Tuberculosis

Question 1

Why is TB still a major problem in the world today?

Answer 1

1. Poverty
2. Health systems
3. HIV

Question 2

Describe the mycobacterium tuberculosis

Answer 2

• “fungus-like bacterium”
• Waxy (mycolic acid rich) cell wall
• Gram positive
• Acid-fast
• slow generation time
• complex metabolic responses in latent/persistent state

Question 3

Describe the pathogensis of TB

Answer 3

• transmission
• primary infection
• latent infection
• active disease

Question 4

What is the mode of transmission of TB

Answer 4

droplet infection

Question 5

What are the main factors influencing infection?

Answer 5

• number of infecting bacilli
• exposure
• immune system of patient

Question 6

How is TB diagnosed?

Answer 6

• tuberculin skin test (TST)
• interferon Gamma Release Assays (IGRA)

Question 7

Draw a timeline of tuberculosis

Answer 7

Question 8

What is pulmonary tubercolsis disease (PTB)?

Answer 8

85% of cases

sputum smear positive

cause the majority of community transmission

Question 9

What are the typical symptoms of PTB?

Answer 9

• cough of > 2-3 weeks, not responding to antibiotics
• sputum production (± haemoptysis)
• fever
• night sweats
• weight loss

Question 10

What are the methods that can be used to determine with soutum contains TB?

Answer 10

• sputum smear microscopy
• sputum culture
• Molecular tests
  
  • GeneXpert
  • Tuberculosis Molecular Bacterial Load Assav - TB-MBLA

Question 11

What is the appearance of primary TB on a chest x-ray?

Answer 11

• Ghon complex
  
  • small (often calcified) focus of pulmonary infections
  • associated with lymphadenopathy

Question 12

What are the characterisitics of miliary TB on a chest x-ray?

Answer 12

foggy lung

Question 13

What is the acronym for TB treatment?

Answer 13

RIPE

Question 14

What are the 4 treatments of TB and how long should they be taken for?

Answer 14

• Rifampicin
  
  • 6 months
• Isoniazid
  
  • 6 months
• Pyrazinamide
  
  • 2 months
• Ethambutol
  
  • 2 months

Question 15

What is the mechanism of action of rifampicin?

Answer 15

inhibits bacterial DNA-dependent RNA polymerase

Highly bactericidal vs rapidly replicating and non-replicating bacteria

Question 16

What is the toxicity associated with rifampicin?

Answer 16

• 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

Question 17

What is the mechanism of action of isoniazid

Answer 17

inhibits mycolic acid biosynthesis in cell wall

High bactericidial vs rapidly replicating bacteria

Question 18

What is the toxicity associated with isoniazid?

Answer 18

• hepatitis
• peripheral neuropathy - minimised by pyridoxine (vitamin B6)
• resistance

Question 19

What is the mechanism of action of Pyrazinamide?

Answer 19

unknown but inhibits fatty acid synthase I

Bacterostatic, but bactericidial at acid pH (inside cells)

Question 20

Toxicity of Pyrazinamide?

Answer 20

hepatitis and hyperuricemia (can exacerbate gout)

Question 21

What is the mechanism of ethanbutol?

Answer 21

bacterostatic

inhibits arabinosyn transferase

Question 22

What is the toxicity of ethambutol?

Answer 22

optic neuritis

Question 23

What are the 2 phases of TB treatment?

Answer 23

Intensive phase = 2 months

continuous phase = 4 months

Question 24

How does antibiotic resistance develop?

Answer 24

• 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

Question 25

What is the method of treament of multi-drug resistant TB?

Answer 25