Genomic epidemiology of artemisinin resistant malaria

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 BarryMaciej 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, Nicholas J. White, Htut Ye, Victoria J. Cornelius, Rachel Giacomantonio, Dawn Muddyman, Christa Henrichs, Cinzia Malangone, Dushyanth Jyothi, Richard D. Pearson, Julian C. Rayner, Gilean McVean, Kirk A. Rockett, Alistair Miles, Paul Vauterin, Ben Jeffery, Magnus Manske, Jim Stalker, Bronwyn Macinnis, Dominic P. Kwiatkowski, MalariaGEN Plasmodium falciparum Community Project

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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.

Original languageEnglish
Article numbere08714
Pages (from-to)1-29
Number of pages29
Issue numberMARCH2016
Publication statusPublished - 4 Mar 2016


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