Title page for ETD etd-05082011-151930


Type of Document Dissertation
Author Mitchell, Sheila
URN etd-05082011-151930
Title Development of a Canine Coccidiosis Model and the Anticoccidial Effects of a New Chemotherapeutic Agent
Degree PhD
Department Biomedical and Veterinary Sciences
Advisory Committee
Advisor Name Title
Lindsay, David S. Committee Chair
Blagburn, Byron L. Committee Member
Sriranganathan, Nammalwar Committee Member
Witonsky, Sharon G. Committee Member
Zajac, Anne M. Committee Member
Keywords
  • animal model
  • monozoic cyst
  • cell culture
  • Toxoplasma gondii
  • treatment
  • Apicomplexa
  • coccidia
  • canine
Date of Defense 2008-04-11
Availability unrestricted
Abstract
Coccidia are obligate intracellular parasites belonging to the phylum Apicomplexa. Many coccidia are of medical and veterinary importance such as Cystoisospora species and Toxoplasma gondii. The need to discover new anticoccidial therapies has increased due to development of resistance by the parasite or toxicity issues in the patient. The goals of this work were to develop a model for canine coccidiosis while proving that Cystoisospora canis is a true primary pathogen in dogs and to determine the efficacy of a new anticoccidial agent. A canine coccidiosis model would be useful in evaluating new anticoccidial treatments. Oral infections with 5 X 104 (n=2) and 1 X 105 (n=20) sporulated C. canis oocysts were attempted in 22 purpose bred beagle puppies. Clinical signs associated with disease were observed in all dogs. Bacterial and viral pathogens were ruled out by transmission electron microscopy (TEM) and bacterial growth assays. Development of C. canis in cell culture was also evaluated.

The efficacy of ponazuril, a new anticoccidial drug, was examined in T. gondii. In vitro studies were conducted to determine the activity of ponazuril on tachyzoites and how this agent affects development of apicomplexcan parasites. The tachyzoite production assay was conducted. Ponazuril at a dose of 1.0 µg/ml had a significant affect on tachyzoite reproduction. Comparisons were made on how ponazuril affects T. gondii and Neospora caninum. Inhibition of T. gondii tachyzoites occurred after the second round of replication and with N. caninum tachyzoites after 4 rounds of replication. Results of TEM revealed ponazuril affects replication of T. gondii and N. caninum differently.

The efficacy of ponazuril to prevent and treat acute and chronic toxoplasmosis was investigated. Mice treated prophylactically with ponazuril were completely protected from developing an acute T. gondii infection. Fatal toxoplasmosis was prevented in mice starting treatment 3 and 6 days post infection at a dose of 20 mg/kg. Immunohistochemistry was used to evaluate ponazuril’s effect on chronic toxoplasmosis. Sections of brain were scored according to the number of tissue cysts present. Ponazuril also proved to be highly active against toxoplasmic encephalitis in an interferon-gamma knockout mouse model.

Files
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  Mitchell_SM_D_2008.pdf 3.57 Mb 00:16:30 00:08:29 00:07:25 00:03:42 00:00:19
  Mitchell_SM_D_2008_Copyright.pdf 1.64 Mb 00:07:34 00:03:53 00:03:24 00:01:42 00:00:08

Browse All Available ETDs by ( Author | Department )

dla home
etds imagebase journals news ereserve special collections
virgnia tech home contact dla university libraries

If you have questions or technical problems, please Contact DLA.