TB Flashcards
Describe features of mycobacterium tuberculosis
- weakly gram-positive
- acid-fast bacilli = resistant to decolourising by acids once stained
- slow-growing
- produces white coloured colonies
What are the 4 populations of M. Tuberculosis?
- actively growing organisms (can be killed by isoniazid)
- semi-dormant organisms inhibited by acid environment (can be killed by pyrazinamide)
- semi-dormant with spurts of active metabolism (killed by rifampicin)
- completely dormant organisms (not killed with standard drugs) - latent disease susceptible to transformation
Describe the pathogenesis of TB infection
- TB bacteria is spread through the air (coughing/speaking)
- person inhales bacteria
- cavitary TB: cavities open into the bronchi containing the infection and allowing further spread
- TB lesion forms in the lung (Ghon complex): can spread to other tissues through haematogenous spread or become reactivated as a lung disease (eg. After immunosuppression/HIV/smoking)
Describe the TB granuloma
- inflammatory cell infiltrate of immune cells which represents a non-replicating TB infection (what allows the infection to lay dormant)
- however provides a survival niche for the infection which can allow it to be reactivated and spread
Describe how a TB granuloma can become resolved
- balanced state
- macrophages in the granuloma undergo differentiation into further specialised cells (foamy macrophages and giant cells)
- adaptive immune system results in periphery of lymphocytes (B and T cells)
- resolved granuloma with bacilli restricted to the centre
Describe how a TB granuloma can become unresolved
- unbalanced state due to necrotic breakdown of the granuloma
- accumulation of caseum and cavitation of granulomas into necrotic material
- collapse of the granuloma allow TB infection to be released into the airway
- driven by both host and bacterial factors that induce cell-death
How can TB infection be detected?
Tests of immunoreactivity to mycobacterial antigens can represent latent infection (HOWEVER, this can also occur after treatment/cleared infection)
Describe the clinical presentation of TB
- Mainly pulmonary (cough +/- haemoptysis + SOB) and constitutional symptoms (eg. Fever, weight loss, fatigue, lymphadenopathy etc.)
- can cause wide variety of systemic symptoms
Describe the symptoms of apical TB disease
- cough
- sputum
- haemoptysis
- fever
- weight loss
- night sweats
How is latent TB diagnosed?
- mantoux (PDD tuberculin is injected into skin and positive = small hard red bump formation)
- interferon gamma release assays: (T-spot TB, quantiferon)
- T-spot TB: detects T cells that have been activated by MTB antigens
- quantiferon: detects IFN-gamma generation by patient’s T cell response to specific MTB antigens
What are the 4 tubes used for in IGRA?
- purple (positive control): low response can indicate inability to generate IFN-gamma
- grey (negative control): adjusts for backgrouns IFN-gamma
- TB1: primarily detects CD4-T cell repsonse
- TB2: optimized for detection of CD4 and CD8 T cell responses
Describe methods of diagnosing active TB
- AFB in respiratory or other sample (positive smear in microbiology, histopathology)
- positive MTB growth in cultures (solid LJ, liquid MGIT culture media)
- clinical/radiological diagnosis
Describe treatment of latent TB
- isoniazid monotherapy for 6 months in adults and children in countries with high and low TB incidence (best)
- <15yo + high incidence = rifampicin + isoniazid for 3 months
- adults + children + high incidence = rifapentine + isoniazid weekly for 3 months
- Low incidence alternatives = 9 months isoniazid, 3-month weekly rifapentine + isoniazid, 3-4 months of isoniazid + rifampicin or just rifampicin
Describe treatment of drug sensitive active TB
6 months
- 2 month intensive phase = rifampicin, isoniazid, ethambutol and pyrazinamide
- 4 month continuation phase = rifampicin and isoniazid
What are the adverse events and interactions of TB treatment?
- rifampicin = enzyme inducer, flu symptoms, orange bodily secretions
- isoniazid = liver damage, lupus
- ethambutol = toxic optic neuropathy
- pyrazinamide = liver injury, raised lactate
