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Title: Genomic epidemiology of artemisinin resistant malaria
Authors: Roberto Amato
Olivo Miotto
Charles J. Woodrow
Jacob Almagro-Garcia
Ipsita Sinha
Susana Campino
Daniel Mead
Eleanor Drury
Mihir Kekre
Mandy Sanders
Alfred Amambua-Ngwa
Chanaki Amaratunga
Lucas Amenga-Etego
Voahangy Andrianaranjaka
Tobias Apinjoh
Elizabeth Ashley
Sarah Auburn
Gordon A. Awandare
Vito Baraka
Alyssa Barry
Maciej F. Boni
Steffen Borrmann
Teun Bousema
Oralee Branch
Peter C. Bull
Kesinee Chotivanich
David J. Conway
Alister Craig
Nicholas P. Day
Abdoulaye Djimdé
Christiane Dolecek
Arjen M. Dondorp
Chris Drakeley
Patrick Duffy
Diego F. Echeverry
Thomas G. Egwang
Rick M. Fairhurst
Abul Faiz
Caterina I. Fanello
Tran Tinh Hien
Abraham Hodgson
Mallika Imwong
Deus Ishengoma
Pharath Lim
Chanthap Lon
Jutta Marfurt
Kevin Marsh
Mayfong Mayxay
Pascal Michon
Victor Mobegi
Olugbenga A. Mokuolu
Jacqui Montgomery
Ivo Mueller
Myat Phone Kyaw
Paul N. Newton
Francois Nosten
Rintis Noviyanti
Alexis Nzila
Harold Ocholla
Abraham Oduro
Marie Onyamboko
Jean Bosco Ouedraogo
Aung Pyae P. Phyo
Christopher Plowe
Ric N. Price
Sasithon Pukrittayakamee
Milijaona Randrianarivelojosia
Pascal Ringwald
Lastenia Ruiz
David Saunders
Alex Shayo
Peter Siba
Shannon Takala-Harrison
Thuy Nhien N. Thanh
Vandana Thathy
Federica Verra
Jason Wendler
Wellcome Trust Sanger Institute
Wellcome Trust Centre for Human Genetics
Mahidol University
Nuffield Department of Clinical Medicine
Medical Research Council Laboratories Gambia
National Institute of Allergy and Infectious Diseases
Navrongo Health Research Center
Institut Pasteur de Madagascar
University of Buea
Menzies School of Health Research
University of Ghana
National Institute for Medical Research Tanga
Universiteit Antwerpen
Walter and Eliza Hall Institute of Medical Research
University of Melbourne
University of Oxford
Kenya Medical Research Institute
Universität Tübingen
London School of Hygiene & Tropical Medicine
NYU School of Medicine
Liverpool School of Tropical Medicine
University of Bamako
Oxford University Clinical Research Unit
Purdue University
Centro Internacional de Entrenamiento e Investigaciones Medicas
Med Biotech Laboratories Uganda
Malaria Research Group and Dev Care Foundation
National Centre for Parasitology, Entomology and Malaria Control
Armed Forces Research Institute of Medical Sciences, Thailand
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU)
University of Health Sciences
Divine Word University
University of Ilorin
Pennsylvania State University
Ministry of Health
Shoklo Malaria Research Unit
Eijkman Institute for Molecular Biology
King Fahd University of Petroleum and Minerals
Malawi-Liverpool-Wellcome Trust
Universite de Kinshasa
Institut de Recherche en Sciences de la Santé
University of Maryland School of Medicine
Organisation Mondiale de la Sante
Universidad Nacional de la Amazonia Peruana, Iquitos
University of Dodoma
Papua New Guinea Institute of Medical Research
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 4-Mar-2016
Citation: eLife. Vol.5, No.MARCH2016 (2016)
Abstract: © 2016, eLife Sciences Publications Ltd. All rights reserved. The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.
ISSN: 2050084X
Appears in Collections:Scopus 2016-2017

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