Tuberculosis (TB)


  • Aerosol spread (small droplets), activate macrophages, CD3 cells form wall around - granuloma. Caseous, non-necrotising fibrotic.

  • Outcomes of exposure: (1) clear it (age, smoking) (2) latent (3) active TB (age, nutrition, HIV, alcohol, DM?)

  • In high-burden settings most MDR-TB is transmitted, rather than drug resistance.

  • Ro: risk of transmission per contact.. x number of contacts x duration of infectiveness

Latent TB

  • No symptoms, not infectious

  • Smear/culture negative, TST/IGRA positive

  • Preventive therapy

Active TB

  • Pulmonary symptoms: cough, haemoptysis, chest pain, SOB

  • Extrapulmonary / Disseminated (spread beyond lungs): meningeal, lymph node, pleural, pericardial, peritoneal, bone, spine (Gibbus), GU, skin (lupus vulgaris)

  • Systemic: Fever, cough, night sweats, weight loss

  • Infectious

  • Smear positive/negative, culture positive, TST/IGRA usually positive.

  • Multidrug therapy


  • wide-spread haematogenous spread

Spectrum of infection


  • Microscopy: ZN stain, acid-fast bacilli (AFB). Specific, not sensitive. Negative (none in 100 field); +1 (<1 /field); +2 (<10/field); +3 (>10/field)

  • Culture: Most sensitive/specific. Species, resistance. Traditional (4-8 weeks) vs. liquid (3 weeks, expensive) culture.

  • Drug sensitivity testing (DST): Genotypic: Line Probe Assay (LPA); 1st/2nd line drug mutations , takes 48 hours, e.g. MODS. Phenotypic: conventional culture-based, around 6 weeks

  • Nucleic acid detection: Gene Xpert (tests for rifampicin resistance). Also Xpert Ultra (more sensitive, more false positive), Xpert Omni (closer to POC test).

  • Interferon Gamma Release Assay (IGRA) e.g. QuantiFERON / Principle: interferon gamma is a cytokine that is critical for innate and adaptive immunity, produced by T helper (CD4) white blood cells. Immune response to antigen derived from M.Tb: antigen presentation will release interferon gamma. Fresh blood samples mixed with antigens and controls. Test of “exposure”: does not distinguish active vs. latent disease. Prior BCG vaccination does not cause a false-positive.

  • Tuberculin (Mantoux) skin test” purified protein derivative (PPD). Delayed hypersensitivity reaction. Test of “exposure”: does not distinguish latent from active. If positive need to screen for active disease. False positive if previous BCG (in children: >5 BCG; >10 no BCG). False negative: HIV, miliary, ....

  • Urine: Lateral Flow Strip (LAM). Immunochromatographic, point-of-care, test. M.Tb antigen in urine. Good for disseminated TB (sens=45%; spec 92%) and HIV especially if CD4<200 or no sputum. Use with Xpert increases diagnostic yield from 50 to 80%.


  • R: Rifampicin (orange urine, hepatitis, ?reduced BMD)

  • H: Isoniazid (peripheral neuropathy)

  • Z: Pyrazinamide (arthralgia, increased uric acid)

  • E: Ethambutol (optic neuritis)

First line: RHZE for 2 months, then continue with RH for 6 months

CNS: 12 months treatment (2-months steroids)


  • Resistance to rifampicin and isoniazid

Second-line treatment (needs updating)

Pyrazinamide PLUS 4 core second-line drugs e.g. Levofloxacin, Kanomycin, Cyloserine, Ethionamide

Intensive phase (6M), continuation phase (20-24 months). Bangladesh 9-12 months.

  • Group A: Fluoroquinolone e.g. levofloxacin

  • Group B: injectable e.g. kanamycin, streptomycin (renal, ototoxicity)

  • Group C:

  • Group D:

  • Pre-XDR: above PLUS resistance to fluroquinolone OR injectable

  • XDR: above, PLUS fluoroquinolone (Group A) AND second-line injectable (Group B)

  • TDR: all

Directly Observed Treatment (DOTS): Suspected case; confirmed cases; default; failed; relapse (same strain)

When to start TB treatment if HIV +? If CD4<50 ART within 2 weeks. If CD4 >50, start within 8 weeks.


BCG (Bacillus Calmette Guerin): live vaccine, protects against severe forms in children e.g. miliary, disseminated. Protection against leprosy/buruli ulcer?? (sustained infection-local lyphadenitis)

IPT (Isoniazid Preventative Therapy): 6-12 months treatment to eradicate latent TB infection

TB worldwide

  • Top 10 causes of death worldwide.

  • In 2015, 10.4 million people fell ill with TB and 1.8 million died from the disease (including 0.4 million among people with HIV). Over 95% of TB deaths occur in low- and middle-income countries.

  • Six countries account for 60% of the total, with India leading the count, followed by Indonesia, China, Nigeria, Pakistan and South Africa.

  • In 2015, an estimated 1 million children became ill with TB and 170 000 children died of TB (excluding children with HIV).

  • TB is a leading killer of HIV-positive people: in 2015, 35% of HIV deaths were due to TB.

  • Globally in 2015, an estimated 480 000 people developed multidrug-resistant TB (MDR-TB).

  • TB incidence has fallen by an average of 1.5% per year since 2000. This needs to accelerate to a 4–5% annual decline to reach the 2020 milestones of the "End TB Strategy".

  • An estimated 49 million lives were saved through TB diagnosis and treatment between 2000 and 2015.

  • Ending the TB epidemic by 2030 is among the health targets of the newly adopted Sustainable Development Goals

Historical aspects

  • Robert Koch

  • Surgical treatments e.g. Plombage 'collapse' therapies

  • 1944: discovery of streptomycin and first ever RCT

Cutaneous TB