SummaryThis paper summarizes and concludes in-depth ®eld investigations on suspected resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70±90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitologically negative 12 weeks after treatment, although the reduction in mean egg counts was within normal ranges (86%). Among other hypotheses to explain the observed low cure rate in this focus, the possibility of drug resistance or tolerance had to be considered. Subsequent ®eld trials with a shorter follow-up period (6±8 weeks) yielded cure rates of 31±36%.Increasing the dose to 2´30 mg/kg did not signi®cantly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resulted in a normal cure rate of 79%. The ef®cacy of praziquantel in this focus could be related to age and pre-treatment intensity but not to other host factors, including immune pro®les and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an urban region with no transmission, and re-treatment after 3 weeks of non-cured individuals within the area resulted in normal cure rates (78±88%). The application of an epidemiological model taking into account the relation between egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reduction after treatment with praziquantel; in average endemic situations, such a drug ef®cacy would result in normal cure rates. Laboratory studies by others on the presence or absence of praziquantel resistance in Senegalese schistosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel-resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and intense transmission in this area.

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Two treatments with praziquantel (PZQ) 40 mg/kg, 40 d apart, were given to individuals in a recently established (< 6 years) Schistosoma mansoni focus in the Senegal River Basin (SRB). Efficacy of treatment was evaluated 4 weeks after each treatment. Among 130 individuals who provided stool samples on days 0, 118 and 153 and were treated on days 85 and 125, 113 (87%) were infected with S. mansoni before treatment. The overall geometric mean faecal egg count of the infected individuals was 478 eggs/g. Four weeks after the first treatment (day 118), the overall cure rate was only 42.5% and the overall reduction in intensity of infection was 70.7%. However, 4 weeks after the second treatment (day 153), the overall cure rate rose to 76.1% and the overall reduction in intensity was 88.1%. The greatest increase in cure rate between the 2 treatments was in those individuals who were initially the most heavily infected (> 1000 eggs/g). There was no apparent difference in cure rate between younger (< 20 years) and older individuals (> 20 years). No evidence for the existence of a PZQ tolerant strain of S. mansoni was found. Two treatments of PZQ 40 mg/kg, 40 d apart, were sufficient to give an adequate cure rate and high reductions in the intensity of infection. As there was insufficient time for reinfection between treatment and follow-up to result in egg production, the low cure rate observed after one treatment was probably the result of a combination of high infection intensity and the maturation of pre-existing prepatents S. mansoni infections.

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,

Journal articleIFPRI3; CRP6EPTDPRCGIAR Research Program on Forest, Trees and Agroforestry (FTA