Characterizing the Blood-Stage Antimalarial Activity of Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum.

This article focuses on evaluating the blood-stage antimalarial activity of tafenoquine, an 8-aminoquinoline, using a controlled human malaria infection model to determine the minimum effective single dose for clearing asexual Plasmodium falciparum parasitemia. In a study with 12 healthy, G6PD-normal adults inoculated with P. falciparum, single oral doses of 400 mg or 600 mg tafenoquine rapidly cleared parasites without regrowth, whereas 200 mg and 300 mg doses were less effective and associated with parasite recrudescence. Pharmacokinetic/pharmacodynamic modeling predicted that doses of approximately 460 mg to 540 mg would be required to clear parasitemia in a typical 60-kg adult in endemic populations, but such doses necessitate prior screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency due to hemolysis risk. The study concludes that while tafenoquine shows potent blood-stage activity, its use in mass drug administration (MDA) for malaria would be limited by the need for G6PD testing, and further research into combination therapies and safe dosing in G6PD-deficient individuals is warranted.