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Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia

BACKGROUND: The Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) is an important P. falciparum merozoite ligand that mediates invasion of erythrocytes by interacting with a chymotrypsin-sensitive “receptor Z”. A large deletion polymorphism is found in the c-terminal ectodomain...

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Autores principales: Diédhiou, Cyrille K., Moussa, Rahama A., Bei, Amy K., Daniels, Rachel, Papa Mze, Nasserdine, Ndiaye, Daouda, Faye, Ngor, Wirth, Dyann, Amambua-Ngwa, Alfred, Mboup, Souleymane, Ahouidi, Ambroise D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636118/
https://www.ncbi.nlm.nih.gov/pubmed/31311552
http://dx.doi.org/10.1186/s12936-019-2868-x
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author Diédhiou, Cyrille K.
Moussa, Rahama A.
Bei, Amy K.
Daniels, Rachel
Papa Mze, Nasserdine
Ndiaye, Daouda
Faye, Ngor
Wirth, Dyann
Amambua-Ngwa, Alfred
Mboup, Souleymane
Ahouidi, Ambroise D.
author_facet Diédhiou, Cyrille K.
Moussa, Rahama A.
Bei, Amy K.
Daniels, Rachel
Papa Mze, Nasserdine
Ndiaye, Daouda
Faye, Ngor
Wirth, Dyann
Amambua-Ngwa, Alfred
Mboup, Souleymane
Ahouidi, Ambroise D.
author_sort Diédhiou, Cyrille K.
collection PubMed
description BACKGROUND: The Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) is an important P. falciparum merozoite ligand that mediates invasion of erythrocytes by interacting with a chymotrypsin-sensitive “receptor Z”. A large deletion polymorphism is found in the c-terminal ectodomain of this protein in many countries around the world, resulting in a truncated, but expressed protein. The varying frequencies by region suggest that there could be region specific immune selection at this locus. Therefore, this study was designed to determine temporal changes in the PfRh2b deletion polymorphism in infected individuals from Thiès (Senegal) and Western Gambia (The Gambia). It was also sought to determine the selective pressures acting at this locus and whether prevalence of the deletion in isolates genotyped by a 24-SNP molecular barcode is linked to background genotype or whether there might be independent selection acting at this locus. METHODS: Infected blood samples were sourced from archives of previous studies conducted between 2007 and 2013 at SLAP clinic in Thiès and from 1984 to 2013 in Western Gambia by MRC Unit at LSHTM, The Gambia. A total of 1380 samples were screened for the dimorphic alleles of the PfRh2b using semi-nested Polymerase Chain Reaction PCR. Samples from Thiès were previously barcoded. RESULTS: In Thiès, a consistent trend of decreasing prevalence of the PfRh2b deletion over time was observed: from 66.54% in 2007 and to 38.1% in 2013. In contrast, in Western Gambia, the frequency of the deletion fluctuated over time; it increased between 1984 and 2005 from (58.04%) to (69.33%) and decreased to 47.47% in 2007. Between 2007 and 2012, the prevalence of this deletion increased significantly from 47.47 to 83.02% and finally declined significantly to 57.94% in 2013. Association between the presence of this deletion and age was found in Thiès, however, not in Western Gambia. For the majority of isolates, the PfRh2b alleles could be tracked with specific 24-SNP barcoded genotype, indicating a lack of independent selection at this locus. CONCLUSION: PfRh2b deletion was found in the two countries with varying prevalence during the study period. However, these temporal and spatial variations could be an obstacle to the implementation of this protein as a potential vaccine candidate. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-019-2868-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-66361182019-07-25 Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia Diédhiou, Cyrille K. Moussa, Rahama A. Bei, Amy K. Daniels, Rachel Papa Mze, Nasserdine Ndiaye, Daouda Faye, Ngor Wirth, Dyann Amambua-Ngwa, Alfred Mboup, Souleymane Ahouidi, Ambroise D. Malar J Research BACKGROUND: The Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) is an important P. falciparum merozoite ligand that mediates invasion of erythrocytes by interacting with a chymotrypsin-sensitive “receptor Z”. A large deletion polymorphism is found in the c-terminal ectodomain of this protein in many countries around the world, resulting in a truncated, but expressed protein. The varying frequencies by region suggest that there could be region specific immune selection at this locus. Therefore, this study was designed to determine temporal changes in the PfRh2b deletion polymorphism in infected individuals from Thiès (Senegal) and Western Gambia (The Gambia). It was also sought to determine the selective pressures acting at this locus and whether prevalence of the deletion in isolates genotyped by a 24-SNP molecular barcode is linked to background genotype or whether there might be independent selection acting at this locus. METHODS: Infected blood samples were sourced from archives of previous studies conducted between 2007 and 2013 at SLAP clinic in Thiès and from 1984 to 2013 in Western Gambia by MRC Unit at LSHTM, The Gambia. A total of 1380 samples were screened for the dimorphic alleles of the PfRh2b using semi-nested Polymerase Chain Reaction PCR. Samples from Thiès were previously barcoded. RESULTS: In Thiès, a consistent trend of decreasing prevalence of the PfRh2b deletion over time was observed: from 66.54% in 2007 and to 38.1% in 2013. In contrast, in Western Gambia, the frequency of the deletion fluctuated over time; it increased between 1984 and 2005 from (58.04%) to (69.33%) and decreased to 47.47% in 2007. Between 2007 and 2012, the prevalence of this deletion increased significantly from 47.47 to 83.02% and finally declined significantly to 57.94% in 2013. Association between the presence of this deletion and age was found in Thiès, however, not in Western Gambia. For the majority of isolates, the PfRh2b alleles could be tracked with specific 24-SNP barcoded genotype, indicating a lack of independent selection at this locus. CONCLUSION: PfRh2b deletion was found in the two countries with varying prevalence during the study period. However, these temporal and spatial variations could be an obstacle to the implementation of this protein as a potential vaccine candidate. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-019-2868-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-16 /pmc/articles/PMC6636118/ /pubmed/31311552 http://dx.doi.org/10.1186/s12936-019-2868-x 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
Diédhiou, Cyrille K.
Moussa, Rahama A.
Bei, Amy K.
Daniels, Rachel
Papa Mze, Nasserdine
Ndiaye, Daouda
Faye, Ngor
Wirth, Dyann
Amambua-Ngwa, Alfred
Mboup, Souleymane
Ahouidi, Ambroise D.
Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia
title Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia
title_full Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia
title_fullStr Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia
title_full_unstemmed Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia
title_short Temporal changes in Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) in Senegal and The Gambia
title_sort temporal changes in plasmodium falciparum reticulocyte binding protein homolog 2b (pfrh2b) in senegal and the gambia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636118/
https://www.ncbi.nlm.nih.gov/pubmed/31311552
http://dx.doi.org/10.1186/s12936-019-2868-x
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