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

[...]we conducted a pilot study in which we inoculated participants with ART-R P. falciparum parasites harbouring the kelch13 gene mutation R539T (K13R539T strain) [4] to determine the safety, tolerability, and clearance of infection with ART-R parasites. Methods Study design We conducted 2 consecutive phase 1, single-centre, open-label studies: a pilot study and a randomised study. ART-R, artemisinin-resistant; ART-S, artemisinin-sensitive; A/P, atovaquone/proguanil; AS, artesunate; DHA/PQP, dihydroartemisinin/piperaquine phosphate; IV, intravenously; PQ, primaquine; qPCR, quantitative PCR https://doi.org/10.1371/journal.pmed.1003203.g001 Development of parasitaemia was monitored daily from Day 3 (pilot study Participant 1) or Day 4 (pilot study Participant 2 and comparative study) until parasites were detected by qPCR, then twice daily until AS administration. Outcomes A primary outcome of both studies was safety and tolerability of infection with ART-R parasites (and of ART-S parasites in the comparative study only), determined by evaluating adverse events, physical examinations, vital signs, clinical biochemistry, haematology, and urinalysis.