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.

• Authors: Rebecca Webster, Hayley Mitchell, Jenny M Peters, Juanita Heunis, Brighid O'Neill, Jeremy Gower, Sean Lynch, Helen Jennings, Fiona H Amante, Stacey Llewellyn, Louise Marquart, Adam J Potter, Geoffrey W Birrell, Michael D Edstein, G Dennis Shanks, James S McCarthy, Bridget E Barber
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 76 Issue 3 Pg. 506-512 (02 08 2023) ISSN: 1537-6591 [Electronic] United States
• PMID: 35731843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antimalarials
• Artemether
• Artemether, Lumefantrine Drug Combination

Topics

• Adult
• Animals
• Humans
• Plasmodium falciparum
• Antimalarials (adverse effects)
• Healthy Volunteers
• Artemether (pharmacology)
• Artemether, Lumefantrine Drug Combination
• Malaria, Falciparum (prevention & control)
• Malaria
• Sporozoites
• Anopheles (parasitology)