A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils.

IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils. Up-regulation of intracellular IL-13 in eosinophils was also associated with eosinophil expression of ST2L, the IL-33 receptor. IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure.

The effect of single dose versus two doses of praziquantel on Schistosoma haematobium infection and pathology among school-aged children in Mali.

The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a standard single dose of 40 mg/kg on cure rates, egg reduction, intensity of infection, and micro-haematuria in Schistosoma haematobium infections. A randomised controlled intervention study was carried out among school-aged children in two different endemic settings with follow-up at 3, 6 and 18 months following drug administration. Differences in cure rates between the two treatment regimens were not significant. However, in high transmission areas, the double treatment regimen was more effective in egg reduction than single treatment regimen and the difference in egg reduction between the two treatments was significant at 3 months (P<0.005), 6 months (P<0.0001) and 18 months (P<0.003) after treatment. There was a significant difference in the effect of the two treatments on prevalence of micro-haematuria at 18-month follow-up in both Koulikoro (P<0.001) and Selingue (P<0.003). The study shows that although no significant difference could be observed in the overall cure-rates between the two treatment regimens, the effect of double treatment was a significant reduction in infection intensity as well as micro-haematuria which may have a great impact in reducing subtle morbidity.

The public health significance of urinary schistosomiasis as a cause of morbidity in two districts in Mali.

Schistosoma haematobium-related morbidity was studied in the perennial irrigation area of Office du Niger and the small reservoirs area of Plateau Dogon in Mali. Questionnaire, clinical, parasitologic, and ultrasound examination data were collected from 1,041 individuals at the baseline survey in 1991; 705 were re-examined one year after treatment. At baseline, the overall prevalence of S. haematobium infection was 55.2%; half of those infected had no clinical symptoms and 30% had pathologic lesions. Both infection and morbidity were more frequent in children than in adults, with a peak prevalence at 7-14 years of age. The rates of lesions were more than twice as high in those heavily infected as in lightly infected individuals. Reagent strip testing for microhematuria was more sensitive in detecting individuals with pathologic lesions than in detecting individuals with infection. One year after treatment with praziquantel, more than 80% of the urinary tract lesions had cleared. It is concluded that S. haematobium-related morbidity is frequent in Mali, but passive case detection for treatment would not cover a great deal of early stages of the disease; active intervention using reagent strip testing for microhematuria at the most peripheral levels would be an efficient system for morbidity control and monitoring of control operations.

Schistosomiasis in Dogon country, Mali: identification and prevalence of the species responsible for infection in the local community.

The prevalence of schistosomiasis amongst the Dogon people in 4 villages and one school of the Bankass district of Mali was determined during 2 surveys in 1992; 1398 urine and 1199 stool samples were examined. The most common schistosome was Schistosoma haematobium, with an overall prevalence of 51.3%; S. mansoni had a prevalence of 12%. No S. intercalatum egg was seen in the stools. Biomphalaria pfeifferi and Bulinus truncatus were found in pools at the base of the Dogon cliffs; Bulinus forskalii was found in smaller numbers in brick pits. Two isolates from urine samples of children were identified as S. haematobium in the laboratory using an alpha-glycerophosphate marker, restriction enzyme analysis of ribosomal deoxyribonucleic acid (rDNA) and random amplification of polymorphic DNA. The isolates did not develop in Bulinus forskalii or B. crystallinus of the B. forskalii group. Some evidence for past hybridization of S. haematobium and S. intercalatum is provided by the enzyme and rDNA results as well as the positive Ziehl-Neelsen staining of polymorphic eggs in urine samples. The findings are discussed in relation to the published observations concerning schistosomiasis in travellers returning from this region of Mali.

Comparison of the circulating anodic antigen detection assay and urine filtration to diagnose Schistosoma haematobium infections in Mali.

The applicability of a circulating Schistosoma antigen detection assay for determining rates of infection and efficacy of chemotherapy was evaluated in Mali. Urine egg counts were compared to circulating anodic antigen enzyme-linked immunosorbent assay (CAA-ELISA) titres in serum, before and 6 weeks after treatment with a single dose of praziquantel (40 mg/kg), in 2 villages in Dogon Country, an area endemic for S. haematobium, the predominant schistosome infection in Mali. In Kassa, a village with a moderate prevalence of infection, the serological prevalence (48%) was significantly higher than the parasitological prevalence (31%). In Boro, a village with high parasitological prevalence (76%), no difference was observed between the results of both methods (prevalence by CAA-ELISA was 75%). Cure rates estimated by CAA-ELISA were lower than those determined parasitologically, suggesting that cure rates are overestimated by egg counting. The sensitivity of the CAA-ELISA was 78%. In both villages, before treatment, a positive correlation was found between the number of eggs in urine and serum CAA titres. It is concluded that, although further simplification and improvement of the sensitivity of the assay is needed, in its present ELISA format the antigen detection assay is useful for monitoring sentinel populations. Furthermore, the serum CAA assay performed adequately in a public health laboratory within an endemic country.

Assessment of cure by detection of circulating antigens in serum and urine, following schistosomiasis mass treatment in two villages of the Office du Niger, Mali.

Eight weeks after mass chemotherapy with 40 mg/kg praziquantel in two villages in Office du Niger (an irrigation area in Mali, endemic for both Schistosoma haematobium and Schistosoma mansoni) the circulating anodic (CAA) and cathodic (CCA) antigen detection assays were carried out on serum and urine samples. Both prior and post treatment highest prevalence was measured with the urine-CCA assay. Cure rates determined by antigen detection were almost half that of the egg counting methods. It was shown that the reduction in intensity should be preferentially assessed by the serum-CAA assay. Compared with egg detection, a single antigen detection assay gave a much better assessment of the impact of chemotherapy.

PIP: Surveys conducted in different regions of Mali, to compare the circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) detection assays with the classical method of parasitologic egg counting in the diagnosis of schistosomiasis, found the highest sensitivity with the urine CCA assay. The present study investigated cure rates in a mixed Schistosoma haematobium/S. mansoni endemic area by applying the CAA and CCA assays on 97 serum and urine specimens from Dogon, Mali. 8 weeks after mass treatment with 40 mg/kg of praziquantel, the cure rate was 87% according to 2 urine egg counts and 96% as determined by a single stool egg count. Both before and after treatment, the highest prevalence was again measured by the urine CCA assay. Cure rates determined by antigen detection were almost one-half that of the egg counting method. Reduction in intensity, as determined by serum CAA concentrations, was above 90% in both villages in the study area. The urine CCA assay, however, showed a reduction in intensity in one site and an increase in the other. These results suggest that the serum CAA assay should be used preferentially to assess the reduction in intensity, since serum antigen levels reflect worm burdens more directly than those in urine, given their influence by renal excretion dynamics. Timing of cure rate determination by using antigen detection should take into account local transmission patterns.

[Geographic distribution and epidemiology of urinary schistosomiasis in Mali: implications for a control program]. / La diversité écoclimatique et l'épidémiologie des schistosomiases au Mali: implications pour un programme de contrôle.

A national survey was conducted in Mali between 1986 and 1990 to determine the geographical distribution of urinary schistosomiasis in order to define an ecologically based national schistosomiasis control programme. Fifty six thousand two hundreds and sixty five individuals randomly selected from 323 villages in the nine ecologically defined areas of the whole country were submitted to urine examination using Filtration Technique. In villages along the Niger and Senegal rivers, in the Dogon Plateau and Office du Niger areas, the prevalence of Schistosoma haematobium infection was the highest, respectively 41.8%, 53.1%, 59.4% et 62.9%. In these areas, more 70% of children aged 7 to 14 years were infected. In the Soudanian and North-Soudanian areas, the prevalence were below 10% and respectively only 5.3% and 11.5% of children aged 7 to 14 years were infected. It is concluded that Schistosoma haematobium infection is of public health importance in dam and irrigation areas and in areas along the Niger and Senegal rivers namely in Kayes, Koulikoro, Segou, Mopti regions and in Bamako district. These areas should be considered as priority areas for active control interventions. The interventions should include community-based mass chemotherapy with praziquantel after community diagnostic using urine examination in school aged children and a good monitoring system.

Impact of mass chemotherapy with praziquantel on Schistosoma haematobium and Schistosoma mansoni infections in Office du Niger, Mali.

Aims This study was carried up to assess the impact of mass chemotherapy with praziquantel on the prevalence and intensity of Schistosoma haematobium and Schistosoma mansoni in Office du Niger. Materials and Methods It was a cross sectional study with two passages about which we compared a test group of 7 villages (n=2342) treated in 1989 to a control group of 7 villages (n=2263). Results One year after mass chemotherapy, baseline prevalence rates of Schistoosma haematobium, Schistoaoma mansoni and those of the double infection decreased by 50%, 54% and 62,9% respectively. The geometric mean egg counts of Schistosma haematobium (GMECSh) was reduced by 66.6% and that of Schistosoma mansoni (GMECSm) by 43.4%. However, in spite of mass treatment, the overall prevalence rates of Schistosoma haematobium and mansoni were always higher than 20% in young people aged of 6-19 years. Conclusion These data show that in irrigated area, efficacy of praziquantel is strongly affected by age. This persistance of infection in population raises up several questions according to host immunity, parasite biology and praziquantel efficacy.

Evaluation of case management in the integrated schistosomiasis-control programme in Mali.

Currently, schistosomiasis control in Mali is mainly based on treatment with praziquantel (PZQ). The policy is to ensure (1). the treatment, every 3 years, of school-age children in all areas where the prevalence of haematuria (an indicator of Schistosoma haematobium infection) in this age-group is >30%, and (2). the sound management of all patients presenting with haematuria or (bloody) diarrhoea (an indicator of S. mansoni infection) at health centres. In the present study, the application of case management was evaluated by visiting 60 healthcare facilities in four geographical areas and interviewing the health-workers at these facilities. The presence of S. haematobium and S. mansoni was reported in the coverage areas of 83% and 37%, respectively, of the healthcare facilities investigated. Health-worker knowledge of the main symptoms of schistosome infection was good and patients exhibiting symptoms attributable to schistosome infection were very likely to receive adequate treatment, particularly (at a frequency of about 80%) when they presented with haematuria. At health-centre level, patients were often directly treated with PZQ, whereas health-workers in district hospitals and private clinics requested a diagnostic test prior to any treatment. PZQ was available in most healthcare facilities but not in the private clinics. The mean cost of treatment of a patient with S. haematobium infection (euro; 2.30) was very similar to the corresponding cost for S. mansoni infection (euro; 2.37). The cost of the PZQ represented approximately 50% of the total costs borne by the patients when presenting at health centres. Patients with the symptoms of S. haematobium infection in Mali can expect adequate diagnosis and treatment in agreement with the recommendations of the World Health Organization. Patients presenting with symptoms related to S. mansoni infection are, however, less likely to be correctly diagnosed. The relatively high costs of treatment and the infrequency with which cases of schistosomiasis seek healthcare necessitate policy decisions, to ensure an affordable and more attractive, clinical system of case management.

Circulating anodic and cathodic antigen in serum and urine of mixed Schistosoma haematobium and S. mansoni infections in Office du Niger, Mali.

In Office du Niger, an area endemic for both Schistosoma haematobium and S. mansoni in Mali, circulating anodic (CAA) and cathodic (CCA) antigen detection assays were performed on pretreatment serum and urine samples from two villages, Rigandé and Siguivoucé, and compared with egg counting methods. The highest prevalence was obtained with the urine-CCA assay which also had the highest sensitivity to S. haematobium, S. mansoni or mixed infection. A single urine-CCA assay was as sensitive as repeated egg counts (one stool+two urine examinations per individual). When the different assays were tested in parallel, several combinations including assays on serum were found to be highly sensitive. As urine sampling is widely accepted, urine assays will be used for further monitoring these villages one and two years after chemotherapy.