Roadmap for the development of diagnostic test for bTB

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

To identify and validate specific molecules, indicators, or signatures that can serve as measurable indicators of infection, disease progression, treatment response, and disease control.
To develop biosignatures (combination of biomarkers) that could inform on the latent/carrier status of an animal and evaluate the risk of Mb shedding and transmission.

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

• Current tests are based on direct detection and/or host immune responses.
• Lack of accepted gold standard or Composite Reference Standard.Identification of pathogen derived markers (metabolic products) and/or host factors that are not dependent on the host’s immune response but are specific for infection.
• Heterogeneity: host immune response to bTB can vary among individuals and even within the same individual over time. This heterogeneity poses a challenge in identifying consistent and reliable biomarkers that can accurately represent the diverse responses seen in different hosts.
• M. bovis strains exhibit genetic diversity
• Standardising protocols and validation criteria for biomarker detection assays is necessary to ensure consistent and reproducible results across different laboratories and settings.
• Harmonisation of methodologies is essential to facilitate the comparability and reliability of biomarker-based diagnostic tests.
• Ensuring the stability and integrity of biomarkers during sample collection, storage, and transportation.
• To understand the different clinical states of TB in cattle akin to what is now established for human TB
• To develop easy and affordable tools to identify biosignatures
• To identify a biosignature in circulating blood (the easiest and less invasive procedures for sampling large numbers of animals)

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

• Detection of non-protein volatile components in air samples with mass spec.
• Biomarkers can also play a role in vaccine development and evaluation by serving as indicators of vaccine effectiveness, helping to identify protective immune responses, and aiding in the selection and monitoring of vaccine candidates.
• Consider latent class analyses.
• Follow STARD and QUADAS-2 guidelines for reporting and designing diagnostic accuracy studies.
• To embrace the One Health approach and work together with human TB specialists

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

To establish robust pipelines with all stakeholders-including bTB surveillance programs- to ensure rigorous and longitudinal follow-up of animals in the field

Existing knowledge including successes and failures