Tuberculosis Flashcards
Why is TB still a major problem in the world today?
- Poverty
- Health systems
- HIV
Describe the mycobacterium tuberculosis
- “fungus-like bacterium”
- Waxy (mycolic acid rich) cell wall
- Gram positive
- Acid-fast
- slow generation time
- complex metabolic responses in latent/persistent state
Describe the pathogensis of TB
- transmission
- primary infection
- latent infection
- active disease
What is the mode of transmission of TB
droplet infection
What are the main factors influencing infection?
- number of infecting bacilli
- exposure
- immune system of patient
How is TB diagnosed?
- tuberculin skin test (TST)
- interferon Gamma Release Assays (IGRA)
Draw a timeline of tuberculosis
What is pulmonary tubercolsis disease (PTB)?
85% of cases
sputum smear positive
cause the majority of community transmission
What are the typical symptoms of PTB?
- cough of > 2-3 weeks, not responding to antibiotics
- sputum production (± haemoptysis)
- fever
- night sweats
- weight loss
What are the methods that can be used to determine with soutum contains TB?
- sputum smear microscopy
- sputum culture
- Molecular tests
- GeneXpert
- Tuberculosis Molecular Bacterial Load Assav - TB-MBLA
What is the appearance of primary TB on a chest x-ray?
- Ghon complex
- small (often calcified) focus of pulmonary infections
- associated with lymphadenopathy
What are the characterisitics of miliary TB on a chest x-ray?
foggy lung
What is the acronym for TB treatment?
RIPE
What are the 4 treatments of TB and how long should they be taken for?
- Rifampicin
- 6 months
- Isoniazid
- 6 months
- Pyrazinamide
- 2 months
- Ethambutol
- 2 months
What is the mechanism of action of rifampicin?
inhibits bacterial DNA-dependent RNA polymerase
Highly bactericidal vs rapidly replicating and non-replicating bacteria
What is the toxicity associated with rifampicin?
- Hepatitis
- itch, rash, GI upset
- discolouration or urine, tears and sweat
- induces liver enzymes (CYP450) increasing clearance of other drugs
- warfarin, OCP, anti-retroviral therapy interactions
What is the mechanism of action of isoniazid
inhibits mycolic acid biosynthesis in cell wall
High bactericidial vs rapidly replicating bacteria
What is the toxicity associated with isoniazid?
- hepatitis
- peripheral neuropathy - minimised by pyridoxine (vitamin B6)
- resistance
What is the mechanism of action of Pyrazinamide?
unknown but inhibits fatty acid synthase I
Bacterostatic, but bactericidial at acid pH (inside cells)
Toxicity of Pyrazinamide?
hepatitis and hyperuricemia (can exacerbate gout)
What is the mechanism of ethanbutol?
bacterostatic
inhibits arabinosyn transferase
What is the toxicity of ethambutol?
optic neuritis
What are the 2 phases of TB treatment?
Intensive phase = 2 months
continuous phase = 4 months
How does antibiotic resistance develop?
- katG mutations account for 50-90% of ISONIAZID RESISTANT TB strains
- inhA mutations account for ~31% of ISONIAZID RESISTANT TB strains
- rpoB mutations account for 96% of RIFAMPICIN RESISTANT TB strains
- Ioniazid preceeds rifampicin
What is the method of treament of multi-drug resistant TB?
