In vitro growth inhibition of Theileria equi by bumped kinase inhibitors

Gimenez, Fernanda; Hines, Siddra; Evanoff, Ryan; Ojo, Kayode K.; Voorhis, Wesley C. Van; Maly, Dustin J.; Vidadala, Rama Subba Rao; Mealey, Robert H.

doi:10.1016/j.vetpar.2017.12.024

Cited by 4 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous compounds have been screened for in vitro efficacy against T . equi , but none have yet been assessed in clinical trials [ 32 , 33 , 34 ]. In addition, numerous new compounds have shown in vitro efficacy against related protozoa, including Cryptosporidia sp., Toxoplasmosis sp., and Babesia sp.…”

Section: Discussionmentioning

confidence: 99%

Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi

et al. 2020

View full text Add to dashboard Cite

Control of Theileria equi, the primary cause of equine theileriosis, is largely reliant on acaracide use and chemosterilization with imidocarb dipropionate (ID). However, it is currently unknown if ID is effective against Theileria haneyi, the recently identified second causative agent of equine theileriosis, or if the drug maintains effectiveness against T. equi in the presence of T. haneyi co-infection. The purpose of this study was to address these questions using ID treatment of the following three groups of horses: (1) five T. haneyi infected horses; (2) three T. haneyi-T. equi infected horses; and (3) three T. equi-T. haneyi infected horses. Clearance was first evaluated using nPCR for each Theileria sp. on peripheral blood samples. ID failed to clear T. haneyi in all three groups of horses, and failed to clear T. equi in two of three horses in group two. For definitive confirmation of infection status, horses in groups two and three underwent splenectomy post-treatment. The T. equi-nPCR-positive horses in group two developed severe clinical signs and were euthanized. Remaining horses exhibited moderate signs consistent with T. haneyi. Our results demonstrate that ID therapy lacks efficacy against T. haneyi, and T. haneyi-T. equi co-infection may interfere with ID clearance of T. equi.

show abstract

Section: Discussionmentioning

confidence: 99%

Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Various other chemotherapeutic agents have been reported to be potentially used against EP, with variable efficacy, mostly in vitro. Among these are anti-malaria compounds [37][38][39], antimicrobial agents [40][41][42][43][44][45], parasite metabolism inhibitors [34,[46][47][48][49][50][51][52][53], replication inhibitors [54,55], pyrimidine synthesis inhibitors [56,57], and various plant-derived compounds [58][59][60][61][62][63]. However, most of these options have never been tested in vivo, and none is widely used.…”

Section: Immunity Treatment and Controlmentioning

confidence: 99%

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

et al. 2020

View full text Add to dashboard Cite

Equine piroplasmosis (EP), caused by the hemoparasites Theileria equi, Theileria haneyi, and Babesia caballi, is an important tick-borne disease of equines that is prevalent in most parts of the world. Infection may affect animal welfare and has economic impacts related to limitations in horse transport between endemic and non-endemic regions, reduced performance of sport horses and treatment costs. Here, we analyzed the epidemiological, serological, and molecular diagnostic data published in the last 20 years, and all DNA sequences submitted to GenBank database, to describe the current global prevalence of these parasites. We demonstrate that EP is endemic in most parts of the world, and that it is spreading into more temperate climates. We emphasize the importance of using DNA sequencing and genotyping to monitor the spread of parasites, and point to the necessity of further studies to improve genotypic characterization of newly recognized parasite species and strains, and their linkage to virulence.

show abstract

“…Large-scale compound library screening experiments have enabled the identification of potentially efficacious drugs in some apicomplexan systems, and similar studies are needed for T. haneyi [ 35 , 36 , 37 , 38 , 39 , 40 ]. Furthermore, while several compounds have demonstrated in vitro efficacy against T. equi , very few have been tested against T. haneyi , or against either parasite in vivo [ 5 , 40 , 41 , 42 , 43 ]. Continued in vivo trials with promising drug candidates are necessary for the sustained control of equine theileriosis across the globe.…”

Section: Discussionmentioning

confidence: 99%

Tulathromycin and Diclazuril Lack Efficacy against Theileria haneyi, but Tulathromycin Is Not Associated with Adverse Clinical Effects in Six Treated Adult Horses

et al. 2023

View full text Add to dashboard Cite

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.

show abstract

In vitro growth inhibition of Theileria equi by bumped kinase inhibitors

Cited by 4 publications

References 37 publications

Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi

Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi

Twenty Years of Equine Piroplasmosis Research: Global Distribution, Molecular Diagnosis, and Phylogeny

Tulathromycin and Diclazuril Lack Efficacy against Theileria haneyi, but Tulathromycin Is Not Associated with Adverse Clinical Effects in Six Treated Adult Horses

Contact Info

Product

Resources

About