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The science of comprehensive TB testing

01 June 2017, at 12:00am

Through a rigorous programme of testing, the UK’s Animal and Plant Health Agency (APHA) is working towards making bovine TB in Great Britain a thing of the past. OV magazine speaks to test consultant Shelley Rhodes, one of the scientists paving the way to eradication.

Shelley Rhodes is a test consultant for APHA’s TB Research Group, and is project manager for the UK agency’s nationwide programme of cattle interferon-gamma TB testing. She works with both colleagues in her agency routine testing laboratories who deliver the test, and with the veterinary and field workers who organise TB testing on farms. Shelley has also been the test consultant for camelid TB serology at APHA since October 2014.

What does your current job entail?

My job includes the analysis of test data and provision of scientific advice for APHA and policy advice colleagues. I work across both research and routine testing to ensure the continued quality of TB test delivery. I also respond to ad hoc queries from private vets and other colleagues external to APHA, and have been invited to various meetings to discuss TB testing at APHA and explain why we test the way we do – providing the rationale and answers to some of the commonest questions.

I maintain interest in TB in other species, for example introducing an interferon-gamma test for TB in domestic cats, working with Danielle Gunn-Moore, Professor of Feline Medicine at Edinburgh University, and others – the test is now run by Biobest in Edinburgh, on a semi-commercial basis with Danielle. More recently I have had the pleasure of working with the deer industry while investigating, and eventually testing out, a confirmed deer herd under TB restrictions. This was achieved using serology tests, and we are currently looking at ways to fund a wider field trial.

What method is best for testing for bTB in cattle?

The primary bTB test for cattle is the tuberculin skin test. Supplementary blood testing, using the interferon-gamma (IFN) test, may be applied in certain circumstances, for example in confirmed Mycobacterium bovis-infected herds.

Why is the skin test the chosen method?

APHA uses the skin test for surveillance purposes because it has a high specificity and good sensitivity. GB data show specificity of 99.98 percent – there is a one-in-5,000 chance of a false-positive – and sensitivity of 81 percent. Should a skin-test-positive animal be found to harbour M. bovis, then the IFN blood test may be used on remaining cattle in that herd. The IFN test has a higher sensitivity than the skin test (GB data show 90 percent) and can detect infection earlier than the skin test, so it can mop up infected animals that have not yet developed skin reactivity.

The lower specificity of the IFN test (GB data show 96.5 percent, i.e. three or four false-positives per 100) prevents its use as a surveillance test. But in infected herds the highest priority is the removal of infection and so specificity is sacrificed slightly to sensitivity. The very fact that the test is mostly only applied to confirmed infected herds also means that the risk of a positive being a false-positive is lower (three or four false-positives per 100 is what you would expect from a truly bTB-free herd, which a confirmed infected herd is not).

What are the most common issues that you encounter with TB test delivery?

There are common misconceptions and questions about the IFN test which I try to address when speaking to vets and farmers, such as “Will repeat skin testing give a false-positive result?” – which it won’t. In fact, it’s more likely to give a false-negative result, particularly with low-level skin responders.

Another common question is “Aren’t IFN responders just showing immune protection?” – this is an interesting one as we know IFN is required generally for immune protection against TB, and that it also contributes to the immunopathology that is TB. What we know about bTB in cattle is that a positive IFN response reflects active infection and that these cattle are more likely to show disease progression (become skin-test reactors and develop visible lesions).

Anergy (a lack of skin-test response in suspected bTB-infected cattle) also concerns people, but the IFN test does have a track record in detecting such animals, as well as identifying those early, skin-test-negative infections mentioned above. Co-infection of bTB restricted herds with Johne’s disease is also a worry for some. Again, it’s false-positives on the IFN test that people worry about, but Johne’s is more likely to result in a false-negative, as it can enhance the response to PPDA (avian PPD) and mask any specific response.

What advice would you offer to OVs with queries about TB testing?

If it’s felt there is a lack of information, then perhaps one way would be to ask Defra or APHA for specific information to be made available on a public site, like the TB Hub.

How could the current method of testing be improved upon? Has there been any promising research in this area recently?

In terms of Johne’s mentioned above, for example, we are planning to provide a new, flexible IFN test option that includes an additional peptide antigen generally used for higher-specificity IFN testing (like for the approximately 0.5 percent of cases we test for non-specific skin reactions). This flexible test could help to identify infected individuals in restricted herds by virtue of a positive peptide response in samples where specific PPDB response has been masked.

How are the methods different for testing in other animals, like deer and camelids?

Our biggest problem is cattle, and so rooting out infection as quickly as possible is the rule. For this, the skin test followed by the IFN test (where required) is the most effective way. Fewer non-bovines appear to be infected with bTB and they are generally regarded as spillover hosts – that problem would eventually disappear following eradication in cattle.

While serology is currently regarded as a third-line ancillary test for cattle (i.e. behind the skin and IFN tests), for these other animals, serological tests may be sufficient. APHA introduced a combined serology test for camelids in October 2014 following a successful field study funded by the Camelid Industry – this can be used flexibly as a high-sensitivity or high-specificity test depending upon circumstances (for example, a confirmed bTB breakdown or a contiguous test respectively).

More recently, APHA has worked with the deer industry to apply serology tests to a confirmed infected deer herd, and could test this herd out of bTB restrictions, demonstrating that the sustained application of skin and ancillary tests can be effective for GB deer too. In both non-bovines, there are question marks over the use of the skin test, especially in camelids where it is known to have very low sensitivity (five to 15 percent).

While for cervids there is better data, the margins for a positive, particularly for severe interpretations, is very small. That said, one major feature of the skin test is the boosting of antibody responses up to levels that are diagnostically useful, and without which the sensitivity of antibody tests would be reduced.

What drove you down the TB research and testing route?

Bovine TB has been controlled before (from the 1950s to the 1970s), and will be again. I’d like to see that happen.

Do you have any advice for OVs wishing to take a similar career path?

Well I am not a vet, just a scientist, but eradication of bTB is going to take all of us working together. There are around 23 years left of Defra’s eradication plan, so there’s plenty of time to be involved. Even afterwards there will be the need to ensure cases stay low nationally (if we can’t remove bTB completely), and that requires a maintained, effective surveillance.

Editor
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