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Tuberculosis

Definition
  • Infection by M. tuberculosis or M. bovis
Risk Factors
  • Low BMI
  • HIV
  • Alcohol
  • Travel
  • Immunosuppressed
  • Genetic component?
  • Crowded living conditions
  • Vegetarianism
  • Elderly / young
  • Lung damage (silicosis etc)
  • Diabetes
  • Renal failure
  • Smoking (20+ => 2-3x risk)
Differential diagnosis
  • Pneumonia
  • Noicardiosis
  • Upper zone fibrosis:
    • Sarcoidosis
    • Lung cancer
    • Extrinsic allergic alveolitis
  • Single unilateral infiltrate
    • Sarcoidosis
    • Carcinoma
  • Bilateral infiltrates
    • Sarcoidosis
  • Hilar lymphadenopathy
    • Sarcoidosis
    • Lymphadenopathy (other cause)
  • Multiple cavities
    • Pneumonia (cf timing)
    • Wegener's granulomatosis
    • PMF (progrssive massive fibrosis)
  • Single cavities
    • Abscess
    • Carcinoma
    • Rheumatoid
  • Legionella
  • Anthrax
  • Mesothelioma (aspestos cancer)
Epidemiology
  • 1/3 of world infected
  • African/asian/indian/eastern europe
  • 2-3 million die per year
  • 1 new infection per second
  • >40/100,000 = 'Endemic'
  • 15 - 23% of AIDS deaths are from TB
  • On the rise
  • 99% of infections don't show (many) symptoms and => latent
  • 10% of latent infections will reactivate later
Aetiology
  • Droplets in air spread mycobacteria
  • Usually infects lungs initially
  • Immune response to bacteria causes damage
Clinical features
  • Upper zone fibrosis
    • Bacteria prefer high up (more oxygen)
  • Night sweats
  • Productive cough
  • Fever and 
  • Weight loss
  • Anorexia
  • Pleural effusion
  • Finger clubbing
  • Rales
  • Pneumonia
Pathophysiology
  • Type IV hypersensitivity
  • Bacteria enveloped by macrophages
    • Waxy cell wall => resistant to breakdown
  • MCHII presentation, T cell activation
    • Primary focus (Gohn focus)
    • Secondary foci in lymph nodes
  • => Il1, IL12, TNFa release
  • => PMN infiltration
  • Macrophages turn into
    • Epitheliod cells
    • Which fuse to form Langhans cells
  • Fibroblasts infiltrate and lay down fibrin
  • => caseating granulomas 
Investigations
  • Hx
  • Mantoux
    • Positive result is:
      • >5mm HIV
      • >10mm high-riskers
      • >15mm everyone else
    • NB false positives
      • Steroids
      • Immunosuppression
      • Milliary TB?
  • Quantiferon-TB Gold
    • => IFN-g levels
  • CXR
    • Nodules
    • Cavities
    • Little scars
    • Hilar caseous lymph nodes
    • Upper lobe
  • Sputum
    • 3 different samples
    • ZN stains
    • Bacteria in sputum (direct visualisation) => infective
    • Bacteria can be cultured => latent?
      • Takes 3 weeks
Management
  • NB DOTS treatment
    • Directly observed treatment, short duration
  • Isoniazid
    • 6 months
    • Blocks mycolic acid synthesis
    • Peripheral neuropathy
      • Prevent with vitamin B6 injections
  • Rifampicin
    • 6 months
    • Inhibits DNA polymerase
    • Stains body fluids pink
  • Ethambutol
  • Pyrazinamide
    • First 2 months only
    • Blocks fatty acid synthesis?
    • Or disrupts membrane potential?
    • Joint pain
  • Pyridoxine
    • 2 months
    • Reduces ioniazid side-effects
Prognosis
  • Untreated active disease kills 50%
  • Miliary TB almost 100% fatal
  • Treatment very effective if followed
  • Secondary TB
    • Peyers patches
    • Mesentary
    • Spine (Pott's spine)
    • Liver
    • Miliary TB (blood-born foci)
    • Scrofula of neck (lymphatic spread)
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