1 B.M. Hajjat1 and F.K. Hajjiri1 1Princess Iman Research and Laboratory Sciences Centre, King Hussein Medical Centre, Amman, Jordan. Received: 21/05/03; accepted: 03/08/03 SUMMARY Cervical smears taken from women referred for a check-up or with vaginal itching/discharge over a period of 3.5 years were reviewed at the King Hussein Medical Centre, Jordan. All smears were fixed with 96% alcohol, stained with Papanicolaou stain and screened microscopically. Of the smears from 1176 women aged 18–70 years, 4.5% were classified as inadequate, 7.7% were normal and 79.9% showed non- specific inflammation. Abnormal vaginal flora was found in 4.8% of cases, Candida albicans in 1.2%, Tri- chomonas vaginalis in 0.9% and actinomycosis in 1 case. Dysphasic changes were rare: 9 cases (0.8%) were classified as atypical squamous cells of undetermined significance (ASCUS) and 2 cases (0.2%) were low-grade squamous intraepithelial lesion (LSIL). No cases of human papillomavirus infection (HPV) or cervical carcinoma were found. Introduction The cervical smear (Papanicolaou, Pap smear) is a routine screening test used for the detection of early cervical abnormali- ties, namely precancerous dysplastic changes of the uterine cervix [1], together with viral, bacterial, and fungal infections of the cervix and vagina. Cervical screen- ing is a relatively simple, low cost and non- invasive method. Regular screening for cervical cancer reduces both the mortality and incidence of cervical carcinoma. Cer- vical neoplasia typically develops into inva- sive cancer over a 10-year period [3–6] and apparent cases of rapidly progressive cer- vical cancer are likely to be among women who have escaped screening and proper follow-up. Annual screening reduces the probability of developing invasive carcino- ma by over 95% [2]. There is also epidemiological and exper- imental evidence that Pap smears are bene- ficial in detecting infections that are risk factors associated with cervical cancer, such as human papillomavirus (HPV) [7,8]. Societies where sexual activity starts at a young age and where multiple partners are common are at a higher risk of exposure to HPV than in conservative societies such as Jordan. HPV is a virus that infects repro- ducing cells, thus enhancing proliferation of the cell population; this increases the risk of transformation to high-grade lesions or carcinomas [9–11]. A cervical smear also detects vaginal infections such as Can- dida albicans, where patients present with physical discomfort, excess vaginal dis- charge, itching and other complaints. In the absence of a national cervical screening programme in Jordan, the aim of 27 Evaluation of cervical smears.pmd 8/17/2005, 11:10 AM676 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 677 this study was to evaluate the prevalence of cervical lesions in cervical smears analysed at the Princess Iman Research and Labora- tory Sciences Centre, Jordan. Methods Over a period of 3.5 years from August 1999 to February 2003, a retrospective re- view was made of records of 1176 cervical smears analysed at the Princess Iman Re- search and Laboratory Sciences Centre at King Hussein Medical Centre in Jordan. Pa- tients were those who had been referred from all military hospitals in Jordan to the gynaecology clinic at the Centre with com- plaints of vaginal itching or discharge, and those who came for a first-time or follow- up cervical smear. Cervical smears were taken by gynae- cologists at the clinics using a specu- lum and brush; endocervical cells were smeared onto slides with direct fixation by 96% ethanol. Smears were sent to the laboratory fixed in 96% ethyl alcohol. All smears were stained with Papanicolaou stain and stained slides were screened microscopically by trained staff comprising 2 cytotechnolo- gists and 1 pathologist. The adequacy of smears was determined by the presence of a good number of ecto- and endocervical components, no air dryness and no arte- facts. All smears were routinely stained by Papanicolaou stain using a Leica Autostain- er programmed for the purpose. Slides were classified into 5 main cate- gories: specific cervicitis, non-specific cer- vicitis, normal, cervical dysplasia, cervical carcinoma and inadequate. Results Of the cervical smears from 1176 women aged from 18–70 years, 91 (7.7%) were normal, while 53 (4.5%) smears were clas- sified as inadequate (Table 1). Of the remaining smears, 940 (79.9%) showed non-specific inflammation, i.e. an inflammatory background with no evi- dence of viral changes or bacteria. Specific inflammation was found in 81 cases: 56 (4.8%) cases showed abnormal vaginal flora, including Gardnerella vagi- nalis, 14 cases had Candida albicans (1.2%), 10 cases (0.9%) had Trichomonas vaginalis and 1 case had actinomycosis (0.1%). No cases of HPV infection were found. Low-grade cervical abnormalities were seen in 11 cases: 9 cases (0.8%) were clas- sified as atypical squamous cells of unde- termined significance (ASCUS) and 2 cases (0.2%) were low-grade squamous intraepithelial lesion (LSIL). No malignant cases were reported within this study peri- Table 1 Classification of 1176 cervical smears Category No. of % smears Inadequate 53 4.5 Normal 91 7.7 Non-specific cervicitis 940 79.9 Specific cervicitis Abnormal vaginal flora, including Gardnerella vaginalis 56 4.8 Candida albicans 14 1.2 Trichomonas vaginalis 10 0.9 Actinomycosis 1 0.1 Cervical dysplasia ASCUS 9 0.8 LSIL 2 0.2 Cervical carcinoma 0 0 Total 1176 100.0 ASCUS = atypical squamous cells of undetermined significance. LSIL = low-grade squamous intraepithelial lesions. 27 Evaluation of cervical smears.pmd 8/17/2005, 11:10 AM677 678 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 od. None of the categories were clustered in any specific age group. Discussion The cervical smear is a widely used routine test with many benefits, especially in de- tecting early cervical changes that can be treated to limit dysplastic processes devel- oping into cancer. Of the cervical smear tests on 1176 women in our hospital, 79.9% showed non-specific inflammation, namely unexplained inflammatory back- ground, thus showing no bacterial or viral features. The remaining cases of inflamma- tion showed 4.8% cases of specific inflam- mation, 1.2% candida infections, 0.9% trichomonal infections and 1 case of acti- nomycosis. The incidence of dysplastic changes in our study (1.0%) was low compared with other studies performed in industrialized countries [1,13,14] and we found no cases of cervical carcinoma. This contrasts, for example, with a study in New England in the United States of America (USA) which found that 11.8% of women aged 20–29 years and 8.4% of those over 30 years had infectious processes and 3.5% and 1.3% respectively showed squamous intraepithe- lial lesions (SIL) [15]. No cases of HPV infection were re- corded in our hospital during this study period. Statistics from the Centers for Dis- ease Control and Prevention’s National Center for HIV, STD, and TB Prevention showed that 5.5 million people in the USA became infected with HPV each year, and infection rates were highest in young wom- en [12]. In Jordan, sexual activity typically starts only after marriage where the marital age is over 16 years, and the cultural and religious traditions of our conservative so- ciety restrict the likelihood of multiple sex- ual partners. This may explain why no cases of sexually transmitted HPV, or cer- vical carcinoma, were found in our study group of women. References 1. Greenlee RT et al. Cancer statistics, 2000. CA: a cancer journal for clinicians, 2000, 50(1):7–33. 2. McCrory DC et al. Evaluation of cervical cytology. Evidence report/technology assessment no.5. Rockville, Maryland, Agency for Health Care Policy and Research, 1999 (AHCPR publication no.99–E010). 3. Schwartz PE et al. Rapidly progressive cervical cancer: the Connecticut experi- ence. American journal of obstetrics and gynecology, 1996, 175:1105–9. 4. Frame PS, Frame JS. Determinants of cancer screening frequency: the ex- ample of screening for cervical cancer. Journal of the American Board of Family Practice, 1998, 11:87–95. 5. Kenter GG et al. The cytological screen- ing history of 469 patients with squamous cell carcinoma of the cervix uteri; does interval carcinoma exist? Acta obstetricia et gynecologica scandi- navica, 1996, 75:400–3. 6. IARC Working Group on Evaluation of Cervical Cancer Screening Pro- grammes. Screening for squamous cer- vical cancer: duration of low risk after negative results of cervical cytology and its implications for screening policies. British medical journal, 1986, 293:659– 64. 7. National Institutes of Health Consensus Development Conference statement on cervical cancer. April 1–3, 1996. Gyneco- logic oncology, 1997, 66:351–61. 27 Evaluation of cervical smears.pmd 8/17/2005, 11:10 AM678 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 679 8. Schiffman MH, Bauer HM, Hoover RN. Epidemiologic evidence that human papillomavirus infection causes most cervical intraepithelial neoplasia. Jour- nal of the National Cancer Institute, 1993, 85:958–64. 9. Stoler MH. A brief synopsis of the role of human papillomavirus in cervical car- cinogenesis. American journal of obstet- rics and gynecology, 1996, 175:1091–8. 10. Richart RM et al. Human papillomavirus, IAC Task Force summary. Acta cytolo- gica, 1998, 42:50–8. 11. Stoler MH. Human papillomavirus and cervical neoplasia: a model for carcino- genesis. International journal of gyneco- logical pathology, 2000, 19:16–28. 12. A closer look at HPV infection. In: Track- ing the hidden epidemics 2000: trends in STDs in the United States. Atlanta, Geor- gia, Centers for Disease Control and Prevention, 2000. 13. Johannesson G, Giersson G, Day N. The effect of mass screening in Iceland, 1965–74, on the incidence and mortality of cervical carcinoma. International jour- nal of cancer, 1978, 21:418–25. 14. Hakama M et al. Effect of organized screening on the risk of cervical cancer in the Nordic countries. In: Miller AB et al., eds. Cancer screening. UICC project on evaluation of screening for cancer. Cam- bridge, United Kingdom, International Union Against Cancer, 1999:153–62. 15. Mount SL, Papillo JL. A study of 10,296 pediatric and adolescent Papanicoleau smear diagnosis in northern New En- gland. Pediatrics, 1999, 103(3):539–45. 27 Evaluation of cervical smears.pmd 8/17/2005, 11:10 AM679 680 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 Case report Glutaric aciduria type 1 in a Kuwaiti infant H.A. Elsori,1 K.K. Naguib2 and M.S. Hammoud3 1Department of Paediatrics, Adan Hospital, Kuwait. 2Medical Genetics Centre, Maternity Hospital, Salmiyah, Kuwait (email: kknaguib@hotmail.com). 3Department of Paediatrics, Faculty of Medicine, University of Kuwait, Kuwait. Received: 25/03/03; accepted: 23/12/03 Introduction Glutaryl-coenzyme A (CoA) dehydrogena- se deficiency (MIM 231670) is a recessive- ly inherited neurometabolic disorder asso- ciated with encephalopathic crises and se- vere extra-pyramidal symptoms [1]. Mac- rocephaly, frontotemporal brain atrophy and acute encephalopathic episodes char- acterize it, with striatal necrosis followed by dystonia [2]. However, some patients develop motor disease without overt crisis and other biochemically affected individu- als remain asymptomatic [3–8]. This is the first report of a Kuwaiti male infant with glutaric aciduria type 1 (GA-1). The clinical picture, the course of the dis- ease, neuro-imaging findings and treatment are discussed. Case report F.A. is a Kuwaiti child, aged 3.5 years, who was admitted to hospital at the age of 10 months because of fever, cough and re- peated vomiting of 1-week duration. After admission, he developed a series of short left-sided seizures followed a few days lat- er by right-sided seizures. Phenobarbital therapy was started. The seizures contin- ued for 5 days. Shortly after, he developed a left hemiplegia, and he was no longer able to sit or crawl and lost his words. He is the sixth and youngest child to first-cousin phenotypically normal parents and has 5 healthy sisters. Pregnancy and delivery were normal. Birth weight was 3.6 kg. Macrocephaly was noted at birth, and his head circumference continued to grow parallel to the 98th centile. His development was said to be entirely normal until the age of 10 months. He sat alone at 7.5 months, was crawling and pulling to stand at 8 months and by 10 months he had 1 or 2 words. He was admitted to hospital at the age of 5 months with suspected meningitis excluded by cerebrospinal fluid (CSF) ex- amination. Examination after the acute episode at 10 months revealed a relatively healthy, mentally normal child, with weight 10 kg and head circumference 51.5 cm. His cra- nial nerves were normal on examination. He had a dystonia of the left side and left hemi- paresis with increased muscle tone and ex- aggerated tendon reflexes on the same side. There were no abnormal neurological signs in the right limb. Examination of chest, heart, abdomen, skin and genitalia showed that all signs were within normal values. Fundus examination revealed no haemor- rhage or other abnormalities. The following 28 Glutaric aciduria type 1.pmd 8/17/2005, 11:10 AM680 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 681 investigations were normal: plasma sodi- um, potassium, urea, creatinine, liver en- zymes and glucose, haemoglobin, white blood cells and platelets, blood pH (7.36) and serum bicarbonate (21.2 nmol/L), pro- thrombin time, thrombin time and fibrino- gen, and serum ammonia, lactic acid and amino acids. Activated partial thromboplas- tin time (APTT) was slightly increased at 42 seconds. Plasma ceruloplasmin was slightly elevated. CSF investigations were normal. However, urinary glutaric acid was 67 µmol/mol creatinine (normal < 14) and 3-hydroxy glutaric acid was 85 µmol/mol creatinine (normal range: traces). Glutaryl- carnitine levels in urine were elevated and glutaryl-CoA dehydrogenase activity in cul- tured fibroblasts was low. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans of the head revealed severe frontotemporal atrophy and bilateral subdural haemorrhage (Figures 1 and 2). His current therapy consists of carnitine 500 mg 6 hourly, with a low protein diet and carbohydrate drinks to be given during infections and sick days. He is also receiv- ing regular physiotherapy. Phenobarbital was gradually discontinued 5 months after the acute episode. He is generally stable, fit-free, and showing mild improvement with left sided hemiparesis. The child is still alive at the time of writing this report. Discussion Since the first description of GA-1 by Goodman et al. in 1975 [9], several reports have been added to the literature describing one of the more frequent inherited metabol- ic disorders [10–12]. GA-1 is an autosomal recessive disorder caused by deficiency of glutaryl-CoA dehydrogenase, a mitochon- drial enzyme involved in the metabolism of lysine, hydroxylysine and tryptophan. The clinical picture typically shows varying de- grees of muscular hypotonia, motor delay, dystonia, dysarthria and dyskinesia begin- ning acutely or gradually in the first few years of life, often in macrocephalic chil- dren [7,13]. Figure 1 Computerized tomography scans of the head shows severe fronto-temporal atrophy Figure 2 Magnetic resonance imaging scans of the head shows fronto-temporal atrophy and bilateral subdural haemorrhage 28 Glutaric aciduria type 1.pmd 8/17/2005, 11:10 AM681 682 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 It is difficult to estimate the incidence of GA-1, as the clinical presentation is vari- able. But the figure of 1:40 000 in Cauca- sians seems a reasonable approximation [14–16]. An incidence as high as 1:30 000 has been suggested [16,17]. The disease is particularly frequent in certain communi- ties such as the Amish people in Pennsyl- vania (1:4000) and Saulteaux/Ojibway Indians in Canada [1,13–15,18]. Few pa- tients have been recorded among Arab pop- ulations [19]. In Kuwait, its incidence has not been estimated so far. However, the frequency of metabolic disorders is com- mon in Kuwait [20]. In the present report, the clinical pic- ture, the course of the disease and the biochemical and radiological findings rep- resent the classic presentation of GA-1. Both the onset and the clinical picture of the patient, who had a viral illness followed by encephalopathic crisis, have been con- sidered common features. However, among 100 cases described worldwide, only 4 asymptomatic homozygotes for the disease have been described [3,11,15]. This variability in presentation sometimes necessitates a high index of suspicion for diagnosis. Page et al. [21] reported a case that presented in the neonatal period with seizures, while Superti-Furga and Hoff- mann [2] emphasized that presentation may start between the early weeks and the 4th to 5th year of life when intercurrent illness- es, viral infections or gastroenteritis may trigger acute encephalopathy. The bio- chemical findings of the present case were highly diagnostic. The diagnosis of GA-1 is suggested by the findings of excess 3-hy- droxyglutaric acid in the urine and this should be found on a urinary organic acid screen. Blood acylcarnitine profile has also been used as a more sensitive test. Howev- er, both tests may show negative results and a strong clinical suspicion is needed [22]. Recognition of the biochemical changes before the brain has been injured is essential for a satisfactory outcome. Diag- nosis depends on the recognition of rela- tively non-specific physical findings such as hypotonia, irritability, macrocephaly and urine organic acid quantification [13]. The low activity of glutaryl-CoA dehydrogenase in cultured fibroblasts confirms the diagno- sis of GA-1. In addition, the radiological finding of fronto-temporal atrophy is typi- cally described in patients with GA-1 [23]. It has been suggested that the combination of wide CSF spaces anterior to the tempo- ral lobe and low-density lesions in the basal ganglia are almost diagnostic of this condi- tion [24]. In addition, the presence of sub- dural haemorrhage has been reported [25]. Glutaryl-CoA dehydrogenase is a multi- functional enzyme, which exists in the mi- tochondrial matrix as a homotetramer of 45-kD subunits. The human gene for glu- taryl-CoA dehydrogenase has been cloned and mapped to the short arm of chromo- some 19p13 [26]. More than 63 mutations have been identified so far in GA-1 families, but no one prevalent mutation was detected and little if any relationship between geno- type and clinical phenotype could be re- cognized. The mutations were widely distributed through the gene, with the larg- est number in exon 10 [27]. Recessive in- heritance of this disorder is confirmed. In conclusion, this report is the first of GA-1 from Kuwait. The clinical, biochemi- cal and radiological findings confirm the di- agnosis. Our patient is now stable but has only minor improvement, which agrees with most of the reported cases in the liter- ature. We hope that continued therapy with carnitine and low protein diet together with emergency regimen with carbohydrate drinks will at least prevent further deterio- ration and encephalopathic crisis. Coordi- nated research is needed to understand the 28 Glutaric aciduria type 1.pmd 8/17/2005, 11:10 AM682 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 683 pathogenesis of the brain pathology, to de- fine the role of dietary therapy and to ex- plore the possibility of neonatal screening. Multi-centre studies are needed to establish the best method for diagnosis and the opti- mal therapy of this disorder. References 1. Hoffmann GF et al. Clinical course, early diagnosis, treatment and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics, 1996, 27:115–23. 2. Superti-Furga A, Hoffman G. Glutaric aci- duria type 1 (glutaryl-CoA-dehydroge- nase deficiency): advances and un- answered questions. European journal of paediatrics, 1997, 156:821–8. 3. Amir N et al. Glutaric aciduria type 1: en- zymatic and neuroradiologic investi- gations of two kindred. Journal of pediatrics, 1989, 114:983–9. 4. Lipkin PH et al. A case of glutaric aci- demia type I: effect of riboflavin and car- nitine. Journal of pediatrics, 1988, 112: 62–5. 5. Hoffman GF et al. Early signs and course of disease of glutaryl-CoA dehydroge- nase deficiency. Journal of inherited metabolic disease, 1995, 18:173–6. 6. Woelfle J et al. Subdural hemorrhage as an initial sign of glutaric aciduria type 1: a diagnostic pitfall. Pediatric radiology, 1996, 26:779–81. 7. Renner C et al. Clinically asymptomatic glutaric aciduria type I in a 4 5/12-year- old girl with bilateral temporal arachnoid cysts. Journal of inherited metabolic dis- ease, 1997, 20:840–1. 8. Pineda M et al. Glutaric aciduria type I with high residual glutaryl-CoA dehydro- genase activity. Developmental medi- cine and child neurology, 1998, 40: 840–2. 9. Goodman S et al. Glutaric aciduria: a “new” disorder of amino acid metabo- lism. Biochemical medicine, 1975, 12: 12–21. 10. Gregersen N et al. Glutaric aciduria: clini- cal and laboratory findings in two broth- ers. Journal of pediatrics, 1977, 90: 740–5. 11. Kyllerman M et al. Dystonia and dyskine- sia in glutaric aciduria type I: clinical heterogeneity and therapeutic consider- ations. Movement disorders, 1994, 9: 22–30. 12. Hgberg B, Kyllerman M, Steen G. Dyski- nesia and dystonia in neurometabolic disorders. Neuropediatrics, 1979, 10: 305–20. 13. Baric I et al. Diagnosis and management of glutaric aciduria type I. Journal of in- herited metabolic disease, 1998, 21: 326–40. 14. Haworth J et al. Phenotypic variabilities in glutaric aciduria type I: report of four- teen cases in five Canadian kindred. Journal of pediatrics, 1991, 118:52–8. 15. Morton DH et al. Glutaric aciduria type I: a common cause of episodic encephal- opathy and spastic paralysis in the Amish of Lancaster county, Pennsylva- nia. American journal of medical genet- ics, 1991, 41:89–95. 16. Ziadeh R, Naylor E, Ginegold D. Identifi- cation of two cases of glutaric aciduria type I through routine neonatal screen- ing using liquid secondary ionization tandem mass spectrometry. Abstracts of the 6th International Congress on Inborn Errors of Metabolism, Milan, Italy, May 27–31, 1994: WS–2. 28 Glutaric aciduria type 1.pmd 8/17/2005, 11:10 AM683 684 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 17. Kyllerman M, Steen G. Glutaric aciduria. A “common” metabolic disorder? Ar- chives francaises de pediatrie, 1980, 37:279. 18. Goodman S, Freeman F. Organic aci- demias due to defects in lysine oxida- tion: 2-ketoadipic academia and glutaric academia. In: Scriver CR et al., eds. The metabolic and molecular bases of in- herited disease, 7th ed. New York, McGraw–Hill, 1995:1451–60. 19. Al-Essa M et al. Glutaric aciduria type 11: observations in seven patients with neo- natal- and late-onset disease. Journal of perinatology, 2000, 20(2):120–8. 20. Teebi AS et al. Phenylketonuria in Ku- wait and Arab countries. European jour- nal of pediatrics, 1987, 146:59–60. 21. Page A et al. Early clinical manifestation of glutaric aciduria type I and nephritic syndrome during the first months of life. Acta paediatrica, 1997, 86(10):1144–7. 22. Hauser S, Peters H. Glutaric aciduria type I: an undiagnosed cause of en- cephalopathy and dystonia-dyskinesia syndrome in children. Journal of pediat- rics and child health, 1998, 34(3):302–4. 23. Martinez-Lage J et al. Macrocephaly dystonia and bilateral temporal arach- noid cysts: glutaric aciduria type 1. Child’s nervous system, 1994, 10:198– 203. 24. Brisman J, Ozand P. CT and MRI of the brain in glutaric aciduria type I. A review of 59 published cases and a report of 5 new patients. American journal of neuroradiology, 1995, 16:675–83. 25. Greenberg C et al. Assignment of hu- man glutaryl-CoA-dehydrogenase gene (GCDH) to the short arm of chromosome 19, 19p13.2, by in situ hybridization and somatic cell hybrid analysis. Genomics, 1994, 21:289–90. 26. Biery BJ et al. Gene structure and muta- tion of glutaryl-coenzyme A dehydro- genase: impaired association of enzyme subunits that is due to an A421V substi- tution causes glutaric acidemia type 1 in the Amish. American journal of human genetics, 1996, 59(5):1006–11. 27. Goodman S et al. Glutaryl-coA dehydro- genase mutations in glutaric acidemia (type 1): review and report of thirty novel mutations. Human mutation, 1998, 12: 141–4. 28 Glutaric aciduria type 1.pmd 8/17/2005, 11:11 AM684 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 685 Case report Maternal death due to severe pulmonary oedema caused by falciparum malaria: a case report I. Adam1 and M.I. Elbashir 2 1New Halfa Teaching Hospital, New Halfa, Sudan. 2Faculty of Medicine, University of Khartoum, Khartoum, Sudan. Received: 12/10/03; accepted: 23/12/03 Introduction Pregnancy increases susceptibility to falci- parum malaria, and the level of disease transmission in an area influences the man- ifestations of the disease during pregnancy. In areas of low and unstable transmission, malaria during pregnancy is usually symp- tomatic, unlike the situation in areas of high endemicity, where patients are usually as- ymptomatic or present with severe anaemia [1,2]. There is some degree of immune suppression during pregnancy, with se- questration of infected red blood cells in the placenta through binding to chondroitin sulfate [3,4]. Malaria constitutes 40% of the infec- tious disease burden and approximately 50%–70% of all outpatient visits to hospi- tals in Sudan [5]. In eastern Sudan, malaria is mesoendemic and the predominant ma- laria species is Plasmodium falciparum [6,7]. We have previously observed differ- ent forms of clinical presentations of se- vere malaria among pregnant Sudanese women, including cerebral malaria, and that all parities were infected [8]. Antima- larial drug resistance is also a growing threat in Sudan [6]. We report a young pregnant woman with severe chloroquine-resistant falci- parum malaria and pulmonary oedema who died of respiratory failure in spite of ade- quate treatment with quinine in hospital. Case report A 24-year-old primigravida presented to New Halfa Teaching Hospital (eastern Sudan) on 28 December 2002 with amen- orrhoea for 34 weeks, fever, headache, productive cough and vomiting for 5 days. Two days before admission she had re- ceived 5 injections of chloroquine after confirmation of P. falciparum infection without improvement. The following findings were recorded on presentation: weight 73 kg, temperature 39.2 °C, pulse 95 beats/minute, blood pres- sure 110/70 mmHg, respiratory rate 30 breaths/minute, haemoglobin 9 g/dL, total white blood cells 8500 cells/µL, blood glu- cose 110 mg/dL, blood urea 25 mg/dL, se- rum creatinine 0.9 mg/dL. Her chest was clear clinically, with no crepitations or rhonchi. Examination of the baby showed a fundal height that correlated with the moth- er’s dates, cephalic presentation and audi- ble heartbeat. The diagnosis of chloroquine-resistant falciparum malaria with or without chest 29 Maternal death due.pmd 8/17/2005, 11:11 AM685 686 La Revue de Santé de la Méditerranée orientale, Vol. 10, No 4/5, 2004 infection was suspected initially. Thick blood films confirmed parasitaemia and the patient was put on quinine hydrochloride infusion in 5% dextrose 600 mg 3 times daily and also given benzyl penicillin 1 mil- lion IU intravenously every 4 hours. After 24 hours the woman’s axillary temperature was slightly lower at 38.8 °C, respiratory rate had risen to 50 breaths/ minute and the blood film was still positive, but she was cyanosed. Pulmonary oedema was suspected and the diagnosis was con- firmed by chest X-ray. The patient was put on intermittent oxygen, furosemide 40 mg/ kg twice daily and 15 mg of morphine was given intramuscularly. Quinine and penicil- lin were continued but there was no im- provement. On the third day the patient’s blood films were negative but she was deeply cy- anosed, respiratory rate was 54 breaths/ minute, temperature was 38.4 °C and she had chest crepitations. She died on the third day from respiratory failure. Discussion This report draws the attention to the threat caused by falciparum malaria in pregnant women in areas of low and unstable malaria transmission such as that in eastern Sudan. However, complications of falciparum ma- laria in adults, especially lung injury and re- nal failure, can occur after several days of treatment when the parasites have de- creased from baseline or even when para- sites disappear from the peripheral blood [9]. This patient presented with manifesta- tions of malaria after 5 days of treatment with chloroquine, a drug that is showing increasingly high failure rates in Sudan [6]. In many Asian and African countries, malaria is reported as one of the main caus- es of maternal mortality [10–14], and in central Sudan it was the leading cause of maternal mortality over the 15 years 1985– 99, accounting for 37% of maternal deaths [12]. Therefore, the utmost care and prompt early treatment with effective drugs is recommended in pregnant women, due to high susceptibility to severe compli- cations in areas of low and unstable trans- mission, and the rising rate of multi-drug resistance in all malaria-endemic areas. The World Health Organization recommends quinine as the drug of choice for severe fal- ciparum malaria [15]. However, it should not be relied upon as the sole treatment, but attention should be also directed to good monitoring of blood pH and gases (services lacking in our centre) and of venous pres- sure to avoid over-hydration that may cause or exacerbate pulmonary oedema. Likewise, intensive care units with a venti- lator are of paramount importance for pa- tients with pulmonary oedema. As in over-hydration, heart failure, renal failure and pulmonary irritants, falciparum malaria should be remembered as a cause of pul- monary oedema. References 1. Brabin BJ et al. A study of the conse- quences of malaria infection in pregnant women and their infants. Parassitologia, 1993, 35(suppl.):9–11. 2. Nosten F et al. Malaria during pregnancy in an area of unstable endemicity. Trans- actions of the Royal Society of Tropical Medicine and Hygiene, 1991, 85:424–9. 3. Fievet N et al. Immune response to Plas- modium falciparum antigens in Came- roonian primigravidae: evolution after delivery and during second preg- nancy. Clinical experimental immunol- ogy, 1997, 107:462–7. 4. Fried M, Duffy PE. Adherence of plasmo- dium falciparum to chondroitin sulfate A 29 Maternal death due.pmd 8/17/2005, 11:11 AM686 Eastern Mediterranean Health Journal, Vol. 10, Nos 4/5, 2004 687 in human placenta. Science, 1996, 272: 1502–4. 5. El Gaddal AA. The experience of the Blue Nile Health Project in the control of malaria and other water associated dis- eases. In: American Association for Ad- vancement of Science. Malaria and development in Africa. A cross-sectoral approach. Washington DC, AAAS, 1991. 6. Adam I et al. In the Sudan: chloroquine resistance is worsening and quinine re- sistance is emerging. Sudan medical journal, 2001, 39:5–11. 7. El Gadal AA. Malaria in the Sudan. In: Buck AA, ed. Proceedings of the confer- ence on malaria in Africa. Washington, DC, American Institute of Biological Sci- ences/USAID, 1986:156–9. 8. Adam I et al. Quinine therapy in severe Plasmodium falciparum malaria during pregnancy in Sudan. Eastern Mediterra- nean health journal, 2004, 10(1/2):159– 66. 9. World Health Organization, Communi- cable Diseases Cluster. Severe falci- parum malaria. Transactions of the Royal Society of Tropical Medicine and Hy- giene, 2000, 94(suppl. 1):S1–90. 10. Wickramasuriya GAW. Malaria and anky- lostomiasis in the pregnant woman. Their more serious complications and sequelae. Oxford, Oxford University Press, 1937. 11. Menon R. Pregnancy and malaria. Medi- cal journal of Malaysia, 1972, 27:115–9. 12. Dafallah SE, El Agib FH, Bushra GO. Ma- ternal mortality in a teaching hospital in Sudan. Saudi medical journal, 2003, 24:369–73. 13. Fawcus S et al. Community based study cause of maternal mortality in rural and urban Zimbabwe. Central African journal of medicine, 1995, 41:105–13. 14. Urassa E et al. Female mortality in the reproductive ages in Dar es Salam, Tan- zania. East African medical journal, 1994, 71:226–31. 15. World Health Organization, Division of Control of Tropical Diseases. Severe and complicated malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1990, 84(suppl. 2):1–65. 29 Maternal death due.pmd 8/17/2005, 11:11 AM687