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Get Free AccessArtemisinin resistant Plasmodium falciparum is advancing across Southeast Asia in 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 standing variation 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.
Roberto Amato, Olivo Miotto, Charles J. Woodrow, Jacob Almagro‐Garcia, Ipsita Sinha, Susana Campino, Daniel G. Mead, Eleanor Drury, Mihir Kekre, Mandy Sanders, Alfred Amambua‐Ngwa, Chanaki Amaratunga, Lucas Amenga–Etego, Tim Anderson, Voahangy Andrianaranjaka, Tobias O. Apinjoh, Elizabeth A. Ashley, Sarah Auburn, Gordon A. Awandare, Vito Baraka, Alyssa E. Barry, Maciej F. Boni, Steffen Borrmann, Teun Bousema, OraLee H. Branch, Peter C. Bull, Kesinee Chotivanich, David J. Conway, Alister Craig, Nicholas Day, Abdoulaye Djimdé, Christiane Dolecek, Arjen M. Dondorp, Chris Drakeley, Patrick E. Duffy, Diego F Echeverri-Garcia, Thomas G. Egwang, Rick M. Fairhurst, Abul Faiz, Caterina Fanello, Tran Tinh Hien, Abraham Hodgson, Mallika Imwong, Deus S. Ishengoma, Pharath Lim, Chanthap Lon, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Victor A. Mobegi, Olugbenga Ayodeji Mokuolu, Jacqui Montgomery, Ivo Müeller, Myat Phone Kyaw, Paul N. Newton, François Nosten, Rintis Noviyanti, Alexis Nzila, Harold Ocholla, Abraham Oduro, Marie Onyamboko, Jean‐Bosco Ouédraogo, Aung Pyae Phyo, Christopher V. Plowe, Ric N. Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Pascal Ringwald, Lastenia Ruiz Mesía, David Saunders, Alex Shayo, Peter Siba, Shannon Takala‐Harrison, Thuy-Nhien Nguyen, Vandana Thathy, Federica Verra, Sir Nicholas White, Ye Htut, Victoria Cornelius, Rachel Giacomantonio, Dawn Muddyman, Christa Henrichs, Claudio Malangone, Dushyanth Jyothi, Richard D. Pearson, Julian C. Rayner, Gilean McVean, Kirk A. Rockett, Alistair Miles, P. Vauterin, Ben Jeffery, Magnus Manske, Jim Stalker, Bronwyn MacInnis, Dominic Kwiatkowski (2015). Genomic epidemiology of the current wave of artemisinin resistant malaria. bioRxiv (Cold Spring Harbor Laboratory), DOI: 10.1101/019737.
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Type
Preprint
Year
2015
Authors
95
Datasets
0
Total Files
0
Language
English
Journal
bioRxiv (Cold Spring Harbor Laboratory)
DOI
10.1101/019737
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