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Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar

BACKGROUND: Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanm...

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Autores principales: Huang, Fang, Li, Shigang, Tian, Peng, Pu, Lahpai Ja Seng, Cui, Yanwen, Liu, Hui, Yang, Lianzhi, Bi, Dahidam Yaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892751/
https://www.ncbi.nlm.nih.gov/pubmed/35241080
http://dx.doi.org/10.1186/s12936-022-04084-y
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author Huang, Fang
Li, Shigang
Tian, Peng
Pu, Lahpai Ja Seng
Cui, Yanwen
Liu, Hui
Yang, Lianzhi
Bi, Dahidam Yaw
author_facet Huang, Fang
Li, Shigang
Tian, Peng
Pu, Lahpai Ja Seng
Cui, Yanwen
Liu, Hui
Yang, Lianzhi
Bi, Dahidam Yaw
author_sort Huang, Fang
collection PubMed
description BACKGROUND: Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanmar was aimed at estimating the underlying drug resistance in this region. METHODS: Blood samples from patients with vivax malaria were collected from Laiza city in northeastern Myanmar in 2020. Drug resistance genes including Pvcrt-o, Pvmdr1, Pvdhfr and Pvdhps were amplified and sequenced. Genetic polymorphisms and haplotypes were analysed to evaluate the prevalence of mutant alleles associated with drug resistance. RESULTS: A total of 149 blood samples from P. vivax patients were collected. The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100.0% and 52.0%, respectively, whereas no single nucleotide polymorphism was present at codon 976. The proportions of single and double mutant types were 48.0% and 52.0%, respectively. A K10 “AAG” insertion in the Pvcrt-o gene was not detected. Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 29.9%, 54.3%, 27.6%, 44.9% and 55.1% of the samples, respectively. Wild type was predominant (46.3%), followed by quadruple and double mutant haplotypes. Of three types of tandem repeat variations of Pvdhfr, Type B, with three copies of GGDN repeats, was the most common. Pvdhps mutations were only detected at codons 383 and 553 and the wild type Pvdhps was dominant (78.0%). Eleven haplotypes were identified when combining the mutations of Pvdhfr and Pvdhps, among which the predominant one was the wild type (33.9%), followed by double mutant alleles S58R/S117N /WT (24.6%). CONCLUSIONS: This study demonstrated resistant P. vivax phenotypes exists in northeastern Myanmar. Continued surveillance of drug resistance markers is needed to update treatment guidelines in this region. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04084-y.
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spelling pubmed-88927512022-03-10 Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar Huang, Fang Li, Shigang Tian, Peng Pu, Lahpai Ja Seng Cui, Yanwen Liu, Hui Yang, Lianzhi Bi, Dahidam Yaw Malar J Research BACKGROUND: Anti-malarial drug resistance is still a major threat to malaria elimination in the Great Mekong Sub-region. Plasmodium vivax parasites resistant to anti-malarial drugs are now found in Myanmar. Molecular surveillance on drug resistance genes in P. vivax parasites from northeastern Myanmar was aimed at estimating the underlying drug resistance in this region. METHODS: Blood samples from patients with vivax malaria were collected from Laiza city in northeastern Myanmar in 2020. Drug resistance genes including Pvcrt-o, Pvmdr1, Pvdhfr and Pvdhps were amplified and sequenced. Genetic polymorphisms and haplotypes were analysed to evaluate the prevalence of mutant alleles associated with drug resistance. RESULTS: A total of 149 blood samples from P. vivax patients were collected. The prevalence of Pvmdr1 mutations at codons 958 and 1076 was 100.0% and 52.0%, respectively, whereas no single nucleotide polymorphism was present at codon 976. The proportions of single and double mutant types were 48.0% and 52.0%, respectively. A K10 “AAG” insertion in the Pvcrt-o gene was not detected. Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 29.9%, 54.3%, 27.6%, 44.9% and 55.1% of the samples, respectively. Wild type was predominant (46.3%), followed by quadruple and double mutant haplotypes. Of three types of tandem repeat variations of Pvdhfr, Type B, with three copies of GGDN repeats, was the most common. Pvdhps mutations were only detected at codons 383 and 553 and the wild type Pvdhps was dominant (78.0%). Eleven haplotypes were identified when combining the mutations of Pvdhfr and Pvdhps, among which the predominant one was the wild type (33.9%), followed by double mutant alleles S58R/S117N /WT (24.6%). CONCLUSIONS: This study demonstrated resistant P. vivax phenotypes exists in northeastern Myanmar. Continued surveillance of drug resistance markers is needed to update treatment guidelines in this region. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04084-y. BioMed Central 2022-03-03 /pmc/articles/PMC8892751/ /pubmed/35241080 http://dx.doi.org/10.1186/s12936-022-04084-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Huang, Fang
Li, Shigang
Tian, Peng
Pu, Lahpai Ja Seng
Cui, Yanwen
Liu, Hui
Yang, Lianzhi
Bi, Dahidam Yaw
Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
title Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
title_full Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
title_fullStr Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
title_full_unstemmed Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
title_short Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar
title_sort genetic polymorphisms in genes associated with drug resistance in plasmodium vivax parasites from northeastern myanmar
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892751/
https://www.ncbi.nlm.nih.gov/pubmed/35241080
http://dx.doi.org/10.1186/s12936-022-04084-y
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