No. 1 Social aspects of genital schistosomiasis in women

Being associated to fecal-oral transmission, cysticercosis is contracted either by auto-infection or by ingestion of food contaminated with eggs from the pork tape worm (Taenia solium). In the stomach, the larvae named cysticercus (Cysticercus cellulosae) hatches from the eggs and invades the host through the mucosa membrane. Human cysticercosis occurs in highly prevalent proportions in many developing countries including Madagascar where hygiene conditions are deplicable. Serology tests applicable to epidemiological surveillance of cysticercosis and associated pathology in the Malagasy population have been developed: an enzyme-linked immunosorbent assay (ELISA) for screening purpose, and an enzyme-linked immunoelectrotransfer blot assay (EITB) for confirmative testing. Two specific bands (13 and 14 kDa) have been identified as significant markers of the cysticercus in an active (vesicle) stage of the infection when cestocidal treatment is strongly indicated. The same bands may on the other hand be absent at early (cyste) as well as late (calcified) stages of the infection. Series of studies, including 4,375 serum samples, have been undertaken from 1994 until 1999 aiming at determinating the cysticercosis sero-prevalence in different provinces of Madagascar. It was confirmed that cysticercosis is highly frequent on the island, and that there exists a marked variation in the prevalence from 7 to 21% between the different provinces: less than 10% in coastal regions (Mahajanga and Toamasina) increasing to 20% in central regions (Ihosy, Ambositra and Mahasolo). It has also been observed that cysticercosis may occur in individuals at any age, and that it is equally distributed in urban as in rural areas. However, it is more frequently detected in women than in men. Madagascar is an endemic country for cysticercosis, which causes major and severe disease with implications in the public health sector. A national control program is, therefore, urgently warranted.

Liee au peril fecal, la cysticercose se contracte lors de l'ingestion d'œufs de ver solitaire (Taenia solium) contaminant les aliments on par autoinfestation par les mains sales. Ces œufs vont se transformer en larves appelees cysticerques (Cysticercus cellulosae). La cysticercose demeure frequente dans de nombreux pays en developpement, en particulier a Madagascar, ou persistent des conditions d'hygiene defectueuse. Pour determiner l'importance de cette parasitose dans la pathologie malgache, deux tests immunologiques pouvant etre appliques a de grandes series ont ete developpes: un test de depistage (ELISA) et un test de confirmation (EITB ou Enzyme-linked Immunoelectro Transfer Blot). Un profil de reconnaissance montrant en EITB les bandes hautement specifiques de 13 et/ou 14 kDa est lie a la forme active (vesicule) des cysticerques, seule forme pouvant reellement justifier l'utilisation d'un cestocide. Ces bandes sont absentes dans les formes transitionnelles (kystes) et calcifiees. Des etudes seroepidemiologiques realisees dans diverses provinces de Madagascar entre 1994 et 1999, et portant sur un total de 4 375 serums, montrent que la cysticercose est une affection frequente a travers l'Ile. Les resultats des tests immunologiques indiquent en effet une seroprevalence de la cysticercose active variant de 7 a 21%: inferieure a 10% dans les regions cotieres (Mahajanga et Toamasina) et plus elevee jusqu'a 20% dans les regions centrales de l'Ile (Ihosy, Ambositra et Mahasolo). La cysticercose peut toucher les sujets de tous les âges. Elle est generalement plus frequente chez les femmes que chez les hommes. Elle est presente tant en milieu urbain que rural. La prevalence nationale de la cysticercose active peut etre estimee a environ 10%, indiquant une forte endemieile qui place Madagascar parmi les pays les plus touches dans le monde. Cette etude confirme que la cysticercose constitue un probleme de sante puiblique a Madagascar. Elle met en exergue lanecessite de la mise en route rapide d'un programme national de lutte contre la cysticercose et le taeniasis.

Lot quality assurance sampling (LQAS) was evaluated for rapid low cost identification of communities where Schistosoma mansoni infection was hyperendemic in southern Madagascar. In the study area, S. mansoni infection shows very focused and heterogeneous distribution requiring multifariousness of local surveys. One sampling plan was tested in the field with schoolchildren and several others were simulated in the laboratory. Randomization and stool specimen collection were performed by voluntary teachers under direct supervision of the study staff and no significant problem occurred. As expected from Receiver Operating Characteristic (ROC) curves, all sampling plans allowed correct identification of hyperendemic communities and of most of the hypoendemic ones. Frequent misclassifications occurred for communities with intermediate prevalence and the cheapest plans had very low specificity. The study confirmed that LQAS would be a valuable tool for large scale screening in a country with scarce financial and staff resources. Involving teachers, appeared to be quite feasible and should not lower the reliability of surveys. We recommend that the national schistosomiasis control programme systematically uses LQAS for identification of communities, provided that sample sizes are adapted to the specific epidemiological patterns of S. mansoni infection in the main regions.

Depuis les annees 1950, la region d'Antananarivo est la moins connue en matiere de bilharziose. En 1994, avant la mise en place du Projet d'Amenagement de la Plaine d'Antananarivo, des enquetes epidemiologiques ont ete realisees en milieu scolaire pour evaluer la situation epidemiologique de la bilharziose intestinale. Les resultats des examens de selles par la methode de Kato-Katz ont montre que 4,3% des 6 169 eleves tires au sort et examines etaient porteurs d'œufs de Schistosoma mansoni. Les quatre villages les plus infestes sont situes le long de la riviere Mamba. La recherche de Schistosoma haematobium par la methode de filtrationa ete negative. En 1999, apres la realisation du Projet d'Amenagement de la Plaine d'Antananarivo, une etude a ete menee dans les memes ecoles primaires publiques (EPP) afin d'etudier l'evolution de l'endemicite billiarzienne. 1 'etude a porte sur 5 222 eleves de 5 a 15 ans selon une methodologie identique a l'enquete de 1994. Le sex-ratio garcon/fille est egal a 1, 4/1. La prevalence globale de la bilharziose intestinale est de 1, 8%. Les prevalences les plus elevees sont celle de l'EPP d'Antanandrano (23,3%) qui se trouve pres de la riviere Mamba, au Nord de la capitale et celle de l'EPP d 'Ambohitsoa (16, 3%) situe pres du lac de Mahazoarivo. Entre 1995 et 1999, la prevalence a significativement diminue (p<10 -1 ) Plusieurs facteurs peuvent expliquer celle diminution: l'education sanitaire, l'absence des conditions favorables au developpement des mollusques hote-intermediaires et l'urbanisation. Par ailleurs, une forte prevalence de l 'ascaridiose (79%) et de la trichocephalose (67%) a ete observee. 4.3% des eleves sont porteurs d'œufs de Taenia sp. La bilharziose est a un niveau hypoendemique dans la plaine d'Antananarivo. La strategie de lutte contre cette maladie doit s'orienter en priorite sur un programme d'Information-Education-Communication ciblant la population scolaire.

In 1994, prior to the Project of Development of the Plain of Antananarivo, an epidemiological survey was conducted in primary schools to assess the level of schistosomiasis. The results of stool examination by the Kato-Katz method demonstrated a prevalence of 4.3% among 6,169 randomized schoolchildren. The most infected four villages are located close the Mamba river. In 1999, after the realization of the project, another study had been done in the same Public Primary School to evaluate the evolution of schistosomiasis endemicity. 5,222 randomized pupils aged 5 to 16 years old took part in the study. The sex ratio was 1.4/1. The global prevalence was 1.8%. High prevalence are respectively notified in Antanandrano Primary school (23%) close to the Mamba river in the Northern part of the capitol and in Ambohitsoa Primary School (16.3%) located near the Mahazoarivo lac. Thus, between 1994 and 1999, a significant overall decrease in prevalence was observed (p < 10(-1)), although a few areas still have relatively high rates. Many factors may explain this improvement, including sanitary education, urbanization and a lack of conditions needed in the development of intermediate host. In addition, a high prevalence of ascaridiasis (79%) and trichocephalosis (67%) was observed. 4.3% of schoolchildren had been infected by Taenia sp. Schistosomiasis is hypoendemic in the plain of Antananarivo. The strategy against this disease must include an IEC programme, focusing in childhood exposure.

In a study in three neighbouring villages of southern Madagascar, where Schistosoma mansoni is hyperendemic, ultrasound examination using the Niamey protocol showed marked differences in the burden of disease from one village to another. Hepatosplenic schistosomiasis was more frequent in the village with the highest geometric mean egg counts and the earliest onset of infections, demonstrating that the morbidity induced by S. mansoni may vary greatly within a given area. True representativeness of study populations, a keystone of epidemiological studies, is mandatory to obtain a clear picture of a wide area. Ultrasound examinations in a small number of villages, or even a single one, may be a questionable approach. Using logistic regression analysis, the explanatory variables found to be significantly associated with a risk of severe hepatosplenic disease in our study were sex, age, village of residence and S. mansoni egg counts. On the other hand, a concurrent infection with an intestinal helminth seems to reduce the risk of severe hepatosplenic disease. Further studies should assess the role and possible impact of intestinal helminths on S. mansoni associated‐morbidity.

Reduction of morbidity is the main component in the National Schistosomiasis Control Program in Madagascar. The lot quality assurance sampling (LQAS) method has previously been shown as a useful tool in assessment of immunization coverage. A study was carried in the western part of Madagascar aiming to evaluate the applicability of the method in measuring the level of Schistosoma haematobium endemic level in different communities. Parasitological examination of urine samples from 1,124 children aged 5 to 19 years from 12 different schools by use of filtration technique constituted the reference in determining the prevalence. Three schools were found hyper-endemic (prevalence more than 60%), 5 schools were intermediate-endemic (prevalence between 30 to 59%), and 4 were hypo-endemic (prevalence less than 30%). Those figures indicate a heterogeneous distribution of S. haematobium in the study area. A sampling plan (16.6) was then tested in the same area while other sampling plans were simulated in the laboratory. School teachers randomized under supervision the children to participate in this study and collected urine samples. All sampling plans (16.6), (14.5), (12.4), (10.3), (8.2), (6.1) et (4.0) allowed correct identification of hyper-endemic and hypo-endemic areas. Misclassifications occurred frequently for intermediate-endemic areas. The study confirms that the LQAS method by use of a (16.6) sampling plan constitute a valuable tool for large scale screening of hyper-endemic areas for therapeutic intervention as part of the control program. The study has also shown that school teachers may offer a potential source of manpower locally in such screening operations.

Summary In a Schistosoma haematobium ‐endemic village in western Madagascar we evaluated ultrasonography and Eosinophil Cationic Protein (ECP) in urine as means to detect the associated urinary tract pathology. 192 individuals were matched according to age and sex, and grouped into infected persons with bladder and, if present, kidney pathology ( n = 96); infected persons without pathology ( n = 48) and noninfected persons without pathology ( n = 48). The median urinary egg count was significantly higher in individuals with ultrasonographically detectable urinary tract pathology (115 eggs/10 ml urine) than in infected persons without (45 eggs/10 ml of urine). At 136 ng/ml, the median ECP level was significantly higher in the 144 infected individuals than in the 48 noninfected persons (0.35 ng/ml). Egg excretion correlated positively with ECP level. The median ECP level was significantly higher in the group with ultrasonographically detectable urinary tract pathology than in the group without (183 ng/ml vs . 67 ng/ml). The results suggest that minor degrees of pathology, particularly at an early stage of infection with S. haematobium , might be overlooked by ultrasonography despite the presence of marked inflammation, as indicated by markedly increased urinary ECP levels in infected individuals without ultrasonographically detectable urinary tract pathology. ECP may therefore provide important information on the evolution of S. haematobium ‐associated urinary tract morbidity.

Les auteurs rapportent les resultats d'une enquete seroepidemiologique dont l'objectif etait d'estimer en juillet 1999 l'importance de la cysticercose dans la ville de Mahajanga. 626 serums issus d'un echantillon de sujets de 2 ans et plus, tires au sort dans la population par sondage en grappes, ont ete etudies en utilisant une technique ELISA pour la recherche des anticorps anti-Cysticercus cellulosae puis une technique EITB pour determiner le profil de reconnaissance. Le taux de prevalence redresse est de 19 p. 100 (15,8-22,7% IC95%). Parmi les sujets porteurs d'anticorps, 31% presentent le profil de reconnaissance CI, 56% le profil C2 et 13% le profil C3. A Mahajanga comme a Madagascar, la cysticercose est un probleme de sante publique qui necessite la mise en oeuvre d'un programme national de lutte.

A seroepidemiological survey was carried out in July 1999 to assess the prevalence of cysticercosis in general population in the Mahajanga City (West of Madagascar). Blood specimens were collected from a randomised sample including 626 individuals more than 2 years old. ELISA and confirmative immunoblot techniques (EITB) were used to measure Cysticercus cellulosae antibodies. The overall prevalence by ELISA test was 19% (15.8-22.7% CI95%). Among positive cases, 87% were also positive by EITB. Cysticercosis is considered as major health problem in Madagascar. A national control programme implementation is imperative.

Cysticercosis in the harbor of Mahajanga is more common than expected": A seroepidemiological survey was carried out in July 1999 to assess the prevalence of cysticercosis in general population in the Mahajanga City (West of Madagascar). Blood specimens were collected from a randomised sample including 626 individuals more than 2 years old. ELISA and confirmative immunoblot techniques (EITB) were used to measure Cysticercus cellulosae antibodies. The overall prevalence by ELISA test was 19% (15.8-22.7% CI95%). Among positive cases, 87% were also positive by EITB. Cysticercosis is considered as major health problem in Madagascar. A national control programme implementation is imperative. Key-words : Prevalence - Cysticercosis - MADAGASCAR.

We measured the concentrations of several serum and urinary fibrosis markers, which are metabolites of extracellular matrix, in schistosomiasis patients to investigate their relationship with the ultrasonographic scoring system and with parasitologic data. This study was conducted in patients with various stages of the disease evaluated by ultrasonography (intestinal disease with no organ involvement, with minor hepatosplenic involvement and with severe disease) and in endemic controls. The level of hyaluronan, which were increased in infected patients compared with controls (P < 0.01), was the only fibrosis marker that correlated with the ultrasonographic score (P = 0.003) and is thus a potential serum marker of schistosomiasis-associated morbidity. Urinary free pyridinoline levels were lower (P < 0.001) in infected patients with fibrosis (score > or = 1) than in nonfibrotic patients. A two-year follow-up of the patients treated with praziquantel showed that type I collagen and hyaluronan decreased during the first year post-treatment, whereas free pyridinolines peaked after 12 months and decreased thereafter.

This study shows the effect of praziquanted as a 12 month treatment on the uro-nephrological consequences of Schistosoma haematobium chronic infection. This was done in a hyperendemic setting in the middle west of Madagascar. 435 people with ova in their urine filtration test were followed up with clinical examination, ultrasonography, urinary sticks and creatininemia. The prevalence of macroscopic hematuria decreased significantly from 32.5% (153 patients) to 4.3% (20 patients) (p < 0.05). Other abnormalities decreased but not significantly. The prevalence of proteinuria decreased from 62.3% (271 cases) to 20.2% (88 cases) (p < 0.05%) when microscopic hematuria varied from 72.4% (315 cases) to 31.5% (271 cases). Leucocyturia remained stable from 49% (213 cases) to 47.8% (207 cases). On ultrasonography, the whole abnormalities varied from 54.1% (256 patients) to 16.7% (79 patients). Prevalence of bladder abnormalities decreased from 50% (237 cases) to 16.3% (77 cases) (p < 0.05); prevalence of vesico-ureteral reflux decreased from 5.1% (23 cases) to 0.2% (1 case) (p < 0.05) and that of pyelocaliceal from 14.6% (54 cases) to 2.5% (12 cases). The reference drug, praziquantel has a clear-cut effect on this chronic pathology. Bladder wail abnormalities are particularly interested by this favourable effects.

To assess the morbidity of S. haematobium infection in women of reproductive age (15–49 years) in the western part of Madagascar, the village of Betalatala with a prevalence of urinary schistosomiasis in women of 75.6% (95% confidence limit 69.3 to 81.9%) was compared with a neighbouring village with similar socio‐economic characteristics and a prevalence of 5.0% (95% confidence limit 0 to 11.75%). The women were questioned in Malagasy about obstetrical history and urogynecological symptoms. They were examined gynaecologically, parasitologically and by ultrasonography. Important STDs were excluded by appropiate diagnostics. In Betalatala significantly more women reported a history of spontaneous abortion (P < 0.01), complaints of irregular menstruation (P < 0.001), pelvic pain (<0.05), vaginal discharge (P < 0.0001), dysuria (P < 0.05) and haematuria (P < 0.01) than in the control village. Biopsies were obtained from the cervix of 36 women with macroscopical lesions, and in 12 cases S. haematobium eggs were found by histological sectioning (33.3%). In the control village no eggs were detected in the histological sections of biopsies taken from 14 women. (P < 0.05). Infections with Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis and Treponema pallidum were found in similar frequencies in both villages. In 9.8% of the women in Betalatala abnormalities of the upper reproductive tract were revealed by ultrasonography versus none in the women from the control village (P < 0.05). Echographic abnormalities of the urinary tract were present in 24% and 3% of the women in the study village and in the control village, respectively (P < 0.0001). These findings were accompanied by an elevated frequency of haematuria (55% versus 20%) and proteinuria (70.4% versus 25%) in the study population (P < 0.0001). Our study indicates that S. haematobium infection in women may not only cause symptoms in the urinary tract, but also frequently in the lower and upper reproductive tract.

This prospective study was designed to look for and describe urologic and nephrologic consequences of urinary bilharziosis due to schistosoma haematobium in a hyperendemic hotbed in the middle west of Madagascar. Methodology included clinical examination, kidney and bladder ultrasonography, urine dipsticks and creatininemia. Amongst a population of 574 persons aged 5 years ore more, 436 (76%) had bilharziosis ova in the urine (filtration method). From the clinical point of view, 257 patients (58.9%) had microscopic hematuria, 178 (40.8%) had presently an hematuria; 111 patients (25.5%) suffered from dysuria; 18 patients (4.1%) had limb oedema when 3 patients had present oedema (0.7%). Among 436 checked people, 267 (61.2%) had an ultrasonography abnormality. In 252, it was bladder wall abnormalities (57.8%). They were wall irregularities in 182 cases (41.7%); vesico-ureteral reflux in 22 cases (5.3%); ureteral dilatations in 22 cases (5.3%) and pyelocalyceal dilatations in 61 cases (13.9%). Prevalence of proteinuria 75.2% (316 amongst 420 checked people) of whom 5.7% (24 cases) had 5 g/l or more. Hematuria was found in 352 patients (83.8%) of whom 238 (56.7%) had more than 250 erythrocytes per microliter. Prevalence of leucocyturia was 56.7% (238 cases). Creatininemia was measured in 140 people with positive filtration; it was normal in all except two patients. This study highlights the parallel evolution between parasitic infection and uronephrological manifestations of the disease.

This study shows the effect of praziquantel as a 12 month treatment on the uro-nephrological consequences of Schistosoma haematobium chronic infection. This was done in a hyperendemic setting in the middle west of Madagascar. 435 people with ova in their urine filtration test were followed up with clinical examination, ultrasonography, urinary sticks and creatininemia. The prevalence of macroscopic hematuria decreased significantly from 32.5% (153 patients) to 4.3% (20 patients) (p < 0.05). Other abnormalities decreased but not significantly. The prevalence of proteinuria decreased from 62.3% (271 cases) to 20.2% (88 cases) (p < 0.05%) when microscopic hematuria varied from 72.4% (315 cases) to 31.5% (271 cases). Leukocyturia remained stable from 49% (213 cases) to 47.8% (207 cases). On ultrasonography, the whole abnormalities varied from 54.1% (256 patients) to 16.7% (79 patients). Prevalence of bladder abnormalities decreased from 50% (237 cases) to 16.3% (77 cases) (p < 0.05); prevalence of vesico-ureteral reflux decreased from 5.1% (23 cases) to 0.2% (1 case) (p < 0.05) and that of pyelocaliceal from 14.6% (54 cases) to 2.5% (12 cases). The reference drug, praziquantel has a clear-cut effect on this chronic pathology. Bladder wall abnormalities are particularly interested by this favourable effects.