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 Hanitriniaina Andrianaranjaka (7) , Tobias Apinjoh (8) , Elizabeth Ashley (2) , Sarah Auburn (9) , Gordon A Awandare (10) , Vito Baraka (11) , Alyssa Barry (12) , Maciej Boni (13) , Steffen Borrmann (14) , Teun Bousema (15) , Oralee Branch (16) , Peter C Bull (14) , Kesinee Chotivanich (17) , David J Conway (4) , Alister Craig (18) , Nicholas P Day (2) , Abdoulaye Djimde (19) , Christiane Dolecek (13) , Arjen M Dondorp (2) , Chris Drakeley (15) , Patrick Duffy (5) , Diego F Echeverry (20) , Thomas G Egwang (21) , Rick M 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 A 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 Pyae P Phyo (34) , Christopher V 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 N 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]
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]
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]
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
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

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: genomics; plasmodium falciparum; infectious disease; microbiology; evolutionary biology; artemisinin; kelch13; malaria; drug resistance

Domains: Genetics

Roberto Amato, Olivo Miotto, Charles J Woodrow, Jacob Almagro-Garcia, Ipsita Sinha, et al.. Genomic epidemiology of artemisinin resistant malaria. eLife, 2016, 48 (8), pp.959-964. ⟨10.7554/eLife.08714⟩. ⟨pasteur-01971950⟩