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K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors
BACKGROUND: Efficacy of artemisinin (ART) agents, a critical element of current malaria control efforts is threatened by emergence and spread of resistance. Mutations in pfkelch13 gene associated with ART-resistance evolved in Southeast Asia (SEA). k13 mutations whose role in ART-resistance remains...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407282/ https://www.ncbi.nlm.nih.gov/pubmed/30846002 http://dx.doi.org/10.1186/s12936-019-2701-6 |
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author | Ocan, Moses Akena, Dickens Nsobya, Sam Kamya, Moses R. Senono, Richard Kinengyere, Alison Annet Obuku, Ekwaro |
author_facet | Ocan, Moses Akena, Dickens Nsobya, Sam Kamya, Moses R. Senono, Richard Kinengyere, Alison Annet Obuku, Ekwaro |
author_sort | Ocan, Moses |
collection | PubMed |
description | BACKGROUND: Efficacy of artemisinin (ART) agents, a critical element of current malaria control efforts is threatened by emergence and spread of resistance. Mutations in pfkelch13 gene associated with ART-resistance evolved in Southeast Asia (SEA). k13 mutations whose role in ART-resistance remains unknown, have subsequently emerged independently across all malaria-affected regions. The aim of this systematic review was to determine the prevalence and identify risk factors of Plasmodium falciparum k13 mutations in malaria-endemic countries. METHODS: An electronic search of studies from 2014 to date was done in MEDLINE via PubMED, SCOPUS, EMBASE and LILACS/VHL databases. Mesh terms and Boolean operators (AND, OR) were used. Two librarians independently conducted this search (RS and AK). The articles were screened for inclusion using a priori criteria set following PRISMA-P and STREGA guidelines. Three independent reviewers (NL, BB, and OM) extracted the data. Data analysis was performed in Open Meta Analyst software. Random effects analysis (DL) was used and heterogeneity established using I(2)-statistic. RESULTS: A total of 482 articles were retrieved from Pubmed = 302, Lilacs/Vhl = 50, Embase = 80, and Scopus = 37; Bibliography/other searches = 13, of which 374 did not meet the inclusion criteria. The aggregate prevalence of single nucleotide polymorphisms (SNPs) in pfkelch13 gene was 27.6% (3694/14,827) (95% CI 22.9%, 32.3%). Sub-group analysis showed that aggregate prevalence of non-synonymous SNPs in pfkelch13 gene was higher, 45.4% (95% CI 35.4%, 55.3%) in Southeast Asia as opposed to 7.6% (95% CI 5.6%, 9.5%) in the African region. A total of 165 independent k13 mutations were identified across malaria-affected regions globally. A total of 16 non-validated k13 mutations were associated with increased ART parasite clearance half-life (t(1/2) > 5 h). The majority, 45.5% (75/165), of the mutations were reported in single P. falciparum parasite infections. Of the 165 k13-mutations, over half were reported as new alleles. Twenty (20) non-propeller mutations in the pfkelch13 gene were identified. CONCLUSION: This review identified emergence of potential ART-resistance mediating k13 mutations in the African region. Diversity of mutations in pfkelch13 gene is highest in African region compared to SEA. Mutations outside the pfkelch13 propeller region associated with increased ART parasite clearance half-life occur in malaria-affected regions. |
format | Online Article Text |
id | pubmed-6407282 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64072822019-03-21 K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors Ocan, Moses Akena, Dickens Nsobya, Sam Kamya, Moses R. Senono, Richard Kinengyere, Alison Annet Obuku, Ekwaro Malar J Research BACKGROUND: Efficacy of artemisinin (ART) agents, a critical element of current malaria control efforts is threatened by emergence and spread of resistance. Mutations in pfkelch13 gene associated with ART-resistance evolved in Southeast Asia (SEA). k13 mutations whose role in ART-resistance remains unknown, have subsequently emerged independently across all malaria-affected regions. The aim of this systematic review was to determine the prevalence and identify risk factors of Plasmodium falciparum k13 mutations in malaria-endemic countries. METHODS: An electronic search of studies from 2014 to date was done in MEDLINE via PubMED, SCOPUS, EMBASE and LILACS/VHL databases. Mesh terms and Boolean operators (AND, OR) were used. Two librarians independently conducted this search (RS and AK). The articles were screened for inclusion using a priori criteria set following PRISMA-P and STREGA guidelines. Three independent reviewers (NL, BB, and OM) extracted the data. Data analysis was performed in Open Meta Analyst software. Random effects analysis (DL) was used and heterogeneity established using I(2)-statistic. RESULTS: A total of 482 articles were retrieved from Pubmed = 302, Lilacs/Vhl = 50, Embase = 80, and Scopus = 37; Bibliography/other searches = 13, of which 374 did not meet the inclusion criteria. The aggregate prevalence of single nucleotide polymorphisms (SNPs) in pfkelch13 gene was 27.6% (3694/14,827) (95% CI 22.9%, 32.3%). Sub-group analysis showed that aggregate prevalence of non-synonymous SNPs in pfkelch13 gene was higher, 45.4% (95% CI 35.4%, 55.3%) in Southeast Asia as opposed to 7.6% (95% CI 5.6%, 9.5%) in the African region. A total of 165 independent k13 mutations were identified across malaria-affected regions globally. A total of 16 non-validated k13 mutations were associated with increased ART parasite clearance half-life (t(1/2) > 5 h). The majority, 45.5% (75/165), of the mutations were reported in single P. falciparum parasite infections. Of the 165 k13-mutations, over half were reported as new alleles. Twenty (20) non-propeller mutations in the pfkelch13 gene were identified. CONCLUSION: This review identified emergence of potential ART-resistance mediating k13 mutations in the African region. Diversity of mutations in pfkelch13 gene is highest in African region compared to SEA. Mutations outside the pfkelch13 propeller region associated with increased ART parasite clearance half-life occur in malaria-affected regions. BioMed Central 2019-03-07 /pmc/articles/PMC6407282/ /pubmed/30846002 http://dx.doi.org/10.1186/s12936-019-2701-6 Text en © The Author(s) 2019 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 Ocan, Moses Akena, Dickens Nsobya, Sam Kamya, Moses R. Senono, Richard Kinengyere, Alison Annet Obuku, Ekwaro K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
title | K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
title_full | K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
title_fullStr | K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
title_full_unstemmed | K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
title_short | K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
title_sort | k13-propeller gene polymorphisms in plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407282/ https://www.ncbi.nlm.nih.gov/pubmed/30846002 http://dx.doi.org/10.1186/s12936-019-2701-6 |
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