A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

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 () and Didier Ménard ()
Additional contact information
Frédéric Ariey: Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France
Benoit Witkowski: Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia
Chanaki Amaratunga: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Johann Beghain: Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France
Anne-Claire Langlois: Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France
Nimol Khim: Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia
Saorin Kim: Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia
Valentine Duru: Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia
Christiane Bouchier: Institut Pasteur, Plate-forme Génomique, 75724 Paris Cedex 15, France
Laurence Ma: Institut Pasteur, Plate-forme Génomique, 75724 Paris Cedex 15, France
Pharath Lim: Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia
Rithea Leang: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
Socheat Duong: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
Sokunthea Sreng: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
Seila Suon: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
Char Meng Chuor: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
Denis Mey Bout: SSA WHO, Drug Monitoring in Cambodia, National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia
Sandie Ménard: Service de Parasitologie et Mycologie, Centre Hospitalier Universitaire de Toulouse, 31059 Toulouse Cedex 9, France
William O. Rogers: Naval Medical Research Unit #2 Detachment, Phnom Penh, Cambodia
Blaise Genton: Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland
Thierry Fandeur: Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France
Olivo Miotto: MRC Centre for Genomics and Global Health, University of Oxford, Oxford OX3 7BN, UK
Pascal Ringwald: Global Malaria Program, World Health Organization, 1211 Geneva, Switzerland
Jacques Le Bras: Centre National de Référence du Paludisme, CHU Bichat-Claude Bernard, APHP, PRES Sorbonne Paris Cité, 75018 Paris, France
Antoine Berry: Service de Parasitologie et Mycologie, Centre Hospitalier Universitaire de Toulouse, 31059 Toulouse Cedex 9, France
Jean-Christophe Barale: Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France
Rick M. Fairhurst: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Françoise Benoit-Vical: Centre National de la Recherche Scientifique, Laboratoire de Chimie de Coordination UPR8241, 31077 Toulouse Cedex 4, France
Odile Mercereau-Puijalon: Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France
Didier Ménard: Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia

Nature, 2014, vol. 505, issue 7481, 50-55

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/nature12876 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:505:y:2014:i:7481:d:10.1038_nature12876

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature12876

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().