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Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction

BACKGROUND: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to refl...

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Autores principales: Lo, Eugenia, Nguyen, Jennifer, Oo, Winny, Hemming-Schroeder, Elizabeth, Zhou, Guofa, Yang, Zhaoqing, Cui, Liwang, Yan, Guiyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833920/
https://www.ncbi.nlm.nih.gov/pubmed/27084511
http://dx.doi.org/10.1186/s12879-016-1482-6
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author Lo, Eugenia
Nguyen, Jennifer
Oo, Winny
Hemming-Schroeder, Elizabeth
Zhou, Guofa
Yang, Zhaoqing
Cui, Liwang
Yan, Guiyun
author_facet Lo, Eugenia
Nguyen, Jennifer
Oo, Winny
Hemming-Schroeder, Elizabeth
Zhou, Guofa
Yang, Zhaoqing
Cui, Liwang
Yan, Guiyun
author_sort Lo, Eugenia
collection PubMed
description BACKGROUND: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. METHODS: A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the ‘post-treatment’ parasite genotype and compared such with the ‘pre-treatment’ genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. RESULTS: Over 30 % of the P. falciprium infections showed delayed clearance of parasitemia after 2–3 days of treatment and 9.5 % showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95 % of the infections indicated cleared parasitemia at days 2–3 of treatment. Four samples were found to be re-infected with new parasite strains based on microsatellite genotypes after initial treatment. CONCLUSION: The appearance of P.falciparum infected samples showing delayed clearance or recurred parasitemia after treatment raises concerns on current treatment and ACT drug resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1482-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-48339202016-04-17 Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction Lo, Eugenia Nguyen, Jennifer Oo, Winny Hemming-Schroeder, Elizabeth Zhou, Guofa Yang, Zhaoqing Cui, Liwang Yan, Guiyun BMC Infect Dis Research Article BACKGROUND: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. METHODS: A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the ‘post-treatment’ parasite genotype and compared such with the ‘pre-treatment’ genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. RESULTS: Over 30 % of the P. falciprium infections showed delayed clearance of parasitemia after 2–3 days of treatment and 9.5 % showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95 % of the infections indicated cleared parasitemia at days 2–3 of treatment. Four samples were found to be re-infected with new parasite strains based on microsatellite genotypes after initial treatment. CONCLUSION: The appearance of P.falciparum infected samples showing delayed clearance or recurred parasitemia after treatment raises concerns on current treatment and ACT drug resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1482-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-16 /pmc/articles/PMC4833920/ /pubmed/27084511 http://dx.doi.org/10.1186/s12879-016-1482-6 Text en © Lo et al. 2016 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 Article
Lo, Eugenia
Nguyen, Jennifer
Oo, Winny
Hemming-Schroeder, Elizabeth
Zhou, Guofa
Yang, Zhaoqing
Cui, Liwang
Yan, Guiyun
Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction
title Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction
title_full Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction
title_fullStr Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction
title_full_unstemmed Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction
title_short Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction
title_sort examining plasmodium falciparum and p. vivax clearance subsequent to antimalarial drug treatment in the myanmar-china border area based on quantitative real-time polymerase chain reaction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833920/
https://www.ncbi.nlm.nih.gov/pubmed/27084511
http://dx.doi.org/10.1186/s12879-016-1482-6
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