Wk 26: TB Flashcards
Which bacteria causes TB?
Mycobacterium TB:
- Aerobic, gram +ve
- Made of mycolic acid: waxy, waterproof - difficult to penetrate
- Able to survive macrophage
What are the types of TB?
- Primary
- Complete clearance
- Post-primary
- Active
- Latent
What is primary TB?
- First infection
- Silent in immunocompetent individuals
- Results in granulomatous inflammation - Ghon focus
What is latent TB?
- Bacillus trapped in granuloma
- Skin prick used to detect
What is active/post-primary active TB?
- Usually reactivation of latent
- If immunocompromised
- Results: aggressive immune reacting causing large granulomas called caseation
- Coughed up in lungs = large cavitating lesion
- Solid organs: pus filled
What is extrapulmonary TB?
- Sites: lymph nodes, pleura, GI tract, bone + CNS
- Bacilli transported in blood or lymphatic system
- Usually in children/immunocompromised
What are the clinical presentation of TB?
- Cough
- WL
- Fever
- Night sweats
- Fatigue
- Dyspnoea
- Chest pain
- Haemoptysis
How is active TB diagnosed - respiratory?
- Chest x-ray
- Acid fast bacilli test + sputum cultures
- Rapid diagnostic NAAT (PCR)
How is active TB diagnosed - non-respiratory?
- Biopsy/needle aspiration
- Culture any surgical/radiological sample
- MRI/CT/Ultrasound
- Chest x-ray
How is pulmonary TB managed in hospital?
- Isolated
- PPE
- Negative pressure room if high risk of multi-drug resistant tb
How is pulmonary TB managed in community?
- Avoid work/school/crowded places
- Wear face mask for first 2 wks
What is the treatment for pulmonary TB?
- Initial: rifampicin, isoniazid, pyrazinamide + ethambutol for 2 months
- Continuation: rifampicin, isoniazid for 4 months
What is the MOA of rifampicin?
- Bactericidal
- Blocks RNA polymerase + prevents protein formation
- Kills slowly replicating bacteria
- More active than isoniazid in anaerobic env of caseous lesion
What are the adverse effects of rifampicin?
- Red/orange discolouration of body fluids
- Liver damage: stop if 4x ULN
What is the MOA of isoniazid?
- Inhibits synthesis of mycolic acid
- Bactericidal
- Kills rapidly multiplying mycobacteria
- Red initial bacterial load
- Caution in severe renal impairment
What are the adverse effects of isoniazid?
More likely in slow acetylates + advanced HIV:
- Hepatotoxicity
- N+V
- Hypersensitivity
- Peripheral neuropathy: supplement vit B6
What is the MOA of pyrazinamide?
- Bacteriostatic
- Only work in acidic pH: macrophage in tuberle
What are the adverse effects of pyrazinamide?
- Hepatotoxicity
- Rashes
- Urticaria
- Gout
What is the MOA of ethambutol?
Bacteriostatic
What are the adverse effects of ethambutol?
More likely in elderly, impaired renal function + prolonged treatment
- Optic neuritis: visual alteration, loss of visual acuity + loss of red-green colour discrimination
What is treatment interruption?
2 wks missed/20% of doses in initial phase:
- Hepatotoxicity/cutaneous reactions: w/draw + re-introduce
- Severe/highly active w/ hepatotoxic/cutaneous reaction: continue w/ streptomycin
What is multidrug resistance TB + extensive drug resistance TB?
- MDR-TB: resistant to rifampicin AND isoniazid
- XDR-TB: resistant to rifampicin/isoniazid/fluoroquinolones/kanamycin/amikacin/capreomycin
What are the therapies for MDR-TB + XDR-TB?
- Bedaquiline
- Delamanid
What is the MOA of bedaquiline?
- Bactericidal
- Inhibits mycobacterial ATP synthase proton pump
- Disables cellular energy dependent processes
What is the MOA of delamanid?
- Nitroimidazole
- Inhibits synthesis of mycolic acid
How is latent infection diagnosed?
- Mantoux test: hh contact of active TB, immunocompromised + from country w/ high TB
- Interferon gamma test used if mantoux positive/unreliable
What is the treatment for latent TB?
3 months isoniazid and rifampicin OR 6 months isoniazid
Who are at an inc risk of developing active TB?
- <5 yrs old
- Excessive alcohol/IV drug use
- Solid organ transplant recipients
- Chemo
- Biologics
- HIV, diabetes, CKD
Who is offered BCG?
High risk under 35 who:
- Health workers
- Prison workers
- From country w/ high prevalence
