Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni.

Severe clinical disease caused by the major human parasite Schistosoma mansoni is the consequence of high and prolonged infections. Epidemiological studies indicate that, for individuals having frequent contacts with cercaria-infested waters, both infection intensities and reinfection after treatment depend, in large part, on their intrinsic susceptibility/resistance to infection, suggesting the role of genetic factors in human resistance to S. mansoni. To investigate whether a major gene controls human susceptibility/resistance to infection by S. mansoni, segregation analysis of infection intensities, adjusted for the factors relevant in schistosomiasis (water contact, age, sex), was performed on 20 Brazilian pedigrees (269 individuals), using both the unified mixed model and the regressive model of analysis. The results are consistent with the hypothesis that there is a codominant major gene controlling human susceptibility/resistance to infection by S. mansoni. Parameter estimates indicate a frequency of .20-.25 for the deleterious allele; thus, about 5% of the population is predisposed to high infections, 60% is resistant, and 35% has an intermediate, although fairly good, level of resistance. These findings provide a genetic basis for earlier observations on the lower resistance and the predisposition to reinfection of certain individuals. In addition to the detection of a major gene effect, the data suggest that immunity to S. mansoni develops progressively during childhood to reach a maximum around the age of puberty. The implications of these results for the strategy to be used in endemic areas to reduce morbidity and to control parasite transmission are discussed.