Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic <i>Schistosoma mansoni</i>
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 Schistosoma mansoni samples and the closely related Schistosoma rodhaini 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, Sm. 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.
Authors
- Muriel Rabone (ORCID: https://orcid.org/0000-0002-8351-2313)
- Stephen R. Doyle (ORCID: https://orcid.org/0000-0001-9167-7532)
- Duncan Berger (ORCID: https://orcid.org/0000-0002-2017-6623)
- Matthew Berriman (ORCID: https://orcid.org/0000-0002-9581-0377)
- Richard E. Sanya (ORCID: https://orcid.org/0000-0001-6348-9075)
- James A. Cotton (ORCID: https://orcid.org/0000-0001-5475-3583)
- Bonnie Lee Webster (ORCID: https://orcid.org/0000-0003-0930-9314)
- Jonathan S. Marchant (ORCID: https://orcid.org/0000-0001-6592-0877)
- Alison M. Elliott (ORCID: https://orcid.org/0000-0003-2818-9549)
- Joanne P. Webster (ORCID: https://orcid.org/0000-0001-8616-4919)
- Sarah K. Buddenborg (ORCID: https://orcid.org/0000-0002-9506-9259)
- Poppy H. L. Lamberton (ORCID: https://orcid.org/0000-0003-1048-6318)
- Moses Adriko (ORCID: https://orcid.org/0000-0001-9748-1207)
- Narcis B. Kabatereine (ORCID: https://orcid.org/0000-0001-7036-5716)
- Fiona Allan (ORCID: https://orcid.org/0000-0001-6836-4124)
- Anouk Gouvras (ORCID: https://orcid.org/0000-0002-7857-4309)
- Thomas Crellen (ORCID: https://orcid.org/0000-0003-2934-1063)
- Aidan Mark Emery (ORCID: https://orcid.org/0000-0001-9028-8586)
- Tushabe John Vianney
- Claire J. Standley (ORCID: https://orcid.org/0000-0002-4291-9723)
- Sang-Kyu Park (ORCID: https://orcid.org/0000-0002-3875-1227)
- Safari Kinung'hi
- Edridah M. Tukahebwa
Institutions
- University of London (GB)
- Natural History Museum (GB)
- Royal Veterinary College (GB)
- University of St Andrews (GB)
- Georgetown University (US)
- Medical College of Wisconsin (US)
- Ealing Hospital (GB)
- Georgetown University Medical Center (US)
- Wellcome Sanger Institute (GB)
- Ministry of Health (CY)
- London Centre for Neglected Tropical Disease Research (GB)
- National Institute for Medical Research (TZ)
- Imperial College London (GB)
- University of Glasgow (GB)
- Uganda Virus Research Institute (UG)
Publication Details
- Journal
- Science Advances
- Published
- 2026-07-17
- DOI
- https://doi.org/10.1126/sciadv.adt3721
- Primary Topic
- Parasites and Host Interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- Wellcome
- National Institutes of Health