Mycobacterium bovis

Bovine tuberculosis

• Epidemiology
  • World-wide disease caused by M. bovis
  • Aerosol transmission between cattle kept in close contact
  • Transmission to calves via ingestion od contaminated milk
  • Wildlife reservoirs include badgers and possibly deer in the Europe

• Pathogenesis and pathogenicity
  • The ability of mycobacteria to survive and multiply within macrophages determines whether disease will occur within the host
  • Survival and multiplication in macrophages at primary site of infection due to prevention of phagosome-lysosome fusion
  • Mycobacteria utilize several virulence factors including cord factor or trehalose dimycolate, surface glycolipid, sulfatides, lipoarabinomannan, heteropolysaccharide, heat shock protein, complement, and tubuloprotein
  • The types of immune responses that are critical in responding to mycobacterial infection are cell-mediated immunity and the delayed hypersensitivity response
  • Pathogenicity of mycobacteria depends on their ability to escape phagocytic killing, mostly imparted by the cell wall consitiutents:
    • Cord factor (trehalose dimycolate) – surface glycolipid responsible for serpentine growth in vitro
    • Suphatides – surface glycolipid containing sulphur which prevents fusion of phagosome with lysosome. cAMP secreted by the bacteria may also facilitate this.
    • LAM – heteropolysaccharide which inhibits macrophage activation by IFNγ and induces macrophages to secrete TNFα which induces fever and IL-10 which suppresses mycobacteria-induced T cell proliferation
    • The wax of the cell wall, peptidoglycans and other glycolipids are responsible for the adjuvant activity – attracts antigen presenting cells
    • Tubuloprotein – important antigen; purified tubuloprotein is the basis of the tuberculin test
  • Mycobacteria are released from macrophages and also migrate within macrophages around the body
  • Waxy cell wall contributes to the host immune response to the mycobacteria and the development of lesions
  • Cell-mediated immune response with activated macrophages and sensitised T cells
  • Delayed-type hypersensitivity response with granuloma formation
  • Lesions contain macrophages, multinucleate giant cells and later a central area of caseous necrosis, giving a cheesy appearance

• Clinical signs
  • Initially asymptomatic
  • Loss of condition
  • Cough and intermittent pyrexia with lung pathology
  • Tuberculous mastitis with transmission via milk

• Diagnosis
  • Tuberculin test - comparative intradermal test
  • Avian and bovine tuberculin (purified protein derivative) is injected intradermally into two different clipped sites on the side of the neck
  • Skin thickness at these sites is compared before and 72 hours after the injection of tuberculin with calipers
  • Increases in skin thickness at the bovine PPD site of more than 4mm greater than the avian PPD site are seen as positive (reactor)
  • Blood tests including the gamma interferon assay are being developed
  • Laboratory examination of lesions, lymph nodes and milk
  • Ziehl-Neelson staining of tissues
  • Isolation requires Lowenstein-Jensen medium

• Control
  • Eradication programs using a test and slaughter policy
  • Reactors positive to the tuberculin test are slaughtered and restrictions applied to the affected herd