A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.
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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
Аннотация
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.).