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 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.

Plasmodium falciparum drug resistance-associated mutations in isolates from children living in endemic areas of Burkina Faso

“…The 436A mutation has been described throughout Africa at varying levels of frequency (41)(42)(43)(44). Detecting the I431V mutation in this study, albeit at a low prevalence, con rms a previous nding from Ghana and Niger, two countries neighboring Burkina Faso (41)(42)(43)(44). The impact of the I431V mutation on the continued use of SP for IPTp remains to be elucidated (45).…”

“…The mutation A437G was not found as well in the study conducted in Niger on symptomatic malaria cases in pre-treatment (41). The 436A mutation has been described throughout Africa at varying levels of frequency (41)(42)(43)(44). Detecting the I431V mutation in this study, albeit at a low prevalence, con rms a previous nding from Ghana and Niger, two countries neighboring Burkina Faso (41)(42)(43)(44).…”

“…The codons 613S, 431V, 436F 436Y, 540E, and 581G were also found at varying frequencies. The mutation A437G was not found as well in the study conducted in Niger on symptomatic malaria cases in pre-treatment (41). The 436A mutation has been described throughout Africa at varying levels of frequency (41)(42)(43)(44).…”

Therapeutic efficacy and tolerability of artemether–lumefantrine for uncomplicated Plasmodium falciparum malaria in Niger, 2020

“…The PCR/Sequencing method for pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes was used to study molecular resistance to anti-malarials [ 14 , 19 ].…”

“…In 2017, a study of pfdhfr and pfdhps markers associated with SP resistance showed 97.4% prevalence for pfdhfrS108N , 92.6% for PfdhfrC59R and 85.0% for PfdhfrN51I in [ 14 ]. A 2018 study showed a prevalence of 59.0% for PfdhpsA437G and 43.1% for PfdhpsS436A [ 15 ].…”