Genomic epidemiology of artemisinin resistant malaria
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Olivo Miotto
- Function : Author
- PersonId : 770355
- ORCID : 0000-0001-8060-6771
Charles J Woodrow
- Function : Author
- PersonId : 945440
Voahangy Hanitriniaina Andrianaranjaka
- Function : Author
- PersonId : 942624
Nicholas P Day
- Function : Author
- PersonId : 796732
- ORCID : 0000-0003-2309-1171
Abdoulaye Djimde
- Function : Author
- PersonId : 1041565
Chris Drakeley
- Function : Author
- PersonId : 784446
- ORCID : 0000-0003-4863-075X
Patrick Duffy
- Function : Author
- PersonId : 1041586
Abul Faiz
- Function : Author
Tran Tinh Hien
- Function : Author
- PersonId : 887270
Ivo Mueller
- Function : Author
- PersonId : 784421
- ORCID : 0000-0001-6554-6889
- IdRef : 241942551
François Nosten
- Function : Author
- PersonId : 768753
- ORCID : 0000-0002-7951-0745
- IdRef : 084012633
Jean-Bosco Ouédraogo
- Function : Author
- PersonId : 776962
- ORCID : 0000-0003-0412-8733
- IdRef : 166738905
Ric Price
- Function : Author
- PersonId : 914108
Gilean Mcvean
- Function : Author
- PersonId : 796749
- ORCID : 0000-0002-5012-4162
Kirk Rockett
- Function : Author
- PersonId : 918293
Dominic Kwiatkowski
- Function : Author
- PersonId : 918296
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.
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Origin : Publication funded by an institution
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