Tafenoquine succinate inhibits the growth of the equine piroplasmosis hemoparasites Theileria equi and Babesia caballi

Authors: CARDILLO, NATALIA - Washington State University; VILLARINO, NICOLAS - Washington State University; Kappmeyer, Lowell; Chung, Chungwon; SUAREZ, CARLOS - Washington State University; Bastos, Reginaldo

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2026
Publication Date: 1/27/2026
Citation: Cardillo, N.N., Villarino, N.F., Kappmeyer, L.S., Chung, C.J., Suarez, C.E., Bastos, R.G. 2026. Tafenoquine succinate inhibits the growth of the equine piroplasmosis hemoparasites Theileria equi and Babesia caballi. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07262-y.
DOI: https://doi.org/10.1186/s13071-026-07262-y

Interpretive Summary: Equine piroplasmosis is an economically important tick-borne disease of horses caused by the blood parasites Theileria equi, Babesia caballi, and the recently identified Theileria haneyi. Acute cases of the disease can be severe, often presenting with anemia, abortion, or sudden death. Surviving animals remain lifelong carriers and reservoirs for parasite transmission. No vaccines are currently available, and control strategies rely on diagnostics followed by drug treatment. Imidocarb dipropionate (ID) is the current standard drug for both acute treatment and radical cure. However, growing concerns regarding ID-resistant parasites and toxicity associated with the drug have highlighted the urgent need for novel, safer, and more effective antiparasitic therapeutics to control equine piroplasmosis. Here, we assessed the efficacy of tafenoquine succinate (TFQ) against T. equi and B. caballi in an in vitro culture system. The data demonstrated that TFQ, at concentrations ranging from 5 to 15 µM, completely abrogated the growth of T. equi. In contrast, TFQ had no effect on B. caballi at 5–10 µM but inhibited its growth at 15 µM. These results were comparable to those obtained with ID. Additionally, TFQ showed no significant cytotoxic effects on equine white blood cells at concentration of 2.5–5 µM, while concentrations higher than 10 µM indicated potential toxicity. These findings suggest TFQ selectively targets parasites over host cells, supporting its therapeutic potential. We conclude that TFQ significantly inhibited T. equi and B. caballi at doses tolerated by equine white blood cells, supporting its potential as an alternative treatment for equine piroplasmosis and warranting further in vivo investigation, particularly for T. equi infection.

Technical Abstract: Background: Equine piroplasmosis (EP) is a tick-borne disease of equids caused by intraerythrocytic apicomplexan parasites Theileria equi, Babesia caballi, and the recently identified T. haneyi. Acute cases can be severe, with anemia, jaundice, abortion, or sudden death. Survivors remain lifelong carriers, serving as reservoirs for tick-borne and iatrogenic transmission. No vaccines are currently available, and control strategies rely heavily on accurate diagnostics and chemotherapeutic intervention. Imidocarb dipropionate (ID) is the current standard of care for both acute treatment and radical cure. However, growing concerns regarding ID-resistant parasite strains and its associated toxicity have highlighted the urgent need for novel, safer, and more effective antiparasitic agents. Here, we assessed the in vitro efficacy of tafenoquine succinate (TFQ), a synthetic 8-aminoquinoline with broad antiparasitic activity, against T. equi and B. caballi as a potential treatment for equine piroplasmosis. Methods: The effect of TFQ on T. equi and B. caballi was evaluated in vitro in parasite cultures. The percentage of parasitized erythrocytes was measured by flow cytometry, and the effect of TFQ on parasite growth was compared to that of ID. TFQ toxicity on horse peripheral blood mononuclear cells (PBMC) was assessed via a colorimetric metabolic assay. Results: TFQ reduced T. equi parasitemia dose-dependently, matching ID efficacy at 72 hours. For B. caballi, TFQ had no effect at 5-10 µM but inhibited growth at 15 µM, similar results to ID. TFQ exhibited approximately threefold greater potency against T. equi [IC50: 5.90 µM (95% CI: 4.99–5.96); IC99: 60.74 µM (95% CI: 37.41–113.3)] compared to B. caballi [IC50: 14.5 µM (95% CI: 13.81–15.23); IC99: 20.44 µM (95% CI: 17.77–28.84)]. The narrower confidence intervals for T. equi suggest a more consistent antiparasitic response across replicates. Cytotoxicity assays showed no significant effects on equine PBMCs at 2.5–5 µM (p > 0.05), while concentrations =10 µM indicated potential toxicity. These findings suggest TFQ selectively targets parasites over host cells, supporting its therapeutic potential. Conclusions: TFQ significantly inhibited T. equi and B. caballi at doses tolerated by equine PBMCs, supporting its potential as an alternative treatment for EP and warranting further in vivo study.