TB Flashcards
What is a characteristic of mycobacterium that other gram positive bacteria don’t have?
They have a thick layer of mycolic acid on the outside of the cell which makes the bacteria very resistant to environmental effects (can survive a long time in dust and intracellularly)
What are the effects of mycobacterium’s slow generation time of 15-20 hours?
- Takes a long time to diagnose in the lab (culture based)
- Chronicity of infection
- Virulence
What is the key property of mycolic acid with staining?
- It confers the unique property of acid fastness
- Long thin pink rods indicate mycobacterium
- The acid and alcohol wash has washed away everything else on the slide but not mycobacterium
Describe the spread of M. TB
- Airborne spread via droplet nuclei (tiny)
- Generated in alveoli
- Remains in the air for a long time if someone coughs
- Deposit in alveoli
What happens in 90% of primary TB infections?
- The bacteria are phagocytosed by alveolar macrophages, forming a granuloma
- If this drains to local lymph nodes it can cause lymphadenitis
- The contained infection in the granuloma leads to latent TB
What happens to 10% of individuals with latent TB?
- The lesions progress after some time to (plaque then) cavitation which destroys lung tissue (CD8 and NK cells?)
- This is post-primary/reactivation TB
- Half of these individuals will have this within 2 years of infection
- For others, it may take up to 50 years
What happens to 5% of people with primary TB infection?
The immune system won’t contain the initial infection and will progress to classic pulmonary TB within 2 years
What percentage of M. TB infections go on to become active TB?
10%
What is the risk of progression/reactivation of TB in AIDS?
10% per year (rather than 10% lifetime risk)
What else can TB do?
Disseminate at any time (even when latent) to any body site via blood/lymphatics esp. if immunocompromised or < 2
What kind of disease is TB and why?
Immunopathological disease
- If have no T cells (AIDS) don’t get cavitation and tissue destruction
- However, the infection can’t be contained so get rapid dissemination and death
What is a significant risk factor for reactivation/progression with dissemination?
CD4 depletion
What is the biggest pathogenic determinant in mycobacteria?
Mycobacterial cell wall - predominant genes associated with pathogenicity are those involved in mycolic acid synthesis
How can you test for TB when it is latent?
- Positive tuberculin skin tests
- IGRA (interferon gamma release assay)
- No symptoms
What are the systemic signs/symptoms in TB?
- Weight loss
- Malaise
- Fever
- Night sweats
What are pulmonary signs/symptoms in TB?
- Non productive cough
- Primary TB pleural effusion/pleurisy leading to SoB (reduced intra-thoracic volume and effective air space) - otherwise SoB more likely to be other infection
What are pulmonary symptoms in late TB?
- Haemoptysis - when have bad cavitation
- SoB
What can happen in fulminant TB?
Haemoptysis and massive pulmonary haemorrhage due to cavities eroding onto pulmonary artery
What are extra-pulmonary findings in TB?
- Cervical lymphadenitis
- Meningitis
- Osteomyelitis
- Renal/gut TB (can get TB anywhere + granulomas)
What radiological findings are there in primary TB?
- Hilar lymphadenopathy (due to primary TB of hilar lymphnodes) - different from normal hilar shadow of pulmonary artery and vein
- Consolidation (upper lobe)
- Pleural effusion in primary TB lesion is sub-pleural on outside of lung
What radiological findings are there in post-primary TB?
- Cavitation (destruction, abscesses) - dense white scarring
- Fibrosis (scarred lung tissue, contracts down and get shrunken lungs)
- Upper lobe predominance (spread to both lungs)
- Tracheal tug due to loss of lung volume in advanced TB
How would you diagnose TB in the context of pleurisy and pleural effusion?
- Pleural tap
- Pleural biopsy
What is the most common site for TB?
Intra-thoracic (53% pulmonary)
What is the second most common site for TB?
Extra-thoracic lymph node TB (23.1%) e.g. cervical
What are other common sites for TB?
GI tract, spine, other bones, TB meningitis
What causes the broken down caseous material in cavitary TB?
- Immune response and NK cells
- Local tissue destruction
- Macrophages break up and release cytotoxic chemicals leading to tissue destruction
How would cervical lymph node TB present?
- Swollen, inflamed, soft and fluctuant cervical lymph node with abscess formation
- Just above collar bone, just outside insertion of SCM in collar bone v likely to be TB
What type of TB tends to occur in immunocompromised patients?
Military TB
- Don’t get cavitation
- Miliary seed type granulomas in the lung
What happens in spinal TB?
- TB osteomyelitis
- Destruction of discs and bone
- These vertebrae eventually collapse leading to kyphosis spine and the patient is hunched over
- This is Pott’s disease (typical of spinal TB)
What happens in TB basal meningitis?
- Inflammation
- Thick adherent white plaques cause occlusive meningitis which blocks CSF flow
- Hydrocephalus is common
How do you diagnose TB?
1) Clinical samples - sputum/lavage, tissue, blood
2) Microscopy
3) Solid/liquid Culture - takes weeks, highest sensitivity
4) PCR - also detects rifampin resistance, v rapid (2 hours), can do directly on sputum, but less sensitive than culture
5) Speciation
Why do you need 4 agents to treat drug-sensitive TB?
- The mutation rate to single agents in TB is high
- A high number will already inherently have rifampicin or isoniazid resistance
What drugs and for how long do you use to treat drug-sensitive TB?
1) Rifampicin (6-12 months)
2) Isoniazid (6-12 months)
3) Pyrazinamide (2 months)
4) Ethambutol (1-2 months)
What are 3 less effective second-line agents only used in drug-resistant TB?
- Levofloxacin
- Streptomycin
- Clarithromycin
What is TB mono-resistance?
Resistance to one first line anti-TB drug only
What is TB poly-resistance?
Resistance to > 1 first line anti-TB drug, other than isoniazid and rifampicin
What is TB multi-drug resistance?
Resistance to at least both isoniazid and rifampicin (most effective drugs) - if resistant to both of these, mortality increases significantly
How might you have to treat someone with extensive drug resistance?
Pneumonectomy (treated as if before TB therapy)
What is DOT?
Directly observed therapy (bc if not compliant will get resistance)
What are some other non-TB mycobacteria (generally skin and soft tissue or bone infections)?
- M.avium
- M.fortuitum
- M.marinum
- M.leprae
- M.ulcerans
- M.kansasii - similar to typical TB
What is granulomatous inflammation?
- Protective response to chronic infection or foreign material, preventing dissemination and restricting inflammation through formation of a granuloma
- Distinctive pattern of the chronic inflammatory reaction
What are causes of granulomatous inflammation?
1) Fungal infections
2) TB
3) Leprosy
4) Schistosomiasis
5) Foreign material
6) Autoimmune diseases
7) RA
8) Crohn’s
9) Sarcoidosis
What happens during granulomatous inflammation in active pulmonary TB?
- M.TB lives in macrophages (intracellular) in the lung so bc the immune system can’t clear bacteria they form granulomas to prevent the spread
- Put down fibrin to wall off the infected macrophages
- Granulomas impair lung function and oxygen exchange
- Top of lung typically affected
