Transmission Blocking Activity of Low-dose Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum.

ABSTRACT

BACKGROUND: Blocking the transmission of parasites from humans to mosquitoes is a key component of malaria control. Tafenoquine exhibits activity against all stages of the malaria parasite and may have utility as a transmission blocking agent. We aimed to characterize the transmission blocking activity of low-dose tafenoquine. METHODS: Healthy adults were inoculated with Plasmodium falciparum 3D7-infected erythrocytes on day 0. Piperaquine was administered on days 9 and 11 to clear asexual parasitemia while allowing gametocyte development. A single 50-mg oral dose of tafenoquine was administered on day 25. Transmission was determined by enriched membrane feeding assays predose and at 1, 4, and 7 days postdose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia after tafenoquine and safety parameters. RESULTS: Six participants were enrolled, and all were infective to mosquitoes before tafenoquine, with a median 86% (range, 22-98) of mosquitoes positive for oocysts and 57% (range, 4-92) positive for sporozoites. By day 4 after tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (interquartile range [IQR] 16-46) and 52% (IQR 40-62), respectively, and by day 7, 81% (IQR 36-92) and 77% (IQR 52-98), respectively. The decline in gametocyte density after tafenoquine was not significant. No significant participant safety concerns were identified. CONCLUSIONS: Low-dose tafenoquine (50 mg) reduces P. falciparum transmission to mosquitoes, with a delay in effect.