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The specificity of schistosome circulating antigen detection was determined in negative individuals from two S. mansoni- endemic countries, Senegal and Burundi, and compared with results from Dutch control individuals. A nearly absolute specificity was achieved for circulating anodic antigen (CAA) detection in serum, irrespective of the target population or sample pretreatment method. Circulating cathodic antigen (CCA) detection in serum and urine resulted in a lower specificity than serum CAA detection. Apparent large differences in specificity of CCA detection between countries were mainly due to pretreatment methods. Apparently, the alkaline/heating pretreatment method is not as effective as trichloroacetic acid (TCA)-pretreatment in removing (certain) interfering components, which may vary between populations. In view of the development of the urine CCA assay into a noninvasive screening test, a slightly lower specificity may still be acceptable. For precise epidemiological analyses the highly specific serum CAA assay remains the method of choice.

Surprisingly low cure rates were repeatedly observed after treatment with a standard dosage of praziquantel in a recently established Schistosoma mansoni focus in northern Senegal. In 4 discrete cohorts from the same population, cure rates were 18-36% and egg count reduction rates were 77-88%. Data and material of 920 compliant subjects from all 4 cohorts were further analyzed to identify possible host-related factors associated with low cure rates. The lowest cure rates were found in the highest egg count groups. However, in low and moderate egg count groups, drug efficacy was also below normal values. Cure rates were similar in males and females, showed no seasonal variation, and were independent of previous praziquantel treatment. They were significantly higher in adults than in children, also after allowing for intensity of infection. Individual water contact behavior and specific humoral immune responses were examined in 2 extreme subgroups, either without significant egg count reduction or showing complete parasitologic cure. There was no significant difference in frequency and duration of water contact between those individuals with complete cure and those that showed little effect of praziquantel treatment. Levels of IgG, IgG1, IgG3, IgG4, IgM, and IgE against adult worm antigen were not different between the 2 subgroups. Thus, the abnormally frequent failure of treatment observed in this focus could not be associated with any host-related factor, other than age and pretreatment egg counts.

Acquired immune resistance is believed to be largely responsible for age-dependent infection and reinfection patterns in schistosomiasis. In a recently established but intense focus of Schistosoma mansoni in Senegal, the humoral immune response was studied in a random population sample of 289. Antibody levels of various isotypes to schistosome worm and egg antigens were determined by ELISA and related to egg counts (eggs per gram of feces [EPG]), age, and sex. Both IgG1 and IgG4 followed age-related patterns similar to egg counts and strongly correlated with EPG, even after allowing for age. Specific IgE levels increased slowly with age. The humoral immune response patterns in this recently infected population appeared to be largely similar to those in chronically infected communities. Thus far, the observations do not support the current hypothesis that age-related resistance to Schistosoma is determined by IgE-mediated protective immunity acquired during many years of exposure.

Quantitative enzyme-linked immunosorbent assays (ELISAs) for the detection of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were applied as an epidemiologic tool in a recent, intense focus of Schistosoma mansoni in Senegal. Both CAA and CCA in serum and CCA in urine were found in 94%, 83%, and 95%, respectively, of the population, of which 91% were positive on stool examination. Circulating antigens were also detectable in sera and urines of most egg-negative individuals. The sensitivities of the urine CCA and serum CAA ELISA were substantially higher than that of a single egg count, and increased with egg output. The CAA and CCA levels correlated well with egg counts and with each other. The age-related evolution of antigen levels followed a similar pattern as egg counts, providing supplementary evidence for a genuine reduction of worm burdens in adults in spite of the supposed absence of acquired immunity in this recently exposed community. The antigen:egg ratios decreased in adults, suggesting lower worm fecundity in children. This would be compatible with a density-dependent reduction of fecundity, but not with anti-fecundity immunity in adults that perhaps has not yet developed in this new focus.

Schistosoma mansoni was introduced in the Richard Toll area (Senegal) around 1988, probably due to man-made ecological changes in the Senegal river basin. Since 1991, we investigate the community of Ndombo, close to Richard Toll. Four random population samples of approximately 400 subjects are surveyed, starting at 8 months intervals. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; and followed up 6-12 weeks, 1 and 2 years after treatment. Water contact patterns and snail densities are longitudinally surveyed. In the first cohort, prevalence of infection was 91%, with 41% excreting over 1000 eggs per gram (epg); the mean egg count was 646 epg, individual counts up to 24,000 epg. Prevalences remained almost 100%, but egg counts declined strongly in adults, in spite of continued exposure and the supposed lack of acquired immunity. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens. Serum circulating anodic antigen (CAA) provided intriguing epidemiological information on worm burdens, while circulating cathodic antigen (CCA) showed promise for non-invasive diagnosis and screening. So far, similar epidemiological results were found in subsequent cohorts, although some variations were observed, possibly due to seasonal transmission fluctuations. IgE levels increased with age, while IgG4 peaked in the age-group 10-19 years. IgE and IgG4-levels against adult worm antigen (AWA) and soluble egg antigen (SEA) increased between cohort 1 and cohort 3 in almost all age-groups. In all 3 cohorts examined so far a strong correlation between IgG4 and pre-treatment egg-load was observed. Further follow-up and analysis, and comparison with chronically infected populations will provide insight in the development of acquired immunity. Abdominal discomfort was reported by 61% and diarrhoea by 33% of the subjects in the first cohort; mild hepatomegaly was found in 16%, splenomegaly in 0.5%. There was no correlation between frequency of symptoms and egg counts. This low morbidity, in spite of intense infections, was confirmed by ultrasound, and may be due to the recent nature of the focus. In the first cohort, 82% of treated subjects still excreted eggs 12 weeks after treatment, though egg counts declined strongly. Antigen detection confirmed these results. Parasitological negativation rates in subsequent cohorts, followed up sooner after treatment, improved but remained remarkably low. The low drug efficacy may be due to very rapid reinfection (though further reinfection after one year was limited), and/or to the lack of immunity in the population. Reduced susceptibility of the local schistosome strain can not be excluded, however. Praziquantel treatment provoked impressive but transient side effects (colics, vomiting, urticaria, oedema), the frequency of which correlated with intensity of infection.