Transient efficacy of buparvaquone against Theileria haneyi in chronically infected horses

Authors: ONZERE, CYNTHIA - Washington State University; HASSAN, AMANY - Washington State University; SEARS, KELLY - Oregon State University; Kappmeyer, Lowell; VILLARINO, NICOLAS - Washington State University; FRY, LINDSAY - Former ARS Employee; Bastos, Reginaldo

Submitted to: PLOS Neglected Tropical Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/5/2024
Publication Date: 8/12/2024
Citation: Onzere, C.K., Hassan, A., Sears, K., Kappmeyer, L.S., Villarino, N.F., Fry, L.M., Bastos, R.G. 2024. Transient efficacy of buparvaquone against Theileria haneyi in chronically infected horses . PLOS Neglected Tropical Diseases. (17):337. https://doi.org/10.1186/s13071-024-06397-0.
DOI: https://doi.org/10.1186/s13071-024-06397-0

Interpretive Summary: The absence of an effective therapeutics against Theileria haneyi, one of the three known parasites that cause equine piroplasmosis, impedes the implementation of strategies to control the disease and posing challenges for the equine industry globally. Previous studies demonstrated that imidocarb, tulathromycin and diclazuril, commonly used therapeutics against parasite infections, failed to eliminate T. haneyi in horses. In this work we evaluated the efficacy of buparvaquone in the treatment of T. haneyi in chronically infected horses. Results demonstrated that administration of the drug label dose (2.5 mg/kg) led to a rapid decrease of T. haneyi levels in the blood, and the parasites remained undetectable for approximately 7 weeks post-treatment. However, after that period, parasites reappeared in the blood. Interestingly, re-treatment of the horses with a higher dose of buparvaquone (6 mg/kg) did fail to eliminate the parasite in the chronically infected horses. Considering the ineffectiveness of buparvaquone in eliminating T. haneyi, future studies are warranted to investigate novel drugs for the control of T. haneyi in horses.

Technical Abstract: Theileria haneyi (T. haneyi) is one of the three known causative agents of equine piroplasmosis. While imidocarb is generally effective in the clearance of the highly pathogenic Theileria equi (T. equi), it is ineffective in the treatment of T. haneyi. Moreover, co-infection with T. haneyi has been shown to impede the successful treatment of T. equi. Furthermore, tulathromycin and diclazuril have demonstrated inefficacy in eradicating T. haneyi. The absence of an effective therapeutic agent against this parasite represents a significant obstacle in managing equine piroplasmosis. To address this issue, we evaluated the efficacy of buparvaquone in the treatment of T. haneyi in chronically infected horses. Our findings showed that treatment of horses with the recommended dose of 2.5 mg/kg of buparvaquone led to a rapid abatement of T. haneyi levels, to a level where the parasites were not detectable by nested PCR. Following treatment, the horses remained PCR negative for a minimum of seven weeks until recrudescence occurred. Subsequent re- administration of buparvaquone at an increased dosage of 6 mg/kg upon recrudescence failed to exert a theilericidal effect on T. haneyi. Throughout the treatment regimen, the hematological parameters of the horses and most components of the chemistry panel remained within the normal range, except for blood urea nitrogen levels, which fell below the normal range in certain instances.