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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
Nature, Volume 505, No. 7481, Year 2014
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Description
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.
Authors & Co-Authors
Ariey, Frédéric
France, Paris
Institut Pasteur, Paris
France, Paris
Cnrs Centre National de la Recherche Scientifique
Witkowski, Benoît
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Amaratunga, Chanaki
United States, Bethesda
National Institutes of Health Nih
Beghain, Johann
France, Paris
Institut Pasteur, Paris
France, Paris
Cnrs Centre National de la Recherche Scientifique
Khim, Nimol
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Kim, Saorin
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Duru, Valentine
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Bouchier, Christiane
France, Paris
Institut Pasteur, Paris
Ma, Laurence
France, Paris
Institut Pasteur, Paris
Lim, Pharath
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
United States, Bethesda
National Institutes of Health Nih
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Leang, Rithea
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Socheat, Duong
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Sreng, Sokunthea
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Suon, Seila
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Chuor, Char Meng
Cambodia, Phnom Penh
National Center for Parasitology, Entomology and Malaria Control
Ménard, Sandie
France, Toulouse
Chu de Toulouse
France, Toulouse
Institut Toulousain Des Maladies Infectieuses et Inflammatoires Infinity
Rogers, William Oscar
Cambodia, Phnom Penh
Naval Medical Research Unit-2
Genton, Blaise
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Fandeur, Thierry
France, Paris
Institut Pasteur, Paris
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Miotto, Olivo
Thailand, Bangkok
Mahidol Oxford Tropical Medicine Research Unit
United Kingdom, Hinxton
Wellcome Sanger Institute
Ringwald, Pascal
Switzerland, Geneva
Organisation Mondiale de la Santé
Le Bras, Jacques L.
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Berry, Antoine
France, Toulouse
Chu de Toulouse
France, Toulouse
Institut Toulousain Des Maladies Infectieuses et Inflammatoires Infinity
Barale, Jean Christophe
France, Paris
Institut Pasteur, Paris
France, Paris
Cnrs Centre National de la Recherche Scientifique
Fairhurst, Rick M.
United States, Bethesda
National Institutes of Health Nih
Benoit-Vical, Françoise
France, Toulouse
Lcc Laboratoire de Chimie de Coordination
France, Toulouse
Université Fédérale Toulouse Midi-pyrénées
Mercereau-Puijalon, Odile
France, Paris
Institut Pasteur, Paris
France, Paris
Cnrs Centre National de la Recherche Scientifique
Menard, Didier
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Statistics
Citations: 1,389
Authors: 28
Affiliations: 15
Identifiers
Doi:
10.1038/nature12876
ISSN:
14764687
Research Areas
Genetics And Genomics
Infectious Diseases