A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

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

doi:10.1056/NEJMoa1513137

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A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

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A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

Didier Ménard, Nimol Khim, Johann Beghain, Ayola A Adegnika, Mohammad Shafiul-Alam, Olukemi Amodu, Ghulam Rahim-Awab, Céline Barnadas, Antoine Berry, Yap Boum, …

New England Journal of Medicine, Vol.374(25), pp.2453-64

23/06/2016

DOI: https://doi.org/10.1056/NEJMoa1513137

PMCID: PMC4955562

PMID: 27332904

Abstract

Algorithms

Artemisinins

Drug Resistance

Endemic Diseases

Genotype

Humans

Lactones

Malaria, Falciparum

Mutation

Plasmodium falciparum

Polymorphism, Genetic

Protozoan Proteins

Sequence Analysis, DNA

Asia, Southeastern

China

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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Title: A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.
Creators - without role: Didier Ménard - Institut Pasteur du Cambodge
Nimol Khim - Institut Pasteur du Cambodge
Johann Beghain - Génétique et Génomique des Insectes vecteurs
Ayola A Adegnika - University of Tübingen
Mohammad Shafiul-Alam - International Centre for Diarrhoeal Disease Research
Olukemi Amodu - University of Ibadan
Ghulam Rahim-Awab - Nangarhar University
Céline Barnadas - Walter and Eliza Hall Institute of Medical Research
Antoine Berry - Centre Hospitalier Universitaire de Toulouse
Yap Boum - Mbarara University of Science and Technology
Maria D Bustos - World Health Organization (WHO), country office for Thailand
Jun Cao - Jiangsu University
Jun-Hu Chen - National Institute of Parasitic Diseases
Louis Collet - Centre Hospitalier de Mayotte
Liwang Cui - Pennsylvania State University
Garib-Das Thakur - Epidemiology and Disease Control division
Alioune Dieye - Institut Pasteur de Dakar
Djibrine Djallé - Institut Pasteur de Bangui
Monique A Dorkenoo - Université de Lomé [Togo]
Carole E Eboumbou-Moukoko - Centre Pasteur du Cameroun
Fe-Esperanza-Caridad J Espino - Research Institute for Tropical Medicine
Thierry Fandeur - Centre International de Recherches Médicales de Franceville
Maria-Fatima Ferreira-Da-Cruz - Fundação Oswaldo Cruz
Abebe A Fola - University of Gondar
Hans-Peter Fuehrer - Institute of Parasitology [Vienna]
Abdillahi M Hassan - World Health Organisation (WHO), country office for Somalia
Socrates Herrera - Caucaseco Scientific Research Center
Bouasy Hongvanthong - National Center for Malariology, Parasitology and Entomology
Sandrine Houzé - Hôpital Bichat-Claude-Bernard
Maman L Ibrahim - Centre de Recherche Médicale et Sanitaire
Mohammad Jahirul-Karim - Directorate General of Health Services
Lubin Jiang - Institut Pasteur
Shigeyuki Kano - Institut Pasteur du Laos
Wasif Ali-Khan - International Centre for Diarrhoeal Disease Research
Maniphone Khanthavong - National Center for Malariology, Parasitology and Entomology
Peter G Kremsner - University of Tübingen
Marcus Lacerda - Fundação de Medicina Tropical
Rithea Leang - National Center for Malaria Control, Parasitology and Entomology
Mindy Leelawong - Henry M. Jackson Foundation
Mei Li - National Institute of Parasitic Diseases
Khin Lin - The Department of Medical Research (Upper Myanmar)
Jean-Baptiste Mazarati - Rwanda Biomedical Center
Sandie Ménard - Centre de Physiopathologie Toulouse Purpan
Isabelle Morlais - Université de Montpellier, Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Hypolite Muhindo-Mavoko - University of Kinshasa
Lise Musset - Institut Pasteur de la Guyane
Kesara Na-Bangchang - Thammasat University
Michael Nambozi - Tropical Diseases Research Center
Karamoko Niaré - Université de Bamako
Harald Noedl - Medical University of Vienna
Jean-Bosco Ouédraogo - Centre Muraz
Dylan R Pillai - Medicines for Malaria Venture
Bruno Pradines - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
Bui Quang-Phuc - National Center for Malariology, Parasitology and Entomology
Michael Ramharter - Medical University of Vienna
Milijaona Randrianarivelojosia - Institut Pasteur de Madagascar
Jetsumon Sattabongkot - Mahidol University
Abdiqani Sheikh-Omar - Ministry of Health and Human Services [Somalia]
Kigbafori D Silué - Université Félix Houphouët-Boigny
Sodiomon B Sirima - Groupe de recherche action en santé
Colin Sutherland - London School of Hygiene and Tropical Medicine
Din Syafruddin - Hasanuddin University
Rachida Tahar - Mère et Enfant en Milieu Tropical
Lin-Hua Tang - National Institute of Parasitic Diseases
Offianan A Touré - Institut Pasteur de Côte d'Ivoire
Patrick Tshibangu-Wa-Tshibangu - University of Kinshasa
Inès Vigan-Womas - Institut Pasteur de Madagascar
Marian Warsame - Global Malaria Programme
Lyndes Wini - Ministry of Health and Medical Services
Sedigheh Zakeri - Institut Pasteur
Saorin Kim - Institut Pasteur du Cambodge
Rotha Eam - Institut Pasteur du Cambodge
Laura Berne - Institut Pasteur du Cambodge
Chanra Khean - Institut Pasteur du Cambodge
Sophy Chy - Institut Pasteur du Cambodge
Malen Ken - Institut Pasteur du Cambodge
Kaknika Loch - Institut Pasteur du Cambodge
Lydie Canier - Institut Pasteur du Cambodge
Valentine Duru - Institut Pasteur du Cambodge
Eric Legrand - Institut Pasteur de la Guyane
Benoît Witkowski - Microbiologie structurale - Structural Microbiology
Barbara Stokes - Columbia University Irving Medical Center
Judith Straimer - Columbia University Irving Medical Center
Benoit Witkowski - Institut Pasteur du Cambodge
David A Fidock - Columbia University Irving Medical Center
Christophe Rogier - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
Pascal Ringwald - Global Malaria Programme
Frederic Ariey - Assistance Publique – Hôpitaux de Paris
Odile Mercereau-Puijalon - Génétique et Génomique des Insectes vecteurs
Publication Details: New England Journal of Medicine, Vol.374(25), pp.2453-64
Grant note: Supported by the Institut Pasteur Paris, Institut Pasteur International Division, Institut Pasteur Cambodia, and the World Health Organization; by a grant (ANR-10-LABX-62-IBEID) from the French Government Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases”; a grant from Natixis Banques; a grant (R01I109023, to Dr. Fidock) from the National Institutes of Health; grants from the Fiocruz Fundação Oswaldo Cruz, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Fundação de Amparo à Pesquisa do Estado do Amazonas, the Brazilian National Council for Scientific and Technological Development, the Agence Nationale de la Recherche (13-BSV3-0018-01 and11-BSV7-009-01), the Austrian Federal Ministry of Science, Research, and Econo-my, the Calgary Laboratory Services, the Centre International de Recherches Médicales de Franceville, the European and Developing Countries Clinical Trials Partnership (CT-2004-31070-001), the Drugs for Neglected Diseases Initiative, the Else Kroener Fresenius Stiftung, the Holger Poehlmann Stiftung, the European Community African–European Research Initiative “IDEA” (HEALTH-F3-2009-241642), the Fonds Wetenschappelijk Onderzoek, the Vlaamse Interuniversitaire Raad–Universitaire Ontwikkelingssamenwerking, the Belgian Technical Cooperation in Democratic Republic of Congo, the European Community Seventh Framework Program (FP7/2007-2013, 242095, and 223601), the European Commission (REGPOT-CT-2011-285837-STRONGER), the Ministère de la Santé Publique du Niger (Laboratoire National de Référence Résistance aux Antipaludiques), the Foundation of National Science and Technology Major Program (2012ZX10004-220), the French Ministry of Health (Institut National de Veille Sanitaire), the Global Fund to Fight AIDS, Tuberculosis and Malaria, the 5% Initiative program (French Ministry of Foreign Affairs, France Expertise Internationale, 12INI109), the Institut Pasteur de Madagascar, the Government of the Philippines, the Institut de Recherche pour le Développement, the Foundation des Treilles, the Délégation Générale pour l’Armement (PDH-2-NRBC-4-B1-402), the Institut Pasteur de Bangui, the International Society for Health Research and Training, the Malaria Research Initiative Bandarban, Vienna, International Centre for Diarrhoeal Disease Research, Bangladesh, the Médecins sans Frontières (Centre Opérationnel Paris, France), Medicines for Malaria Venture, the National Research Council of Thailand, the Thammasat University, the National Natural Science Foundation of China (81271870, 81361120405, and 81271863), the Natural Science Foundation of Jiangsu Province (BK20130114 and BK20150001), the Jiangsu Science and Technology Department (BM2015024), the National Institutes of Health (R01 AI11646601, AI109023, and ICEMR U19AI089702, U19AI089672), the Pasteur Institute of Iran, the Malaria Division of the Iranian Center for Diseases Management and Control, Public Health England (Malaria Reference Service Contract), the Government of Rwanda, the U.S. Department of Defense Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (P0463-14-N6), the Fogarty International Center of the National Institutes of Health training (D43 TW007393), the Mahidol-Oxford Research Unit, the Government of Japan (Science and Technology Agency, Agency for Medical Research and Development, Japan International Cooperation Agency, and Science and Technology Research Partnership for Sustainable Development), and the President’s Malaria Initiative of the U.S. Agency for International Development.
Identifiers: 9934762009311
Academic Unit: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Language: English
Resource Type: Journal article
Local Fields: pasteur-01336483