Background Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and methods Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.

中文翻译：

---

双氢青蒿素/哌喹对喀麦隆雅温得非复杂性恶性疟原虫疟疾患者的疗效

背景 双氢青蒿素/哌喹在非洲越来越多地用于治疗非复杂性恶性疟原虫疟疾。这种组合在喀麦隆的疗效记录很少，而对双氢青蒿素/哌喹的耐药性很容易在东南亚蔓延。目的 本研究评估双氢青蒿素/哌喹在喀麦隆的临床疗效，以及收集的分离株对双氢青蒿素和哌喹的分子谱和表型敏感性。患者和方法 对 138 名非复杂性恶性疟患者进行 42 天双氢青蒿素/哌喹疗效随访。在第 7 天测定了 124 名患者的哌喹浓度。kelch13 基因多态性 (n = 150) 和 plasmepsin2 基因扩增 (n = 148) 分别被确定为对双氢青蒿素和哌喹抗性的分子标记。寄生虫对双氢青蒿素和哌喹的敏感性是使用经过验证的体外存活试验确定的。结果经PCR校正后双氢青蒿素/哌喹治疗有效率100%。再感染与第 7 天哌喹浓度的变化无关。百分之九十六 (144/150) 的样本呈现出 kelch13 基因的 WT 等位基因。2% (3/150) 的非同义突变 A578S 与对双氢青蒿素的耐药性无关。没有观察到 plasmepsin2 基因的重复（0/148）。通过存活试验在体外测试的所有样品（n = 87）都对双氢青蒿素和哌喹敏感。结论 双氢青蒿素/哌喹在喀麦隆雅温得显示出优异的治疗效果，没有证据表明出现青蒿素或哌喹耐药。这一观察结果表明，与东南亚不同，如果在以前没有青蒿素和哌喹抗性寄生虫的地区实施，双氢青蒿素/哌喹可能是恶性疟的可持续治疗解决方案。