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Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar

BACKGROUND: Artemisinin resistance has been reported in Greater Mekong Sub-region countries, including Myanmar. After discovery of artemisinin resistance marker (K13), molecular surveillance on artemisinin resistance in endemic regions have been conducted. As the migrant population represents a high...

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Autores principales: Nyunt, Myat Htut, Wang, Bo, Aye, Khin Myo, Aye, Kyin Hla, Han, Jin-Hee, Lee, Seong-Kyun, Han, Kay Thwe, Htut, Ye, Han, Eun-Taek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333451/
https://www.ncbi.nlm.nih.gov/pubmed/28249583
http://dx.doi.org/10.1186/s12936-017-1753-8
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author Nyunt, Myat Htut
Wang, Bo
Aye, Khin Myo
Aye, Kyin Hla
Han, Jin-Hee
Lee, Seong-Kyun
Han, Kay Thwe
Htut, Ye
Han, Eun-Taek
author_facet Nyunt, Myat Htut
Wang, Bo
Aye, Khin Myo
Aye, Kyin Hla
Han, Jin-Hee
Lee, Seong-Kyun
Han, Kay Thwe
Htut, Ye
Han, Eun-Taek
author_sort Nyunt, Myat Htut
collection PubMed
description BACKGROUND: Artemisinin resistance has been reported in Greater Mekong Sub-region countries, including Myanmar. After discovery of artemisinin resistance marker (K13), molecular surveillance on artemisinin resistance in endemic regions have been conducted. As the migrant population represents a high percentage of malaria cases, molecular surveillance of artemisinin resistance among migrant workers is of great concern. METHODS: A cross-sectional survey was conducted in Shwegyin Township, where migrants work in the goldmines. Blood samples were collected from uncomplicated Plasmodium falciparum-infected migrant workers by active and passive cases screening with rapid diagnostic testing (RDT) and microscopy. Amplification and sequence analysis of artemisinin resistance molecular markers, such as k13, pfarps10, pffd, pfmdr2, pfmrp1, pfrad5, and pfcnbp, were carried out and pfmdr1 copy number analysis was conducted by real-time PCR. RESULTS: Among the 100 falciparum-infected patients, most were male (90%), of working age (20–40 years) with median parasite density of 11,166 parasites/µL (range 270–110,472 parasites/µL). Artemisinin resistance molecular marker, k13 mutations were detected in (21/100, 21.0%) in which composed of a validated marker, C580Y (9/21, 42.9%) and candidate markers such as P574L (5/21, 23.8%), P667T (5/21, 23.8%) and M476I (2/21, 9.5%). Underlying genetic markers predisposing to become k13 mutants were found as V127M of pfarps10 (41/100, 41.0%), D153Y of pffd (64/100, 64.0%), T484I of pfmdr2 (58/100, 58.0%) and F1390I of pfmrp1 (24/100, 24.0%). The pfmdr1 copy number analysis revealed six copy numbers (1/100, 1.0%), three (2/100, 2.0%), two (8/100, 8.0%) and only one copy number (89/100, 89.0%). Only one sample showed both k13 mutation (P667T) and multiple copy number of pfmdr1. CONCLUSIONS: High mutant rate of artemisinin resistance markers and relatively high pfmdr1 copy number among isolates collected from migrant goldmine workers alert the importance of containment measures among this target population. Clinical and molecular surveillance of artemisinin resistance among migrants should be scaled up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1753-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-53334512017-03-06 Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar Nyunt, Myat Htut Wang, Bo Aye, Khin Myo Aye, Kyin Hla Han, Jin-Hee Lee, Seong-Kyun Han, Kay Thwe Htut, Ye Han, Eun-Taek Malar J Research BACKGROUND: Artemisinin resistance has been reported in Greater Mekong Sub-region countries, including Myanmar. After discovery of artemisinin resistance marker (K13), molecular surveillance on artemisinin resistance in endemic regions have been conducted. As the migrant population represents a high percentage of malaria cases, molecular surveillance of artemisinin resistance among migrant workers is of great concern. METHODS: A cross-sectional survey was conducted in Shwegyin Township, where migrants work in the goldmines. Blood samples were collected from uncomplicated Plasmodium falciparum-infected migrant workers by active and passive cases screening with rapid diagnostic testing (RDT) and microscopy. Amplification and sequence analysis of artemisinin resistance molecular markers, such as k13, pfarps10, pffd, pfmdr2, pfmrp1, pfrad5, and pfcnbp, were carried out and pfmdr1 copy number analysis was conducted by real-time PCR. RESULTS: Among the 100 falciparum-infected patients, most were male (90%), of working age (20–40 years) with median parasite density of 11,166 parasites/µL (range 270–110,472 parasites/µL). Artemisinin resistance molecular marker, k13 mutations were detected in (21/100, 21.0%) in which composed of a validated marker, C580Y (9/21, 42.9%) and candidate markers such as P574L (5/21, 23.8%), P667T (5/21, 23.8%) and M476I (2/21, 9.5%). Underlying genetic markers predisposing to become k13 mutants were found as V127M of pfarps10 (41/100, 41.0%), D153Y of pffd (64/100, 64.0%), T484I of pfmdr2 (58/100, 58.0%) and F1390I of pfmrp1 (24/100, 24.0%). The pfmdr1 copy number analysis revealed six copy numbers (1/100, 1.0%), three (2/100, 2.0%), two (8/100, 8.0%) and only one copy number (89/100, 89.0%). Only one sample showed both k13 mutation (P667T) and multiple copy number of pfmdr1. CONCLUSIONS: High mutant rate of artemisinin resistance markers and relatively high pfmdr1 copy number among isolates collected from migrant goldmine workers alert the importance of containment measures among this target population. Clinical and molecular surveillance of artemisinin resistance among migrants should be scaled up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1753-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-01 /pmc/articles/PMC5333451/ /pubmed/28249583 http://dx.doi.org/10.1186/s12936-017-1753-8 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
Wang, Bo
Aye, Khin Myo
Aye, Kyin Hla
Han, Jin-Hee
Lee, Seong-Kyun
Han, Kay Thwe
Htut, Ye
Han, Eun-Taek
Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar
title Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar
title_full Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar
title_fullStr Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar
title_full_unstemmed Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar
title_short Molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in Myanmar
title_sort molecular surveillance of artemisinin resistance falciparum malaria among migrant goldmine workers in myanmar
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333451/
https://www.ncbi.nlm.nih.gov/pubmed/28249583
http://dx.doi.org/10.1186/s12936-017-1753-8
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