Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic Schistosoma mansoni
14 affiliations
- 1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK
- 2Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
- 3School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK
- 4Division of Biomedical Engineering, University of Glasgow, G12 8LT Glasgow, UK
- 5Vector Borne & Neglected Tropical Disease Control Division, Ministry of Health, Kampala, Uganda
- 6Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- 7Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK
- 8Center for Global Health Science and Security, Georgetown University, 3900 Reservoir Rd NW, Washington DC 20007, USA
- 9Global Schistosomiasis Alliance, Podium Space - Ealing Cross, 85 Uxbridge Road, London, W5 5BW, UK
- 10National Institute for Medical Research (NIMR) Mwanza Centre, P.O Box 1462, Mwanza, United Republic of Tanzania
- 11helminGuard, Süelfeld, Germany
- 12Department of Life Sciences, The Natural History Museum, London, SW7 5BD, UK; Wolfson Wellcome Biomedical Laboratories, Department of Life Sciences, The Natural History Museum, London, SW7 5BD, UK, London Centre for Neglected Tropical Disease Research (LCNTDR), London, UK
- 13Current address: School of Institute of Infection & Immunity, College of Medical, Veterinary & Life Sciences, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK
- 14Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Herts, UK
Abstract
Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPM PZQ , a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPM PZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles. One Sentence Summary Population genomics and functional genetics of praziquantel resistance in Schistosoma mansoni
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BibTeX
@article{berger2026extensive,
title = {{Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic Schistosoma mansoni}},
author = {Duncan Berger and Sang-Kyu Park and Thomas Crellen and John Vianney Tushabe and Narcis B. Kabatereine and James Anthony Cotton and Richard E. Sanya and Alison M. Elliott and Edridah Muheki Tukahebwa and Moses Adriko and Claire J. Standley and Anouk Gouvras and Safari Kinung'hi and Helmut Haas and Muriel Rabone and Aidan Emery and Poppy H. L. Lamberton and Bonnie Lee Webster and Fiona Allan and Sarah Buddenborg and Matthew Berriman and Jonathan S. Marchant and Stephen R. Doyle and Joanne P. Webster},
journal = {Science Advances},
year = {2026},
month = jul,
doi = {10.1126/sciadv.adt3721},
url = {https://doi.org/10.1126/sciadv.adt3721},
note = {CC BY},
}
RIS
TY - JOUR
TI - Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic Schistosoma mansoni
AU - Duncan Berger
AU - Sang-Kyu Park
AU - Thomas Crellen
AU - John Vianney Tushabe
AU - Narcis B. Kabatereine
AU - James Anthony Cotton
AU - Richard E. Sanya
AU - Alison M. Elliott
AU - Edridah Muheki Tukahebwa
AU - Moses Adriko
AU - Claire J. Standley
AU - Anouk Gouvras
AU - Safari Kinung'hi
AU - Helmut Haas
AU - Muriel Rabone
AU - Aidan Emery
AU - Poppy H. L. Lamberton
AU - Bonnie Lee Webster
AU - Fiona Allan
AU - Sarah Buddenborg
AU - Matthew Berriman
AU - Jonathan S. Marchant
AU - Stephen R. Doyle
AU - Joanne P. Webster
PY - 2026
DA - 2026/07/17
JO - Science Advances
DO - 10.1126/sciadv.adt3721
UR - https://doi.org/10.1126/sciadv.adt3721
AB - Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPM PZQ , a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPM PZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles. One Sentence Summary Population genomics and functional genetics of praziquantel resistance in Schistosoma mansoni
SN - 2375-2548
ER -