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The effectiveness of artemisinin-based combination therapies (ACTs) depends not only on that of artemisinin but also on that of partner molecules. This study aims to evaluate the prevalence of mutations in the Pfdhfr, Pfdhps, and Pfmdr1 genes from isolates collected during a clinical study. Plasmodium genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the Pfdhfr (codons 51, 59, 108, and 164), Pfdhps (codons 436, 437, 540, 581, and 613), and Pfmdr1 (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were sequenced for the Pfdhfr, Pfdhps, and Pfmdr1 genes. A high prevalence of mutations in the Pfdhfr gene was observed at the level of the N51I (84.97%), C59R (92.62%), and S108N (97.39%) codons. The key K540E mutation in the Pfdhps gene was not observed. Only one isolate was found to harbor a mutation at codon I431V. The most common mutation on the Pfmdr1 gene was Y184F in 71.43% of the mutations found, followed by N86Y in 10.20%. The triple-mutant haplotype N51I/C59R/S108N (IRN) was detected in 97% of the samples. Single-mutant (ICS and NCN) and double-mutant (IRS, NRN, and ICN) haplotypes were prevalent at 97% and 95%, respectively. Double-mutant haplotypes of the Pfdhps (581 and 613) and Pfmdr (86 and 184) were found in 3% and 25.45% of the isolates studied, respectively. The study focused on the molecular analysis of the sequencing of the Pfdhfr, Pfdhps, and Pfmdr1 genes. Although a high prevalence of mutations in the Pfdhfr gene have been observed, there is a lack of sulfadoxine pyrimethamine resistance. There is a high prevalence of mutation in the Pfmdr184 codon associated with resistance to amodiaquine. These data will be used by Niger’s National Malaria Control Program to better monitor the resistance of Plasmodium to partner molecules in artemisinin-based combination therapies.

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Introduction le paludisme chez la femme enceinte est un problème majeur de santé publique en Afrique. Il a des conséquences graves aussi bien sur la mère, le fœtus que le nouveau-né. Il est responsable d´un fort taux de morbi-mortalité maternelle et infantile. L´objectif de l´étude est de déterminer la prévalence de l´infection plasmodiale chez la femme enceinte, décrire ses signes cliniques et ses complications éventuelles, analyser les facteurs associés et proposer des mesures de prévention. Méthodes il s´agit d´une étude transversale, conduite du 1 er juin au 30 novembre 2017 à la Maternité Issaka Gazobi (MIG) de Niamey. Le diagnostic a été fait par microscopie. Résultats deux cents quarante-neuf (249) femmes ont été incluses dans cette étude. La prévalence de l´infection plasmodiale était de 36,5% (IC95%; [30,6; 42,9]). La densité parasitaire moyenne était de 177 P/μl (DS: 121; [40; 800]). Toutes les infections étaient à P. falciparum. Un peu plus de soixante-treize pourcent (73,6%). Seules 26,4% (24/91) ont fait un paludisme non compliqué ; 9,6% (6/91) ont avorté ; 38,4% des nouveau-nés avaient un faible poids à la naissance et 26,51% (66/249) ont développé un paludisme congénital. Le taux de létalité était de 1,1% (1/91). Le traitement préventif intermittent (TPI) protège significativement contre le paludisme gestationnel (p=0,01). Conclusion l´infection des femmes enceintes par le P. falciparum est très fréquente au Niger. Ce portage est le plus souvent asymptomatique mais peut évoluer vers un paludisme non compliqué ou même sévère. Les principales conséquences sont l´avortement, le faible poids à la naissance, le retard de croissance intra utero, le paludisme congénital et le décès maternel. Le TPI et l´utilisation de la moustiquaire imprégnée d´insecticide à longue durée d´action (MILDA) permettent de prévenir l´infection.

Background: Artemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum kelch gene (Pfkelch13) propeller domains have been associated with delayed parasite clearance even with ACT treatment. Methods: The Pfkelch13gene was sequenced from P. falciparum infected patients (n=159) with uncomplicated malaria in Niger.An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n=4) patients had treatment failure (TF) that were not reinfections - two of which had late parasitological failures (LPF) and two had late clinical failures (LCF). Results: Thirteen single nucleotide polymorphisms (SNPs) were identified of which eight were non synonymous (NSY) (C469R, T508S, S515T, A578S, I465V, I437V, E506L, N197D), and five were synonymous (SY) (H298H, H385H, P443P, P715P, L514L). Six SNP (C469R, H298H, E506L, N197D, H385H, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, S515T, L514L, P443P, I437V, I465V) were selected by Artemether lumefantrine (AL) - five of which were non synonymous (C469R, T508S, S515T, I437V, I465V). Artesunate amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs - C469R, T508S, S515T. This study demonstrates intra host selection of Pfkelch13 gene NS by AL. Conclusions: The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common S515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations. GenBank accession numbers: MZ364160, MZ364-213