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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.

Original publication

DOI

10.1038/nature12876

Type

Journal article

Journal

Nature

Publication Date

02/01/2014

Volume

505

Pages

50 - 55

Keywords

Alleles, Animals, Antimalarials, Artemisinins, Blood Cells, Cambodia, Drug Resistance, Genetic Markers, Half-Life, Humans, Malaria, Falciparum, Mutation, Parasitic Sensitivity Tests, Plasmodium falciparum, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Protozoan Proteins, Time Factors