Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Korea.
Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et le Service de Santé Militaire, Libreville, 20404, Gabon.
Malar J. 2023 Jun 14;22(1):183. doi: 10.1186/s12936-023-04615-1.
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.
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.
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 SN(88.24%, n = 60), NI(85.29%, n = 58), CR(79.41%, n = 54); however, IL(2.94%, n = 2) showed low frequency mutation. No wild haplotype existed for Pfdhps, and there were no mutations at the KE, AG, and AT/S positions. However, the mutation rate at AG(93.38%, n = 62) was the highest, followed by SA/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.
High polymorphism frequencies of Pfdhfr and Pfdhps genes were observed, with alternative alanine/phenylalanine mutation at SA/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.
加蓬是一个疟疾威胁严重的国家，恶性疟原虫单一感染存在稳定且高度流行的传播。抗疟药物耐药性在世界各地许多流行国家广泛传播，包括加蓬。抗叶酸类药物和青蒿素为基础的联合治疗（ACT）耐药性的分子监测是对抗疟疾的策略之一。由于疟原虫寄生虫继续对现有抗疟药物产生耐药性，因此本研究评估了加蓬寄生虫分离株中与这种现象相关的多态性和遗传多样性的频率。
为了评估利伯维尔疟疾感染人群中耐药单倍型的传播，筛选了与磺胺多辛-乙胺嘧啶（SP）和青蒿素药物耐药相关的单核苷酸多态性，以检测恶性疟原虫二氢叶酸还原酶（Pfdhfr）、恶性疟原虫二氢蝶酸合成酶（Pfdhps）和恶性疟原虫 Kelch 13-螺旋桨结构域（Pfk13）点突变。
对 70 个疟疾阳性患者样本进行了多态性分析，结果显示 Pfdhfr 中有 92.65%（n=63）突变体对 7.35%（n=5）野生寄生虫群体，SN（88.24%，n=60）、NI（85.29%，n=58）、CR（79.41%，n=54）的高流行突变；然而，IL（2.94%，n=2）的突变频率较低。Pfdhps 不存在野生单倍型，KE、AG 和 AT/S 位置没有突变。然而，AG（93.38%，n=62）的突变率最高，其次是 SA/F（15.38%，n=10）。在 Pfdhfr-Pfdhps 组合中观察到更高频率的四联体 IRNI-SGKAA（69.84%）而非五联体 IRNI-（A/F）GKAA（7.94%）突变。此外，在 Pfk13 中没有观察到与 ACT 耐药性相关的突变，尤其是在非洲常见的突变。
观察到 Pfdhfr 和 Pfdhps 基因的高多态性频率，首次在 SA/F（7.69%，n=5）观察到替代丙氨酸/苯丙氨酸突变。与该国其他地区一样，多态性模式与药物压力下的选择一致。尽管在所研究的人群中没有发现药物失败的单倍型，但在加蓬利伯维尔应定期监测 ACT 药物的疗效。
