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Genomic epidemiology of artemisinin resistant malaria

Roberto Amato 1 Olivo Miotto 2 Charles J Woodrow 2 Jacob Almagro-Garcia 3 Ipsita Sinha 2 Susana Campino 1 Daniel Mead 1 Eleanor Drury 1 Mihir Kekre 1 Mandy Sanders 1 Alfred Amambua-Ngwa 4 Chanaki Amaratunga 5 Lucas Amenga-Etego 6 Voahangy Andrianaranjaka 7 Tobias Apinjoh 8 Elizabeth Ashley 2 Sarah Auburn 9 Gordon Awandare 10 Vito Baraka 11 Alyssa Barry 12 Maciej Boni 13 Steffen Borrmann 14 Teun Bousema 15 Oralee Branch 16 Peter Bull 14 Kesinee Chotivanich 17 David Conway 4 Alister Craig 18 Nicholas Day 2 Abdoulaye Djimde 19 Christiane Dolecek 13 Arjen M Dondorp 2 Chris Drakeley 15 Patrick Duffy 5 Diego F Echeverry 20 Thomas Egwang 21 Rick Fairhurst 5 Abul Faiz Caterina Fanello 2 Tran Tinh Hien 13 Abraham Hodgson 6 Mallika Imwong 2 Deus Ishengoma 11 Pharath Lim 5 Chanthap Lon 22 Jutta Marfurt 9 Kevin Marsh 14 Mayfong Mayxay 23 Pascal Michon 24 Victor Mobegi 4 Olugbenga Mokuolu 25 Jacqui Montgomery 26 Ivo Mueller 27 Myat Phone Kyaw 28 Paul N Newton 23 François Nosten 2 Rintis Noviyanti 29 Alexis Nzila 30 Harold Ocholla 31 Abraham Oduro 6 Marie Onyamboko 32 Jean-Bosco Ouédraogo 33 Aung Phyo 34 Christopher Plowe 35 Ric Price 36 Sasithon Pukrittayakamee 37 Milijaona Randrianarivelojosia 7 Pascal Ringwald 38 Lastenia Ruiz 39 David Saunders 22 Alex Shayo 40 Peter Siba 41 Shannon Takala-Harrison 35 Thuy-Nhien Thanh 36 Vandana Thathy 14 Federica Verra 15 Jason Wendler 3 Nicholas White 42 Htut Ye 28 Victoria Cornelius 3 Rachel Giacomantonio 3 Dawn Muddyman 1 Christa Henrichs 3 Cinzia Malangone 1 Dushyanth Jyothi 1 Richard Pearson 3 Julian Rayner 1 Gilean Mcvean 3 Kirk Rockett 3 Alistair Miles 3 Paul Vauterin 3 Ben Jeffery 3 Magnus Manske 1 Jim Stalker 1 Bronwyn Macinnis 1 Dominic Kwiatkowski 1
1 The Wellcome Trust Sanger Institute [Cambridge]
2 Mahidol Oxford Tropical Medicine Research Unit
3 The Wellcome Trust Centre for Human Genetics [Oxford]
4 MRC - Medical Research Council Unit The Gambia
5 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
6 NHRC - Navrongo Health Research Centre [Navrongo, Ghana]
7 IPM - G4 malaria group [Antananarivo, Madagascar]
8 University of Buéa
9 Global and Tropical Health Division [Rocklands, Australia]
10 WACCBIP - West African Centre for Cell Biology of Infectious Pathogens [Legon, Ghana]
University of Ghana
11 NIMR - National Institute for Medical Research [Tanzania]
12 WEHI - The Walter and Eliza Hall Institute of Medical Research
13 OUCRU - Oxford University Clinical Research Unit [Ho Chi Minh City]
14 KWTRP - KEMRI-Wellcome Trust Research Programme
15 LSHTM - London School of Hygiene and Tropical Medicine
16 New York University School of Medicine
17 Faculty of Tropical Medicine [Bangkok, Thailand]
18 LSTM - Liverpool School of Tropical Medicine
19 FMPOS - Faculté de Médecine, de pharmacie et d’Odonto-Stomatologie [Bamako, Mali]
20 Department of Entomology [West Lafayette]
Purdue University [West Lafayette]
21 MBL - Med Biotech Laboratories [Kampala, Ouganda]
22 AFRIMS - Armed Forces Research Institute of Medical Sciences [Bangkok]
23 LOMWRU - Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit
24 Faculty of Medicine and Health Sciences [Madang, Papouasie-Nouvelle-Guinée]
25 University of Ilorin
26 Department of Entomology [University Park]
Penn State - Pennsylvania State University
27 University of Melbourne
28 MoHS - Ministry of health and sport [Yangon, Myanmar]
29 Eijkman Institute for Molecular Biology [Jakarta]
30 KFUPM - King Fahd University of Petroleum and Minerals
31 MLW - Malawi Liverpool Wellcome Trust Clinical Research Programme
University of Liverpool, LSTM - Liverpool School of Tropical Medicine, University of Malawi, Wellcome Trust
32 UNIKIN - University of Kinshasa
33 Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz
34 SMRU - Shoklo Malaria Research Unit [Mae Sot, Thailand]
35 University of Maryland School of Medicine
36 Centre for Tropical Medicine and Global Health [Oxford, UK]
37 Faculty of Tropical Medicine - Department of Clinical Tropical Medicine [Bangkok, Thailand]
38 Global Malaria Programme
39 UNAP - Universidad Nacional de la Amazonía Peruana [Loreto, Perou]
40 UDOM - University of Dodoma [Tanzanie]
41 PNG-IMR - Papua New Guinea Institute of Medical Research
42 MORU - Mahidol Oxford Tropical Medicine Research Unit
Abstract : 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.
Keywords : artemisinin evolutionary biology microbiology genomics drug resistance malaria infectious disease plasmodium falciparum kelch13
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Roberto Amato, Olivo Miotto, Charles J Woodrow, Jacob Almagro-Garcia, Ipsita Sinha, et al.. Genomic epidemiology of artemisinin resistant malaria. eLife, eLife Sciences Publication, 2016, 48 (8), pp.959-964. ⟨10.7554/eLife.08714⟩. ⟨pasteur-01971950⟩

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