Journal
NATURE
Volume 505, Issue 7481, Pages 50-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12876
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Funding
- Global Fund Grant Malaria Program [CAM-607-G10M-CNM3, CAM-S10-G14-M]
- Bill and Melinda Gates Foundation
- USAID (through the World Health Organization)
- US DOD Global Epidemic Information System
- Intramural Research Program, NIAID, NIH
- Banque Natixis
- Laboratoire d'Excellence IBEID (Agence Nationale de la Recherche, France)
- Institut Pasteur, Division International [ACIP A-10-2010]
- Institut Pasteur, Division International
- French Ministry of Foreign Affairs
- Wellcome Trust [098051, 090770/Z/09/Z]
- MRC [G0600718]
- Rotary Club-Versailles
- Medical Research Council [G0600718] Funding Source: researchfish
- MRC [G0600718] Funding Source: UKRI
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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.
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