A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.
Ariey F., Witkowski B., Amaratunga C., Beghain J., Langlois A-C., Khim N., Kim S., Duru V., Bouchier C., Ma L., Lim P., Leang R., Duong S., Sreng S., Suon S., Chuor CM., Bout DM., Ménard S., Rogers WO., Genton B., Fandeur T., Miotto O., Ringwald P., Le Bras J., Berry A., Barale J-C., Fairhurst RM., Benoit-Vical F., Mercereau-Puijalon O., Ménard D.
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.