{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:08:58Z","timestamp":1740146938358,"version":"3.37.3"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673113"],"award-info":[{"award-number":["81673113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"WHO Mekong Malaria Programme","award":["WP\/10\/MVP\/005837"],"award-info":[{"award-number":["WP\/10\/MVP\/005837"]}]},{"name":"USAID-PMI"},{"DOI":"10.13039\/100004417","name":"Global Fund","doi-asserted-by":"crossref","award":["Round 6 (CHN-607-G09-M) and 10 (CHN-011-G15-M)"],"award-info":[{"award-number":["Round 6 (CHN-607-G09-M) and 10 (CHN-011-G15-M)"]}],"id":[{"id":"10.13039\/100004417","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Backgrounds<\/jats:title>\n<jats:p>The therapeutic efficacy studies of DHA-PIP for uncomplicated <jats:italic>Plasmodium falciparum<\/jats:italic> patients were implemented from 2012 to 2016 along China (Yunnan province)-Myanmar border, which verified the high efficacy of DHA-PIP. With the samples collected in these studies, the genetic characteristics of <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> parasites based on <jats:italic>in vivo<\/jats:italic> parasite clearance time (PCT) was investigated to explore if these parasites had developed resistance to DHA and PIP at molecular level.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The genetic characteristics were investigated based on K13 genotypes, copy numbers of genes pfpm2 and pfmdr1, and nine microsatellite loci (Short Tandem Repeats, STR) flanking the K13 gene on chromosome 13. The PCT 50s were compared based on different K13 genotypes, sites, periods and copy numbers.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In the NW (North-West Yunnan province bordering with Myanmar) region, F446I was the main K13 genotype. No significant differences for PCT 50s presented among three K13 genotypes. In SW (South-West Yunnan province bordering with Myanmar) region, only wild K13 genotype was detected in all parasite isolates whose PCT 50s was significantly longer than those in NW region. For the copy numbers of genes, parasite isolates containing multiple copies of pfmdr1 gene were found in both regions, but only single copy of pfpm2 gene was detected. Though the prevalence of parasite isolates with multiple copies of pfmdr1 gene in SW region was higher than that in NW region, no difference in PCT 50s were presented between isolates with single and multiple copies of pfmdr1 gene. The median <jats:italic>He<\/jats:italic> values of F446I group and Others (Non-F446I K13 mutation) group were 0.08 and 0.41 respectively. The mean <jats:italic>He<\/jats:italic> values of ML group (Menglian County in SW) and W (wild K13 genotype in NW) group were 0 and 0.69 respectively. The mean F<jats:italic>st<\/jats:italic> values between ML and W groups were significantly higher than the other two K13 groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p><jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> isolates in NW and SW regions had very different genetic characteristics. The F446I was hypothesized to have independently appeared and spread in NW region from 2012 and 2016. The high susceptibility of PIP had ensured the efficacy of DHA-PIP <jats:italic>in vivo<\/jats:italic>. Multiple copy numbers of pfmdr1 gene might be a potential cause of prolonged clearance time of ACTs drugs along China-Myanmar border.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>Trial registration: ISRCTN, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.isrctn.com\/ISRCTN11775446\" xlink:type=\"simple\">ISRCTN 11775446<\/jats:ext-link>. Registered 17 April 2020\u2014Retrospectively registered, the registered name was Investigating resistance to DHA-PIP for the treatment of Plasmodium falciparum malaria and chloroquine for the treatment of Plasmodium vivax malaria in Yunnan, China. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.isrctn.com\/ISRCTN11775446\" xlink:type=\"simple\">http:\/\/www.isrctn.com\/ISRCTN11775446<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0293590","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T18:27:39Z","timestamp":1699640859000},"page":"e0293590","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic characteristics of P. falciparum parasites collected from 2012 to 2016 and anti-malaria resistance along the China-Myanmar border"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-3098","authenticated-orcid":true,"given":"Mei","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linhua","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henglin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Dorina Geluz","family":"Bustos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Ringwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"issue":"11","key":"pone.0293590.ref001","first-page":"1936","article-title":"Epidemiological characteristics of public health emergencies of communicable diseases in cross border area of Yunnan, 2008\u20132017","volume":"46","author":"YC Jia","year":"2019","journal-title":"Mod Prevent Med"},{"issue":"6","key":"pone.0293590.ref002","first-page":"401","article-title":"Malaria situation in the People\u2019s Republic of China in 2010","volume":"29","author":"SS Zhou","year":"2011","journal-title":"Chin J Parasitol Parasit 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