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Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar

BACKGROUND: Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes...

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Autores principales: Bonnington, Craig A., Phyo, Aung Pyae, Ashley, Elizabeth A., Imwong, Mallika, Sriprawat, Kanlaya, Parker, Daniel M., Proux, Stephane, White, Nicholas J., Nosten, Francois
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702082/
https://www.ncbi.nlm.nih.gov/pubmed/29178921
http://dx.doi.org/10.1186/s12936-017-2128-x
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author Bonnington, Craig A.
Phyo, Aung Pyae
Ashley, Elizabeth A.
Imwong, Mallika
Sriprawat, Kanlaya
Parker, Daniel M.
Proux, Stephane
White, Nicholas J.
Nosten, Francois
author_facet Bonnington, Craig A.
Phyo, Aung Pyae
Ashley, Elizabeth A.
Imwong, Mallika
Sriprawat, Kanlaya
Parker, Daniel M.
Proux, Stephane
White, Nicholas J.
Nosten, Francois
author_sort Bonnington, Craig A.
collection PubMed
description BACKGROUND: Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with the clinical phenotype. METHODS: Between February and December 2013, parasite clearance was assessed in 35 patients with uncomplicated P. falciparum treated with artesunate monotherapy followed by 3-day ACT in an isolated area on the Myanmar–Thai border with relatively low artemisinin drug pressure. Molecular testing for k13 mutations was performed on dry blood spots collected on admission. RESULTS: The proportion of k13 mutations in these patients was 41.7%, and only 5 alleles were detected: C580Y, I205T, M476I, R561H, and F446I. Of these, F446I was the most common, and was associated with a longer parasite clearance half-life (median) 4.1 (min–max 2.3–6.7) hours compared to 2.5 (min–max 1.6–8.7) in wildtype (p = 0·01). The prevalence of k13 mutant parasites was much lower than the proportion of k13 mutants detected 200 km south in a much less remote setting where the prevalence of k13 mutants was 84% with 15 distinct alleles in 2013 of which C580Y predominated. CONCLUSIONS: This study provides evidence of artemisinin resistance in a remote part of eastern Myanmar. The prevalence of k13 mutations as well as allele diversity varies considerably across short distances, presumably because of historical patterns of artemisinin use and population movements. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-017-2128-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-57020822017-12-04 Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar Bonnington, Craig A. Phyo, Aung Pyae Ashley, Elizabeth A. Imwong, Mallika Sriprawat, Kanlaya Parker, Daniel M. Proux, Stephane White, Nicholas J. Nosten, Francois Malar J Research BACKGROUND: Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with the clinical phenotype. METHODS: Between February and December 2013, parasite clearance was assessed in 35 patients with uncomplicated P. falciparum treated with artesunate monotherapy followed by 3-day ACT in an isolated area on the Myanmar–Thai border with relatively low artemisinin drug pressure. Molecular testing for k13 mutations was performed on dry blood spots collected on admission. RESULTS: The proportion of k13 mutations in these patients was 41.7%, and only 5 alleles were detected: C580Y, I205T, M476I, R561H, and F446I. Of these, F446I was the most common, and was associated with a longer parasite clearance half-life (median) 4.1 (min–max 2.3–6.7) hours compared to 2.5 (min–max 1.6–8.7) in wildtype (p = 0·01). The prevalence of k13 mutant parasites was much lower than the proportion of k13 mutants detected 200 km south in a much less remote setting where the prevalence of k13 mutants was 84% with 15 distinct alleles in 2013 of which C580Y predominated. CONCLUSIONS: This study provides evidence of artemisinin resistance in a remote part of eastern Myanmar. The prevalence of k13 mutations as well as allele diversity varies considerably across short distances, presumably because of historical patterns of artemisinin use and population movements. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-017-2128-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-25 /pmc/articles/PMC5702082/ /pubmed/29178921 http://dx.doi.org/10.1186/s12936-017-2128-x Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bonnington, Craig A.
Phyo, Aung Pyae
Ashley, Elizabeth A.
Imwong, Mallika
Sriprawat, Kanlaya
Parker, Daniel M.
Proux, Stephane
White, Nicholas J.
Nosten, Francois
Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar
title Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar
title_full Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar
title_fullStr Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar
title_full_unstemmed Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar
title_short Plasmodium falciparum Kelch 13 mutations and treatment response in patients in Hpa-Pun District, Northern Kayin State, Myanmar
title_sort plasmodium falciparum kelch 13 mutations and treatment response in patients in hpa-pun district, northern kayin state, myanmar
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702082/
https://www.ncbi.nlm.nih.gov/pubmed/29178921
http://dx.doi.org/10.1186/s12936-017-2128-x
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