Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
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
_version_ 1783232604465528832
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
work_keys_str_mv AT ruizendaalesmee increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT tahitamarcc increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT geskusronaldb increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT versteeginge increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT scottsusana increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT dalessandroumberto increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT lompopalpouguini increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT derrakarim increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT traorecoulibalymaminata increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT dejongmennod increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT schallighenkdfh increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT tintohalidou increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso
AT menspetraf increaseintheprevalenceofmutationsassociatedwithsulfadoxinepyrimethamineresistanceinplasmodiumfalciparumisolatescollectedfromearlytolatepregnancyinnanoroburkinafaso