Genomic epidemiology of artemisinin resistant malaria

MalariaGEN Plasmodium falciparum Community Project

Research output: Contribution to journalArticle

66 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere08714
JournaleLife
Volume5
Issue numberMARCH2016
DOIs
StatePublished - Mar 4 2016

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Epidemiology
Southeastern Asia
Malaria
Geographical regions
Mutation
Public health
Genes
Public Health Surveillance
Amino Acids
Plasmodium falciparum
artemisinine

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

MalariaGEN Plasmodium falciparum Community Project (2016). Genomic epidemiology of artemisinin resistant malaria. eLife, 5(MARCH2016), [e08714]. https://doi.org/10.7554/eLife.08714
MalariaGEN Plasmodium falciparum Community Project. / Genomic epidemiology of artemisinin resistant malaria. In: eLife. 2016 ; Vol. 5, No. MARCH2016.
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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.",
author = "{MalariaGEN Plasmodium falciparum Community Project} and Roberto Amato and Olivo Miotto and Woodrow, {Charles J.} and Jacob Almagro-Garcia and Ipsita Sinha and Susana Campino and Daniel Mead and Eleanor Drury and Mihir Kekre and Mandy Sanders and Alfred Amambua-Ngwa and Chanaki Amaratunga and Lucas Amenga-Etego and Voahangy Andrianaranjaka and Tobias Apinjoh and Elizabeth Ashley and Sarah Auburn and Awandare, {Gordon A.} and Vito Baraka and Alyssa Barry and Boni, {Maciej F.} and Steffen Borrmann and Teun Bousema and Oralee Branch and Bull, {Peter C.} and Kesinee Chotivanich and Conway, {David J.} and Alister Craig and Day, {Nicholas P.} and Abdoulaye Djimd{\'e} and Christiane Dolecek and Dondorp, {Arjen M.} and Chris Drakeley and Patrick Duffy and Echeverry, {Diego F.} and Egwang, {Thomas G.} and Fairhurst, {Rick M.} and Abul Faiz and Fanello, {Caterina I.} and Hien, {Tran Tinh} and Abraham Hodgson and Mallika Imwong and Deus Ishengoma and Pharath Lim and Chanthap Lon and Jutta Marfurt and Kevin Marsh and Mayfong Mayxay and Pascal Michon and Victor Mobegi",
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MalariaGEN Plasmodium falciparum Community Project 2016, 'Genomic epidemiology of artemisinin resistant malaria', eLife, vol. 5, no. MARCH2016, e08714. https://doi.org/10.7554/eLife.08714

Genomic epidemiology of artemisinin resistant malaria. / MalariaGEN Plasmodium falciparum Community Project.

In: eLife, Vol. 5, No. MARCH2016, e08714, 04.03.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genomic epidemiology of artemisinin resistant malaria

AU - MalariaGEN Plasmodium falciparum Community Project

AU - Amato, Roberto

AU - Miotto, Olivo

AU - Woodrow, Charles J.

AU - Almagro-Garcia, Jacob

AU - Sinha, Ipsita

AU - Campino, Susana

AU - Mead, Daniel

AU - Drury, Eleanor

AU - Kekre, Mihir

AU - Sanders, Mandy

AU - Amambua-Ngwa, Alfred

AU - Amaratunga, Chanaki

AU - Amenga-Etego, Lucas

AU - Andrianaranjaka, Voahangy

AU - Apinjoh, Tobias

AU - Ashley, Elizabeth

AU - Auburn, Sarah

AU - Awandare, Gordon A.

AU - Baraka, Vito

AU - Barry, Alyssa

AU - Boni, Maciej F.

AU - Borrmann, Steffen

AU - Bousema, Teun

AU - Branch, Oralee

AU - Bull, Peter C.

AU - Chotivanich, Kesinee

AU - Conway, David J.

AU - Craig, Alister

AU - Day, Nicholas P.

AU - Djimdé, Abdoulaye

AU - Dolecek, Christiane

AU - Dondorp, Arjen M.

AU - Drakeley, Chris

AU - Duffy, Patrick

AU - Echeverry, Diego F.

AU - Egwang, Thomas G.

AU - Fairhurst, Rick M.

AU - Faiz, Abul

AU - Fanello, Caterina I.

AU - Hien, Tran Tinh

AU - Hodgson, Abraham

AU - Imwong, Mallika

AU - Ishengoma, Deus

AU - Lim, Pharath

AU - Lon, Chanthap

AU - Marfurt, Jutta

AU - Marsh, Kevin

AU - Mayxay, Mayfong

AU - Michon, Pascal

AU - Mobegi, Victor

PY - 2016/3/4

Y1 - 2016/3/4

N2 - 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.

AB - 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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MalariaGEN Plasmodium falciparum Community Project. Genomic epidemiology of artemisinin resistant malaria. eLife. 2016 Mar 4;5(MARCH2016). e08714. https://doi.org/10.7554/eLife.08714