A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. - Institut Pasteur Access content directly
Journal Articles New England Journal of Medicine Year : 2016

A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

Didier Ménard (1) , Nimol Khim (1) , Johann Beghain (2) , Ayola A Adegnika (3, 4, 5) , Mohammad Shafiul-Alam (6) , Olukemi Amodu (7) , Ghulam Rahim-Awab (8, 9) , Céline Barnadas (10, 11, 12) , Antoine Berry (13) , Yap Boum (14, 15) , Maria D Bustos (16) , Jun Cao (17) , Jun-Hu Chen (18) , Louis Collet (19) , Liwang Cui (20) , Garib-Das Thakur (21) , Alioune Dieye (22, 23) , Djibrine Djallé (24) , Monique A Dorkenoo (25) , Carole E Eboumbou-Moukoko (26, 27) , Fe-Esperanza-Caridad J Espino (28) , Thierry Fandeur (29) , Maria-Fatima Ferreira-Da-Cruz (30) , Abebe A Fola (31, 10) , Hans-Peter Fuehrer (32) , Abdillahi M Hassan (33) , Socrates Herrera (34) , Bouasy Hongvanthong (35) , Sandrine Houzé (36, 37) , Maman L Ibrahim (38) , Mohammad Jahirul-Karim (39) , Lubin Jiang (40) , Shigeyuki Kano (41, 42) , Wasif Ali-Khan (6) , Maniphone Khanthavong (35) , Peter G Kremsner (3, 4) , Marcus Lacerda (43, 44) , Rithea Leang (45) , Mindy Leelawong (46, 47) , Mei Li (18) , Khin Lin (48) , Jean-Baptiste Mazarati (49) , Sandie Ménard (50) , Isabelle Morlais (51) , Hypolite Muhindo-Mavoko (52, 53) , Lise Musset (54) , Kesara Na-Bangchang (55) , Michael Nambozi (56) , Karamoko Niaré (57) , Harald Noedl (58) , Jean-Bosco Ouédraogo (59) , Dylan R Pillai (60, 61) , Bruno Pradines (62, 63) , Bui Quang-Phuc (35) , Michael Ramharter (58, 4, 5) , Milijaona Randrianarivelojosia (64) , Jetsumon Sattabongkot (9) , Abdiqani Sheikh-Omar (65) , Kigbafori D Silué (66, 67) , Sodiomon B Sirima (68) , Colin Sutherland (69) , Din Syafruddin (70, 71) , Rachida Tahar (37) , Lin-Hua Tang (18) , Offianan A Touré (72) , Patrick Tshibangu-Wa-Tshibangu (52) , Inès Vigan-Womas (64) , Marian Warsame (61) , Lyndes Wini (73) , Sedigheh Zakeri (74) , Saorin Kim (1) , Rotha Eam (1) , Laura Berne (1) , Chanra Khean (1) , Sophy Chy (1) , Malen Ken (1) , Kaknika Loch (1) , Lydie Canier (1) , Valentine Duru (1) , Eric Legrand (2, 54, 75) , Benoît Witkowski (76) , Barbara Stokes (77) , Judith Straimer (77) , Benoit Witkowski (1) , David A Fidock (77) , Christophe Rogier (62, 64, 78) , Pascal Ringwald (61) , Frederic Ariey (79, 80, 2) , Odile Mercereau-Puijalon (2)
1 Institut Pasteur du Cambodge
2 Génétique et Génomique des Insectes vecteurs
3 Eberhard Karls Universität Tübingen = University of Tübingen
4 Centre de Recherche Médicale de Lambaréné, Albert Schweitzer
5 LUMC - Leiden University Medical Center
6 ICDDR,B - International Centre for Diarrhoeal Disease Research, Bangladesh
7 University of Ibadan
8 Nangarhar University
9 Mahidol University [Bangkok]
10 WEHI - The Walter and Eliza Hall Institute of Medical Research
11 University of Melbourne
12 PNGIMR - Papua New Guinea Institute for Medical Research
13 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
14 MUST - Mbarara University of Science and Technology [Mbarara]
15 Epicentre Ouganda [Mbarara] [Médecins Sans Frontières]
16 World Health Organization (WHO), country office for Thailand
17 JiangSu University
18 National Institute of Parasitic Diseases
19 Centre Hospitalier de Mayotte
20 Penn State - Pennsylvania State University
21 EDCD - Epidemiology and Disease Control division
22 Institut Pasteur de Dakar
23 UCAD - Université Cheikh Anta Diop de Dakar [Sénégal]
24 Institut Pasteur de Bangui
25 Université de Lomé [Togo]
26 Université de Douala
27 Centre Pasteur du Cameroun
28 Research Institute for Tropical Medicine
29 CIRMF - Centre International de Recherches Médicales de Franceville
30 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
31 University of Gondar
32 Institute of Parasitology [Vienna]
33 World Health Organisation (WHO), country office for Somalia
34 Caucaseco scientific research center = Centro de Investigación Científica Caucaseco
35 National Center for Malariology, Parasitology and Entomology
36 Hôpital Bichat - Claude Bernard
37 MERIT - UMR_D 216 - Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique
38 CERMES - Centre de Recherche Médicale et Sanitaire (Niamey, Niger)
39 DGHS - Directorate General of Health Services
40 IPS-CAS - Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences
41 NCGM - National Center for Global Health and Medicine [Japan]
42 Institut Pasteur du Laos
43 ILMD - Instituto Leônidas e Maria Deane - Fiocruz Amazônia [Manaus, Brésil]
44 FMT-HVD - Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
45 National Center for Malaria Control, Parasitology and Entomology
46 HJM - Henry M. Jackson Foundation for the Advancement of Military Medicine
47 U.S. Naval Medical Research
48 The Department of Medical Research (Upper Myanmar)
49 RBC - Rwanda Biomedical Center
50 CPTP - Centre de Physiopathologie Toulouse Purpan
51 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
52 UNIKIN - University of Kinshasa
53 UA - University of Antwerp
54 Institut Pasteur de la Guyane
55 TU - Thammasat University
56 TDRC - Tropical Diseases Research Center
57 Université de Bamako
58 Medizinische Universität Wien = Medical University of Vienna
59 Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz
60 MMV - Medicines for Malaria Venture
61 Global Malaria Programme
62 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
63 Centre National de Référence du Paludisme
64 Institut Pasteur de Madagascar
65 Ministry of Health and Human Services [Somalia]
66 CSRS-CI - Centre Suisse de Recherches Scientifiques en Cote d'Ivoire [Abidjan]
67 UFHB - Université Félix Houphouët-Boigny
68 GRAS - Groupe de recherche action en santé
69 LSHTM - London School of Hygiene and Tropical Medicine
70 University of Hasanuddin
71 Eijkman Institute for Molecular Biology [Jakarta]
72 Institut Pasteur de Côte d'Ivoire
73 Ministry of Health and Medical Services
74 Institut Pasteur d'Iran
75 CNR - laboratoire associé - Centre National de Référence du Paludisme [Cayenne, Guyane française]
76 Microb. Struc. (UMR_3528 / U-Pasteur_5) - Microbiologie structurale - Structural Microbiology
77 CUIMC - Columbia University Irving Medical Center
78 IRBA - Institut de Recherche Biomédicale des Armées [Antenne Marseille]
79 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
80 UPD5 - Université Paris Descartes - Paris 5
Didier Ménard
Nimol Khim
  • Function : Author
  • PersonId : 764211
  • IdRef : 184142334
Jun Cao
  • Function : Author
Lise Musset
Inès Vigan-Womas
Benoit Witkowski
  • Function : Author
  • PersonId : 751218
  • IdHAL : bwitkowski

Abstract

BACKGROUND: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.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.).

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Parasitology
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pasteur-01336483 , version 1 (29-12-2023)

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Didier Ménard, Nimol Khim, Johann Beghain, Ayola A Adegnika, Mohammad Shafiul-Alam, et al.. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.. New England Journal of Medicine, 2016, 374 (25), pp.2453-64. ⟨10.1056/NEJMoa1513137⟩. ⟨pasteur-01336483⟩
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