Identifying the drivers of heterogeneity in disease spread in mycobacterial infections is a major global priority, with regard to both human and animal health. Tuberculosis is thought to kill more humans globally than any other infectious disease, and bovine tuberculosis (bTB) is the most economically significant zoonotic disease of livestock and wildlife in the UK. In this project we will use an extraordinarily rich and globally unique dataset from a 50-year longitudinal study of bTB in European badgers at Woodchester Park, led by the Animal & Plant Heath Agency (APHA), to identify the origins of heterogeneity in the acquisition-of-infection, disease progression, and the triggering of onward transmission. The project builds on a long-standing close collaboration between Exeter and APHA.

Specifically, we will extend recent work on efficient Bayesian inference methodology for fitting mechanistic infectious disease models to individual-level data, to gain important insights into key drivers of infection heterogeneity, including the roles of (i) host senescence (given our evidence of senescence in relevant immune parameters and fitness components in this population), (ii) genetic differences among hosts (exploiting a genetic pedigree to test for heritable variation in key epidemiological parameters), (iii) how duration of infection affects mortality and diagnostic test performance, (iv) whether proxy measures of immune response impact transmission potential over time, and (v) exogenous causes of variation in disease spread.

While elucidating the key drivers of disease spread is critical for the design of effective interventions, attempts to do so in human populations are hampered by the concurrent use of biomedical interventions to manage active disease. Our project offers an unprecedented opportunity to advance understanding of the infection biology of a globally significant infectious disease, and develop statistical tools that could be applied to other infectious disease systems utilising individual-level data, such as bTB in livestock.