SummaryIn an epidemic focus in northern Senegal, adults had lower intensities of infection than adolescents, a phenomenon that could not be attributed to immunity acquired over the previous 10-15 years of exposure to the parasite because all age groups had had the same number of years' experience of the worm. This article considers whether this pattern could have been because of higher levels of exposure to the parasite in younger age groups. Personal contact with infected water was recorded using a questionnaire in Schistosoma mansoni foci not more than 3 years old and in another, 10-year-old focus. Many aspects of contact (e.g. frequency, duration or time of day of contact) may contribute to the number of encounters with infective cercariae (true exposure), so various assumptions regarding the relationship between water contact and true exposure were tested resulting in a range of exposure indices. People reported a mean of 4.4 separate contacts, and spent a median of 57 min per day in water. Patterns of water contact differed depending on the exposure index used, e.g. considering duration, males spent a longer time in water than females (P < 0.001). But using frequency, females had more contacts with water than males in most villages (P < 0.001). Generally, exposure levels dropped as people become aged (P < 0.001) and residents of the older focus were more exposed than residents of other foci (P < 0.002). Intensity of (re)infection was not related to exposure either alone or in models incorporating age, sex and/or village irrespective of the index used. There is therefore evidence that age, sex and place of residence determine exposure but none to suggest that exposure had an influence on the relationship between these factors and intensity of infection. We propose therefore that in this population other factors have principal importance in determining intensity of infection.keywords Schistosoma mansoni, human, Senegal, water contact correspondence J. Scott,
Abstract. 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.In a recently established focus of Schistosoma mansoni in the Senegal River Basin, praziquantel treatment apparently showed a lower efficacy and induced more side effects than usually reported. 1,2 In an initial cohort of 400 subjects, only 18% was found to be parasitologically negative 12 weeks after treatment with the standard single oral dosage of 40 mg/kg. However, egg reduction rates were substantial (86%) in those remaining positive. Results were confirmed by determination of circulating antigens excreted by metabolically active adult worms.2 Similar low cure rates were found in 3 subsequent cohorts from the same focus (Stelma FF, unpublished data). An increased dosage of praziquantel, given at the same day, showed no significant improvement, 3 while normal cure rates were found after treatment with oxamniquine, 4 or after repeated treatment with praziquantel within a period of 40 days. 5Possible explanations for these findings can be divided into 3 main categories: 1) parasite-related, including reduced strain susceptibility to praziquantel, 2) drug-related, including drug quality or bioavailability, and 3) host-related, including high initial intensity of infection, prepatent infections, rapid reinfection, and still under-developed pharmacosynergistic humoral immune responses. 2 This paper focuses on the third category of hypotheses. We use data from all four cohorts to analyze the contribution of host-related factors on the efficacy of praziquantel treatment in this area, with emphasis on the variabl...
In recently exposed communities, intensity of schistosomiasis infection increases as children age and then drops again in adulthood, indicating that host maturity is an important aspect of resistance to schistosomiasis. We investigated whether the cellular immune response to the parasite was correlated with age in subjects with similar daily patterns of exposure, current intensities of infection and number of years of exposure. The cellular immune response of subjects with either 'low' (under 200 eggs per gram (EPG)) or 'high' (over 400 EPG) intensities of infection was investigated, in a recently established focus where subjects had similar histories of exposure and number of years of experience with Schistosoma mansoni. Subject's whole blood was cultured with adult worm antigen (AWA), a mixture of phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), or left unstimulated, and culture supernatants were tested for IL-4, IL-5, IL-10 and IFN-gamma. Children and adults tended to respond differently to schistosome antigen. The most statistically significant illustration of this was the negative correlation between age and IL-5 produced by samples from people with low intensities of infection cultured with AWA (P < 0.003, P < 0.05 after Bonferroni correction). IL-10 produced by samples cultured with PHA and LPS was also notably lower in children than in adults, although not formally significant after Bonferroni correction. This indicates that it is possible for age, independently of intensity of infection or experience with the parasite, to influence the immune response to schistosomiasis.
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