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.

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; Dennis Shanks, G; McCarthy, James S; Barber, Bridget E
Journal	Clinical Infectious Diseases
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Date	1/01/2022
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URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1093/cid/ciac503