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Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)

BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance w...

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Autores principales: Nyunt, Myat Htut, Soe, Myat Thu, Myint, Hla Win, Oo, Htet Wai, Aye, Moe Moe, Han, Soe Soe, Zaw, Ni Ni, Cho, Cho, Aung, Phyo Zaw, Kyaw, Khin Thiri, Aye, Thin Thin, San, Naychi Aung, Ortega, Leonard, Thimasarn, Krongthong, Bustos, Maria Dorina G., Galit, Sherwin, Hoque, Mohammad Rafiul, Ringwald, Pascal, Han, Eun-Taek, Kyaw, Myat Phone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557565/
https://www.ncbi.nlm.nih.gov/pubmed/28806957
http://dx.doi.org/10.1186/s12936-017-1983-9
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author Nyunt, Myat Htut
Soe, Myat Thu
Myint, Hla Win
Oo, Htet Wai
Aye, Moe Moe
Han, Soe Soe
Zaw, Ni Ni
Cho, Cho
Aung, Phyo Zaw
Kyaw, Khin Thiri
Aye, Thin Thin
San, Naychi Aung
Ortega, Leonard
Thimasarn, Krongthong
Bustos, Maria Dorina G.
Galit, Sherwin
Hoque, Mohammad Rafiul
Ringwald, Pascal
Han, Eun-Taek
Kyaw, Myat Phone
author_facet Nyunt, Myat Htut
Soe, Myat Thu
Myint, Hla Win
Oo, Htet Wai
Aye, Moe Moe
Han, Soe Soe
Zaw, Ni Ni
Cho, Cho
Aung, Phyo Zaw
Kyaw, Khin Thiri
Aye, Thin Thin
San, Naychi Aung
Ortega, Leonard
Thimasarn, Krongthong
Bustos, Maria Dorina G.
Galit, Sherwin
Hoque, Mohammad Rafiul
Ringwald, Pascal
Han, Eun-Taek
Kyaw, Myat Phone
author_sort Nyunt, Myat Htut
collection PubMed
description BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10, pffd and pfmdr2. METHODS: A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013. Therapeutic efficacy of ACT was assessed by longitudinal follow ups. Molecular markers analysis was done on all available day 0 samples. RESULTS: True recrudescence treatment failures cases and day 3 parasite positivity were detected at only the southern Myanmar sites. Day 3 positive and k13 mutants with higher prevalence of underlying genetic foci predisposing to become k13 mutant were detected only in southern Myanmar since 2009 and comparatively fewer mutations of pfarps10, pffd, and pfmdr2 were observed in western Myanmar. K13 mutations, V127M of pfarps10, D193Y of pffd, and T448I of pfmdr2 were significantly associated with day 3 positivity (OR: 6.48, 3.88, 2.88, and 2.52, respectively). CONCLUSIONS: Apart from k13, pfarps10, pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported. Appropriate action to eliminate the resistant parasites and surveillance on artemisinin resistance should be strengthened in Myanmar. Trial registration This study was registered with ClinicalTrials.gov, identifier NCT02792816.
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spelling pubmed-55575652017-08-16 Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013) Nyunt, Myat Htut Soe, Myat Thu Myint, Hla Win Oo, Htet Wai Aye, Moe Moe Han, Soe Soe Zaw, Ni Ni Cho, Cho Aung, Phyo Zaw Kyaw, Khin Thiri Aye, Thin Thin San, Naychi Aung Ortega, Leonard Thimasarn, Krongthong Bustos, Maria Dorina G. Galit, Sherwin Hoque, Mohammad Rafiul Ringwald, Pascal Han, Eun-Taek Kyaw, Myat Phone Malar J Research BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10, pffd and pfmdr2. METHODS: A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013. Therapeutic efficacy of ACT was assessed by longitudinal follow ups. Molecular markers analysis was done on all available day 0 samples. RESULTS: True recrudescence treatment failures cases and day 3 parasite positivity were detected at only the southern Myanmar sites. Day 3 positive and k13 mutants with higher prevalence of underlying genetic foci predisposing to become k13 mutant were detected only in southern Myanmar since 2009 and comparatively fewer mutations of pfarps10, pffd, and pfmdr2 were observed in western Myanmar. K13 mutations, V127M of pfarps10, D193Y of pffd, and T448I of pfmdr2 were significantly associated with day 3 positivity (OR: 6.48, 3.88, 2.88, and 2.52, respectively). CONCLUSIONS: Apart from k13, pfarps10, pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported. Appropriate action to eliminate the resistant parasites and surveillance on artemisinin resistance should be strengthened in Myanmar. Trial registration This study was registered with ClinicalTrials.gov, identifier NCT02792816. BioMed Central 2017-08-14 /pmc/articles/PMC5557565/ /pubmed/28806957 http://dx.doi.org/10.1186/s12936-017-1983-9 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
Nyunt, Myat Htut
Soe, Myat Thu
Myint, Hla Win
Oo, Htet Wai
Aye, Moe Moe
Han, Soe Soe
Zaw, Ni Ni
Cho, Cho
Aung, Phyo Zaw
Kyaw, Khin Thiri
Aye, Thin Thin
San, Naychi Aung
Ortega, Leonard
Thimasarn, Krongthong
Bustos, Maria Dorina G.
Galit, Sherwin
Hoque, Mohammad Rafiul
Ringwald, Pascal
Han, Eun-Taek
Kyaw, Myat Phone
Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)
title Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)
title_full Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)
title_fullStr Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)
title_full_unstemmed Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)
title_short Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009–2013)
title_sort clinical and molecular surveillance of artemisinin resistant falciparum malaria in myanmar (2009–2013)
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557565/
https://www.ncbi.nlm.nih.gov/pubmed/28806957
http://dx.doi.org/10.1186/s12936-017-1983-9
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