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Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso
BACKGROUND: Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy (IPTp-SP) is widely impleme...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410088/ https://www.ncbi.nlm.nih.gov/pubmed/28454537 http://dx.doi.org/10.1186/s12936-017-1831-y |
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author | Ruizendaal, Esmée Tahita, Marc C. Geskus, Ronald B. Versteeg, Inge Scott, Susana d’Alessandro, Umberto Lompo, Palpouguini Derra, Karim Traore-Coulibaly, Maminata de Jong, Menno D. Schallig, Henk D. F. H. Tinto, Halidou Mens, Petra F. |
author_facet | Ruizendaal, Esmée Tahita, Marc C. Geskus, Ronald B. Versteeg, Inge Scott, Susana d’Alessandro, Umberto Lompo, Palpouguini Derra, Karim Traore-Coulibaly, Maminata de Jong, Menno D. Schallig, Henk D. F. H. Tinto, Halidou Mens, Petra F. |
author_sort | Ruizendaal, Esmée |
collection | PubMed |
description | BACKGROUND: Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P. falciparum are associated with SP resistance. In this study the prevalence of SP resistance mutations was determined among P. falciparum found in pregnant women and the general population (GP) from Nanoro, Burkina Faso and the association of IPTp-SP dosing and other variables with mutations was studied. METHODS: Blood spots on filter papers were collected from pregnant women at their first antenatal care visit (ANC booking) and at delivery, from an ongoing trial and from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified by nested PCR and products were sequenced to identify mutations conferring resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was estimated with generalized estimating equations and for multivariate analyses mixed effects logistic regression was used. RESULTS: The prevalence of the triple dhfr mutation was high, and significantly higher in the GP and at delivery than at ANC booking, but it did not affect birth weight. Furthermore, quintuple mutations (triple dhfr and double dhps mutations) were found for the first time in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of the mutations, but high transmission season was associated with increased mutation prevalence in delivery samples. It is unclear why the prevalence of mutations was higher in the GP than in pregnant women at ANC booking. CONCLUSION: The high number of mutants and the presence of quintuple mutants in Burkina Faso confirm concerns about the efficacy of IPTp-SP in the near future. Other drug combinations to tackle malaria in pregnancy should, therefore, be explored. An increase in mutation prevalence due to IPTp-SP dosing could not be confirmed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1831-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5410088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54100882017-05-02 Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso Ruizendaal, Esmée Tahita, Marc C. Geskus, Ronald B. Versteeg, Inge Scott, Susana d’Alessandro, Umberto Lompo, Palpouguini Derra, Karim Traore-Coulibaly, Maminata de Jong, Menno D. Schallig, Henk D. F. H. Tinto, Halidou Mens, Petra F. Malar J Research BACKGROUND: Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P. falciparum are associated with SP resistance. In this study the prevalence of SP resistance mutations was determined among P. falciparum found in pregnant women and the general population (GP) from Nanoro, Burkina Faso and the association of IPTp-SP dosing and other variables with mutations was studied. METHODS: Blood spots on filter papers were collected from pregnant women at their first antenatal care visit (ANC booking) and at delivery, from an ongoing trial and from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified by nested PCR and products were sequenced to identify mutations conferring resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was estimated with generalized estimating equations and for multivariate analyses mixed effects logistic regression was used. RESULTS: The prevalence of the triple dhfr mutation was high, and significantly higher in the GP and at delivery than at ANC booking, but it did not affect birth weight. Furthermore, quintuple mutations (triple dhfr and double dhps mutations) were found for the first time in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of the mutations, but high transmission season was associated with increased mutation prevalence in delivery samples. It is unclear why the prevalence of mutations was higher in the GP than in pregnant women at ANC booking. CONCLUSION: The high number of mutants and the presence of quintuple mutants in Burkina Faso confirm concerns about the efficacy of IPTp-SP in the near future. Other drug combinations to tackle malaria in pregnancy should, therefore, be explored. An increase in mutation prevalence due to IPTp-SP dosing could not be confirmed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1831-y) contains supplementary material, which is available to authorized users. BioMed Central 2017-04-28 /pmc/articles/PMC5410088/ /pubmed/28454537 http://dx.doi.org/10.1186/s12936-017-1831-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 Ruizendaal, Esmée Tahita, Marc C. Geskus, Ronald B. Versteeg, Inge Scott, Susana d’Alessandro, Umberto Lompo, Palpouguini Derra, Karim Traore-Coulibaly, Maminata de Jong, Menno D. Schallig, Henk D. F. H. Tinto, Halidou Mens, Petra F. Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso |
title | Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso |
title_full | Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso |
title_fullStr | Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso |
title_full_unstemmed | Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso |
title_short | Increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso |
title_sort | increase in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in plasmodium falciparum isolates collected from early to late pregnancy in nanoro, burkina faso |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410088/ https://www.ncbi.nlm.nih.gov/pubmed/28454537 http://dx.doi.org/10.1186/s12936-017-1831-y |
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