Abstract
BackgroundIn 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. Because SP is still used for intermittent preventive treatment in pregnant women (IPTp) and seasonal malaria chemoprevention (SMCP) in Benin, the prevalence of Pfdhfr and Pfdhps SNPs in P. falciparum isolates collected in 2017 were investigated.MethodsThis study was carried out in two sites where the transmission of P. falciparum malaria is hyper-endemic: Klouékanmey and Djougou. Blood samples were collected from 178 febrile children 6–59 months old with confirmed uncomplicated P. falciparum malaria and were genotyped for SNPs associated with SP resistance.ResultsThe Pfdhfr triple mutant IRN (N51I, C59R, and S108N) was the most prevalent (84.6%) haplotype and was commonly found with the Pfdhps single mutant A437G (50.5%) or with the Pfdhps double mutant S436A and A437G (33.7%). The quintuple mutant, PfdhfrIRN/PfdhpsGE (A437G and K540E), was rarely observed (0.8%). The A581G and A613S mutant alleles were found in 2.6 and 3.9% of isolates, respectively. Six isolates (3.9%) were shown to harbour a mutation at codon I431V, recently identified in West African parasites.ConclusionsThis study showed that Pfdhfr triple IRN mutants are near fixation in this population and that the highly sulfadoxine-resistant Pfdhps alleles are not widespread in Benin. These data support the continued use of SP for chemoprevention in these study sites, which should be complemented by periodic nationwide molecular surveillance to detect emergence of resistant genotypes.
Highlights
In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria
In 2004, Benin joined many other countries in Svigel et al Malar J (2021) 20:72. Africa in changing their recommended first-line treatment of uncomplicated malaria to artemisinin-based combination therapy (ACT) [2] due to reported high treatment failure rates in children treated with sulfadoxine-pyrimethamine (SP) for uncomplicated malaria [3,4,5]
Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in two genes that code for enzymes involved in Plasmodium falciparum folate metabolism: P. falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps), which are targeted by pyrimethamine and sulfadoxine, respectively
Summary
In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. In 2004, Benin joined many other countries in Svigel et al Malar J (2021) 20:72 Africa in changing their recommended first-line treatment of uncomplicated malaria to artemisinin-based combination therapy (ACT) [2] due to reported high treatment failure rates in children treated with sulfadoxine-pyrimethamine (SP) for uncomplicated malaria [3,4,5]. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in two genes that code for enzymes involved in Plasmodium falciparum folate metabolism: P. falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps), which are targeted by pyrimethamine and sulfadoxine, respectively. At least five SNPs in Pfdhps are involved in resistance to sulfadoxine: S436A/F, A437G, K540E, A581G, and A613S/T [8,9,10,11,12]
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