Mairet-Khedim Mélissa, Nsango Sandrine, Ngou Christelle, Menard Sandie, Roesch Camille, Khim Nimol, Srun Sreynet, Iriart Xavier, Lanot Thomas, Otam Laure, Abega Francis, Ayong Lawrence, Morlais Isabelle, Gandia Peggy, Witkowski Benoit, Berry Antoine
Malaria Translational Research Unit, Pasteur International Unit, Pasteur International Network, Phnom Penh, Cambodia and Paris, France.
Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.
J Antimicrob Chemother. 2021 Oct 11;76(11):3037-3044. doi: 10.1093/jac/dkab281.
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.
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.
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.
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.
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.
双氢青蒿素/哌喹越来越多地用于治疗非洲的非复杂性恶性疟原虫疟疾。该联合用药在喀麦隆的疗效记录较少，而对双氢青蒿素/哌喹的耐药性在东南亚迅速蔓延。
本研究评估了双氢青蒿素/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特征及表型敏感性。
对138例非复杂性恶性疟患者随访42天，观察双氢青蒿素/哌喹的疗效。测定了124例患者第7天的哌喹浓度。分别测定kelch13基因多态性（n = 150）和疟原虫天冬氨酸蛋白酶2基因扩增（n = 148），作为对双氢青蒿素和哌喹耐药的分子标志物。采用经验证的体外存活试验测定寄生虫对双氢青蒿素和哌喹的敏感性。
PCR校正后双氢青蒿素/哌喹治疗的疗效为100%。再感染与第7天哌喹浓度的变化无关。96%（144/150）的样本呈现kelch13基因的野生型等位基因。2%（3/150）呈现非同义突变A578S，该突变与对双氢青蒿素的耐药性无关。未观察到疟原虫天冬氨酸蛋白酶2基因的重复（0/148）。通过存活试验体外检测的所有样本（n = 87）对双氢青蒿素和哌喹均敏感。
在喀麦隆雅温得，双氢青蒿素/哌喹已显示出优异的治疗效果，没有出现青蒿素或哌喹耐药性的迹象。这一观察结果表明，如果在以前没有青蒿素和哌喹耐药寄生虫的地区实施，双氢青蒿素/哌喹可能是治疗恶性疟原虫疟疾的一种可持续治疗方案，这与东南亚不同。
