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
No symptoms, not infectious
Smear/culture negative, TST/IGRA positive
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
Smear positive/negative, culture positive, TST/IGRA usually positive.
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 / T.spot-TB. 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)
Pre-XDR: above PLUS resistance to fluroquinolone OR injectable
XDR: above, PLUS fluoroquinolone (Group A) AND second-line injectable (Group B)
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
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
Surgical treatments e.g. Plombage 'collapse' therapies
1944: discovery of streptomycin and first ever RCT