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...

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Main Authors: Ruizendaal, E, Tahita, M, Geskus, R, Versteeg, I, Scott, S, d'Alessandro, U, Lompo, P, Derra, K, Traore-Coulibaly, M, de Jong, M, Schallig, H, Tinto, H, Mens, P
Format: Journal article
Language:English
Published: BioMed Central 2017
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author Ruizendaal, E
Tahita, M
Geskus, R
Versteeg, I
Scott, S
d'Alessandro, U
Lompo, P
Derra, K
Traore-Coulibaly, M
de Jong, M
Schallig, H
Tinto, H
Mens, P
author_facet Ruizendaal, E
Tahita, M
Geskus, R
Versteeg, I
Scott, S
d'Alessandro, U
Lompo, P
Derra, K
Traore-Coulibaly, M
de Jong, M
Schallig, H
Tinto, H
Mens, P
author_sort Ruizendaal, E
collection OXFORD
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.
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spelling oxford-uuid:c41ae409-68b0-4388-a690-7ae06d01a46b2022-03-27T06:21:12ZIncrease in the prevalence of mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina FasoJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c41ae409-68b0-4388-a690-7ae06d01a46bEnglishSymplectic Elements at OxfordBioMed Central2017Ruizendaal, ETahita, MGeskus, RVersteeg, IScott, Sd'Alessandro, ULompo, PDerra, KTraore-Coulibaly, Mde Jong, MSchallig, HTinto, HMens, PBACKGROUND: 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.
spellingShingle Ruizendaal, E
Tahita, M
Geskus, R
Versteeg, I
Scott, S
d'Alessandro, U
Lompo, P
Derra, K
Traore-Coulibaly, M
de Jong, M
Schallig, H
Tinto, H
Mens, P
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
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