{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:33:42Z","timestamp":1791347622885,"version":"4.3.1"},"reference-count":39,"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":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Western Cambodia is recognized as the epicenter of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            multidrug resistance. Recent reports of the efficacy of dihydroartemisinin (DHA)-piperaquine (PP), the latest of the artemisinin-based combination therapies (ACTs) recommended by the WHO, have prompted further investigations. The clinical efficacy of dihydroartemisinin-piperaquine in uncomplicated falciparum malaria was assessed in western and eastern Cambodia over 42 days. Day 7 plasma piperaquine concentrations were measured and day 0 isolates tested for\n            <jats:italic>in vitro<\/jats:italic>\n            susceptibilities to piperaquine and mefloquine, polymorphisms in the\n            <jats:italic>K13<\/jats:italic>\n            gene, and the copy number of the\n            <jats:italic>Pfmdr-1<\/jats:italic>\n            gene. A total of 425 patients were recruited in 2011 to 2013. The proportion of patients with recrudescent infections was significantly higher in western (15.4%) than in eastern (2.5%) Cambodia (\n            <jats:italic>P<\/jats:italic>\n            &lt;10\n            <jats:sup>\u22123<\/jats:sup>\n            ). Day 7 plasma PP concentrations and median 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            ) of PP were independent of treatment outcomes, in contrast to median mefloquine IC\n            <jats:sub>50<\/jats:sub>\n            , which were found to be lower for isolates from patients with recrudescent infections (18.7 versus 39.7 nM;\n            <jats:italic>P<\/jats:italic>\n            = 0.005). The most significant risk factor associated with DHA-PP treatment failure was infection by parasites carrying the\n            <jats:italic>K13<\/jats:italic>\n            mutant allele (odds ratio [OR], 17.5; 95% confidence interval [CI], 1 to 308;\n            <jats:italic>P<\/jats:italic>\n            = 0.04). Our data show evidence of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            resistance to PP in western Cambodia, an area of widespread artemisinin resistance. New therapeutic strategies, such as the use of triple ACTs, are urgently needed and must be tested. (This study has been registered at the Australian New Zealand Clinical Trials Registry under registration no. ACTRN12614000344695.)\n          <\/jats:p>","DOI":"10.1128\/aac.00835-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:24:53Z","timestamp":1432740293000},"page":"4719-4726","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":275,"title":["Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment"],"prefix":"10.1128","volume":"59","author":[{"given":"Rithea","family":"Leang","sequence":"first","affiliation":[{"name":"National Centre for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter R. J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"National Centre for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"},{"name":"Service de M\u00e9decine Tropicale et Humanitaire, H\u00f4pitaux Universitaires de Gen\u00e8ve, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis Mey","family":"Bouth","sequence":"additional","affiliation":[{"name":"National Centre for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"},{"name":"World Health Organization, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijiang","family":"Song","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand"},{"name":"Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-4030","authenticated-orcid":false,"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand"},{"name":"Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng Chuor","family":"Char","sequence":"additional","affiliation":[{"name":"National Centre for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saorin","family":"Kim","sequence":"additional","affiliation":[{"name":"Institut Pasteur du Cambodge, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Institut Pasteur du Cambodge, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Duru","sequence":"additional","affiliation":[{"name":"Institut Pasteur du Cambodge, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Domergue","sequence":"additional","affiliation":[{"name":"Institut Pasteur du Cambodge, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimol","family":"Khim","sequence":"additional","affiliation":[{"name":"Institut Pasteur du Cambodge, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Ringwald","sequence":"additional","affiliation":[{"name":"World Health Organization, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Menard","sequence":"additional","affiliation":[{"name":"Institut Pasteur du Cambodge, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.4269\/ajtmh.1986.35.246","article-title":"Treatment of falciparum malaria with quinine and tetracycline or combined mefloquine\/sulfadoxine\/pyrimethamine on the Thai-Kampuchean border","volume":"35","author":"Meek SR","year":"1986","unstructured":"Meek SR, Doberstyn EB, Gauzere BA, Thanapanich C, Nordlander E, Phuphaisan S. 1986. Treatment of falciparum malaria with quinine and tetracycline or combined mefloquine\/sulfadoxine\/pyrimethamine on the Thai-Kampuchean border. Am J Trop Med Hyg 35:246\u2013250.","journal-title":"Am J Trop Med Hyg"},{"key":"e_1_3_3_3_2","first-page":"172","article-title":"Drug-resistance in falciparum malaria in South-East Asia","volume":"18","author":"Sandosham AA","year":"1964","unstructured":"Sandosham AA, Eyles DE, Montgomery R. 1964. Drug-resistance in falciparum malaria in South-East Asia. Med J Malaysia 18:172\u2013183.","journal-title":"Med J Malaysia"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000830"},{"key":"e_1_3_3_5_2","volume-title":"Global report on antimalarial drug efficacy and drug resistance (2000\u20132010)","author":"WHO","year":"2010","unstructured":"WHO. 2010. Global report on antimalarial drug efficacy and drug resistance (2000\u20132010). World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2006.01739.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2006.01690.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2004.09.002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0805011"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70181-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12876"},{"key":"e_1_3_3_13_2","first-page":"281","article-title":"Field observations on the antimalarial piperaquine","volume":"95","author":"Chen L","year":"1982","unstructured":"Chen L, Qu FY, Zhou YC. 1982. Field observations on the antimalarial piperaquine. Chin Med J 95:281\u2013286.","journal-title":"Chin Med J"},{"key":"e_1_3_3_14_2","first-page":"602","article-title":"Randomised comparison on the treatment of falciparum malaria with dihydroartemisinin and piperaquine","volume":"73","author":"Guo XB","year":"1993","unstructured":"Guo XB. 1993. Randomised comparison on the treatment of falciparum malaria with dihydroartemisinin and piperaquine. Zhonghua Yi Xue Za Zhi 73:602\u2013604. (In Chinese.).","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"e_1_3_3_15_2","first-page":"163","article-title":"In vivo sensitivity of Plasmodium falciparum to piperaquine phosphate assayed in Linshui and Baisha counties, Hainan Province","volume":"7","author":"Lan CX","year":"1989","unstructured":"Lan CX, Lin X, Huang ZS, Chen YS, Guo RN. 1989. In vivo sensitivity of Plasmodium falciparum to piperaquine phosphate assayed in Linshui and Baisha counties, Hainan Province. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 7:163\u2013165. (In Chinese.)","journal-title":"Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/344647"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2006.01786.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-233"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0584-8"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02746-14"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-153"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006358"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00686-12"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00687-13"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1403007"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70049-6"},{"key":"e_1_3_3_27_2","volume-title":"Methods for surveillance of antimalarial drug efficacy","author":"WHO","year":"2009","unstructured":"WHO. 2009. Methods for surveillance of antimalarial drug efficacy. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00486-07"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(98)01340-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2005.03.031"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-010-0804-7"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2008.01.006"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.254"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2008.79.620"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.6.2407-2411.2005"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05163-14"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06350-11"},{"key":"e_1_3_3_39_2","first-page":"201","article-title":"Monitoring antimalarial drug efficacy in the Greater Mekong Subregion: an overview of in vivo results from 2008 to 2010","volume":"44","author":"Bustos MD","year":"2013","unstructured":"Bustos MD, Wongsrichanalai C, Delacollette C, Burkholder B. 2013. Monitoring antimalarial drug efficacy in the Greater Mekong Subregion: an overview of in vivo results from 2008 to 2010. Southeast Asian J Trop Med Public Health 44(Suppl 1):201\u2013230.","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"e_1_3_3_40_2","first-page":"372","article-title":"Therapeutic efficacy and safety of compound dihydroartemisinin\/piperaquine for uncomplicated Plasmodium falciparum infection in Laiza City of Myanmar bordering on China","volume":"29","author":"Sun XD","year":"2011","unstructured":"Sun XD, Zhang ZX, Wang J, Deng Y, Yang YC, Lasi JH, Sun XY, Wang H. 2011. Therapeutic efficacy and safety of compound dihydroartemisinin\/piperaquine for uncomplicated Plasmodium falciparum infection in Laiza City of Myanmar bordering on China. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 29:372\u2013375. (In Chinese.)","journal-title":"Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00835-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00835-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T23:05:06Z","timestamp":1645484706000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00835-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1128\/AAC.00835-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.00835-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8]]},"assertion":[{"value":"2015-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}