Improving the diagnosis of tuberculosis in domestic ruminants through the use of new antigens and test platforms

Bovine tuberculosis (BTB) presents a significant challenge to animal and public health globally. BTB is also a significant cause of zoonotic TB (zTB), mainly in developing/low and middle income countries (LMIC) as highlighted in the recently published roadmap to zTB eradication jointly produced by WHO, WOAH and the International Union against TB & Lung Disease (UTLD). Their One Health approach acknowledged that TB eradication in animals will impact zTB in humans. Eradication could be accelerated by improved diagnostic tests that overcome limitations associated with Purified Protein Derivative (PPD) tuberculin: limited performance, standardisation, vaccine-interference. These could be overcome by defined antigens. PPDs are used both in tuberculin skin tests and blood interferon-gamma release assays (IGRA).

More sensitive blood test platforms that complement the IGRA test could further enhance diagnostic performance. BTB tests primarily target cellular immunity, yet serological tests can also be useful for additional case detection. Thus, our proposal aims to address these constraints to optimise test performance in an inter-connected manner. We will conduct field validation for test sensitivity and specificity of the defined antigen formulation DST-F (fusion protein of ESAT6, CFP10, Rv3615c) in domestic ruminants (cattle, goats, buffalos) in different epidemiological settings (WP1, skin test, IGRA). Environmental exposure to mycobacteria in the farms will be also evaluated. We will develop a multi-cytokine platform (MCP) to enhance test performance beyond the current IGRA, (WP2) and also develop novel antigen capture and lateral flow assays (WP3). The performance of these innovative tests will be assessed with samples generated in WP1. WP4 will critically assess data generated in WP1-3 and provide recommendations for the optimal combinations of test platforms to accelerate BTB eradication.