Browsing by Author "Laurence Ma"

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    A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
    (2014-01-01) 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
    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.