Development of a Canine Coccidiosis Model and the Anticoccidial Effects of a New Chemotherapeutic Agent

dc.contributor.authorMitchell, Sheilaen
dc.contributor.committeechairLindsay, David S.en
dc.contributor.committeememberBlagburn, Byron L.en
dc.contributor.committeememberWitonsky, Sharon G.en
dc.contributor.committeememberSriranganathan, Nammalwaren
dc.contributor.committeememberZajac, Anne M.en
dc.contributor.departmentBiomedical and Veterinary Sciencesen
dc.date.accessioned2014-03-14T20:11:44Zen
dc.date.adate2011-06-16en
dc.date.available2014-03-14T20:11:44Zen
dc.date.issued2008-04-11en
dc.date.rdate2011-06-16en
dc.date.sdate2011-05-08en
dc.description.abstractCoccidia 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.en
dc.description.degreePh. D.en
dc.identifier.otheretd-05082011-151930en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05082011-151930/en
dc.identifier.urihttp://hdl.handle.net/10919/27600en
dc.publisherVirginia Techen
dc.relation.haspartMitchell_SM_D_2008.pdfen
dc.relation.haspartMitchell_SM_D_2008_Copyright.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectanimal modelen
dc.subjectmonozoic cysten
dc.subjectcell cultureen
dc.subjectToxoplasma gondiien
dc.subjecttreatmenten
dc.subjectApicomplexaen
dc.subjectcoccidiaen
dc.subjectcanineen
dc.titleDevelopment of a Canine Coccidiosis Model and the Anticoccidial Effects of a New Chemotherapeutic Agenten
dc.typeDissertationen
thesis.degree.disciplineBiomedical and Veterinary Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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