Tulathromycin and diclazuril lack efficacy against Theileria haneyi, but tulathromycin is not associated with adverse clinical effects in six treated adult horses

Authors: ONZERE, CYNTHIA - Washington State University; HULBERT, MORGAN - Cornell University; SEARS, KELLY - Oregon State University; WILLIAMS, LAURA - Washington State University; Fry, Lindsay

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2023
Publication Date: 3/14/2023
Citation: Onzere, C.K., Hulbert, M., Sears, K.P., Williams, L.B., Fry, L.M. 2023. Tulathromycin and diclazuril lack efficacy against Theileria haneyi, but tulathromycin is not associated with adverse clinical effects in six treated adult horses. Pathogens. 12(3). Article 453. https://doi.org/10.3390/pathogens12030453.
DOI: https://doi.org/10.3390/pathogens12030453

Interpretive Summary: Theileria haneyi is a blood parasite of horses that is spread by ticks and is one cause of equine theileriosis. This infection can cause anemia, exercise intolerance, and sometimes death of affected horses. Equine theileriosis-free countries, including the United States, have implemented rigorous international restrictions on equine movement to prevent importation of infected horses, leading to significant economic costs for the equine industry. The drug imidocarb dipropionate is the only treatment option available for equine theileriosis in the United States, but it does not work against T. haneyi. Our group recently determined that two readily available veterinary drugs, tulathromycin and ponazuril, are able to inhibit Theileria sp. proliferation in the laboratory. Thus, the goal of this work was to test whether tulathromycin and diclazuril (a drug closely related to ponazuril) are able to clear T. haneyi in infected horses. A second goal was to provide additional data on the safety of tulathromycin use in adult horses. We found that both tulathromycin and diclazuril are unable to clear T. haneyi infection at the doses utilized in this study. We also found that repeated doses of tulathromycin over an eight-week period did not result in any adverse effects in adult horses. Additional studies, such as drug library screening studies, are needed to discover drugs that are able to clear T. haneyi in horses. Tulathromycin is likely safe to use for the treatment of susceptible bacterial infections in adult horses.

Technical Abstract: Equine theileriosis, caused by Theileria haneyi and Theileria equi, leads to anemia, exercise intolerance, and occasionally, death. Theileriosis-free countries prohibit the importation of infected horses, resulting in significant costs for the equine industry. Imidocarb dipropionate is the only treatment for T. equi in the United States, but lacks efficacy against T. haneyi. The goal of this study was to assess the in vivo efficacy of tulathromycin and diclazuril against T. haneyi. Fourteen T. haneyi-infected horses were utilized. Six were treated with eight weekly 2.5 mg/kg doses of tulathromycin. Three were treated daily for eight weeks with 2.5 mg/kg diclazuril. Three were pre-treated with 0.5 mg/kg diclazuril daily for one month to determine whether low-dose diclazuril prevents infection. Following infection, the dose was increased to 2.5 mg/kg for eight weeks. Two infected horses remained untreated as controls. The horses were assessed via nested PCR, physical exams, complete blood counts, serum chemistry panels, and cytology. Tulathromycin and diclazuril failed to clear T. haneyi and the treated and control groups exhibited similar parasitemia and packed cell volume declines. To obtain additional safety data on tulathromycin use in adult horses, necropsy and histopathology were performed on tulathromycin-treated horses. No significant lesions were detected.