Population genetic perturbations of intermediate hosts, often a consequence of human pressure on environmental resources, can precipitate unexpectedly severe disease outbreaks. Such disturbances are set to become increasingly common following range changes concomitant with climate shifts, dwindling natural resources and major infrastructure changes such as hydroprojects. Construction of the Diama dam in the Senegal River Basin (SRB) reduced river salinity, enabling the freshwater snail intermediate host Biomphalaria pfeifferi to rapidly expand its distribution. A serious public health problem ensued, with an epidemic of intestinal schistosomiasis occurring in the previously schistosome-free Richard-Toll region within 2 years. The current study aimed to assess the population variability of B. pfeifferi in the SRB, and speculate upon its subsequent impact on host-parasite interactions following such engineered ecological change. Genetic variation at nine polymorphic microsatellite loci revealed little population differentiation in SRB snails compared with those from natural habitats in Zimbabwe, where Schistosoma mansoni transmission is much lower. ‘Open’ SRB habitats are associated with greater water contact, smaller population sizes and less genetic diversity, with sites downstream of Richard-Toll showing greater inter- and intrapopulation variation, concomitant with less frequent human contact. These observations may be explained by rapid expansion into pristine habitat selecting for high fecundity genotypes at the expense of schistosome resistance, presenting S. mansoni with genetically homogenous highly fecund susceptible populations around the focal point, promoting development of a highly compatible host-parasite relationship. Longitudinal study of such systems may prove important in predicting public health risks engendered by future environmental engineering projects.