{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:31:29Z","timestamp":1791235889727,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant\n Plasmodium falciparum<\/jats:named-content>\n malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for\n ex vivo<\/jats:italic>\n drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC\n 50<\/jats:sub>\n ] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of\n P. falciparum<\/jats:named-content>\n multidrug resistance 1 gene (Pf\n mdr1<\/jats:italic>\n ) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the\n P. falciparum<\/jats:named-content>\n chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had\n P. falciparum<\/jats:named-content>\n kelch13<\/jats:italic>\n mutations, indicative of artemisinin resistance.\n Ex vivo<\/jats:italic>\n bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial\n in vivo<\/jats:italic>\n drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the\n P. falciparum<\/jats:named-content>\n mdr1<\/jats:italic>\n copy number, as a stop-gap measure in areas of DHA-PPQ failure.\n <\/jats:p>","DOI":"10.1128\/aac.00366-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:24:53Z","timestamp":1432740293000},"page":"4631-4643","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":68,"title":["Ex Vivo<\/i>\n Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance"],"prefix":"10.1128","volume":"59","author":[{"given":"Suwanna","family":"Chaorattanakawee","sequence":"first","affiliation":[{"name":"Department of Immunology and 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Immunology and Medicine, Armed Forces Research Institute of Medical Science, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soklyda","family":"Chann","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youry","family":"Se","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Yom","sequence":"additional","affiliation":[{"name":"National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thay Kheng","family":"Heng","sequence":"additional","affiliation":[{"name":"National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nareth","family":"Kong","sequence":"additional","affiliation":[{"name":"National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worachet","family":"Kuntawunginn","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuntida","family":"Tangthongchaiwiriya","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Jacob","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute\/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Takala-Harrison","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute\/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Plowe","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute\/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica T.","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Char 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