Equine Protozoal Myeloencephalitis: investigating immunopathogenesis and treatment efficacy in mouse models and clinically affected horses

Equine protozoal myeloencephalitis (EPM), predominantly caused by the protozoa Saracocystis neurona, is a common neurologic disease in horses from North America. Equine exposure to the parasite occurs frequently as the protozoa is excreted in opossum (Didelphis virginiana) feces and contaminates the horse's environment. However, clinical neurologic disease only emerges in a small fraction of exposed horses. The seemingly protective immune response that develops in some exposed horses but not all is not fully defined. Previous reports utilizing horse EPM models and immune compromised mouse models, which develop disease simulating EPM after infection with S. neurona, have reported a role of T-lymphocytes and the cytokine interferon gamma, in disease protection. As part of this dissertation, the role of T-lymphocytes and IFNγ was further elucidated. It was determined that IFNγ production is essential for T-lymphocytes to offer protection against S. neurona induced encephalitis, in immune compromised mice. Another factor hindering prognosis of EPM affected horses is treatment failure. The efficacy of the antiprotozoal decoquinate, was tested and found to be ineffective at preventing S. neurona encephalitis, in immune compromised mice. However, the antiprotozoal, diclazuril, was found to be effective at preventing S. neurona encephalitis in immunocompromised mice but once treatment was terminated, infection persisted, and neurologic disease developed. In-situ methods were employed to extensively evaluate the immunopathology of spinal cord tissue samples collected from EPM affected horses. A novel in-situ hybridization technique was successfully utilized to identify S. neurona in tissue samples collected from horses with EPM. This technique will create new opportunities for investigating the immunopathology of EPM. Overall results from the studies conducted in this dissertation suggest that IFNγ production from T lymphocytes is essential for them to offer protection against S. neurona encephalitis. Additionally, further insight on FDA approved and non-FDA approved treatment options for S. neurona infection was gained through the use of the B6Ifnγ -/- mouse model. Collectively, these studies expanded on the knowledge of an understudied equine neurologic disease.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Animal and Poultry Sciences

Department dc:contributor.department

Animal and Poultry Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2020

Author dc:creator

• Hay, Alayna N.

Chair dc:contributor.committeechair

• Leeth, Caroline M.

Committee members dc:contributor.committeemember

• Lindsay, David S.
• Witonsky, Sharon G.
• Johnson, Sally E.

• Neurologic disease
• Horse
• EPM

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:23869

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/96373