Imidocarb Dipropionate lacks efficacy against Theileria haneyi and fails to consistently clear Theileria equi in horses co-infected with T. haneyi

Authors: SEARS, KELLY - Washington State University; KNOWLES, DONALD - Washington State University; DINKEL, KELCEY - Washington State University; MSHELIA, PHILP - Washington State University; ONZERE, CYNTHIA - Washington State University; SILVA, MARTA - Washington State University; Fry, Lindsay

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2020
Publication Date: 12/10/2020
Citation: Sears, K.P., Knowles, D.P., Dinkel, K.D., Mshelia, P.W., Onzere, C., Silva, M., Fry, L.M. 2020. Imidocarb Dipropionate lacks efficacy against Theileria haneyi and fails to consistently clear Theileria equi in horses co-infected with T. haneyi. Pathogens. 9(12). Article 1035. https://doi.org/10.3390/pathogens9121035.
DOI: https://doi.org/10.3390/pathogens9121035

Interpretive Summary: The apicomplexan parasite Theileria equi is the primary cause of equine theileriosis and is endemic in both tropical and subtropical regions of the world. The few remaining, non-endemic countries employ stringent importation testing and prohibit entry of positive equids, resulting in ongoing economic and regulatory challenges regarding international horse transport. Five distinct T. equi clades are currently recognized, and recent work has provided sufficient evidence to define a second species of equine-infective Theileria, known as Theileria haneyi. T. haneyi-infected equids have been identified in South Africa, The Gambia, and at the US-Mexico border. Both Theileria organisms cause persistent, asymptomatic infection, and simultaneous co-infection of horses with both parasites has been reported. The majority of co-infected horses are unable to spontaneously clear either species, and, as there is not yet a vaccine, control strategies are centered on tick control, surveillance testing, and the use of chemotherapeutic drugs to clear infection. Currently, the only drug known to be effective in achieving T. equi chemosterilization is imidocarb dipropionate (ID), but its efficacy against T. haneyi, and, against T. equi in horses co-infected with both parasites, is unknown. In this study, we infected horses with T. haneyi alone or with both T. equi and T. haneyi, and attempted to clear them of infection using ID treatment. We found that ID is ineffective against T. haneyi, and that, in the face of co-infection, ID is inconsistently efficacious against T. equi. These findings support further studies to identify new therapeutic strategies for equine theileriosis.

Technical Abstract: Equine theileriosis, caused primarily by the apicomplexan hemoparasite Theileria equi, remains one of the major barriers to unrestricted movement of horses globally. The detection of a second causative organism, Theileria haneyi, has raised new, critical issues regarding parasite surveillance and control. Recent publications have documented simultaneous infection of horses with both Theileria species, and mounting prevalence data supports a transcontinental distribution of T. haneyi similar to that of T. equi. Control strategies for T. equi are largely reliant on acaracide use and chemosterilization using imidocarb dipropionate (ID). However, it is currently unknown if ID is effective against T. haneyi, or if the drug maintains its effectiveness against T. equi in the presence of T. haneyi. Thus, the purpose of the current, in vivo study was to determine if ID therapy results in parasite clearance of horses infected with T. haneyi alone or of horses co-infected with T. equi and T. haneyi. Eleven horses were utilized for this study, and were divided into three groups as follows: 1. Five horses infected with T. haneyi alone; 2. Three horses infected first with T. haneyi and superinfected with T. equi; and 3. Three horses infected first with T. equi and superinfected with T. haneyi. ID failed to clear T. haneyi in 5/5 horses in group 1, based on peripheral blood nPCR. Furthermore, 6/6 horses in groups 2 and 3 remained positive for T. haneyi after ID treatment. Importantly, 2/3 horses from group 2 failed to clear T. equi after ID treatment, based on nPCR testing of peripheral blood. To provide definitive confirmation of parasite infection status, all horses in groups 2 and 3 underwent splenectomy following ID therapy. The two T. equi-positive horses from group 2 developed severe clinical signs consistent with fulminant T. equi infection, and were euthanized. Remaining horses exhibited transient, mild clinical disease consistent with expansion of T. haneyi parasitemia. Our results demonstrate the ID therapy lacks efficacy against T. haneyi, and that T. haneyi-T. equi co-infection may interfere with clearance of T. equi by ID.