Lot quality assurance sampling for screening communities hyperendemic for Schistosoma mansoni.

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.

[The current epidemiological situation of cysticercosis in Madagascar]. / Situation épidémiologique actuelle de la cysticercose à Madagascar.

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.

[Validation of questionnaire methods to identify Schistosoma haematobium bilharziasis hyperendemic zones in Madagascar]. / Validation de la méthode du questionnaire pour identifier les zones hyperendémiques de la bilharziose à Schistosoma haematobium à Madagascar.

Schistosomiasis is a major public health problem in Madagascar. The aim of the national control program is to reduce the morbidity in hyperendemic areas. A prospective study has been conducted in Morombe and Ampanihy to elaborate a simple method to identify Shistosoma haematobium hyperendemic communities. The study included 1,373 children from 5 to 15 years old in 17 primary schools. Moderate sensitivity and Negative Predictive Value, with high specificity and Positive Predictive Value of "blood in urine" and "Schistosomiasis" have been found. Those diagnosis values increase with age. The first symptom should be used in older children.

[Current epidemiological situation of bilharziasis in the Antananarivo plain]. / Situation épidémiologique actuelle des bilharzioses dans la plaine d'Antananarivo.

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.

Geographic differences in hepatosplenic complications of schistosomiasis mansoni and explanatory factors of morbidity.

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.

[Identification of communities endemic for urinary bilharziosis by the "Lot Quality Assurance Sampling" method in Madagascar]. / Identification des communautés cibles en zone de bilharziose urinaire par la méthode de "Lot Quality Assurance Sampling" à Madagascar.

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.

Morbidity of schistosomiasis mansoni in the highlands of Madagascar and comparison of current sonographical classification systems.

To study the morbidity of schistosomiasis mansoni in the highlands of Madagascar, a cross-sectional study examined the extent to which liver fibrosis occurred in a rural community. The Managil and the Cairo classification systems were used. A second purpose was to investigate the effect of the measurements of 2 different branches of the portal vein (either segmental or sub-segmental branches) on the resulting staging of morbidity using the Cairo classification system. In a rice farmer village, 656 inhabitants (95% of the total population) were parasitologically examined; 561 patients underwent sonographic work-up based on the Managil scoring system, and in 307 randomized patients the outer to outer diameters of both the segmental and the sub-segmental branches of the portal vein were measured and scored by the Cairo classification system. Overall prevalence of schistosomiasis mansoni in the study area in 1994 was 68.3%. Upon sonographic examination and scoring by the Managil system 23.4% of the population showed liver changes (Managil degree I/II/III, 20%/2.5%/0.9%). Measuring the sub-segmental branches only and scoring by the Cairo classification, 19% of the study population were found to have liver changes, none with severe fibrosis. By contrast, 82% were found to have liver changes (Cairo degree 1/2/3, 70%/11%/2%) when the segmental branches were measured. The diameters of the sub-segmental branches were about two-thirds of those of the segmental branches. Both the Cairo- and the Managil-examination protocols have pitfalls. Using the Cairo classification, a considerable systematic error in classifying morbidity is created by measuring different branches of the portal vein.

"Identification des communautes cibles en zone de bilharziose urinaire par la methode de ""Lot Quality Assurance Sampling"" a Madagascar"

"Use of lot quality assurance sampling in the identification of Schistosoma haematobium endemic communities in Madagascar"": 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"

Morbidity assessment in urinary schistosomiasis infection through ultrasonography and measurement of eosinophil cationic protein (ECP) in urine.

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.

[Cysticercosis in the port of Mahajanga: more frequent than we thought!]. / La cysticercose dans le port de Mahajanga: plus fréquente qu'on ne l'imagine!

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.

Relationships between several markers of extracellular matrix turn-over and ultrasonography in human Schistosomiasis mansoni.

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.

Reversibility of Schistosoma mansoni-associated morbidity after yearly mass praziquantel therapy: ultrasonographic assessment.

A parasitological, clinical and ultrasonographic longitudinal study was undertaken in 1993 in a focus hyperendemic for Schistosoma mansoni infection in the central highlands of Madagascar. All the inhabitants were systematically treated with praziquantel. A complete examination and treatment were repeated each year. Among the 289 villagers who underwent the complete 3 years' follow up, 65.9% excreted eggs at the initial survey and the mean egg count of infected individuals was 202 eggs/g. In 1996, the prevalence of infection was 19.3% with a mean egg count of 27 eggs/g and, among inhabitants aged > 44 years, only one was found to be infected. The proportion of individuals complaining of bloody stool decreased from 24.9% in 1993 to 8.4% in 1996. Compared to the initial clinical examination, the age-adjusted prevalence of splenomegaly was significantly lower in 1996, but remained high: 62% in the 10-14 years age group and 59% in individuals aged > 24 years. Ultrasonographic examination after 3 years of praziquantel therapy showed a marked decrease of the overall prevalence of schistosomal hepatic fibrosis, from 28% in 1993 to 10.3% in 1996. This improvement had already been achieved during the second year of follow-up for most subjects. Usually, the reversal of morbidity affected individuals classified as stage 1 at the beginning of the study. Stage 3 was not observed in the last 2 surveys. One patient's ascites disappeared during the follow-up, associated with a significant reversal of periportal fibrosis. Our results indicate that repeated praziquantel therapy can lead to improvement of liver morbidity and the prevention of the development of schistosomal hepatic fibrosis, even in an old-established hyperendemic focus.

[Prevalence of uro-nephrologic complications of urinary bilharziasis in hyperendemic focus in Madagascar]. / Prévalence des retentissements uro-néphrologiques de la bilharziose urinaire dans un foyer hyperendémique de Madagascar.

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.

[Effect of praziquantel on the uro-nephrologic complications of urinary bilharziasis]. / Effet du praziquantel sur les retentissements uro-néphrologiques de la bilharziose urinaire.

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.

Serum concentrations of sICAM-1, sE-, sP- and sL-selectins in patients with Schistosoma mansoni infection and association with disease severity.

Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1, CD54) and of soluble E- (CD62E), but not soluble P- (CD62P) and L- (CD62 L) selectins, were detected in Malagasy patients living in an hyperendemic focus of Schistosoma mansoni. Levels of sICAM-1 remained elevated for several months after treatment with praziquantel. Serum levels of ICAM-1, but not of other markers, were significantly correlated with the disease severity, as indicated by ultrasonographical data, and with some circulating fibrosis markers (at least hyaluronic acid). sICAM-1 level may reflect endothelial inflammatory reactions, probably harmful, in the liver and may be useful for monitoring morbidity evolution in schistosomiasis mansoni.

Clinical findings in female genital schistosomiasis in Madagascar.

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 appropriate 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.

[Epidemiologic study of the main human intestinal nematodes in the middle west of Madagascar]. / Etude épidémiologique des principales nématodoses intestinales humaines dans le Moyen-ouest de Madagascar.

An epidemiological study of human intestinal helminthiasis was conducted during July and August 1995, in the middle west of Madagascar, with 4571 adults and children ranging from six months to 90 years, in 61 communities between Betafo and Miandrivazo. Faecal examination utilising the MIF concentration method revealed that ascariasis was the dominant nematodosis in the middle west with high prevalences in the high-altitude communities. Ascaris lumbricoides prevalences increase among children and women. Interesting more than 50% of the pattern, ascariasis is a public health problem and its association with infant malnutrition is statistically significant. Hookworm infection prevalence is higher in low-altitude communities, it increases among adults. The Trichuris trichiura prevalences were lower than the prevalences of ascariasis and hookworm infection in all of the communities. Important variations of the prevalences of intestinal helminthiasis are observed essentially in relation with climatic conditions.

Schistosoma haematobium induced lesions in the female genital tract in a village in Madagascar.

Female genital schistosomiasis, FGS, was investigated in a gynaecological study as part of an overall community based morbidity survey, including parasitological and ultrasonographical examination, of a Schistosoma haematobium endemic area in Madagascar. Women (103), of childbearing age (15-49 years), were included for a gynaecological examination and visible lesions of vagina and cervix were biopsied in order to determine the origin of the lesion. Furthermore all women were screened for the presence of schistosome ova using PAP smears from the vagina and the endo/exo cervix. In total 15 women showed schistosome ova in the vagina and/or cervix (median age 24 years and range 15-36 years). Of 36 women with cervical abnormalities, 12 eggs were detected by cervical biopsy (33%). In addition, two of the 12 presented vaginal induration, which contained eggs. Six women had eggs in their PAP smears of which three were egg negative by cervical biopsy. The prevalence of positive S. haematobium egg excretion in the urine among the 103 women was 69% and the geometric mean egg count of positive individuals was 51 eggs/10 ml of urine. Five of the 15 women with confirmed FGS had < or = 1 egg/10 ml of urine. Bladder lesions and congestive changes in the kidneys were demonstrated by ultrasonographic examination in 33 and 9% of the 103 women, respectively. None of the 15 women with confirmed FGS had renal congestion. Our study demonstrates that FGS is a common manifestation of the infection with S. haematobium, even in lightly infected individuals.