A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.

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Ariey, Frédéric | Witkowski, Benoit | Amaratunga, Chanaki | Beghain, Johann | Langlois, Anne-Claire | Khim, Nimol | Kim, Saorin | Duru, Valentine | Bouchier, Christiane | Ma, Laurence | Lim, Pharath | Leang, Rithea | Duong, Socheat | Sreng, Sokunthea | Suon, Seila | Chuor, Char Meng | Bout, Denis Mey | Ménard, Sandie | Rogers, William O | Genton, Blaise | Fandeur, Thierry | Miotto, Olivo | Ringwald, Pascal | Le Bras, Jacques | Berry, Antoine | Witkowski, Benoît | Fairhurst, Rick M | Benoit-Vical, Françoise | Mercereau-Puijalon, Odile | Ménard, Didier

Edité par CCSD ; Nature Publishing Group -

International audience. Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

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