12.12.17 TB

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

    • 2 months

  • Blocks arabinosyl transferase

    • • => blocks cell wall production

    • Colour vision -

  • 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)