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Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study

BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials we...

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Autores principales: Apinjoh, Tobias O., Mugri, Regina N., Miotto, Olivo, Chi, Hanesh F., Tata, Rolland B., Anchang-Kimbi, Judith K., Fon, Eleanor M., Tangoh, Delphine A., Nyingchu, Robert V., Jacob, Christopher, Amato, Roberto, Djimde, Abdoulaye, Kwiatkowski, Dominic, Achidi, Eric A., Amambua-Ngwa, Alfred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674235/
https://www.ncbi.nlm.nih.gov/pubmed/29110722
http://dx.doi.org/10.1186/s40249-017-0350-y
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author Apinjoh, Tobias O.
Mugri, Regina N.
Miotto, Olivo
Chi, Hanesh F.
Tata, Rolland B.
Anchang-Kimbi, Judith K.
Fon, Eleanor M.
Tangoh, Delphine A.
Nyingchu, Robert V.
Jacob, Christopher
Amato, Roberto
Djimde, Abdoulaye
Kwiatkowski, Dominic
Achidi, Eric A.
Amambua-Ngwa, Alfred
author_facet Apinjoh, Tobias O.
Mugri, Regina N.
Miotto, Olivo
Chi, Hanesh F.
Tata, Rolland B.
Anchang-Kimbi, Judith K.
Fon, Eleanor M.
Tangoh, Delphine A.
Nyingchu, Robert V.
Jacob, Christopher
Amato, Roberto
Djimde, Abdoulaye
Kwiatkowski, Dominic
Achidi, Eric A.
Amambua-Ngwa, Alfred
author_sort Apinjoh, Tobias O.
collection PubMed
description BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. METHODS: Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon. Plasmodium falciparum malaria parasitaemic blood, screened by light microscopy, was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform. RESULTS: A total of 259 participants were enrolled in this study from three different altitudes. While some alleles associated with drug resistance in pfdhfr, pfmdr1 and pfcrt were highly prevalent, less than 3% of all samples carried mutations in the pfkelch13 gene, none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia. The most prevalent haplotypes were triple mutants Pfdhfr I (51) R (59) N (108) I (164)(99%), pfcrt- C(72)V(73) I (74) E (75) T (76) (47.3%), and single mutants PfdhpsS(436) G (437)K(540)A(581)A(613)(69%) and Pfmdr1 N(86) F (184)D(1246) (53.2%). CONCLUSIONS: The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-017-0350-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-56742352017-11-15 Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study Apinjoh, Tobias O. Mugri, Regina N. Miotto, Olivo Chi, Hanesh F. Tata, Rolland B. Anchang-Kimbi, Judith K. Fon, Eleanor M. Tangoh, Delphine A. Nyingchu, Robert V. Jacob, Christopher Amato, Roberto Djimde, Abdoulaye Kwiatkowski, Dominic Achidi, Eric A. Amambua-Ngwa, Alfred Infect Dis Poverty Research Article BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. METHODS: Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon. Plasmodium falciparum malaria parasitaemic blood, screened by light microscopy, was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform. RESULTS: A total of 259 participants were enrolled in this study from three different altitudes. While some alleles associated with drug resistance in pfdhfr, pfmdr1 and pfcrt were highly prevalent, less than 3% of all samples carried mutations in the pfkelch13 gene, none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia. The most prevalent haplotypes were triple mutants Pfdhfr I (51) R (59) N (108) I (164)(99%), pfcrt- C(72)V(73) I (74) E (75) T (76) (47.3%), and single mutants PfdhpsS(436) G (437)K(540)A(581)A(613)(69%) and Pfmdr1 N(86) F (184)D(1246) (53.2%). CONCLUSIONS: The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-017-0350-y) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-06 /pmc/articles/PMC5674235/ /pubmed/29110722 http://dx.doi.org/10.1186/s40249-017-0350-y 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 Article
Apinjoh, Tobias O.
Mugri, Regina N.
Miotto, Olivo
Chi, Hanesh F.
Tata, Rolland B.
Anchang-Kimbi, Judith K.
Fon, Eleanor M.
Tangoh, Delphine A.
Nyingchu, Robert V.
Jacob, Christopher
Amato, Roberto
Djimde, Abdoulaye
Kwiatkowski, Dominic
Achidi, Eric A.
Amambua-Ngwa, Alfred
Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study
title Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study
title_full Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study
title_fullStr Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study
title_full_unstemmed Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study
title_short Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study
title_sort molecular markers for artemisinin and partner drug resistance in natural plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount cameroon: cross-sectional study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674235/
https://www.ncbi.nlm.nih.gov/pubmed/29110722
http://dx.doi.org/10.1186/s40249-017-0350-y
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