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A worldwide map of Plasmodium falciparum K13-propeller polymorphisms

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

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Official URL: http://edoc.unibas.ch/54241/

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Abstract

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.).
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Hetzel, Manuel W
Item Type:Article, refereed
Publisher:Massachusetts Medical Society
ISSN:1533-4406
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:20 Apr 2017 12:44
Deposited On:20 Apr 2017 12:44

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