Genomic epidemiology of the current wave of artemisinin resistant malaria

Roberto Amato,Olivo Miotto,Charles J Woodrow,Jacob Almagrogarcia,Ipsita Sinha,Susana Campino,Daniel Mead,Eleanor Drury,Mihir Kekre,Mandy Sanders,Alfred Amambuangwa,Chanaki Amaratunga,Lucas Amengaetego,Tim Jc 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 G Craig, N P Day,Abdoulaye A Djimde,Christiane Dolecek,Arjen M Dondorp,Chris Drakeley,Patrick E Duffy, Diego F Echeverrigarcia,Thomas G Egwang,Rick M Fairhurst,M A Faiz,Caterina I 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 A Mokuolu,Jacqui Montgomery,Ivo Mueller,Myat Phone Kyaw,Paul N Newton,Francois Nosten,Rintis Noviyanti,Alexis Nzila,Harold Ocholla,Abraham Oduro,Marie A Onyamboko,Jeanbosco Ouedraogo,Aung Pyae Phyo,Christopher V Plowe,Ric N Price,Sasithon Pukrittayakamee,Milijaona Randrianarivelojosia,Pascal Ringwald,Lastenia Ruiz,David Saunders,Alex Shayo,Peter Siba,Shannon Takalaharrison,Thuynhien Nguyen Thanh,Vandana Thathy, F Verra,Nicholas J White,Ye Htut,Victoria 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

mag(2015)

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摘要
Artemisinin resistant is advancing across Southeast Asia in a soft selective sweep involving at least 20 independent mutations. In a large global survey, we find that mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African mutations have originated locally, and that 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, 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 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.
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