A worldwide map of Plasmodium falciparum K13-propeller polymorphisms
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 3747091
Author(s) Ménard, Didier; Khim, Nimol; Beghain, Johann; Adegnika, Ayola A.; Shafiul-Alam, Mohammad; Amodu, Olukemi; Rahim-Awab, Ghulam; Barnadas, Céline; Berry, Antoine; Boum, Yap; Bustos, Maria D.; Cao, Jun; Chen, Jun-Hu; Collet, Louis; Cui, Liwang; Thakur, Garib-Das; Dieye, Alioune; Djallé, Djibrine; Dorkenoo, Monique A.; Eboumbou-Moukoko, Carole E.; Espino, Fe-Esperanza-Caridad J.; Fandeur, Thierry; Ferreira-da-Cruz, Maria-Fatima; Fola, Abebe A.; Fuehrer, Hans-Peter; Hassan, Abdillahi M.; Herrera, Socrates; Hongvanthong, Bouasy; Houzé, Sandrine; Ibrahim, Maman L.; Jahirul-Karim, Mohammad; Jiang, Lubin; Kano, Shigeyuki; Ali-Khan, Wasif; Khanthavong, Maniphone; Kremsner, Peter G.; Lacerda, Marcus; Leang, Rithea; Leelawong, Mindy; Li, Mei; Lin, Khin; Mazarati, Jean-Baptiste; Ménard, Sandie; Morlais, Isabelle; Muhindo-Mavoko, Hypolite; Musset, Lise; Na-Bangchang, Kesara; Nambozi, Michael; Niaré, Karamoko; Noedl, Harald; Ouédraogo, Jean-Bosco; Pillai, Dylan R.; Pradines, Bruno; Quang-Phuc, Bui; Ramharter, Michael; Randrianarivelojosia, Milijaona; Sattabongkot, Jetsumon; Sheikh-Omar, Abdiqani; Silué, Kigbafori D.; Sirima, Sodiomon B.; Sutherland, Colin; Syafruddin, Din; Tahar, Rachida; Tang, Lin-Hua; Touré, Offianan A.; Tshibangu-wa-Tshibangu, Patrick; Vigan-Womas, Inès; Warsame, Marian; Wini, Lyndes; Zakeri, Sedigheh; Kim, Saorin; Eam, Rotha; Berne, Laura; Khean, Chanra; Chy, Sophy; Ken, Malen; Loch, Kaknika; Canier, Lydie; Duru, Valentine; Legrand, Eric; Barale, Jean-Christophe; Stokes, Barbara; Straimer, Judith; Witkowski, Benoit; Fidock, David A.; Rogier, Christophe; Ringwald, Pascal; Ariey, Frederic; Mercereau-Puijalon, Odile; Karma Consortium,
Author(s) at UniBasel Hetzel, Manuel
Year 2016
Title A worldwide map of Plasmodium falciparum K13-propeller polymorphisms
Journal The New England journal of medicine
Volume 374
Number 25
Pages / Article-Number 2453-2464

Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.; We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.; We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.; No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

Publisher Massachusetts Medical Society
ISSN/ISBN 1533-4406
edoc-URL http://edoc.unibas.ch/54241/
Full Text on edoc No
Digital Object Identifier DOI 10.1056/NEJMoa1513137
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/27332904
ISI-Number WOS:000378271700009
Document type (ISI) Article

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