Assessment of morbidity in Schistosoma haematobium infection: current methods and future tools.

Recently, new potential tools for assessment of Schistosoma haematobium related morbidity have emerged. The tools are based on detection of S. haematobium egg antigens in urine or detection of eosinophil cationic protein (ECP) in urine, which may reflect the inflammatory response in the urinary tract. So far two markers have been assessed in long-term post treatment follow-up studies, allowing for an evaluation both before treatment and during regression and reappearance of infection and urinary tract morbidity. The results from these studies and the usefulness of the markers as morbidity assessment tools are discussed.

Urine circulating soluble egg antigen in relation to egg counts, hematuria, and urinary tract pathology before and after treatment in children infected with Schistosoma haematobium in Kenya.

A cohort of 117 school children infected with Schistosoma haematobium was followed-up after therapy with praziquantel (0, 2, 4, 6, 12, and 18 months) and various infection and morbidity parameters (egg counts, hematuria, soluble egg antigen [SEA] in urine, and ultrasonography-detectable pathology) were quantified. At the onset of the study, 97% of the children were positive for S. haematobium with a geometric mean egg count of 45.7 eggs/10 ml of urine. Eighty-one percent of the children were positive for SEA in urine with a geometric mean SEA concentration of 218.8 ng/ml of urine. Ninety-two percent and 56% of the children were microhematuria positive and macrohematuria positive, respectively. Two months after treatment, all infection and morbidity indicators had significantly decreased. Reinfection after treatment as determined by detection of eggs in urine was observed by four months post-treatment while the other parameters remained low. The clearance of SEA was slower than that of egg counts while pathology resolved at an even slower pace. Levels of SEA and egg output showed similar correlations with ultrasound detectable pathology; these correlations were better than the correlation between hematuria and pathology.

Parameters associated with Schistosoma haematobium infection before and after chemotherapy in school children from two villages in the coast province of Kenya.

We evaluated the impact of praziquantel therapy (40 mg/kg body weight) on indicators of infection with Schistosoma haematobium by following a cohort of infected children from schools located 12 km apart in the Coast province of Kenya, at 0, 2, 4, 6, 12 and 18 months after treatment. Within this period, measurements of infection parameters pertaining to egg counts and haematuria (micro-, macro- and history) were evaluated at all time points. The initial prevalence of 100% dropped significantly 8 weeks after treatment with a similar trend in the intensity of infection. Microhaematuria followed the same trend as observed for egg counts while macrohaematuria remained low after treatment. Reinfection following successful therapy differed significantly between schools; in one school the children were reinfected immediately while those in the other remained uninfected despite similar starting prevalences, intensities of infection and cure rates. Transmission between the two areas looked homogeneous before treatment but when both groups were treated, contrasting transmission patterns became evident. In a regression model we evaluated factors that might be associated with reinfection, and after allowing for pretreatment infection level, age and sex, area (school) remained a highly significant predictor.

Detection and quantification of soluble egg antigen in urine of Schistosoma haematobium-infected children from Kenya.

While research on alternative diagnostic and morbidity markers for infection with Schistosoma haematobium has been going on for a long time, egg counts continue to be used as the gold standard, and infection intensity is thought to reflect the severity of the disease. However, this relationship is not always clear and fluctuation in egg output makes it difficult to classify prevalence correctly. The use of circulating adult worm antigen detection as an alternative diagnostic technique has been applied with varying success. However, this is a measure of worm burden and does not reflect the tissue egg load(s). In the present study we have used an assay that detects soluble egg antigen (SEA) in urine of S. haematobium-infected children, and we have evaluated the applicability of the assay as a diagnostic and morbidity indicator. To evaluate this assay, we have studied a group of 470 children from two schools (Tsunguni and Kibaokiche) in the Coast province of Kenya; 84.8% and 77% were egg-positive while the percentage positive as determined by the SEA-ELISA were 78.8% and 76.2% in Tsunguni and Kibaokiche, respectively. In both schools, SEA levels in urine of S. haematobium-infected children significantly correlated with egg counts (Pearson's r=0.73, P < 0.0001) and with hematuria (Spearman's r=0.65, P < 0.0001). In addition, urinary tract pathology as determined by ultrasound significantly correlated with the SEA levels in urine (Spearman's r=0.3, P < 0.001). The SEA-ELISA compared well with microhematuria within egg count classes and with egg counts within hematuria classes.

Use of monoclonal antibodies prepared against Schistosoma mansoni hatching fluid antigens for demonstration of Schistosoma haematobium circulating egg antigens in urine.

A panel of 17 monoclonal antibodies (MAbs) against Schistosoma soluble egg antigens (SEAs) was produced from BALB/c mice immunized with antigens secreted/excreted by Schistosoma mansoni eggs. In this study, we demonstrate that 16 MAbs were reactive with S. haematobium SEA in addition to S. mansoni SEA. The MAbs were tested as potential immunodiagnostic reagents in a homologous sandwich ELISA format to detect circulating soluble egg antigens (CSEAs) in serum and urine samples of S. mansoni- or S. haematobium-infected individuals. When samples of S. mansoni-infected individuals were tested, none of these MAbs performed as good as the previously described S. mansoni-specific 114-5B1-A and 114-4D12-A MAbs. However, 11 MAbs (of the IgM isotype) detected CSEA in urine samples of S. haematobium-infected individuals. Three MAbs, 290-2E6-A, 291-3D5-A, and 291-5D5-A, were selected for a pilot study with 47 urine samples of S. haematobium-infected individuals from Kenya. The CSEA levels detected with each of these ELISAs showed a significant correlation with urinary egg counts (Spearman rho > 0.37, P < 0.01) and with each other (Spearman rho > 0.74, P < 0.001). Based on the 92% specificity and 90% sensitivity of the assay, the ELISA using MAb 290-2E6-A was found to be the most promising assay for immunodiagnosis of S. haematobium infections.

The dynamics of a soluble egg antigen of Schistosoma haematobium in relation to egg counts, circulating anodic and cathodic antigens and pathology markers before and after chemotherapy.

A cohort of Schistosoma haematobium infected schoolchildren from Cameroon (n = 146) was studied for urine circulating soluble egg antigen (SEA), in comparison to other urine infection parameters: the circulating adult worm-derived antigens, circulating anodic and cathodic antigens (CAA and CCA), egg counts and the reagent strip index (RSI). Before treatment, SEA prevalence was 90%, while 89% and 65% of the children were positive for CCA and CAA respectively. The children were treated with 2 doses of praziquantel (2 x 40 mg/kg bodyweight) at an interval of 10 days and followed-up at 1, 2, 3, 5 and 12 months after treatment. Urine SEA correlated significantly with egg counts and RSI; levels of CAA and CCA were also significantly correlated with those of SEA. The levels of SEA showed a better correlation to both egg counts and RSI than did the levels of CAA and CCA. SEA levels dropped sharply 1 month after treatment, with few children excreting any SEA whereas egg counts decreased less rapidly. The prevalence and levels of SEA remained low during the whole post-treatment period whereas egg counts, RSI and CCA in urine rose progressively in the post-treatment period with a final egg count prevalence of 78%. The results of the present study indicate that for S. haematobium infections, measurement of SEA in urine is a valuable additional diagnostic parameter.