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

Malaria Journal

Research

Dong-Il Chung¹  Zin Moon¹  Sylvatrie-Danne Dinzouna-Boutamba¹  Yeonchul Hong¹  Ja Moon Aung¹  Youn-Kyoung Goo¹  Sanghyun Lee²  Berthe Amélie Iroungou³  Lauriane Yacka-Mouele³  Falone Larissa Akombi³ 

[1] Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University, 41944, Daegu, Korea;Division of Bio Bigdata, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, 28159, Cheongju, Korea;Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et le Service de Santé Militaire, 20404, Libreville, Gabon;

关键词: Malaria;    Mutation;    Haplotypes;    Artemisinin combination therapy;    Resistance;    Libreville;   

DOI  :  10.1186/s12936-023-04615-1

 received in 2023-02-10, accepted in 2023-06-04,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGabon 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.MethodsTo 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.ResultsThe 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.ConclusionsHigh polymorphism frequencies of Pfdhfr and Pfdhps genes were observed, with alternative alanine/phenylalanine mutation at S436A/F (7.69%, n = 5) for the first time. Similar to that of other areas of the country, the patterns of multiple polymorphisms were consistent with selection owing to drug pressure. Although there was no evidence of a medication failure haplotype in the studied population, ACT drug efficacy should be regularly monitored in Libreville, Gabon.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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