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Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia

BACKGROUND: Western Cambodia is recognized as the epicentre of emergence of Plasmodium falciparum multi-drug resistance. The emergence of artemisinin resistance has been observed in this area since 2008–2009 and molecular signatures associated to artemisinin resistance have been characterized in k13...

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Autores principales: Dwivedi, Ankit, Khim, Nimol, Reynes, Christelle, Ravel, Patrice, Ma, Laurence, Tichit, Magali, Bourchier, Christiane, Kim, Saorin, Dourng, Dany, Khean, Chanra, Chim, Pheaktra, Siv, Sovannaroth, Frutos, Roger, Lek, Dysoley, Mercereau-Puijalon, Odile, Ariey, Frédéric, Menard, Didier, Cornillot, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908689/
https://www.ncbi.nlm.nih.gov/pubmed/27301553
http://dx.doi.org/10.1186/s12936-016-1370-y
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author Dwivedi, Ankit
Khim, Nimol
Reynes, Christelle
Ravel, Patrice
Ma, Laurence
Tichit, Magali
Bourchier, Christiane
Kim, Saorin
Dourng, Dany
Khean, Chanra
Chim, Pheaktra
Siv, Sovannaroth
Frutos, Roger
Lek, Dysoley
Mercereau-Puijalon, Odile
Ariey, Frédéric
Menard, Didier
Cornillot, Emmanuel
author_facet Dwivedi, Ankit
Khim, Nimol
Reynes, Christelle
Ravel, Patrice
Ma, Laurence
Tichit, Magali
Bourchier, Christiane
Kim, Saorin
Dourng, Dany
Khean, Chanra
Chim, Pheaktra
Siv, Sovannaroth
Frutos, Roger
Lek, Dysoley
Mercereau-Puijalon, Odile
Ariey, Frédéric
Menard, Didier
Cornillot, Emmanuel
author_sort Dwivedi, Ankit
collection PubMed
description BACKGROUND: Western Cambodia is recognized as the epicentre of emergence of Plasmodium falciparum multi-drug resistance. The emergence of artemisinin resistance has been observed in this area since 2008–2009 and molecular signatures associated to artemisinin resistance have been characterized in k13 gene. At present, one of the major threats faced, is the possible spread of Asian artemisinin resistant parasites over the world threatening millions of people and jeopardizing malaria elimination programme efforts. To anticipate the diffusion of artemisinin resistance, the identification of the P. falciparum population structure and the gene flow among the parasite population in Cambodia are essential. METHODS: To this end, a mid-throughput PCR-LDR-FMA approach based on LUMINEX technology was developed to screen for genetic barcode in 533 blood samples collected in 2010–2011 from 16 health centres in malaria endemics areas in Cambodia. RESULTS: Based on successful typing of 282 samples, subpopulations were characterized along the borders of the country. Each 11-loci barcode provides evidence supporting allele distribution gradient related to subpopulations and gene flow. The 11-loci barcode successfully identifies recently emerging parasite subpopulations in western Cambodia that are associated with the C580Y dominant allele for artemisinin resistance in k13 gene. A subpopulation was identified in northern Cambodia that was associated to artemisinin (R539T resistant allele of k13 gene) and mefloquine resistance. CONCLUSIONS: The gene flow between these subpopulations might have driven the spread of artemisinin resistance over Cambodia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-016-1370-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-49086892016-06-16 Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia Dwivedi, Ankit Khim, Nimol Reynes, Christelle Ravel, Patrice Ma, Laurence Tichit, Magali Bourchier, Christiane Kim, Saorin Dourng, Dany Khean, Chanra Chim, Pheaktra Siv, Sovannaroth Frutos, Roger Lek, Dysoley Mercereau-Puijalon, Odile Ariey, Frédéric Menard, Didier Cornillot, Emmanuel Malar J Research BACKGROUND: Western Cambodia is recognized as the epicentre of emergence of Plasmodium falciparum multi-drug resistance. The emergence of artemisinin resistance has been observed in this area since 2008–2009 and molecular signatures associated to artemisinin resistance have been characterized in k13 gene. At present, one of the major threats faced, is the possible spread of Asian artemisinin resistant parasites over the world threatening millions of people and jeopardizing malaria elimination programme efforts. To anticipate the diffusion of artemisinin resistance, the identification of the P. falciparum population structure and the gene flow among the parasite population in Cambodia are essential. METHODS: To this end, a mid-throughput PCR-LDR-FMA approach based on LUMINEX technology was developed to screen for genetic barcode in 533 blood samples collected in 2010–2011 from 16 health centres in malaria endemics areas in Cambodia. RESULTS: Based on successful typing of 282 samples, subpopulations were characterized along the borders of the country. Each 11-loci barcode provides evidence supporting allele distribution gradient related to subpopulations and gene flow. The 11-loci barcode successfully identifies recently emerging parasite subpopulations in western Cambodia that are associated with the C580Y dominant allele for artemisinin resistance in k13 gene. A subpopulation was identified in northern Cambodia that was associated to artemisinin (R539T resistant allele of k13 gene) and mefloquine resistance. CONCLUSIONS: The gene flow between these subpopulations might have driven the spread of artemisinin resistance over Cambodia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-016-1370-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-14 /pmc/articles/PMC4908689/ /pubmed/27301553 http://dx.doi.org/10.1186/s12936-016-1370-y Text en © The Author(s) 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
Dwivedi, Ankit
Khim, Nimol
Reynes, Christelle
Ravel, Patrice
Ma, Laurence
Tichit, Magali
Bourchier, Christiane
Kim, Saorin
Dourng, Dany
Khean, Chanra
Chim, Pheaktra
Siv, Sovannaroth
Frutos, Roger
Lek, Dysoley
Mercereau-Puijalon, Odile
Ariey, Frédéric
Menard, Didier
Cornillot, Emmanuel
Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia
title Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia
title_full Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia
title_fullStr Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia
title_full_unstemmed Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia
title_short Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia
title_sort plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in cambodia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908689/
https://www.ncbi.nlm.nih.gov/pubmed/27301553
http://dx.doi.org/10.1186/s12936-016-1370-y
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