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Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana

Malaria is a significant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous antimalarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Artemisinin-based Combination Therapy (ACT) has served as the primary treatment...

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Autores principales: Dieng, Cheikh Cambel, Morrison, Victoria, Donu, Dickson, Cui, Liwang, Amoah, Linda, Afrane, Yaw, Lo, Eugenia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652499/
https://www.ncbi.nlm.nih.gov/pubmed/37974079
http://dx.doi.org/10.1186/s12879-023-08812-w
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author Dieng, Cheikh Cambel
Morrison, Victoria
Donu, Dickson
Cui, Liwang
Amoah, Linda
Afrane, Yaw
Lo, Eugenia
author_facet Dieng, Cheikh Cambel
Morrison, Victoria
Donu, Dickson
Cui, Liwang
Amoah, Linda
Afrane, Yaw
Lo, Eugenia
author_sort Dieng, Cheikh Cambel
collection PubMed
description Malaria is a significant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous antimalarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Artemisinin-based Combination Therapy (ACT) has served as the primary treatment of uncomplicated malaria in Ghana since 2005. However, a growing concern has emerged due to the escalating reports of ACT resistance, particularly in Southeast Asia, and its encroachment into Africa. Specifically, mutations in the Kelch propeller domain on chromosome 13 (Pfk13) have been linked to ACT resistance. Yet, our understanding of mutation prevalence in Africa remains largely uncharted. In this study, we compared Pfk13 sequences obtained from 172 P. falciparum samples across three ecological and transmission zones in Ghana. We identified 27 non-synonymous mutations among these sequences, of which two of the mutations, C580Y (found in two samples from the central region) and Y493H (found in one sample from the north), had previously been validated for their association with artemisinin resistance, a phenomenon widespread in Southeast Asia. The Pfk13 gene diversity was most pronounced in the northern savannah than the central forest and south coastal regions, where transmission rates are lower. The observed mutations were not significantly associated with geographical regions, suggesting a frequent spread of mutations across the country. The ongoing global surveillance of artemisinin resistance remains pivotal, and our findings provides insights into the potential spread of resistant parasites in West Africa. Furthermore, the identification of novel codon mutations in this study raises their potential association to ACT resistance, warranting further investigation through in vitro assays to ascertain their functional significance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08812-w.
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spelling pubmed-106524992023-11-16 Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana Dieng, Cheikh Cambel Morrison, Victoria Donu, Dickson Cui, Liwang Amoah, Linda Afrane, Yaw Lo, Eugenia BMC Infect Dis Research Malaria is a significant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous antimalarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Artemisinin-based Combination Therapy (ACT) has served as the primary treatment of uncomplicated malaria in Ghana since 2005. However, a growing concern has emerged due to the escalating reports of ACT resistance, particularly in Southeast Asia, and its encroachment into Africa. Specifically, mutations in the Kelch propeller domain on chromosome 13 (Pfk13) have been linked to ACT resistance. Yet, our understanding of mutation prevalence in Africa remains largely uncharted. In this study, we compared Pfk13 sequences obtained from 172 P. falciparum samples across three ecological and transmission zones in Ghana. We identified 27 non-synonymous mutations among these sequences, of which two of the mutations, C580Y (found in two samples from the central region) and Y493H (found in one sample from the north), had previously been validated for their association with artemisinin resistance, a phenomenon widespread in Southeast Asia. The Pfk13 gene diversity was most pronounced in the northern savannah than the central forest and south coastal regions, where transmission rates are lower. The observed mutations were not significantly associated with geographical regions, suggesting a frequent spread of mutations across the country. The ongoing global surveillance of artemisinin resistance remains pivotal, and our findings provides insights into the potential spread of resistant parasites in West Africa. Furthermore, the identification of novel codon mutations in this study raises their potential association to ACT resistance, warranting further investigation through in vitro assays to ascertain their functional significance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-023-08812-w. BioMed Central 2023-11-16 /pmc/articles/PMC10652499/ /pubmed/37974079 http://dx.doi.org/10.1186/s12879-023-08812-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Dieng, Cheikh Cambel
Morrison, Victoria
Donu, Dickson
Cui, Liwang
Amoah, Linda
Afrane, Yaw
Lo, Eugenia
Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
title Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
title_full Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
title_fullStr Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
title_full_unstemmed Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
title_short Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
title_sort distribution of plasmodium falciparum k13 gene polymorphisms across transmission settings in ghana
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652499/
https://www.ncbi.nlm.nih.gov/pubmed/37974079
http://dx.doi.org/10.1186/s12879-023-08812-w
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