Location: Animal Disease Research
Project Number: 2090-32000-044-000-D
Project Type: In-House Appropriated
Start Date: Nov 3, 2021
End Date: Nov 2, 2026
Objective:
Objective 1: Perform prevalence estimation (Theileria haneyi), host-parasite interaction (T. haneyi vs. Theileria equi), and drug susceptibility profile (T. haneyi) of U.S. equine Theileria sp. isolates.
Sub-objective 1.A: Using molecular and serologic assays and characterize (in collaboration with APHIS) the prevalence of T. haneyi in the United States.
Sub-objective 1.B: Characterize the host-parasite interface (T. haneyi vs. T. equi) and drug susceptibility profile (T. haneyi) of U.S. equine Theileria sp. isolates.
Objective 2: Determine competent, native U.S. tick vectors of Theileria orientalis Ikeda (2016 VA isolate), assess potential T. orientalis Ikeda treatment strategies, and develop improved diagnostic and vaccine strategies for control of T. orientalis Ikeda.
Sub-objective 2.A: Characterize competence of native U.S. ticks to acquire and transmit Theileria orientalis Ikeda (2016 VA isolate) to cattle.
Sub-objective 2.B: Identify potential diagnostic and subunit vaccine targets for T. orientalis Ikeda (2016 VA isolate) and develop an improved serologic assay for T. orientalis Ikeda.
Sub-objective 2.C: Provide more complete characterization of the drug susceptibility profile and virulence of the U.S. T. orientalis Ikeda isolate.
Approach:
Theileria orientalis Ikeda and Theileria haneyi recently emerged as novel threats to the United States cattle and horse industries, respectively. The development of improved treatment, diagnostic, and preventive strategies for bovine and equine theileriosis is urgently needed.
In the first objective, focused on equine theileriosis, we will first work to assess the potential risk of Theileria haneyi to U.S. horses by performing a study to estimate its prevalence at the southern border and in high-risk populations throughout the U.S. USDA-APHIS Veterinary Services will assist in obtaining samples. We will utilize our newly developed T. haneyi ELISA, in concert with previously published PCR and western blot assays to test the equine samples. We will then work with USDA-APHIS Center for Epidemiology and Animal Health to perform statistical analysis. Using this sample pool, we will also perform basic validation of our new T. haneyi ELISA. Next, we will work to improve current control strategies for equine Theileriosis by determining immune correlates of protection via assessment of the equine immune response using immune cell phenotyping, cytokine assessment, and cell function assays. In concert, we will utilize genomics and transcriptomics to identify parasite virulence factors and potential vaccine candidate antigens. Finally, we will begin to characterize the drug susceptibility profile of T. haneyi by performing 1. In vivo assessment of several drugs approved to treat other pathogens of horses and 2. In vitro assessment of compound libraries to identify novel compounds with potential anti-Theileria efficacy.
In the second objective, focused on bovine theileriosis, we will first perform studies to determine if additional U.S. tick species are competent vectors of T. orientalis Ikeda. This work will utilize tick colonies and cattle maintained by our research unit, and will provide information on the potential range of spread of T. orientalis Ikeda in the U.S. Next, we will work to improve current control strategies for bovine Theileriosis by determining immune correlates of protection via assessment of the bovine immune response using immune cell phenotyping, cytokine assessment, and cell function assays. In concert, we will utilize genomics and transcriptomics to identify parasite virulence factors and potential diagnostic and vaccine candidate antigens. Using a subset of these antigens, we will work with collaborators to develop and perform initial validation of a serologic assay to diagnose T. orientalis Ikeda. Finally, we will begin to characterize the drug susceptibility profile of T. orientalis by performing 1. In vivo assessment of several drugs approved to treat other pathogens of cattle and 2. In vitro assessment of multiple compound libraries to identify novel compounds with potential anti-Theileria efficacy.
The data from this project will assist in the development and execution of theileriosis control strategies within the U.S. U.S. stakeholders to be served by the data generated by this project include the USDA-APHIS, veterinarians, beef and dairy producers, the equine industry, and the veterinary biomedical industry.
