QIMR Berghofer Medical Research Institute, Herston Australia.
Medicine for Malaria Venture, Meyrin, Switzerland.
J Infect Dis. 2022 Mar 15;225(6):1062-1069. doi: 10.1093/infdis/jiaa287.
Interventions that effectively target Plasmodium vivax are critical for the future control and elimination of malaria. We conducted a P. vivax volunteer infection study to characterize the antimalarial activity of artefenomel, a new drug candidate.
Eight healthy, malaria-naive participants were intravenously inoculated with blood-stage P. vivax and subsequently received a single oral 200-mg dose of artefenomel. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma artefenomel concentration. Mosquito feeding assays were conducted before artefenomel dosing to investigate parasite transmissibility.
Initial parasite clearance occurred in all participants after artefenomel administration (log10 parasite reduction ratio over 48 hours, 1.67; parasite clearance half-life, 8.67 hours). Recrudescence occurred in 7 participants 11-14 days after dosing. A minimum inhibitory concentration of 0.62 ng/mL and minimum parasiticidal concentration that achieves 90% of maximum effect of 0.83 ng/mL were estimated, and a single 300-mg dose was predicted to clear 109 parasites per milliliter with 95% certainty. Gametocytemia developed in all participants and was cleared 4-8 days after dosing. At peak gametocytemia, 75% of participants were infectious to mosquitoes.
The in vivo antimalarial activity of artefenomel supports its further clinical development as a treatment for P. vivax malaria.
NCT02573857.
针对间日疟原虫的有效干预措施对未来疟疾的控制和消除至关重要。我们开展了一项间日疟原虫志愿者感染研究，以评估新型候选药物阿法特梅尔的抗疟活性。
8 名健康、无疟疾史的参与者静脉接种间日疟原虫血期虫株，随后单次口服 200mg 阿法特梅尔。采集血样以监测寄生虫血症的发生和清除情况，并检测血浆中阿法特梅尔的浓度。在给予阿法特梅尔之前进行蚊虫感染性实验，以评估寄生虫的传播能力。
所有参与者在给予阿法特梅尔后均迅速清除初始寄生虫（48 小时内对数 10 寄生虫减少比为 1.67；寄生虫清除半衰期为 8.67 小时）。7 名参与者在给药后 11-14 天出现复发。估计最小抑制浓度为 0.62ng/ml，达到最大效应 90%的最小杀菌浓度为 0.83ng/ml，单次 300mg 剂量预计可清除每毫升 109 个寄生虫，有 95%的把握。所有参与者均出现配子体血症，在给药后 4-8 天清除。在配子体血症高峰期，75%的参与者对蚊子具有感染性。
阿法特梅尔在体内的抗疟活性支持其进一步开发为治疗间日疟原虫疟疾的药物。
NCT02573857。
