{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:42:39Z","timestamp":1789098159103,"version":"build-2803163510"},"posted":{"date-parts":[[2024,8,30]]},"group-title":"Genomics","reference-count":91,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:italic>Schistosoma mansoni<\/jats:italic>\n                  samples (and the closely related outgroup species,\n                  <jats:italic>S. rodhaini)<\/jats:italic>\n                  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\n                  <jats:sub>PZQ<\/jats:sub>\n                  , a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPM\n                  <jats:sub>PZQ<\/jats:sub>\n                  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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>\n                    Population genomics and functional genetics of praziquantel resistance in\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.08.29.610291","type":"posted-content","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T22:00:12Z","timestamp":1725055212000},"source":"Crossref","is-referenced-by-count":17,"title":["Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic\n                  <i>Schistosoma mansoni<\/i>"],"prefix":"10.64898","author":[{"given":"Duncan J.","family":"Berger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Kyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Crellen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushabe John","family":"Vianney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narcis B.","family":"Kabatereine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Cotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sanya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Elliot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edridah M.","family":"Tukahebwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses","family":"Adriko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire J.","family":"Standley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Gouvras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safari","family":"Kinung\u2019hi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Haas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Rabone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan","family":"Emery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poppy H. 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