Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin

Bertin, Gwladys; Briand, Valérie; Bonaventure, Diana; Carrieu, Ambre; Massougbodji, Achille; Cot, Michel; Deloron, Philippe

doi:10.1186/1475-2875-10-196

Cited by 37Malaria Research and ControlPharmacogenetics and Drug MetabolismDrug Transport and Resistance Mechanisms

Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin

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Bertin, Gwladys, Briand, Valérie, Bonaventure, Diana, Carrieu, Ambre, Massougbodji, Achille, Cot, Michel, Deloron, Philippe·2011·Malaria Journal

DOI 10.1186/1475-2875-10-196PMC PMC3199903

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Abstract

Background: The prevention of malaria faces with the repeated emergence of Plasmodium falciparum resistance to drugs, often involving point mutations of the target gene. In the pregnant woman, currently the WHO recommendation is the administration of an intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine. Sulphadoxine-pyrimethamine (SP) resistance has increased for several years in Africa, stressing the need for alternative molecules. In this context, the first randomized clinical trial comparing the efficacy of SP and mefloquine for IPTp has been conducted recently in Benin. Using samples from this trial, the current study evaluated and quantified the prevalence of mutations on the pfdhfr and pfdhps genes as well as the copy number of the pfmdr1 gene in parasites from P. falciparum-infected pregnant women before first and second IPTp administration, and at delivery. Methods: PCR-restriction fragment length polymorphism of polymorphic codons of the pfdhfr gene (51, 59, 108, and 164) was performed. The identification of mutations in three codons of the pfdhps gene (436, 437 and 540) was achieved by PCR and sequencing. Copy number quantification for pfmdr1 gene was performed using real-time PCR. Results: Results show a high prevalence rate of mutant parasites in women taking IPTp with sulphadoxine-pyrimethamine or mefloquine. The prevalence of triple and quadruple mutants was high before first drug regimen administration (79/93, 85%), and remained similar until delivery. Infection with mutant parasites was not correlated with low birth weight nor placental infection. In all samples, the copy number of pfmdr1 gene was equal to one. Conclusions: The clinical trial comparing SP and mefloquine efficacy during IPTp showed SP remained efficacious in preventing low birth weight. The present study shows a high prevalence of triple and quadruple mutations implicated in SP resistance. Although the pfdhfr/pfdhps triple and quadruple mutations were frequent, there was no evidence of correlation between these genotypes and the lack of efficacy of SP in the context of IPTp. Nevertheless, it is now obvious that SP will soon be compromised in whole Africa. Molecular markers have been recommended to monitor SP efficacy for IPTp, but given the current prevalence of mutant parasites their usefulness is questionable.

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A study in Benin showed that, despite the presence of molecular markers of resistance, SP remained efficacious.
“A study in Benin has showed that, despite the presence of molecular markers of resistance, SP remained efficacious.105”
From Malaria in pregnancy. (2013) · cites this paper as [105]

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Authors: Bertin, G., Briand, V., Bonaventure, D., Carrieu, A., Massougbodji, A., Cot, M., & Deloron, P.
Affiliations: Santé Internationale de la mère et de l'enfant (FR)
Université d'Abomey-Calavi (BJ)
Corresponding author: Deloron, Philippe
ORCID: Bertin, Gwladys
Briand, Valérie
Massougbodji, Achille
Cot, Michel
Deloron, Philippe
Venue: Malaria Journal
Publisher: Springer Science and Business Media LLC
Published: 2011-07-19
Volume: 10
Issue: 1
Pages: 196-196
ISSN: 1475-2875 (ISSN-L)
DOI: 10.1186/1475-2875-10-196
PMC: PMC3199903
OpenAlex: W2167615615
Cited by: 37
References: 27
Citations by year: 2026: 1 · 2024: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 6
FWCI: 5.03
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Malaria Journal (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Institut de Recherche pour le Développement
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords: sulfadoxine-pyrimethamine resistance, intermittent preventive treatment in pregnancy, Plasmodium falciparum, pfdhfr mutations, pfdhps mutations, mefloquine, drug resistance markers, low birth weight, placental malaria, Benin
MeSH terms: Adult, Antimalarials, Benin, Clinical Trials as Topic, Dihydropteroate Synthase, Drug Combinations, Drug Resistance, Female, Genotype, Humans, Plasmodium falciparum, Pregnancy, Pregnancy Complications, Pyrimethamine, Sulfadoxine, Tetrahydrofolate Dehydrogenase, Biomarkers, Mefloquine, Malaria, Falciparum, Gene Dosage, Chemoprevention, Mutation, Missense, Multidrug Resistance-Associated Proteins, ATP-Binding Cassette, Sub-Family C Proteins

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Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin

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