Effect of novel antimalarial ZY-19489 on Plasmodium falciparum viability in a volunteer infection study

Bridget E Barber and colleagues published a first-in-human study of the antimalarial activity of ZY-19489, a novel triaminopyrimidine, in healthy volunteers. In this study, rapid initial parasite clearance, with a half-life of approximately 7 h, occurred in all 15 participants after administration of a single dose of either 200 mg, 300 mg, or 900 mg, with the rate of initial clearance being dose-independent.

Published: 7 June 2022 05:00

This observation suggests that the maximal killing rate might saturate at doses as low as 200 mg. However, we have previously shown that parasite clearance, as measured by quantitative PCR (qPCR), might not fully capture the parasite killing activity of antimalarial drugs.

Previously, we developed a method to assess parasite viability after in-vivo exposure to an antimalarial drug,which was used to compare total circulating parasite number (traditionally measured by microscopy or PCR) with viable parasite number (measured by an ex-vivo viability assay) in another volunteer infection study.

Our analysis revealed that parasites are rendered non-viable by artesunate more rapidly than previously thought suggesting that measuring circulating parasite number and its decline after drug administration (referred to as parasite clearance) alone might not accurately assess in-vivo drug activity.