Tuberculosis

Etiology

• Majority of infections with M. bovis Mycobacterium bovis; however, other species of the Mycobacterium tuberculosis Mycobacterium tuberculosis complex occasionally affect cattle.
• The M. bovis genome has been evaluated, with 11 major spoligotypes identified in the UK in 2014:
  • Spoligotypes can be further classified using a method known as variable numbers of tandem repeat (VNTR) typing.
  • These two molecular methods used for sub-typing strains has become a useful epidemiological tool and has shown that sub-strains tend to have specific geographical ranges.

Predisposing factors

• Herd-level risk factors most consistently identified:
  • Cattle movement (estimated to contribute <20% in some GB and Irish studies).
  • Occurrence of TB on contiguous premises and/or level of TB in surrounding areas (infection pressure).
  • Herd size.
• Other herd-level risk factors identified in some studies:
  • Contact with contiguous cattle.
  • Indicators of badger density/activity.
  • Sourcing cattle from herds with TB history.
  • Providing cattle feed inside housing.
  • Use of multiple premises.
  • Housing type.
  • Herd type.
  • Farmland habitat.
  • Fertilizer usage.
  • Mineral deficiencies, eg selenium Selenium and Vitamin E.
  • Use of silage clamps.
  • Rotational grazing.
• Other:
  • Maintenance of residual infection within a herd, due to low sensitivity of the diagnostic skin test. This risk increases with herd size - herd size of >300 is considered an inherent risk factor for bovine TB. 
  • Concurrent disease, by direct immunosuppression (such as BVD infection Bovine viral diarrhea or trace element deficiencies Assessing mineral status) and/or interference with diagnostics, eg Fasciola hepatica Fasciola hepatica, liver fluke and other wildtype Mycobacteria such as Mycobacterium Avium subspecies paratuberculosis - MAP MAP and Johne's.

Pathophysiology

• Two stages: primary complex (lesion at the point of entry), followed by post-primary dissemination, eg acute miliary tuberculosis, discrete nodular lesions, or chronic organ tuberculosis.
• Clinical signs vary due to site of involvement, however an underlying toxemia develops which causes weakness, debility and eventual death.

Timecourse

• Variable; many infections result in a period of latency before progression to clinical disease.
• M. bovis Mycobacterium bovis infection rarely presents as clinical disease and it normally appears as apparently healthy animals reacting to the diagnostic tests or incidentally at abbatoir before clinical signs occur.

Epidemiology

• Complex and much remains uncertain.
• Multiple risk factors including biological, behavioural, environmental and genetic.
• Cattle to cattle M. bovis Mycobacterium bovis transmission occurs primarily by the respiratory route through the inhalation of aerosols containing the bacteria when the animals are in close contact.
• Oral route of infection due to the ingestion of mycobacteria from the environment is also possible.
• The risk of a bovine TB varies both between countries and within countries.
• Including within herds with some herds experiencing multiple breakdowns over time, whilst others appear to remain free of infection.
• Cattle and other bovids considered the "primary host" species in most of the world including the UK.
• "Spillover host" species include any other species that can develop the disease, which includes almost all other mammals and birds.
• Domestic species including dogs, cats, camelids and other farmed species including pigs, sheep and deer can all be affected.
• Spillover into non-bovine species that have close contact with humans could potentially lead to an increase in human M.bovis infections.
• Transmission thought to occur by both direct and indirect contact.
• Survival of M.bovis in the environment can occur for significant periods of time under optimal conditions (cool, moist environments, eg winter months).
• M. bovis is inactivated when exposed to high UV and/or dry environments and may only survive for days on pasture during the summer months.
• M. bovis has been shown to survive in manure for up to six months.
• One study found that slurry stored for under two months and spread on grazing was associated with an increased risk of bTB.
• Further information on TB survival in the environment can be found via TB Hub, this information has been provided by the University of Exeter.
• Current recommendations are to store slurry for 6 months and to delay grazing for 2 months after spreading slurry.

Badgers (UK)

• Badgers are the most significant UK spillover host species in terms of maintaining incidence of the disease in endemic areas, due to their ability to develop the disease and live with it for relatively long periods, and their ecology and interaction with cattle in buildings and on grazing pastures.
• The first badger infected with M.bovis in the UK was discovered in Gloucestershire in 1971.
• Between April 1971 and April 1973, examination of 165 carcases of wild badgers showed 36 to be infected and, of 112 samples of feces, 12 were infected.
• From 1973 to 1976, 1206 badger carcases underwent post mortem. Tuberculosis was the major cause of natural death, killing 39% of the natural death cases, followed by bite wounds and starvation. Road traffic accidents were the greatest single cause of death.
• In Thornbury, from 1975, widespread repeated culling of badgers by gassing was undertaken and by 1981 the last badgers were removed and natural recolonization was allowed to occur. Incidences of bTB were reduced significantly with no confirmed incidents in the ten years post culling.
• Between 1998 and 2005, the largest ever study into bovine TB in the UK, the Randomized Badger Culling Trial (RBCT) found that 16.6% of the badgers subjected to standard post mortem were infected with M.bovis. The sensitivity of the post mortem was calculated to be 54·6% (95% CI 44.9-69.8%), meaning around half of the infected badgers were detected.
• The RBCT consisted of thirty trial areas divided into ten matched triplicates, each around 100Km².  Each area was then randomly assigned to one of three treatments, survey only, repeated widespread (proactive) culling or localized (reactive) culling. Reactive culling was stopped after it appeared to increase the incidence of bTB. The initial results published at the end of the study found that proactive culling reduced bTB incidence by 23.2% however the incidence increased in the surrounding un-culled areas (up to 2Km from the boundary). This increase is thought to be due to changes in badger behaviour, also known as perturbation.
• A follow up study found that the beneficial effects of proactive culling persisted and were greater after the cessation of culling with confirmed breakdowns inside proactively culled areas 37.6% lower (95% CI 24.6-48.4%) than that inside survey only areas. Importantly the detrimental effect observed in the surrounding unculled areas did not occur post culling.
• In Gloucestershire from 2006 to 2009, 1201 badgers were caught, anesthetized and triple tested for M.bovis (see diagnostics for further detail). Of the 1,201 badger's tested 449 were found to be positive. The sensitivity of the triple test is 61-86%.
• Research into the role of badgers in the spread of TB is ongoing.
• In 2013 licenses were issued to allow industry led culling to take place in Somerset and Gloucestershire, to assess the practicalities and impact of caged trapping and controlled shooting.
• Trial badger culls have met with much resistance from wildlife groups and there are various ethical and animal welfare issues that have been raised in relation to such schemes.
• Initial assessment of the two pilot cull areas, after adjusting for confounding factors showed that reductions in bTB incidence were associated with culling in the first 2 years in both the Somerset and Gloucestershire intervention areas when compared to matched areas with no culling.
• As with the RBCT an increase in incidence in the surrounding area was seen in Somerset, however this effect was not evident in Gloucestershire.
• In 2017 further licenses for badger control were granted in Devon, Cornwall, Wiltshire, Somerset, Cheshire, Dorset, Herefordshire and Gloucestershire.
• The Bacille Calmette-Guérin (BCG) vaccine has been used in badgers throughout the UK and Ireland and has been shown experimentally to reduce disease severity and lesion size.
• The Badger Edge Vaccination Scheme (BEVS) currently provides grants to contribute towards the cost of vaccinating badgers against bovine TB in the Edge Area of England using the BCG vaccine.
• Between 2010-15 the UK Government invested £24.7million in R&D for bTB vaccines for cattle and badgers.
• One area of interest is the development of an oral badger vaccine with studies currently investigating potential baits, bait delivery systems and vaccine efficacy.
• There is currently no direct experimental evidence of reduced transmission of bTB to and between cattle following the use of the BCG vaccine in either cattle or badgers.