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A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

Ariey, Frédéric and Witkowski, Benoit and Amaratunga, Chanaki and Beghain, Johann and Langlois, Anne-Claire and Khim, Nimol and Kim, Saorin and Duru, Valentine and Bouchier, Christiane and Ma, Laurence and Lim, Pharath and Leang, Rithea and Duong, Socheat and Sreng, Sokunthea and Suon, Seila and Chuor, Char Meng and Bout, Denis Mey and Ménard, Sandie and Rogers, William O. and Genton, Blaise and Fandeur, Thierry and Miotto, Olivo and Ringwald, Pascal and Le Bras, Jacques and Berry, Antoine and Barale, Jean-Christophe and Fairhurst, Rick M. and Benoit-Vical, Françoise and Mercereau-Puijalon, Odile and Ménard, Didier. (2014) A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature, Vol. 505, H. 7481. pp. 50-55.

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Official URL: http://edoc.unibas.ch/dok/A6223637

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Clinical Epidemiology (Genton)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Genton, Blaise
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Macmillan
ISSN:0028-0836
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Jan 2016 07:59
Deposited On:18 Jul 2014 09:10

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