Quantitative interferon-gamma responses predict future disease progression in badgers naturally infected with Mycobacterium bovis

Abstract

The diagnosis and control of Mycobacterium bovis infection (bovine tuberculosis: TB) continues to present huge challenges to the British cattle industry. A clearer understanding of the magnitude and duration of immune response to M. bovis infection in the European badger (Meles meles) - a wildlife maintenance host - may assist with the future development of diagnostic tests, and vaccination and disease management strategies. Here, we analyse 5280 diagnostic test results from 550 live wild badgers from a naturally-infected population to investigate whether one diagnostic test (a gamma interferon release [IFNγ] assay, n = 550 tests) could be used to predict future positive results on two other tests for the same disease (a serological test [n = 2342 tests] and mycobacterial culture [n = 2388 tests]) and hence act as an indicator of likely bacterial excretion or disease progression. Badgers with the highest IFNγ optical density (OD) values were most likely to subsequently test positive on both serological and culture tests, and this effect was detectable for up to 24 months after the IFNγ test. Furthermore, the higher the original IFNγ OD value, the greater the chance that a badger would subsequently test positive using serology. Relationships between IFNγ titres and mycobacterial culture results from different types of clinical sample suggest that the route of infection may affect the magnitude of immune response in badgers. These findings identify further value in the IFNγ test as a useful research tool, as it may help us to target studies at animals and groups that are most likely to succumb to more progressive disease.

Keywords: Diagnosis; epidemiology; immunology; tuberculosis (TB); wildlife.

Fig. 1.

Rate ratios for subsequently obtaining a positive Stat-Pak test result in badgers after varying follow-up periods, in relation to their initial IFNγ titre (category 1 = lowest IFNγ titre; category 4 = highest IFNγ titre: see Table 1 for details of categories) compared with badgers with a negative IFNγ titre (category zero). A badger with a rate ratio of 15 can be interpreted as having a 15 times higher chance of testing positive on Stat-Pak within the indicated follow-up period than a badger with a negative IFNγ titre. Solid lines indicate significant relationships, and dashed lines indicate relationships that were not found to be significant (see Tables 2 and 3 for 95% confidence intervals). Data derived from 550 badgers tested with Stat-Pak a total of 2342 times at Woodchester Park from July 2006 to October 2013.

Fig. 2.

Distribution of IFNγ OD values stratified by mycobacterial culture result across a range of different clinical samples. Data shown includes 2205 observations from 546 badgers. + = positive culture result, − = negative culture result. Outliers are not shown.