{
  "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",
  "abstract_shown": true,
  "affiliations": [
    "Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK",
    "Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA",
    "School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK",
    "Division of Biomedical Engineering, University of Glasgow, G12 8LT Glasgow, UK",
    "Vector Borne & Neglected Tropical Disease Control Division, Ministry of Health, Kampala, Uganda",
    "Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda",
    "Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK",
    "Center for Global Health Science and Security, Georgetown University, 3900 Reservoir Rd NW, Washington DC 20007, USA",
    "Global Schistosomiasis Alliance, Podium Space - Ealing Cross, 85 Uxbridge Road, London, W5 5BW, UK",
    "National Institute for Medical Research (NIMR) Mwanza Centre, P.O Box 1462, Mwanza, United Republic of Tanzania",
    "helminGuard, Süelfeld, Germany",
    "Department 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",
    "Current address: School of Institute of Infection & Immunity, College of Medical, Veterinary & Life Sciences, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK",
    "Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Herts, UK"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Duncan Berger",
      "orcid": "0000-0002-2017-6623"
    },
    {
      "affs": [
        1
      ],
      "name": "Sang-Kyu Park",
      "orcid": "0000-0002-3875-1227"
    },
    {
      "affs": [
        2,
        0
      ],
      "name": "Thomas Crellen",
      "orcid": "0000-0003-2934-1063"
    },
    {
      "affs": [
        3
      ],
      "name": "John Vianney Tushabe",
      "orcid": "0009-0003-4152-2550"
    },
    {
      "affs": [
        4
      ],
      "name": "Narcis B. Kabatereine",
      "orcid": "0000-0001-7036-5716"
    },
    {
      "affs": [
        2,
        0
      ],
      "name": "James Anthony Cotton",
      "orcid": "0000-0001-5475-3583"
    },
    {
      "affs": [
        5
      ],
      "name": "Richard E. Sanya",
      "orcid": "0000-0001-6348-9075"
    },
    {
      "affs": [
        6,
        5
      ],
      "name": "Alison M. Elliott",
      "orcid": "0000-0003-2818-9549"
    },
    {
      "affs": [
        4
      ],
      "name": "Edridah Muheki Tukahebwa",
      "orcid": "0000-0002-0624-2890"
    },
    {
      "affs": [
        4
      ],
      "name": "Moses Adriko",
      "orcid": "0000-0001-9748-1207"
    },
    {
      "affs": [
        7
      ],
      "name": "Claire J. Standley",
      "orcid": "0000-0002-4291-9723"
    },
    {
      "affs": [
        8
      ],
      "name": "Anouk Gouvras",
      "orcid": "0000-0002-7857-4309"
    },
    {
      "affs": [
        9
      ],
      "name": "Safari Kinung'hi",
      "orcid": "0000-0001-8902-0312"
    },
    {
      "affs": [
        10
      ],
      "name": "Helmut Haas"
    },
    {
      "affs": [
        11
      ],
      "name": "Muriel Rabone"
    },
    {
      "affs": [
        11
      ],
      "name": "Aidan Emery"
    },
    {
      "affs": [
        2
      ],
      "name": "Poppy H. L. Lamberton",
      "orcid": "0000-0003-1048-6318"
    },
    {
      "affs": [
        11
      ],
      "name": "Bonnie Lee Webster",
      "orcid": "0000-0003-0930-9314"
    },
    {
      "affs": [
        11
      ],
      "name": "Fiona Allan"
    },
    {
      "affs": [
        0
      ],
      "name": "Sarah Buddenborg"
    },
    {
      "affs": [
        12,
        0
      ],
      "name": "Matthew Berriman",
      "orcid": "0000-0002-9581-0377"
    },
    {
      "affs": [
        1
      ],
      "name": "Jonathan S. Marchant",
      "orcid": "0000-0001-6592-0877"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephen R. Doyle",
      "orcid": "0000-0001-9167-7532"
    },
    {
      "affs": [
        13
      ],
      "name": "Joanne P. Webster",
      "orcid": "0000-0001-8616-4919"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cjny1xe56n69j.bib",
  "cited_by": 22,
  "doi": "10.1126/sciadv.adt3721",
  "fulltext_url": null,
  "id": "cjny1xe56n69j",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://doi.org/10.1126/sciadv.adt3721",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2405|Parasites and Host Interactions"
    ]
  ],
  "openalex": "W7169507609",
  "pdf_url": null,
  "pmcid": "PMC11383708",
  "pmid": "39257780",
  "published": "2026-07-17",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/cjny1xe56n69j.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:09Z",
      "native_id": "W7169507609",
      "source": "openalex",
      "url": "https://doi.org/10.1126/sciadv.adt3721"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2405|Parasites and Host Interactions",
      "subfield": "microbiology"
    }
  ],
  "title": "Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic Schistosoma mansoni",
  "title_text": "Extensive parasite transmission and variation in a functional receptor associated with drug resistance in endemic Schistosoma mansoni",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:11Z",
  "url": "https://research.draconitic.com/paper/cjny1xe56n69j",
  "venue": "Science Advances",
  "versions": []
}