Transmission blocking activity of low dose tafenoquine in healthy volunteers experimentally infected with Plasmodium falciparum

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 P. 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 pre-dose and at 1, 4 and 7 days post-dose. Artemether-lumefantrine was administered following the final assay. Outcomes were the reduction in mosquito infection and gametocytemia post-tafenoquine, and safety parameters. Results Six participants were enrolled, and all were infective to mosquitoes pre-tafenoquine, with a median 86% (range: 22-98) of mosquitoes positive for oocysts and 57% (range: 4-92) positive for sporozoites. By day 4 post-tafenoquine, the oocyst and sporozoite positivity rate had reduced by a median 35% (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 post-tafenoquine was not significant. No significant participant safety concerns were identified. Conclusion Low dose tafenoquine reduces P. falciparum transmission to mosquitoes, with a delay in effect. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12620000995976). Funding QIMR Berghofer Medical Research Institute.