|De Lisle, Geoffrey|
Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2007
Publication Date: 6/21/2007
Citation: Hines, M.E., Stabel, J.R., Sweeney, R.W., Griffin, F., Talaat, A.M., Bakker, D., Benedictus, G., Davis, W.C., De Lisle, G.W., Gardner, I.A. 2007. Experimental Challenge Models for Johne's Disease: A Review and Proposed International Guidelines. Veterinary Microbiology. 122(2007):197-222. Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle characterized by diarrhea, reduced feed intake, weight loss and death. Cattle usually become infected as young calves by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced milk production by these animals, they also present a potential infective threat to the rest of the herd. Johne's disease is difficult to manage and control on-farm. Development of new vaccines or therapeutics for treatment is contingent upon a good animal model that can be used for testing. This paper reviews historical information on the development and utilization of animal models for Mycobacterium avium subsp. paratuberculosis infection in cattle, sheep, goats, cervids, and rodents. A uniform animal model will provide a better understanding of the pathogenesis of disease and aid in new preventative and therapeutic regimes.
Technical Abstract: An international expert committee of Johne's Disease (JD) researchers was convened to review and develop guidelines for JD challenge studies in multiple animal species. A series of components essential for the development of long term and acute infection models was outlined and harmonized to provide some insight into a "best fit" JD challenge model for cattle, goats, sheep, cervids, and mice. The intent was to develop and propose international standard guidelines for models based on animal species that would gain acceptance worldwide. These models will be useful to study host-pathogen interactions, host immunity to infection at the local and systemic level, and provide a standardized experimental platform for the evaluation of vaccine candidates and therapeutics. The consensus guidelines for models agreed upon by this committee include recommendations for experimental challenge studies listed by animal species for strains of Mycobacterium avium subsp. paratuberculosis used, challenge dose, dose frequency, age of challenge, route of challenge, preparation of inoculum, experimental animal selection, quality control and minimal experimental endpoints.