Population genomics reveals multi-scale mechanisms sustaining schistosomiasis re-emergence in a near-elimination setting.

In China, sustained snail control, environmental management, and mass drug administration with praziquantel reduced schistosomiasis to near-elimination levels, yet re-emergence in Sichuan Province during the early 2000s exposed vulnerabilities in elimination efforts. We used population genomics to investigate the multi-scale population processes underlying Schistosoma japonicum re-emergence in Sichuan. We sequenced whole genomes from 270 miracidia collected from 53 human hosts across 17 villages in 2007, one year after re-emergence was documented. Population genomic analyses identified a broadly cohesive regional schistosome population with weak geographic structuring. Genome-wide diversity remained substantial, and demographic reconstructions revealed no recent decline in effective population size, suggesting that parasite populations had not undergone regional demographic collapse prior to re-emergence and were likely maintained in non-human reservoir hosts. At finer spatial scales, several villages exhibited reduced genomic diversity and elevated inbreeding, consistent with localized transmission maintained by relatively small founding populations. Estimates of pairwise genetic relatedness revealed dense within-village sibling clusters alongside second- and third-degree relationships spanning villages, and rare first- and second-degree cross-village links, supporting predominantly local transmission embedded within a connected regional transmission network. Genomic inference of minimum reproducing worm pairs identified substantial heterogeneity in host-level worm burden, ranging from one to eleven adult worm pairs, although uneven sampling limited absolute estimates. Together, these findings indicate that parasite persistence in this near-elimination setting was sustained by interacting processes operating across multiple biological scales, including diverse regional parasite populations, localized transmission networks connecting villages, and marked heterogeneity in host-level worm burden. More broadly, this work demonstrates how population genomics can reconstruct otherwise hidden patterns of parasite persistence and transmission, providing a valuable complement to conventional epidemiological surveillance in complex, multi-host parasite systems.