There is anecdotal evidence pointing to differences in resistance to infection with M. bovis between European cattle breeds and zebu (Bos indicus) regions. In the UK, there is no clear evidence of differences between cattle breeds in terms of susceptibility to TB. While there is evidence that dairy herds are more likely to experience a TB breakdown than beef herds, this is not necessarily due to breed differences. However, pedigree analyses funded by the Government have shown evidence of genetic variation to bovine TB susceptibility within Holstein-Friesian dairy cattle in the UK, and similar evidence exists from Ireland and NI. However, the actual impact (if any) of genetic selection for bovine TB resistance on the incidence of TB in cattle has yet to be determined. TB Advantage is a genetic index published by AHDB Dairy, to help dairy farmers make informed decisions to breed cows which have an improved resistance to bovine TB.
No. There is no proven relationship between trace element supplementation and decreased susceptibility to bovine TB. As a general rule, cattle should be fed a balanced nutritional diet according to their production status, and any deficiencies of trace elements in cattle rations should be corrected as a matter of good husbandry practice.
Background
Much of the soil in the UK is deficient in one or more minerals, and deficiencies of copper, selenium, cobalt and iodine can occur in farmed animals. Mineral supplements for cattle are desirable to help alleviate this, where it occurs. There is limited evidence for selenium deficiency as a risk factor for an increased susceptibility to M. bovis infection in cattle, and no evidence of this in badgers. Furthermore, there is also no correlation between selenium levels in UK soils and the incidence of bovine TB in either the High Risk or Edge areas. The association between M. bovis infection and trace elements such as selenium, copper and vitamin B12 status of cattle was investigated as part of the Defra funded project “Pathogenesis and diagnosis of tuberculosis in cattle – complementary field studies” (project SE3013). This study found that blood levels of an obligatory selenium-dependant enzyme were lower in cattle that tested positive to the tuberculin skin test than control animals. Unfortunately, it was not possible from this type of retrospective study to conclude if that association was a cause or an effect of infection with M. bovis. As an explanation for that trend, the study cited previous work on the mechanisms behind selenium deficiently, impaired immunity and a resultant increase in risk to developing mastitis. We are not aware of any biochemical or immunological data showing changes in the cattle immune response to M. bovis resulting from a dietary deficiency in selenium.
There is no conclusive evidence to support this hypothesis at present and modify the interpretation of the comparative skin test in specific herds with confirmed liver fluke infestation. Nevertheless, farmers are advised that, where possible, medicines and routine veterinary treatments (including wormers) should not be given to cattle on the first day of the tuberculin skin test, or shortly before a test. If possible wait until the test results are read on the second day and animals have passed the test. The hypothesis that concurrent infestations, including liver fluke, may impact on TB test sensitivity is not new. An independent, systematic and thorough review of the veterinary literature on this topic was conducted by a team of Liverpool University academics and published in 2019. This suggests that any effect that liver fluke infection may have on the progression of TB infection in cattle and its diagnosis by the tuberculin skin test and interferon-gamma blood test is likely to be modest and of little practical significance. A high prevalence of fasciolosis in cattle is not thought to be a significant factor in the persistence of bovine TB in the endemic regions of the UK. Therefore, there is no substance in the theory that claims that liver fluke is masking detection of M. bovis-infected cattle and resulting in under-reporting and an apparent low incidence of bovine TB in certain parts of the country where liver fluke is highly prevalent in cattle. Moreover, since all cattle carcases are routinely inspected for TB in abattoirs by Food Standards Agency (FSA) inspectors, if such masking was happening at the farm level (when herds are tested for TB), we would expect to see higher rates of bovine TB lesions in carcases of animals from areas where liver fluke is more common, which is not the case.
Reference
Howell AK, McCann CM, Wickstead F, Williams DJL (2019). Co-infection of cattle with Fasciola hepatica or F. gigantica and Mycobacterium bovis: A systematic review. PLoS ONE 14(12): e0226300. https://doi.org/10.1371/journal.pone.0226300
Potentially. Infection of cattle with Mycobacterium avium subspecies paratuberculosis (the bacterium that causes Johne’s disease), and vaccination against the disease can cause cross reactivity to the skin and interferon-gamma tests for bovine TB.
Background
Johne’s disease, caused by infection with the bacterium Mycobacterium avium subspecies paratuberculosis (abbreviated MAP), is a chronic and insidious disease of cattle and other ruminants. It is believed to be endemic in the UK and many other countries worldwide. It is well known that exposure of cattle and other animals (including man) to MAP and environmental mycobacteria can cause cross reactivity to components of the bovine PPD tuberculin used in the skin and interferon-gamma tests for bovine TB. In particular, this reduces the specificity of the single tuberculin skin test (in the neck or the caudal fold) in TB-free herds infected with (or vaccinated against) MAP. In the UK and Ireland, responses to avian-PPD are used alongside bovine PPD tuberculin in the routine screening test for bovine TB. This provides a comparative measure of cattle exposed to non-pathogenic environmental mycobacteria and the bacterium that causes TB in birds, which is antigenically very similar to MAP. Hence the higher specificity (i.e. lower probability of false positive results) of the comparative skin test over the single test. The same principle applies to the Bovigam test, where optical density levels of interferon-gamma released by white blood cells stimulated with avian tuberculin are subtracted from those measured in blood stimulated with bovine tuberculin to reduce the probability of false positives. We have no direct data on the effect of (MAP) infection on the sensitivity of the comparative skin and interferon-gamma tests for bovine TB in GB. Experimental studies in calves pre-sensitised with M. avium subspecies avium (a bacterium closely related to MAP) have shown that raised responses to avian tuberculin in the comparative skin and interferon-gamma tests may mask the detection of M. bovis infection, even when the specific antigens (ESAT-6 and CFP-10) are employed (Howard et al. 2002, Hope et al. 2005). In Spain, Aranaz et al. (2006) studied a herd with both MAP and bovine TB infection that was followed up for 3.5 years. The comparative tuberculin skin test, interferon-gamma assay and a serological test for MAP were used in parallel. Overall, the skin test detected 65.2% of all animals in the herd that were culture-positive for bovine TB and the interferon-gamma test detected 69.6% of them. These percentages are in the lower part of the accepted normal range. Both the skin and gamma tests were able to detect TB-infected animals in the first part of the trial, but the blood test was the only test able to detect such animals in the last three tests. So, in GB, where the comparative skin test is used, the main impact of MAP infection or vaccination would be in reducing the sensitivity of the test, i.e. its ability to detect animals concurrently infected with M. bovis and MAP. To counter this, a more severe interpretation of the skin test and/or a combination of skin and interferon-gamma testing in parallel interpretation may be used in specific herds where this is suspected to be a problem. Additionally, a flexible extended format of the interferon-gamma test can be applied, which uses M. bovis specific synthetic antigens ESAT6 and CFP10 that are not expressed by MAP in addition to the conventional PPDA and PPDB antigens. Blood samples from animals co-infected with M. bovis and MAP release interferon-gamma when stimulated with M. bovis specific antigens ESAT6 and CFP10, even if they still show an avian ‘bias’ on the conventional (comparative PPD) interferon-gamma test.
Johne’s disease is caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). The few studies that have investigated the effect of tuberculin skin testing on diagnostic antibody tests for MAP in dairy herds have demonstrated a rise in MAP test-positivity following injection of avian and bovine tuberculins used in the skin test. This effect is transient and it is unclear whether this represents a non-specific increase to be avoided (hence the current advice to test for MAP after this effect has waned) or a useful boost of MAP-specific antibodies in genuinely MAP-infected animals. The effect of a recent tuberculin skin test could therefore be to:
- decrease the specificity of Johne’s screening, leading to more false positive results (animals that are uninfected but test positive), or
- increase the sensitivity of Johne’s screening leading to greater detection of truly infected animals, or
- a combination of both
Due to this uncertainty, it is currently recommended that an interval is left between the tuberculin skin test and taking blood or milk samples for Johne’s disease screening. For Johne’s testing using milk samples, it’s recommended that there is an interval of at least 43 days (six weeks) between the tuberculin skin test and milk sampling. For Johne’s testing using blood samples, it’s recommended that the interval is longer at 70 days (10 weeks). For routine surveillance TB testing, farmers can plan ahead and time their blood and milk sampling for Johne’s disease testing accordingly. In herds undergoing short interval testing (SIT) due to a TB breakdown, blood samples for Johne’s disease screening could still be taken just before the next SIT, as practically speaking the interval between SITs is usually more than 70 days.
References
- Kennedy, A. E., Da Silva, A., Byrne, N., Govender, R., MacSharry, J., O’Mahony, J. and Sayers, R. G. (2014) The single intradermal cervical comparative test interferes with Johne’s disease ELISA diagnostics. Frontiers in Immunology. 5, 564 https://doi.org/10.3389/fimmu.2014.00564
- Barden, M., Smith, R. F., Higgins, H. M. (2020) The interpretation of serial Johne’s disease milk antibody results is affected by test characteristics, pattern of test results and parallel bovine tuberculosis testing. Preventive Veterinary Medicine. 183 https://doi.org/10.1016/j.prevetmed.2020.105134
- Bridges, N., van Winden, S. (2021) The occurrence of Mycobacterium avium subsp. paratuberculosis positive milk antibody ELISA results in dairy cattle under varying time periods after skin testing for bovine tuberculosis. MDPI Animals. 11, 1224. https://doi.org/10.3390/ani11051224
It is possible that any infective agent that suppresses an animal’s immune response mechanism such as occurs in cattle when infected with BVD virus, will increase the susceptibility to and ability to fight other infectious diseases such as TB. For instance, concurrent TB and other infections are frequently seen in people infected with HIV, but there has been limited work to demonstrate a similar risk for cattle infected with BVD virus.
Background
Bovine viral diarrhoea (BVD) is most common in young cattle (6-24 months old). Serologic surveys indicate that BVD virus is distributed worldwide and the virus is regarded as endemic in most parts of the world. A small experiment with five neonatal calves artificially infected with BVD virus and M. bovis BCG was carried out by Charleston et al. (2001). The results showed that infection of cattle with this virus could transiently reduce interferon-gamma responses to M. bovis in the two weeks after BVD virus inoculation and resulted in a failure to identify TB-infected cattle. There is therefore some experimental proof of the principle that BVD virus infection could suppress the immune response of cattle against M. bovis in some cattle, but it is far from clear that this is a significant issue or a widespread cause of false-negative skin test results under normal field conditions. BVD virus infection appears to be widespread in Australia, yet bovine TB was successfully eradicated from that country in the late 1990s through a programme of regular skin testing of herds, slaughter of reactors and movement restrictions, supplemented by slaughterhouse surveillance (and interferon-gamma testing in the final years of the eradication campaign).
Potentially, however it is unlikely that it would have enough of an effect to impact the result of the test. If the immune system of an animal is compromised for any reason, it is more susceptible to infection and may be less likely to react to the test (i.e. infected animals may be missed). Reasons for depression of the immune system in cattle include infection with viruses e.g. Bovine Viral Diarrhoea (BVD), drug treatment (e.g. steroids) and during the early post-calving period.
There is currently no evidence to support this.
Although M. bovis bacteria can be transmitted in saliva and other secretions, there is no evidence to support transmission between cattle via this route.