Comparing malaria transmission blocking efficacy of Primaquine and Tafenoquine with in vivo pre-clinical models
Abstract
Background: The 8-aminoquinoline primaquine is used as a single low dose with antimalarial treatment to reduce malaria transmission. An alternative 8-aminoquinoline, tafenoquine has a substantially longer half-life and may therefore provide more sustained transmission-blocking activity, but direct comparisons with primaquine are limited. We compare the transmission-blocking activity and pharmacokinetics of these drugs in vivo.
Methods: We assess primaquine dose response in Plasmodium berghei -infected mice and compare an equimolar dose of tafenoquine in a mouse-to-mosquito-to-mouse transmission model. We also assess both drugs against Plasmodium falciparum gametocytes in humanized immunodeficient mice using bioluminescence and microscopy, and measure plasma drug concentrations. Dose-response relationships are modeled using generalized linear and nonlinear regression, with appropriate statistical tests for transmission and parasite endpoints.
Results: Here we show that primaquine produces stronger early transmission-blocking activity, reducing mosquito infection more effectively than tafenoquine 24 hours after treatment. In contrast, tafenoquine retains greater activity at later time points, coinciding with prolonged systemic exposure. Similar temporal differences are observed when the drugs are combined with the schizonticide sulphadiazine. In humanized mice, both drugs reduce gametocyte abundance in a dose-dependent manner, while tafenoquine shows sustained exposure for several days compared with the more rapid decline of parent primaquine.
Conclusions: Primaquine and tafenoquine have distinct temporal transmission-blocking profiles in vivo. Sustained activity of tafenoquine is consistent with prolonged exposure rather than greater intrinsic potency. These findings are observed across multiple models, both in the absence or presence of a partner schizonticide and thus demonstrate a potential advantage of the utilization of tafenoquine when compared to primaquine.
Related
- Predicting the impact of primaquine on Plasmodium falciparum transmission using multiscale modelling
- Therapeutic efficacy of chloroquine plus primaquine in the treatment of uncomplicated P.vivax in Shecha Health Center, South Ethiopia.
- A Prospective, Randomized, Non-inferiority Clinical Protocol Comparing the Efficacy and Safety of Single-port versus Multiport Extraperitoneal Robotic Radical Prostatectomy Using the KangDuo Robotic System
- Comparing the efficacy of virtual reality and flat screen delivery of breath control training for anxiety management
- USFDA Oncology Drug Approvals from 2014- 2025: Comparing non-immunotherapy and immunotherapy approvals, their endpoints, and their efficacy.
BibTeX
@article{duffey2026comparing,
title = {{Comparing malaria transmission blocking efficacy of Primaquine and Tafenoquine with in vivo pre-clinical models}},
author = {Maëlle Duffey and Sara E. Zakutansky and Christin Gumpp and Michael J. Delves and Katarzyna A. Sala and Ellie Sherrard-Smith and Jake Baum and Didier Leroy and Matthias Rottmann and Andrew M. Blagborough},
journal = {Communications Medicine},
year = {2026},
month = nov,
doi = {10.1038/s43856-026-01977-w},
url = {https://www.nature.com/articles/s43856-026-01977-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparing malaria transmission blocking efficacy of Primaquine and Tafenoquine with in vivo pre-clinical models
AU - Maëlle Duffey
AU - Sara E. Zakutansky
AU - Christin Gumpp
AU - Michael J. Delves
AU - Katarzyna A. Sala
AU - Ellie Sherrard-Smith
AU - Jake Baum
AU - Didier Leroy
AU - Matthias Rottmann
AU - Andrew M. Blagborough
PY - 2026
DA - 2026/11/10
JO - Communications Medicine
DO - 10.1038/s43856-026-01977-w
UR - https://www.nature.com/articles/s43856-026-01977-w
AB - Background: The 8-aminoquinoline primaquine is used as a single low dose with antimalarial treatment to reduce malaria transmission. An alternative 8-aminoquinoline, tafenoquine has a substantially longer half-life and may therefore provide more sustained transmission-blocking activity, but direct comparisons with primaquine are limited. We compare the transmission-blocking activity and pharmacokinetics of these drugs in vivo. Methods: We assess primaquine dose response in Plasmodium berghei -infected mice and compare an equimolar dose of tafenoquine in a mouse-to-mosquito-to-mouse transmission model. We also assess both drugs against Plasmodium falciparum gametocytes in humanized immunodeficient mice using bioluminescence and microscopy, and measure plasma drug concentrations. Dose-response relationships are modeled using generalized linear and nonlinear regression, with appropriate statistical tests for transmission and parasite endpoints. Results: Here we show that primaquine produces stronger early transmission-blocking activity, reducing mosquito infection more effectively than tafenoquine 24 hours after treatment. In contrast, tafenoquine retains greater activity at later time points, coinciding with prolonged systemic exposure. Similar temporal differences are observed when the drugs are combined with the schizonticide sulphadiazine. In humanized mice, both drugs reduce gametocyte abundance in a dose-dependent manner, while tafenoquine shows sustained exposure for several days compared with the more rapid decline of parent primaquine. Conclusions: Primaquine and tafenoquine have distinct temporal transmission-blocking profiles in vivo. Sustained activity of tafenoquine is consistent with prolonged exposure rather than greater intrinsic potency. These findings are observed across multiple models, both in the absence or presence of a partner schizonticide and thus demonstrate a potential advantage of the utilization of tafenoquine when compared to primaquine.
SN - 2730-664X
ER -