Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic <i>Schistosoma mansoni</i>.

Abstract

Mass drug administration (MDA) with praziquantel is the cornerstone of schistosomiasis control and elimination efforts. To assess how long-term MDA affects parasite populations, we analyzed whole-genome sequence data from 570 <i>Schistosoma mansoni</i> samples and the closely related <i>Schistosoma rodhaini</i> across eight countries, combining new parasite material with publicly available sequence data. We observed a broad-scale genetic structure between countries alongside evidence of extensive long-distance transmission. Functional profiling of the recently identified transient receptor potential melastatin ion channel, <i>Sm.</i>TRPM_PZQ, revealed four naturally occurring variants associated with reduced praziquantel sensitivity, indicating standing variation for resistance. Analyses of parasite infrapopulations collected from people pre- and post-praziquantel treatment further identified instances of treatment failure, supporting the potential for praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem, with interruption of transmission in selected regions by 2030, our study provides a comprehensive genomic framework for endemic populations, highlights an approach to detect potential resistance, and endorses the development of precision surveillance and adaptive treatment strategies.