{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T22:50:29Z","timestamp":1769727029522,"version":"3.49.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bill & Melinda Gates Foundation and Global Fund\/UNOPS","award":["#15SANIN211"],"award-info":[{"award-number":["#15SANIN211"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In early 2016, in Preah Vihear, Northern Cambodia, artesunate\/mefloquine was used to cope with dihydroartemisinin\/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged. However, the lack of a viable alternative led Cambodia to adopt artesunate\/mefloquine countrywide, raising concerns about a surge of triple-resistant P. falciparum strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To assess the prevalence of triple-resistant parasites after artesunate\/mefloquine implementation countrywide in Cambodia and to characterize their phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>For this multicentric study, 846 samples were collected from 2016 to 2019. Genotyping of molecular markers associated with artemisinin, piperaquine and mefloquine resistance was coupled with phenotypic analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Only four triple-resistant P. falciparum isolates (0.47%) were identified during the study period. These parasites combined the pfk13 polymorphism with pfmdr1 amplification, pfpm2 amplification and\/or pfcrt mutations. They showed significantly higher tolerance to artemisinin, piperaquine and mefloquine and also to the mefloquine and piperaquine combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The use of artesunate\/mefloquine countrywide in Cambodia has not led to a massive increase of triple-resistant P. falciparum parasites. However, these parasites circulate in the population, and exhibit clear resistance to piperaquine, mefloquine and their combination in vitro. This study demonstrates that P. falciparum can adapt to more complex drug associations, which should be considered in future therapeutic designs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac403","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T17:58:51Z","timestamp":1670867931000},"page":"411-417","source":"Crossref","is-referenced-by-count":5,"title":["Prevalence and characterization of piperaquine, mefloquine and artemisinin derivatives triple-resistant <i>Plasmodium falciparum<\/i> in Cambodia"],"prefix":"10.1093","volume":"78","author":[{"given":"M\u00e9lissa","family":"Mairet-Khedim","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3528, Unit\u00e9 de Microbiologie Structurale , F-75015 Paris , France"},{"name":"Institut Pasteur, Pasteur International Unit, Pasteur International Network, Malaria Translational Research Unit, Phnom Penh , Cambodia and Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5119-0655","authenticated-orcid":false,"given":"Camille","family":"Roesch","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Pasteur International Unit, Pasteur International Network, Malaria Translational Research Unit, Phnom Penh , Cambodia and Paris , France"},{"name":"Malaria Molecular Epidemiology Unit, Pasteur Institute of Cambodia , Phnom Penh , Cambodia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nimol","family":"Khim","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Pasteur International Unit, Pasteur International Network, Malaria Translational Research Unit, Phnom Penh , Cambodia and Paris , France"},{"name":"Malaria Molecular Epidemiology Unit, Pasteur Institute of Cambodia , Phnom Penh , 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