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Low dose TB infection in cattle: disease dynamics and diagnostic strategies - SE3024

Description
In order to understand the dynamics of disease progression in cattle infected with Mycobacterium bovis, it is necessary to study cattle experimentally infected with low doses of M. bovis that result in pathology which resembles that occurring during natural infection. At present, minimal infectious doses capable of inducing bovine tuberculosis in cattle and the dose-related kinetics of disease progression are ill defined. In addition, the exact infection route(s) and primary site(s) of infection also require experimental reassessment along with better definition of the times at which cattle are most likely to shed and transmit organisms. Elucidation of these parameters will help in the risk assessment of cattle-to-cattle transmission of M. bovis in Great Britain. This in turn will inform the development of improved disease control strategies for cattle. These issues will be addressed by comparing the disease in cattle caused by challenge with low doses of M. bovis via the intratrachael or aerosol routes. We will perform systematic analysis of the kinetics of the immune response during experimental infection in order to define immunological correlates of protection and disease. This knowledge may also lead to the development of immuno-diagnostic strategies capable of detecting infected animals earlier than conventional diagnostic strategies and also of detecting animals of different infection status. The study will also address whether cattle that receive a low-dose of M. bovis infection that results in animals which are negative by tuberculin-based diagnostic methods constitute a potential disease reservoir, or whether such animals are in fact protected against reinfection. In addition, we will evaluate whether animals that control disease are protected from subsequent re-infections using a ¡¥memory model¡¦ of bovine TB in cattle. The effect of ¡¥recovery¡¦ from infection on the outcome of standard diagnostic tests will also be studied using this model. Taken together, this proposal directly addresses the issues raised in R.21 of the Research Requirements document. The results obtained from this study will not only further our understanding of disease dynamics in bovine TB in cattle but will also facilitate the formulation of novel control strategies and the development of novel immunodiagnosis strategies or vaccines.
Objective
Objective 1 (VLA/IAH/QUB): To define the relationship between low infectious doses of M. bovis and immunological parameters, diagnostic tests and severity of pathology in cattle (March 2003)

Objective 2 (VLA/IAH): To define the degree of protection conferred to cattle by low doses of M. bovis against subsequent high-dose M. bovis re-challenge and what impact this outcome has on the sensitivity of diagnostic tests. (March 2004)

Objective 3 (VLA/IAH): To define how diagnostically useful immune parameters (e.g. skin test responses, IFN-ƒ× response) develop over time in animals that recover from primary M. bovis infection and to test whether such animals are protected against subsequent re-infection (cattle memory model). (March 2006)

Objective 4 (QUB/VLA/IAH): To establish and validate M. bovis aerosol challenge model for cattle. (March 2006)

Objective 5: To prepare and submit annual and final project reports to DEFRA. (March 2006)

Project Documents
• Final Report : Low dose TB infection in cattle: disease dynamics and diagnostic strategies   (1943k)
Time-Scale and Cost
From: 2002

To: 2006

Cost: £2,560,207
Contractor / Funded Organisations
University - Belfast - Queens, Veterinary Laboratories Agency
Keywords
Animal Health              
Biotechnology              
Bovine Tuberculosis              
Diagnosis              
Pathogenesis              
Plants and Animals              
Zoonoses              
Fields of Study
Animal Health