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Background: 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. 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. Methods: This 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. Results: The 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. Conclusions: This 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. [ABSTRACT FROM AUTHOR]

Background: Despite widespread parasite resistance to sulphadoxine-pyrimethamine (SP) its use for intermittent preventative treatment during pregnancy remains the policy in Benin and throughout most of sub-Saharan Africa. Methods: In a prospective study, 982 pregnant women were recruited in Benin and followed until delivery. The prevalence of point mutations in the pfdhfr and pfdhps genes associated with Plasmodium falciparum resistance to SP during consecutive antenatal visits was determined. Parasites clearance among women infected at SP intake was assessed by microscopy and PCR. Association between the persistence of parasites and malaria consequences, were investigated. Recurrent parasites were genotyped to identify recrudescences from re-infections. Results: The prevalence of pfdhfr/pfdhps quadruple mutants (triple pfdhfr + single pfdhps) was consistently above 80% while quintuple and sextuple mutants remained low. Importantly the higly mutated parasites apparently never included the two key mutations, pfdhfr 164 L or pfdhps 540E. Based on PCR results, SP failed to clear existing parasitaemia in half (48%) of the women who were infected at IPTp schedule. The frequency of recrudescence reached 76% after the second dose. Women with persistent parasitaemia had an increased prevalence of anaemia (P = 0.03). Conclusion: The data presented here, highlight the inability of SP to ensure optimal antiplasmodial protection in late pregnancy, and invite urgent consideration of an alternative drug or strategy. [ABSTRACT FROM AUTHOR]