Genetic diversity and structure of

China was once a major endemic zone for Schistosoma japonicum, but decades of control efforts have dramatically reduced transmission. Suzhou City, in Jiangsu Province, a former hyperendemic area, achieved transmission interruption in 1995. However, the intermediate host Oncomelania hupensis persists and new habitats in non-endemic villages pose resurgence risks if parasites are reintroduced. To evaluate genetic resilience and dispersal potential, we analyzed six O. hupensis populations (214 snails) from ecologically distinct habitats in Wuzhong district, Suzhou (2018 to 2021): Guangfu (GF20 and GF21: wetlands), Jinting (JT18, JT19, and JT20: isolated island), and Dongshan (DS19: lakeside hills). Using nine microsatellite loci, we identified 91 alleles and assessed genetic diversity, structure, and demography. All populations exhibited low observed heterozygosity (Ho < 0.5), with bottlenecks detected in GF21, GF20, and JT20. Paradoxically, infinite effective population sizes (Ne) at 95% CI upper limits suggested retained adaptive potential. Significant genetic differentiation (FST = 0.287, p < 0.01) reflected habitat-driven isolation: Jinting’s island populations diverged markedly from Dongshan and Guangfu, while bidirectional gene flow (Nm > 1) between Guangfu’s temporally sampled populations indicated sustained genetic connectivity over time. DIYABC modeling traced JT20’s ancestry to admixture between Jinting (JT18) and Guangfu (GF20) sources, implicating flood-mediated dispersal. Despite local control efficacy, snails retain resilience via large Ne. These findings mandate habitat-tailored strategies: habitat modification and intensified molluscicide campaigns in Guangfu and targeted eradication of Jinting’s isolated populations. Integrating genetic surveillance into snail monitoring programs will be critical to sustaining transmission interruption and achieving elimination in ecologically complex regions.