Prevalence of Mutations in the Pfdhfr, Pfdhps, and Pfmdr1 Genes of Malarial Parasites Isolated from Symptomatic Patients in Dogondoutchi, Niger

Abstract

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 <i>Pfdhfr</i>, <i>Pfdhps,</i> and <i>Pfmdr1</i> genes from isolates collected during a clinical study. <i>Plasmodium</i> genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the <i>Pfdhfr</i> (codons 51, 59, 108, and 164), <i>Pfdhps</i> (codons 436, 437, 540, 581, and 613), and <i>Pfmdr1</i> (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were sequenced for the <i>Pfdhfr, Pfdhps,</i> and <i>Pfmdr1</i> genes. A high prevalence of mutations in the <i>Pfdhfr</i> 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 <i>Pfdhps</i> gene was not observed. Only one isolate was found to harbor a mutation at codon I431V. The most common mutation on the <i>Pfmdr1</i> 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 <i>Pfdhps</i> (581 and 613) and <i>Pfmdr</i> (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 <i>Pfdhfr</i>, <i>Pfdhps,</i> and <i>Pfmdr1</i> genes. Although a high prevalence of mutations in the <i>Pfdhfr</i> gene have been observed, there is a lack of sulfadoxine pyrimethamine resistance. There is a high prevalence of mutation in the <i>Pfmdr184</i> codon associated with resistance to amodiaquine. These data will be used by Niger's National Malaria Control Program to better monitor the resistance of <i>Plasmodium</i> to partner molecules in artemisinin-based combination therapies.