TB

Question 1

What are the 2 different classifications of mycobacteria?

Answer 1

1. Tubercle bacilli: (takes 2-12 weeks to grow)
   - M tuberculosis
   - M africanum
   - M bovis
   - M bovis BCG
2. M. Leprae:
   - causative agent of leprosy
   - no in vitro growth

Question 2

What are the main problems with mycobacteria? (staining + treating)

Answer 2

1. resistant to decolourisation with acid due to lipid rich cell walls
2. grows very slowly
3. causes chronic infection
4. antibiotic resistance
5. cell mediated immune response needed for infection (no antibody effect)

Question 3

What is the pathophysiology of primary TB?

Answer 3

• mycobacteria inhaled and settle in alveoli, underneath the pleura (where O2 concentration is high)
• initiates inflammatory response (neutrophils) –> phagocytose bacteria and the bacteria is usually killed
• in the immunocompromised the neutrophils are unable to destroy the bacteria (bacteria has a waxy coat and this prevents penetration by toxic compunds)
• the neutrophils release cytokines which recruit macrophages and T-lymphocytes, and the neutrophils die
• when the neutrophils die this results in a caseous necrosis appearance where bacteria are able to survive
• macrophages form a ring around the caseous tissue and phagocytose the bacteria
• some of the bacteria still remains
• macrophages form giant/Langerhan cells
• more cytokines are released to attract lymphocytes
• wall of fibroblasts form
• accumulation of macrophages and other cells, forming a granuloma
• granuloma = ghon focus –> attempt to ‘wall off’ the bacteria

Question 4

How does TB appear on CXR?

Answer 4

• opacities (bilateral): mainly in upper zone with a patchy nodular appearance
• cavitation (usually in apices)
• calcification (usually surrounding Ghon foci)
• hilar shadowing
• diffuse nodular shadowing in miliary TB

Question 5

What is post-primary TB?

Answer 5

When a healthy individual becomes immunocompromised and the bacteria escape the Ghon focus 
can be caused by:
- alcohol
- diabetes
- old age

Question 6

What is primary progressive TB?

Answer 6

inability to mount a vigorous enough immune response –> bacteria spreads further, granuloma can enlarge

Question 7

What is open/active TB?

Answer 7

live TB bacilli in sputum

Question 8

What are the clinical signs of active TB?

Answer 8

Constitutional:

• fever
• malaise
• weight loss
• night sweats

Local:

• cough
• haemoptysis
• chest pain

Question 9

How is TB diagnosed?

Answer 9

1. Clinical signs
2. CXR
3. 3 resp samples:
   - deep cough or induced sputum
   - bronchoscopy and lavage
4. Culture
5. Nucleic acid amplification test

Question 10

What sites, other than the lungs can be affected by TB?

Answer 10

• genitourinary system: urogenital TB
• bones and joints: Potts disease
• pleura: TB pleurisy
• CNS: TB meningitis
• Lymphatic system

Question 11

What stain is used for mycobacterium? How will normal cells appear compared to the bacterial cells?

Answer 11

Ziehl-Neeson
Normal cells: blue
Bacterial cells: pink ribbons

Question 12

What is the Mantoux test? What do different results mean?

Answer 12

• Standard dose of tuberculin is injected intradermally
• -> tuberculin = glycerol extract of tubercle bacillus
• skin reaction viewed after 48-72 hours
• measure widest diameter of the induration

Results:

• Small (5-9mm) = high risk (immunocompromised)
• Medium (10-15mm) = medium risk (drug users, prisoners, homeless)
• Large (>15 mm) = sign of active infection in individuals with no known risk of TB

Question 13

What is the BCG vaccine? How effective is it?

Answer 13

Strain of attenuated live mycobacterium bovis

Can be anywhere from 0-80% effective in preventing TB for a duration of 15 years

Question 14

How is TB treated?

Answer 14

4-drug regimen:

1. Rifampicin
2. Isoniazid
3. Pyrazinamide
4. Ethambutol (or streptomycin)

Question 15

How does treatment for TB change after 2 months?

Answer 15

• pyrazinamide can be stopped
• isoniazid plus rifampicin are continued daily or intermittent therapy for 4 months
• if pt shows resistance to isoniazid, then stop and continue with rifampicin, pyrazinamide and ethambutol for the entire 6 months
• therapy must be extended if pt has cavitary disease and remains culture positive for 2 months after treatment

Question 16

What is the MOA of rifampicin?

Answer 16

inhibits bacterial DNA-dependent RNA synthesis by inhibiting DNA dependent RNA polymerase

Question 17

What is the MOA of isoniazid?

Answer 17

prevents synthesis of mycolic acid

• bactericidal: fast growing mycobacteria
• bacteriostatic: slow growing bacteria

Question 18

What is the MOA of pyrazinamide?

Answer 18

inhibits fatty acid synthase 2

- required by mycobacterium to synthesise fatty acids

Question 19

What is the MOA of ethambutol?

Answer 19

bacteriostatic against actively growing TB bacilli

- prevents formation of cell wall

Question 20

What is the MOA of streptomycin? When is it used?

Answer 20

Antibiotic aminoglycoside

• severe side effects
• only really used in MDRTB

Question 21

When is TB considered ‘multi-drug resistant’? What drugs should be used and for how long?

Answer 21

• resistance against rifampicin and isoniazid
• use aminoglycosides, fluoroquinolones, thioamides, cycloserine, terizidone, para-aminosalicylic acid, bedquilline
• use for 18-24 months