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?

To identify the transmission pathway(s) whereby the pathogen gets from infected to susceptible animals – within- and between species.

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

• Establishing how infection spreads between species – domestic animals, wildlife, and humans.
• To deploy mathematical model(s) to investigate TB transmission pathways from routinely captured surveillance data.
• Under ascertainment of infected host status due to test sensitivity issues; need more sensitive detection of
  exposure/infection, especially when attempting molecular/genomic epidemiology, including phylodynamics
  (evolutionary theory plus genome epidemiology).
• Molecular and genome epidemiology currently require specialist positive cultures from affected hosts and environmental sampling.
• Conventional molecular epidemiology lacks resolution for estimating transmission pathways, other than at a large scale.
• Require temporal signal in whole-genome sequencing data i.e., require structured longitudinal sampling and biobank over time.
• Model systems or non-invasive ways to study intraspecies transmission

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

• Much has been gleaned about transmission pathways and TB epidemiology from mathematical modelling and molecular epidemiology based on TB test, location, and movement data.
• Define specific case studies and ensure maximal sampling of affected hosts etc.
• Establishing excretion levels from infected animal of various species including M. tuberculosis by people in contact with livestock.
• Simulation modelling supported by molecular epidemiology

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

• Possible to simulate (agent-based) and model transmission from estimated transmission parameters.
  Structured, longitudinal pathogen sampling required for investigating transmission pathways using genome epidemiology.
• Establishing the infectious dose; mathematical and phylodynamic models can help estimate disease parameters.
• Establishing the sources of infection including wildlife reservoirs and humans.
• Establishing the contact networks allowing spread within and between herds.

Existing knowledge including successes and failures