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Title: A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Authors: Frédéric Ariey
Benoit Witkowski
Chanaki Amaratunga
Johann Beghain
Anne Claire Langlois
Nimol Khim
Saorin Kim
Valentine Duru
Christiane Bouchier
Laurence Ma
Pharath Lim
Rithea Leang
Socheat Duong
Sokunthea Sreng
Seila Suon
Char Meng Chuor
Denis Mey Bout
Sandie Ménard
William O. Rogers
Blaise Genton
Thierry Fandeur
Olivo Miotto
Pascal Ringwald
Jacques Le Bras
Antoine Berry
Jean Christophe Barale
Rick M. Fairhurst
Françoise Benoit-Vical
Odile Mercereau-Puijalon
Didier Ménard
Institut Pasteur, Paris
CNRS Centre National de la Recherche Scientifique
Institut Pasteur du Cambodge
National Institute of Allergy and Infectious Diseases
National Center for Parasitology, Entomology and Malaria Control
CHU de Toulouse
Naval Medical Research Unit-2
Swiss Tropical and Public Health Institute (Swiss TPH)
University of Oxford
Mahidol University
Wellcome Trust Sanger Institute
Organisation Mondiale de la Sante
Hopital Bichat-Claude-Bernard AP-HP
Universite de Toulouse
Keywords: Multidisciplinary
Issue Date: 1-Jan-2014
Citation: Nature. Vol.505, No.7481 (2014), 50-55
Abstract: 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. © 2014 Macmillan Publishers Limited.
ISSN: 14764687
Appears in Collections:Scopus 2011-2015

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