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)