Tuberculosis Flashcards
Epidemiology
Commonest cause of infectious disease-related deaths
WHO: 1/4 global population has latent TB
Global incidence falling - 12 million 2018
8% HIV positive
1.5 million deaths a year
Increasing drug resistance (3.4% new cases of multi-drug resistant TB & 18.4% of previously treated cases)
500 new cases in UK (72% of these born outside UK)
Pathogenesis
Airborne droplet spread
Inhaled deposited in terminal airspaces
Macrophages ingest bacilli - replicate with endosomes
Transported to regional lymph node (here killed/multiply/dormant and can proliferate after period of latency - reactivation)
Approx 50% develop active disease within 5 yrs of exposure
Risk of developing TB 10-15% over lifetime, if immunocompetent, and 10% per year if HIV positive
Pathology
Aerobic bacillus, divides every 16-20 hours - slow
Cell wall, but lacks phospholipid outer membrane
Does not stain strongly with Gram stain - weakly +ve
Retains stains after treatment w acids - acid fast bacillus
Granulatomous inflammation: rim of lymphocytes, fibroblasts, central infected macrophages (giant cells); central necrosis - caseation; secretion of cytokines (INF gamma) activates macrophages; AFBs in granulomas
Transmission Risk
Close contacts of infectious cases (smear)
Contact with high risk groups - high incidence country/frequent travel to high incidence areas
Immune deficiency - HIV, steroids, chemo and biologics, nutritional deficiency, diabetes, end stage renal failure
Lifestyle factors: drug/alcohol misuse, homelessness/overcrowding/hostels, prisons
Genetic Susceptibility
Disease Progression
Primary TB: 1-5% cases; bacilli overcome immune system quickly
Latent: immune memory of exposure to TB
Active TB: identify infected are, isolate organism, obtain info regarding susceptibility to anti-bacterials
Latent TB: identify immune response to TB proteins or TB specific antigens
Tests for TB
Mantoux: requires circulating memory T cells and ability to mount a delayed hypersensitivity reaction; cross reactive with other mycobacterial antigens (non-specific); may be falsely negative in severely ill/immunocompromised
Interferon Gamma Release Assays: Elispot/Elisa - enzyme linked immunological assay of release of interferon gamma in whole blood, following stimulation by specific TB antigen; more specific; doesn’t differentiate between latent infection and disease; T-spot/Quantiferon Gold
Pulmonary vs Extrapulmonary TB
Pulmonary: majority of cases (55%), infection risk/cavitatory disease, cough/haemoptysis/chest pain/weight loss/fever/night sweats, diagnosis using chest imaging/sputum/BAL
Extrapulmonary: more common in non-UK born, reactivation, lymphnodes/CNS/None (Pott’s disease)/GI/genintourinary/disseminated/miliary
Extrapulmonary - TB lymphadenitis & disseminated/miliary TB
TB lymphadenitis: often gets worse on treatment; can form sinus tracts with chronic discharge; cold abscess formation
Disseminated TB: fever, sweats, weight loss; GI or CNS symptoms in 20% including abdominal pain, diarrhoea, hepatomegaly, headache, confusion
Other Extrapulmonary TB
Skeletal: 15-30% of all extrapulmonary cases
Genitourinary: kidney/bladder/pelvic involvement; pus in urine
TB enteritis: ileo-caecal; weight loss, diarrhoea blood in stool
TB of eye: any part of eye; quite common
Pericardial TB
CNS TB: TB meningitis, TB arachnoiditis, tuberculoma; spinal cord compression; 1% of all TB cases; more common in HIV +ve patientes; mortality 15-40%
Control of TB
Government global policy, contact tracing
Consider the diagnosis
Early diagnosis & treatment -> optimal treatment and adherence (DOT/VOT/section)
Prevention - BCG vaccination
Latent treatment programmes
TB first-line drugs
2 months of initial stage (isoniazid, rifampicin, pyraziamide and ethambutol - quadruple therapy), followed by 4 months of continuation phase (isoniazid and rifampicin - dual therapy)
Treatment taken all together on empty stomach 1 hour before breakfast - compliance is essential
If there is CNS involvement, continuation phase takes 10 months
Latent treatment: 3 months of rifampicin/isoniazid or 6 months of rifampicin
Side Effects: joint pain, hepatoxicity, fever, optimal and peripheral neuropathy, nausea and skin rashes
