The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread

Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability pr...

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Main Authors: Woodrow, C, White, N
Format: Journal article
Published: Oxford University Press 2017
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author Woodrow, C
White, N
author_facet Woodrow, C
White, N
author_sort Woodrow, C
collection OXFORD
description Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately P. falciparuminfections with mutations in the ‘K13’ gene, with reduced ring-stage susceptibility to artemisinins, and slowparasite clearance in patients treated with ACTs, are now widespread in southeast Asia. We review clinical efficacy data from the region (2000-2015) that provides strong evidence that the loss of first-lineACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance, and ACT failure, are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multi-drug resistant parasite genotypes are taking overand threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency.
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spelling oxford-uuid:3f88836f-4208-4a36-b5a9-b2a998e8f0a92022-03-26T14:32:39ZThe clinical impact of artemisinin resistance in southeast Asia and the potential for future spreadJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3f88836f-4208-4a36-b5a9-b2a998e8f0a9Symplectic Elements at OxfordOxford University Press2017Woodrow, CWhite, NArtemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately P. falciparuminfections with mutations in the ‘K13’ gene, with reduced ring-stage susceptibility to artemisinins, and slowparasite clearance in patients treated with ACTs, are now widespread in southeast Asia. We review clinical efficacy data from the region (2000-2015) that provides strong evidence that the loss of first-lineACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance, and ACT failure, are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multi-drug resistant parasite genotypes are taking overand threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency.
spellingShingle Woodrow, C
White, N
The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread
title The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread
title_full The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread
title_fullStr The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread
title_full_unstemmed The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread
title_short The clinical impact of artemisinin resistance in southeast Asia and the potential for future spread
title_sort clinical impact of artemisinin resistance in southeast asia and the potential for future spread
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