Transmission Blocking Activity of Low-dose Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum. (22nd June 2022)

• Record Type: Journal Article
• Authors: Webster, Rebecca; Mitchell, Hayley; Peters, Jenny M; Heunis, Juanita; O'Neill, Brighid; Gower, Jeremy; Lynch, Sean; Jennings, Helen; Amante, Fiona H; Llewellyn, Stacey; Marquart, Louise; Potter, Adam J; Birrell, Geoffrey W; Edstein, Michael D; Shanks, G Dennis; McCarthy, James S; Barber, Bridget E
• Is Part Of: Clinical infectious diseases. Volume 76:Number 3(2023)
• Page Start: 506
• Page End: 512
• Publication Date: 2022-06-22
• Subjects: tafenoquine -- Plasmodium falciparum -- transmission -- malaria -- volunteer infection study; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciac503
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : A single low dose of tafenoquine (50 mg orally) reduces the transmission of Plasmodium falciparum parasites from healthy adult volunteers with induced blood-stage malaria to Anopheles mosquitoes. A delay in the onset of transmission blocking activity after dosing was evident.