A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

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. A molecular marker is required to monitor artemisinin-resistant Plasmodium falciparum parasites in southeast Asia; here mutations in K13-propeller are associated with artemisinin resistance in vitro and in vivo and also cluster in Cambodian provinces where resistance is prevalent. A marker for artemisinin-resistant malaria The spread of resistance to artemisinin in isolates of the malaria pathogen Plasmodium falciparum in southeast Asia threatens to undermine efforts to eliminate the disease around the world. The important task of monitoring resistance has been hampered by the lack of a molecular marker. Frédéric Ariey and colleagues have now identified a major determinant of P. falciparum artemisinin resistance that could provide such a marker. They show that mutations in the PF3D7_1343700 kelch propeller domain (K-13 propeller) of the parasite were linked to the recent spread of resistance. Comparison with samples collected between 2001 and 2012 shows that the marker has increased in frequency in line with the spread of resistance. As well as suggesting a useful marker, these findings could further understanding of how resistance develops, and suggest ways of circumventing resistance in the search for novel antimalarials.