1. Safety and parasite clearance of artemisinin-resistant Plasmodium falciparum infection: A pilot and a randomised volunteer infection study in Australia
- Author
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von Seidlein, L, Watts, RE, Odedra, A, Marquart, L, Webb, L, Abd-Rahman, AN, Cascales, L, Chalon, S, Rebelo, M, Pava, Z, Collins, KA, Pasay, C, Chen, N, Peatey, CL, Mohrle, JJ, McCarthy, JS, von Seidlein, L, Watts, RE, Odedra, A, Marquart, L, Webb, L, Abd-Rahman, AN, Cascales, L, Chalon, S, Rebelo, M, Pava, Z, Collins, KA, Pasay, C, Chen, N, Peatey, CL, Mohrle, JJ, and McCarthy, JS
- Abstract
Background Artemisinin resistance is threatening malaria control. We aimed to develop and test a human model of artemisinin-resistant (ART-R) Plasmodium falciparum to evaluate the efficacy of drugs against ART-R malaria. Methods and findings We conducted 2 sequential phase 1, single-centre, open-label clinical trials at Q-Pharm, Brisbane, Australia, using the induced blood-stage malaria (IBSM) model, whereby healthy participants are intravenously inoculated with blood-stage parasites. In a pilot study, participants were inoculated (Day 0) with approximately 2,800 viable P. falciparum ART-R parasites. In a comparative study, participants were randomised to receive approximately 2,800 viable P. falciparum ART-R (Day 0) or artemisinin-sensitive (ART-S) parasites (Day 1). In both studies, participants were administered a single approximately 2 mg/kg oral dose of artesunate (AS; Day 9). Primary outcomes were safety, ART-R parasite infectivity, and parasite clearance. In the pilot study, 2 participants were enrolled between April 27, 2017, and September 12, 2017, and included in final analyses (males n = 2 [100%], mean age = 26 years [range, 23–28 years]). In the comparative study, 25 participants were enrolled between October 26, 2017, and October 18, 2018, of whom 22 were inoculated and included in final analyses (ART-R infected participants: males n = 7 [53.8%], median age = 22 years [range, 18–40 years]; ART-S infected participants: males n = 5 [55.6%], median age = 28 years [range, 22–35 years]). In both studies, all participants inoculated with ART-R parasites became parasitaemic. A total of 36 adverse events were reported in the pilot study and 277 in the comparative study. Common adverse events in both studies included headache, pyrexia, myalgia, nausea, and chills; none were serious. Seven participants experienced transient severe falls in white cell counts and/or elevations in liver transaminase levels which were considered related to malaria. Additionally, 2 pa
- Published
- 2020