{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:23:47Z","timestamp":1788639827754,"version":"build-2803163510"},"reference-count":0,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,6]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Ivermectin (IVM) is a widely used anthelmintic. However, with widespread use comes the risk of the emergence of IVM resistance, particularly in strongyloidiasis. Adenosine triphosphate (ATP)-binding cassette (ABC) transporter genes play an important role in the IVM-resistance mechanism. Here, we aimed to establish an animal experimental model of IVM resistance by frequent treatment of <jats:italic>Strongyloides ratti<\/jats:italic> with subtherapeutic doses of IVM, resistance being evaluated by the expression levels of ABC transporter genes. Rats infected with <jats:italic>S. ratti<\/jats:italic> were placed in experimental groups as follows: 1) untreated control (control); 2) treated with the mutagen ethyl methanesulfonate (EMS); 3) injected with 100 \u00b5g\/kg body weight of IVM (IVM); 4) treated with a combination of EMS and IVM (IVM+EMS). Parasites were evaluated after four generations. Extent of IVM resistance was assessed using IVM sensitivity, larval development, and expression of ABC genes. By the F4 generation, <jats:italic>S. ratti<\/jats:italic> in the IVM group exhibited significantly higher levels of IVM resistance than did other groups according to in\u00a0vitro drug-sensitivity tests and inhibition of larval development (IC<jats:sub>50<\/jats:sub> = 36.60 ng\/mL; 95% CI: 31.6, 42.01). Expression levels of ABC isoform genes (<jats:italic>ABCA<\/jats:italic>, <jats:italic>ABCF<\/jats:italic>, and <jats:italic>ABCG<\/jats:italic>) were statistically significantly higher in the IVM-resistant line compared with the susceptible line. In conclusion, IVM subtherapeutic doses induced IVM resistance in <jats:italic>S. ratti<\/jats:italic> by the F4 generation with corresponding upregulation of some ABC isoform genes. The study provides a model for inducing and assessing drug resistance in <jats:italic>Strongyloides<\/jats:italic>.<\/jats:p>","DOI":"10.4269\/ajtmh.21-0377","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T13:57:25Z","timestamp":1627912645000},"page":"1117-1123","source":"Crossref","is-referenced-by-count":14,"title":["Repeated Ivermectin Treatment Induces Ivermectin Resistance in Strongyloides ratti by Upregulating the Expression of ATP-Binding Cassette Transporter Genes"],"prefix":"10.4269","volume":"105","author":[{"given":"Chatchawan","family":"Sengthong","sequence":"first","affiliation":[{"name":"1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"},{"name":"2Medical Technology Unit of Bangkatum Hospital, Phitsanulok, Thailand;"},{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manachai","family":"Yingklang","sequence":"additional","affiliation":[{"name":"1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"},{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitti","family":"Intuyod","sequence":"additional","affiliation":[{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"},{"name":"4Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornuma","family":"Haonon","sequence":"additional","affiliation":[{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"},{"name":"5Faculty of Medical Technology, Nakhonratchasima College, Nakhon Ratchasima, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porntip","family":"Pinlaor","sequence":"additional","affiliation":[{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"},{"name":"6Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanakan","family":"Jantawong","sequence":"additional","affiliation":[{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"},{"name":"7Science Program in Biomedical Science, Khon Kaen University, Khon Kaen, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuttanan","family":"Hongsrichan","sequence":"additional","affiliation":[{"name":"1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"},{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thewarach","family":"Laha","sequence":"additional","affiliation":[{"name":"1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"},{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirirat","family":"Anutrakulchai","sequence":"additional","affiliation":[{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"},{"name":"8Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ubon","family":"Cha\u2019on","sequence":"additional","affiliation":[{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"},{"name":"9Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paiboon","family":"Sithithaworn","sequence":"additional","affiliation":[{"name":"1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somchai","family":"Pinlaor","sequence":"additional","affiliation":[{"name":"1Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;"},{"name":"3Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen Province, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/105\/4\/article-p1117.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/105\/4\/article-p1117.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T19:13:06Z","timestamp":1633547586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/105\/4\/article-p1117.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.21-0377","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,6]]}}}