Following a 4-year annual praziquantel (PZQ) treatment campaign, the resulting prevalence of was seen to differ among individual villages along the Kenyan shore of Lake Victoria. We have investigated possible inherent differences in snail-related aspects of transmission among such 10 villages, including six persistent hotspot (PHS) villages (≤ 30% reduction in prevalence following repeated treatments) located along the west-facing shore of the lake and four PZQ-responding (RESP) villages (> 30% prevalence reduction following repeated treatment) along the Winam Gulf. When taking into account all sampling sites, times, and water hyacinth presence/absence, shoreline-associated from PHS and RESP villages did not differ in relative abundance or prevalence of infection. Water hyacinth intrusions were associated with increased abundance. The deeper water snail was significantly more abundant in the PHS villages, and prevalence of among villages both before and after control was positively correlated with abundance. Worm recoveries from sentinel mice did not differ between PHS and RESP villages, and abundance of non-schistosome trematode species was not associated with abundance. provides an alternative, deepwater mode of transmission that may favor greater persistence of in PHS villages. As we found evidence for ongoing transmission in all 10 villages, we conclude that conditions conducive for transmission and reinfection occur ubiquitously. This argues for an integrated, basin-wide plan for schistosomiasis control to counteract rapid reinfections facilitated by large snail populations and movements of infected people around the lake.