Disease Profiling and Enhanced Diagnosis of Bovine Tuberculosis

Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a progressive respiratory disease with substantial global impact on animal health and welfare as well as on national and international trade. Estimates of annual costs associated with disease control mount to €3billion globally. Annual costs of €100 million are reported for Ireland. The currently approved ante- and post-mortem diagnostic tests detect the majority of animals with bTB but limitations in test performances result in a proportion of infected animals remaining within herds with the potential for onward spread. Uncertainty over the true disease status of tested animals is exacerbated by: the insensitivity of abattoir inspection in confirming detection; key knowledge gaps surrounding disease transmission; and the impact of residually infected animals within herds. In this thesis, a detailed laboratory-based post-mortem (PM) inspection protocol was designed to enhance the detection of bTB. This established semi-quantitative lesion scores for study animals from defined categories (standard reactor, long duration infected, no visible lesionproducing and bTB-free populations). These scores were correlated with ante-mortem test results, to determine an animal’s true disease status and to identify trends within and between study groups. The detailed laboratory-based inspection protocol confirmed more than three times as many lesions of bTB than routine abattoir PM inspection in skin test reactor animals and highlighted how multiple examinations, carried out in parallel, were required to confirm an animal’s disease status. A two-year longitudinal study tracking key pro-inflammatory immune responses and potential shedding of M. bovis by naturally infected cattle found that overall animal lesion scores did not progress substantially, bacterial shedding was not demonstrated and, periodic fluctuations aside, pro-inflammatory responses remained persistently elevated. This suggests disease progression is restricted at the expense of persistently enhanced host immunological responses. A study focused on animals categorised with what is termed non-specific infection (NSI), found no evidence that such animals were reactive to ante-mortem tests for bTB in the absence of disease. A separate study on bTB-free animals showed that serological assays would not enhance the overall performance of the screening tests for bTB currently used in Ireland. In the final chapter, a review of the literature explored how residual infection within herds could be impeding eradication and how improvements in the performance of diagnostic tests would detect a higher proportion of these animals.