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. 2023 Feb 8;76(3):506-512.
doi: 10.1093/cid/ciac503.

Transmission Blocking Activity of Low-dose Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum

Rebecca Webster  1 , Hayley Mitchell  1 , Jenny M Peters  1 , Juanita Heunis  1 , Brighid O'Neill  1 , Jeremy Gower  1 , Sean Lynch  1 , Helen Jennings  1 , Fiona H Amante  1 , Stacey Llewellyn  1 , Louise Marquart  2 , Adam J Potter  1 , Geoffrey W Birrell  3 , Michael D Edstein  3 , G Dennis Shanks  3 , James S McCarthy  1   4 , Bridget E Barber  1
Affiliations

Transmission Blocking Activity of Low-dose Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum

Rebecca Webster et al. Clin Infect Dis. .

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.

Keywords: Plasmodium falciparum; malaria; tafenoquine; transmission; volunteer infection study.

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Conflict of interest statement

Potential conflicts of interest . B. E. B. declares receipt of funding support from the Bill and Melinda Gates Foundation and Medicines for Malaria Venture (MMV) and receipt of equipment (piperaquine) for clinical trial from Medicines for Malaria Venture. J. S. M. declares grant support from MMV to undertake this study. G. D. S. declares participation on an Expert Scientific Advisory Committee for MMV and participation on Data Safety Monitoring Boards for multiple MMV-sponsored clinical chemotherapy trials done at QIMR. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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