{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:33:41Z","timestamp":1791347621591,"version":"4.3.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","funder":[{"DOI":"10.13039\/501100003762","name":"Institut Pasteur (FR)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004423","name":"World Health Organization (CH)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"published-print":{"date-parts":[[2015,12]]},"DOI":"10.1186\/s12916-015-0539-5","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T07:50:08Z","timestamp":1450770608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":179,"title":["Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations"],"prefix":"10.1186","volume":"13","author":[{"given":"Valentine","family":"Duru","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimol","family":"Khim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithea","family":"Leang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saorin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Domergue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimol","family":"Kloeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sopheakvatey","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophy","family":"Chy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotha","family":"Eam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanra","family":"Khean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaknika","family":"Loch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malen","family":"Ken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dysoley","family":"Lek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Beghain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Ariey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe J.","family":"Guerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekol","family":"Huy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Mercereau-Puijalon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Witkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Menard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,22]]},"reference":[{"key":"539_CR1","unstructured":"World Health Organization. World malaria report 2014. 2014. http:\/\/www.who.int\/malaria\/publications\/world_malaria_report_2014\/en\/ . Accessed on the 12th December 2015."},{"key":"539_CR2","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. Guidelines for the treatment of malaria. Geneva: WHO; 2015."},{"issue":"5","key":"539_CR3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMoa0808859","volume":"361","author":"AM Dondorp","year":"2009","unstructured":"Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361(5):455\u201367.","journal-title":"N Engl J Med"},{"issue":"24","key":"539_CR4","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1056\/NEJMc0805011","volume":"359","author":"H Noedl","year":"2008","unstructured":"Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008;359(24):2619\u201320.","journal-title":"N Engl J Med"},{"issue":"11","key":"539_CR5","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S1473-3099(12)70181-0","volume":"12","author":"C Amaratunga","year":"2012","unstructured":"Amaratunga C, Sreng S, Suon S, Phelps ES, Stepniewska K, Lim P, et al. Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis. 2012;12(11):851\u20138.","journal-title":"Lancet Infect Dis"},{"key":"539_CR6","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/1475-2875-11-355","volume":"11","author":"TT Hien","year":"2012","unstructured":"Hien TT, Thuy-Nhien NT, Phu NH, Boni MF, Thanh NV, Nha-Ca NT, et al. In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province. Vietnam Malar J. 2012;11:355.","journal-title":"Vietnam Malar J"},{"issue":"3","key":"539_CR7","doi-asserted-by":"crossref","first-page":"e57689","DOI":"10.1371\/journal.pone.0057689","volume":"8","author":"MP Kyaw","year":"2013","unstructured":"Kyaw MP, Nyunt MH, Chit K, Aye MM, Aye KH, Aye MM, et al. Reduced susceptibility of Plasmodium falciparum to artesunate in southern Myanmar. PLoS One. 2013;8(3):e57689.","journal-title":"PLoS One"},{"issue":"9830","key":"539_CR8","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1016\/S0140-6736(12)60484-X","volume":"379","author":"AP Phyo","year":"2012","unstructured":"Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R, et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet. 2012;379(9830):1960\u20136.","journal-title":"Lancet"},{"key":"539_CR9","volume-title":"Status report on artemisinin resistance","author":"World Health Organization, Global Malaria Programme","year":"2014","unstructured":"World Health Organization, Global Malaria Programme. Status report on artemisinin resistance. Geneva: WHO; 2014."},{"key":"539_CR10","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1093\/infdis\/jiv249","volume":"212","author":"F Huang","year":"2015","unstructured":"Huang F, Takala-Harrison S, Jacob CG, Liu H, Sun X, Yang H, et al. A single mutation in K13 predominates in southern China and is associated with delayed clearance of Plasmodium falciparum following artemisinin treatment. J Infect Dis. 2015;212:1629\u201335.","journal-title":"J Infect Dis"},{"issue":"12","key":"539_CR11","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/S1473-3099(13)70252-4","volume":"13","author":"B Witkowski","year":"2013","unstructured":"Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, et al. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis. 2013;13(12):1043\u20139.","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"539_CR12","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1056\/NEJMc1403007","volume":"371","author":"DL Saunders","year":"2014","unstructured":"Saunders DL, Vanachayangkul P, Lon C. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014;371(5):484\u20135.","journal-title":"N Engl J Med"},{"issue":"6","key":"539_CR13","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S1473-3099(15)70049-6","volume":"15","author":"MD Spring","year":"2015","unstructured":"Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, et al. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015;15(6):683\u201391.","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"539_CR14","doi-asserted-by":"crossref","first-page":"e93138","DOI":"10.1371\/journal.pone.0093138","volume":"9","author":"C Lon","year":"2014","unstructured":"Lon C, Manning JE, Vanachayangkul P, So M, Sea D, Se Y, et al. Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in northern Cambodia: an open-label randomized trial. PLoS One. 2014;9(3):e93138.","journal-title":"PLoS One"},{"issue":"2","key":"539_CR15","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1128\/AAC.00686-12","volume":"57","author":"R Leang","year":"2012","unstructured":"Leang R, Barrette A, Bouth DM, Menard D, Abdur R, Duong S, et al. Efficacy of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax in Cambodia, 2008 to 2010. Antimicrob Agents Chemother. 2012;57(2):818\u201326.","journal-title":"Antimicrob Agents Chemother"},{"key":"539_CR16","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1128\/AAC.00835-15","volume":"59","author":"R Leang","year":"2015","unstructured":"Leang R, Taylor WR, Bouth DM, Song L, Tarning J, Char MC, et al. Evidence of falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother. 2015;59:4719\u201326. doi: 10.1128\/AAC.00835-15 .","journal-title":"Antimicrob Agents Chemother"},{"issue":"7481","key":"539_CR17","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature12876","volume":"505","author":"F Ariey","year":"2014","unstructured":"Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505(7481):50\u20135.","journal-title":"Nature"},{"issue":"5","key":"539_CR18","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","volume":"371","author":"EA Ashley","year":"2014","unstructured":"Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371(5):411\u201323.","journal-title":"N Engl J Med"},{"issue":"6220","key":"539_CR19","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1126\/science.1260867","volume":"47","author":"J Straimer","year":"2015","unstructured":"Straimer J, Gn\u00e4dig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, et al. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science. 2015;47(6220):428-31. doi: 10.1126\/science.1260867 .","journal-title":"Science"},{"key":"539_CR20","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1128\/AAC.00366-15","volume":"59","author":"S Chaorattanakawee","year":"2015","unstructured":"Chaorattanakawee S, Saunders DL, Sea D, Chanarat N, Yingyuen K, Sundrakes S, et al. Ex vivo drug susceptibility and molecular profiling of clinical Plasmodium falciparum isolates from Cambodia in 2008-2013 suggest emerging piperaquine resistance. Antimicrob Agents Chemother. 2015;59:4631\u201343. doi: 10.1128\/AAC.00366-15 .","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"539_CR21","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1128\/AAC.00955-07","volume":"52","author":"J Tarning","year":"2008","unstructured":"Tarning J, Ashley EA, Lindegardh N, Stepniewska K, Phaiphun L, Day NP, et al. Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand. Antimicrob Agents Chemother. 2008;52(3):1052\u201361.","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"539_CR22","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1128\/AAC.02350-12","volume":"57","author":"CJ Woodrow","year":"2013","unstructured":"Woodrow CJ, Dahlstrom S, Cooksey R, Flegg JA, Le Nagard H, Mentre F, et al. High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool. Antimicrob Agents Chemother. 2013;57(7):3121\u201330.","journal-title":"Antimicrob Agents Chemother"},{"issue":"8","key":"539_CR23","doi-asserted-by":"crossref","first-page":"3908","DOI":"10.1128\/AAC.01793-10","volume":"55","author":"RT Eastman","year":"2011","unstructured":"Eastman RT, Dharia NV, Winzeler EA, Fidock DA. Piperaquine resistance is associated with a copy number variation on chromosome 5 in drug-pressured Plasmodium falciparum parasites. Antimicrob Agents Chemother. 2011;55(8):3908\u201316.","journal-title":"Antimicrob Agents Chemother"},{"key":"539_CR24","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1128\/AAC.05163-14","volume":"59","author":"P Lim","year":"2015","unstructured":"Lim P, Dek D, Try V, Sreng S, Suon S, Fairhurst RM. Decreasing pfmdr1 copy number suggests that Plasmodium falciparum in Western Cambodia is regaining in vitro susceptibility to mefloquine. Antimicrob Agents Chemother. 2015;59:2934\u20137.","journal-title":"Antimicrob Agents Chemother"},{"issue":"12","key":"539_CR25","doi-asserted-by":"crossref","first-page":"7390","DOI":"10.1128\/AAC.03337-14","volume":"58","author":"MI Veiga","year":"2014","unstructured":"Veiga MI, Osorio NS, Ferreira PE, Franzen O, Dahlstrom S, Lum JK, et al. Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response. Antimicrob Agents Chemother. 2014;58(12):7390\u20137.","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"539_CR26","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1086\/606009","volume":"200","author":"S Dahlstrom","year":"2009","unstructured":"Dahlstrom S, Ferreira PE, Veiga MI, Sedighi N, Wiklund L, Martensson A, et al. Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa. J Infect Dis. 2009;200(9):1456\u201364.","journal-title":"J Infect Dis"},{"issue":"11","key":"539_CR27","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1128\/AAC.00687-13","volume":"57","author":"P Lim","year":"2013","unstructured":"Lim P, Dek D, Try V, Eastman RT, Chy S, Sreng S, et al. Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in western, northern, and eastern Cambodia, 2011-2012: association with molecular markers. Antimicrob Agents Chemother. 2013;57(11):5277\u201383.","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"539_CR28","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ng.2624","volume":"45","author":"O Miotto","year":"2014","unstructured":"Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA, et al. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat Genet. 2014;45(6):648\u201355.","journal-title":"Nat Genet"},{"issue":"3","key":"539_CR29","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ng.3189","volume":"47","author":"O Miotto","year":"2015","unstructured":"Miotto O, Amato R, Ashley EA, MacInnis B, Almagro-Garcia J, Amaratunga C, et al. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet. 2015;47(3):226\u201334.","journal-title":"Nat Genet"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-015-0539-5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T22:18:02Z","timestamp":1498256282000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.biomedcentral.com\/1741-7015\/13\/305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["539"],"URL":"https:\/\/doi.org\/10.1186\/s12916-015-0539-5","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]},"article-number":"305"}}