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 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 (50 mg) reduces P. falciparum transmission to mosquitoes, with a delay in effect.

Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reducePlasmodium falciparumtransmission: a phase 2 single-blind randomised clinical trial in Ouelessebougou, Mali

“…27 In a controlled human malaria infection trial, the transmission-blocking efficacy of a single 50 mg dose of tafenoquine showed modest reduction of mosquito infection rate at day 4 of 35% and 81% by day 7. 28 This dose is approximately half of that given in the current trial (1•66 mg/kg) which resulted in a median reduction in mosquito infection rate of 100% (IQR 100-100), while participant infectivity dropped from 70% (n/N=14/20) to 10% (n/N=2/20). 17 Although it is likely to have a prolonged transmission-blocking, there remain concerns for the safely of tafenoquine in G6PD deficient individuals.…”

Artemether–lumefantrine with or without single-dose primaquine and sulfadoxine–pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali

“… 27 In a controlled human malaria infection trial, the transmission-blocking efficacy of a single 50 mg dose of tafenoquine showed modest reduction of mosquito infection rate at day 4 of 35% and 81% by day 7. 28 This dose is approximately half of that given in the current trial (1·66 mg/kg), which resulted in a median reduction in mosquito infection rate of 100% (IQR 100–100), while participant infectivity dropped from 14 (70%) to two (10%) of 20. 17 …”

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

“…Thus, it seems unlikely that the doses required to clear asexual parasitemia could be safely administered in MDA without G6PD screening. However, we and others have demonstrated that single low doses of tafenoquine (<100-mg adult dose) can reduce the transmission of P. falciparum to mosquitoes [ 24 , 25 ]. Thus, the use of tafenoquine for this purpose, in combination with partner drugs to clear asexual parasitemia, may be worthy of investigation.…”