Saturday, June 04, 2016

A (nother) new test for TB

Making the headlines this week, is another new screening test - [link] for zTB. This is a blood test, with results available in 6 hours, and aims to find TB bacteria circulating in blood, ahead of any lesions forming.

The test has been developed by a team at The University of Nottingham led by Dr Cath Rees, an expert in microbiology in the School of Biosciences and Dr Ben Swift from the School of Veterinary Medicine and Science.

The researchers have used this new method to show that cattle diagnosed with bovine tuberculosis (bTB) have detectable levels of the bacterium Mycobacterium bovis (M. bovis) - which causes this bTB - in their blood. The research: ‘Evidence of Mycobacterium tuberculosis complex bacteraemia in intradermal skin test positive cattle detected using phage-RPA' has been published online in the peer reviewed medical journal Virulence = [link]

The full paper is behind a paywall. More information is available from the authors.

 In her introduction Dr Rees explains: “This test delivers results within 48 hours and the frequency in which viable mycobacteria were detected in the blood of skin test positive animals, changes the paradigm of this disease."
This new, simple and inexpensive blood test detects very low levels of mycobacteria in blood using a bacteriophage-based technique developed by The University of Nottingham. The group has patented an improved version of the method that delivers results in just six hours. More recently ‘proof of principal’ experiments have shown that this is even more sensitive. This is currently licenced to a spin out company, PBD Biotech Ltd.
This test uses amplified DNA, and is explained by the authors thus:
Bacteriophage amplification technology was developed 20 years ago as a method to rapidly detect and enumerate slow growing pathogenic mycobacteria. In addition it can be used as a tool to rapidly detect antibiotic resistance and to investigate mycobacterial dormancy. The assay detects the growth of broad host range mycobacteriophage, capable of infecting a wide range of both pathogenic and non-pathogenic mycobacteria.
Any diagnostic test with a decent pedigree, is welcome, and having heard the guff circulating about the sensitivity of the internationally used skin test, many will latch on to these discoveries like the Holy Grail.
But tests such as this for cattle, would still be supplementary to the primary skin test. Just like Gamma ifn - [link] and Enferplex - [link] and even qPCR - [link]

But only a scientist on a mission could come up with the following two statements - and keep a straight face:
"Routine testing for Bovine TB uses the Single Intradermal Comparative Cervical Tuberculin (SICCT) skin test for M. bovis infection and all healthy cattle are regularly tested this way. However, it is known that this test is only 90 per cent sensitive at best and misses many infected animals."
and then in describing the test results:
"The data we are getting has taken the scientific community by surprise. In our paper we show that when blood samples from (45) skin test negative cattle were tested for M. bovis cells, all the samples proved negative."

Dr Rees then explains that the test showed:
"viable Mycobacterium tuberculosis complex bacteria (MTC) were detected in 66 per cent of samples (27/41) from skin test positive animals."
So this test agreed 100 per cent with the 45 skin test negative animals and 'found' 66 per cent of the skin test positives? We're trying to get our collective heads around that one, but suggest the remaining skin test positives would be NVL at post mortem. That is, both the skin test and this blood screen, had, in some cattle, picked up mycobacterium bovis circulating ahead of lesions. Dr. Rees explains:
“More excitingly, using our new more sensitive six-hour method, this figure is even higher - all animals with visible lesions were MTC positive, and even 26 out of 28 animals where the lesions were not yet visible also were positive suggesting that M. bovis is commonly found in the circulating blood of infected animals. Using our bacteriophage-based test the hope is that we can help improve herd control by finding animals at the early stages of infection and helping farmers control outbreaks of bTB more rapidly. ”
The Nottingham team are working with the United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, to set up the first animal trial using the blood test to detect M. bovis in the blood of experimentally infected animals to determine exactly how soon this test can detect infection.

Dr Rees said: “The test also offers the potential for new, better tests for other farm animals. We are directly detecting the bacteria and so the method will work using blood samples from any animal species – so far we have detected mycobacteria in the blood of cattle, sheep and horses, but it could also be used for deer, goats or llamas. Not only that, we can detect any type of mycobacteria, we have use the same method to detect other diseases, such as Johne’s disease, not just bTB.”

Why only this suggested use on 'farm animals'? What about infected Badgers? Don't mention the 'B' word.

It could be useful. Just like non invasive qPCR on badger latrines and sputum could be useful. But it won't be used, as the responsibility for eradication of this Grade 3 zoonotic pathogen then becomes Defra's, not that of a farmer with a cage or a rifle trying to jump through Natural England's increasingly  convoluted hoops.

Finding cattle exposed to mycobacterium bovis, presently screened by the Intradermal skin test, and confirmed by this method is fine. As long as continuing  upspill from wildlife is then excluded. Otherwise, as now, we will shoot the messenger in ever increasing numbers, while gaining nothing at all.

Our take is that this test correlated very snugly with the results of the skin test, on the cattle which were examined.  

The paper is available to purchase on this link - [link]
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