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The challenges of diagnosing bTB

18 April 2019

Bovine tuberculosis (bTB) is a zoonotic disease, affecting both humans and animals, but particularly cattle. It is caused by Mycobacterium bovis, a species closely related to the cause of human tuberculosis, Mycobacterium tuberculosis. bTB causes infections in a wide range of animals, particularly cattle but also deer, buffalo and camelids, where the bacteria reside within the lungs and lymph nodes of infected animals, causing gross lesions of tuberculosis, often described as granulomas, formed of infected cells and dying tissue.

Incidence of bTB has been particularly high in countries such as the UK, New Zealand, the US and Mexico, but many countries have been described as TB-free, except the UK. Here, bTB continues to cause significant problems within the UK, with ~4,000 herd breakdowns alone in 2017 and an average costs of £100 million per year to UK taxpayers.

Currently, there are only two approved tests for bTB infection of animals, the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA), both of which detect only the immune response to bTB infection, rather than the presence or absence of M. bovis. Culturing of M. bovis from infected tissues also enables identification of infected cattle, but this takes even longer and can be up to 30 days.

The TST, or also known as the single intradermal comparative cervical tuberculin test (SICCT), is based on injection of a mixture of proteins extracted from a culture of M. bovis and measuring the inflammatory response. If the immune system of the animal has previously been exposed to M. bovis, either through current or previous infection, then an inflammatory response occurs with a peak at 48–72 hours, but the test can easily be confounded by previous exposure to species of bacteria related to M. bovis or BCG vaccination.

The IGRA is the most recently implemented test, developed in Australia in the 1990s, with approval for use within the EU from 2002 and rolled out in the UK in 2006 after extensive evaluation. The IGRA test works by measuring the levels of a specific immune system protein (cytokine) called interferon-gamma (or IFNγ) in a fresh blood sample that is stimulated with tuberculin proteins, like in the TST. As it is a blood test, it enables identification of infected animals much earlier than the TST or pathological signs, but again, like the TST, it only measures the immune response to M. bovis rather than identification or isolation of bacteria.

The difficulties with using both tests is that sensitivity (if an animal is infected and correctly identified as infected by the test – false negative) and specificity (if an animal is free of infection, but the test identifies it as infected – false positive) are not ideal. Due to the varying sensitivities, 25% and 10% of infected cattle are missed with the TST and IGRA test, respectively. Though the IGRA offers higher sensitivity than the TST, its specificity is lower, with 34 in every 1000 cattle wrongly classified as infected, whereas 1 in 2500 cattle are wrongly classified as infected with the TST.

Due to both tests implemented suffering from sensitivity and specificity problems, a new rapid bTB test is urgently needed. In partnership with the University of Bristol, Microgenetics has developed SwiftDetect bTB, a rapid and innovative diagnostic for bTB, capable of detecting one single bacterial cell in volumes up to 100 ml. Our technology is based on cutting edge PCR technologies routinely used in diagnostic laboratories across the world. Recently, we were given approval to conduct a trial on visible and non-visible lesion cattle in partnership with the Animal Plant and Health Agency (APHA), with testing currently ongoing and results expected in early 2019.