Genomic epidemiology of artemisinin resistant malaria.

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 freq...

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Main Authors: MalariaGEN Plasmodium falciparum Community Project, Miotto, O, Woodrow, C, Almagro-Garcia, J, Sinha, I, Ashley, E, Boni, M, Bull, P, Day, N, Dolecek, C, Dondorp, A, Fanello, C, Newton, P, Nosten, F, Price, R, White, N, Cornelius, V, Giacomantonio, R, Henrichs, C, Pearson, R, McVean, G, Rockett, K, Miles, A, Jeffery, B, Kwiatkowski, D
Format: Journal article
Language:English
Published: eLife Sciences 2016
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author MalariaGEN Plasmodium falciparum Community Project
Miotto, O
Woodrow, C
Almagro-Garcia, J
Sinha, I
Ashley, E
Boni, M
Bull, P
Day, N
Dolecek, C
Dondorp, A
Fanello, C
Newton, P
Nosten, F
Price, R
White, N
Cornelius, V
Giacomantonio, R
Henrichs, C
Pearson, R
McVean, G
Rockett, K
Miles, A
Jeffery, B
Kwiatkowski, D
author_facet MalariaGEN Plasmodium falciparum Community Project
Miotto, O
Woodrow, C
Almagro-Garcia, J
Sinha, I
Ashley, E
Boni, M
Bull, P
Day, N
Dolecek, C
Dondorp, A
Fanello, C
Newton, P
Nosten, F
Price, R
White, N
Cornelius, V
Giacomantonio, R
Henrichs, C
Pearson, R
McVean, G
Rockett, K
Miles, A
Jeffery, B
Kwiatkowski, D
author_sort MalariaGEN Plasmodium falciparum Community Project
collection OXFORD
description 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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spelling oxford-uuid:4b95f36e-8219-4708-85cf-e2380aa986f42022-03-26T15:44:35ZGenomic epidemiology of artemisinin resistant malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4b95f36e-8219-4708-85cf-e2380aa986f4EnglishSymplectic Elements at OxfordeLife Sciences2016MalariaGEN Plasmodium falciparum Community ProjectMiotto, OWoodrow, CAlmagro-Garcia, JSinha, IAshley, EBoni, MBull, PDay, NDolecek, CDondorp, AFanello, CNewton, PNosten, FPrice, RWhite, NCornelius, VGiacomantonio, RHenrichs, CPearson, RMcVean, GRockett, KMiles, AJeffery, BKwiatkowski, DThe 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.
spellingShingle MalariaGEN Plasmodium falciparum Community Project
Miotto, O
Woodrow, C
Almagro-Garcia, J
Sinha, I
Ashley, E
Boni, M
Bull, P
Day, N
Dolecek, C
Dondorp, A
Fanello, C
Newton, P
Nosten, F
Price, R
White, N
Cornelius, V
Giacomantonio, R
Henrichs, C
Pearson, R
McVean, G
Rockett, K
Miles, A
Jeffery, B
Kwiatkowski, D
Genomic epidemiology of artemisinin resistant malaria.
title Genomic epidemiology of artemisinin resistant malaria.
title_full Genomic epidemiology of artemisinin resistant malaria.
title_fullStr Genomic epidemiology of artemisinin resistant malaria.
title_full_unstemmed Genomic epidemiology of artemisinin resistant malaria.
title_short Genomic epidemiology of artemisinin resistant malaria.
title_sort genomic epidemiology of artemisinin resistant malaria
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