Roadmap for development of disease control strategies for bTB

What are we trying to achieve and why? What is the problem we are trying to solve?

Establish the various hosts that can be infected and act as a source infection for livestock and humans. Determine the
molecular underpinning of true host adaptation which determine if an animal can be infected and if it can then disseminate infection.

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

• Challenging to establish whether natural or spillover host.
• Challenging to undertake structured and sufficiently powered surveillance; diagnostic tools may lack sensitivity.
• Challenge to distinguish associated from causal.
• Challenge to establish directionality in multi-host and environmental systems.
• Likely to find some positives during wildlife surveillance; challenging to determine role and risk posed.

What approaches could/should be taken to address the research question?

• Establish the range of wildlife species that can develop active infections in an area.
• Maximise surveillance through targeted sampling, post-mortem and histopathology and consider transmission dynamics studies; likely to be under powered to detect effects in under sampled hosts.

What else needs to be done before we can solve this need?

Literature review.
Consider wildlife surveillance needs and context dependent plausibility as infectious hosts.

Existing knowledge including successes and failures

• Good work done over the years showing that M. bovis and M. tuberculosis exhibit distinct tropisms. In vivo infections of cattle with both pathogens have demonstrated different pathologies.
• Ex vivo / in vitro infections have demonstrated divergent transcriptomics, methylation patterns and transcriptional regulation of M. bovis vs M. tuberculosis. Similarly, microscopic pathology differs considerably between both pathogens.
• Across M. bovis lineages could we expect to see similar heterogeneity in outcomes that might affect epidemiology?