Safety and parasite clearance of artemisinin-resistant < i > Plasmodium falciparum < /i > infection: A pilot and a randomised volunteer infection study in Australia

by Rebecca E. Watts, Anand Odedra, Louise Marquart, Lachlan Webb, Azrin N. Abd-Rahman, Laura Cascales, Stephan Chalon, Maria Rebelo, Zuleima Pava, Katharine A. Collins, Cielo Pasay, Nanhua Chen, Christopher L. Peatey, J örg J. Möhrle, James S. McCarthy BackgroundArtemisinin 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 findingsWe 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 viableP.falciparum ART-R parasites. In a comparative study, participants were randomised to receive approximately 2,800 viableP.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 (malesn = 2 [100%], mean age = 26 years [range, 23 –28 years]). In the comparative study, 25 participants were enrolled between October 26, 2017,...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research