Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon

• Published in: Malaria Journal
• Main Authors: Sylvatrie-Danne Dinzouna-Boutamba, Berthe Amélie Iroungou, Falone Larissa Akombi, Lauriane Yacka-Mouele, Zin Moon, Ja Moon Aung, Sanghyun Lee, Dong-Il Chung, Yeonchul Hong, Youn-Kyoung Goo
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2023
• Subjects: Malaria; Mutation; Haplotypes; Artemisinin combination therapy; Resistance; Libreville; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic; Irni
• Online Access: https://doi.org/10.1186/s12936-023-04615-1; https://doaj.org/article/d93ff032821340b3843c31518d452973

Abstract Background Gabon is a malaria-threatened country with a stable and hyperendemic transmission of Plasmodium falciparum monoinfection. Malaria drug resistance is widely spread in many endemic countries around the world, including Gabon. The molecular surveillance of drug resistance to antifolates and artemisinin-based combination therapy (ACT) is one of the strategies for combating malaria. As Plasmodium parasites continue to develop resistance to currently available anti-malarial drugs, this study evaluated the frequency of the polymorphisms and genetic diversity associated with this phenomenon among the parasites isolates in Gabon. Methods To assess the spread of resistant haplotypes among the malaria-infected population of Libreville, single nucleotide polymorphisms linked to sulfadoxine–pyrimethamine (SP) and artemisinin drugs resistance were screened for P. falciparum dihydrofolate reductase (Pfdhfr), P. falciparum dihydropteroate synthase (Pfdhps), and P. falciparum kelch 13-propeller domain (Pfk13) point mutations. Results The analysis of 70 malaria-positive patient samples screened for polymorphism showed 92.65% (n = 63) mutants vs. 7.35% (n = 5) wild parasite population in Pfdhfr, with high prevalence mutations at S108N(88.24%, n = 60), N51I(85.29%, n = 58), C59R(79.41%, n = 54); however, I164L(2.94%, n = 2) showed low frequency mutation. No wild haplotype existed for Pfdhps, and there were no mutations at the K540E, A581G, and A613T/S positions. However, the mutation rate at A437G(93.38%, n = 62) was the highest, followed by S436A/F(15.38%, n = 10). A higher frequency of quadruple IRNI–SGKAA (69.84%) than quintuple IRNI–(A/F)GKAA (7.94%) mutations was observed in the Pfdhfr–Pfdhps combination. Furthermore, none of the mutations associated with ACT resistance, especially those commonly found in Africa, were observed in Pfk13. Conclusions High polymorphism frequencies of Pfdhfr and Pfdhps genes were observed, with alternative alanine/phenylalanine mutation at S436A/F (7.69%, n = 5) for the first ...