Lecture 1

Question 1

What tests are you required to do if you enter the UK for, a country with common TB infections ?

Answer 1

Sputum test and x-ray

Question 2

Define latent

Answer 2

You are infected with the bacteria but do not have the signs or symptoms

Question 3

What patients are at more risk if they develop TB?

Answer 3

HIV patients

Question 4

What are the symptoms of TB?

Answer 4

More than 3 weeks cough that is getting worse persistent and productive, temperature,fever, night sweats and chills - occurring at different times of the day, unexplained weight loss and coughing up blood

Question 5

How do we diagnose TB?

Answer 5

X-rays, clinical examination, PCR test (rapid within 2 hrs)

Question 6

How do we diagnose latent TB?

Answer 6

Tuberculin Skin Test (Mantoux test), molecular tests (interferon gamma release assay)

Question 7

What is the tuberculin skin test ?

Answer 7

Tuberculin injected sc into forearm possible if skin lesion >10 mm diameter post 48-72 hrs

Question 8

Describe stage 1 of TB

Answer 8

Inhaled in droplets, settle in alveoli of the lung, start to grow, stimulates an immune response and macrophages come out,they are phagocytosed by macrophages but they do not kill the bacilli

Question 9

Describe stage 2 of TB

Answer 9

Asymptomatic/ mild fever, body isn’t effective at removing TB, bacteria multiple in size, macrophages in lungs 7-21 days, macrophages burst and incoming macrophages phagocytose release M.TB and the cycle repeats. This continues for 3-4 weeks

Question 10

Describe stage 3 of TB

Answer 10

At 6 weeks symptoms of disease start to appear, cell mediated response initiated (T cell, B cell, fibroblasts), collagen fibres form around affected sites, granulomas (tubercules) formed in lung

Question 11

Describe stage 4 of TB

Answer 11

Bacteria multiply inside macrophage, granuloma burst - uncontrolled lysis. Bacteria spread - new sites of infection process repeats. Enzymes released - destroys local tissues causing lesions

Question 12

What is disseminated TB?

Answer 12

Spreads throughout body and can infect multiple organs

Question 13

Name the 1st line treatments for active TB

Answer 13

Combination of 4 drugs over 6-9 months
Rifampicin and isoniazid - 6-9 months
Pyrazinamide and ethambutol for the first 2 months

Question 14

Name the 1st line treatment for latent TB

Answer 14

Isoniazid 6 months or Rifampicin and isoniazid for 3 months

Question 15

Describe the MoA of Rifampicin

Answer 15

Bactericidal to all metabolising cells
Targets mRNA production
Inhibits RNA polymerase
Oral
Absorption affected by food

Question 16

What are the side effects of Rifampicin?

Answer 16

Liver damage, hypersensitivity, increased activity of other drugs eg.contraceptive pill. Red colour in body fluids e.g. urine

Question 17

Define the MoA of isoniazid

Answer 17

TB specific
Synthesis of mycolic acid
Pro drug
Oral
Bactericidal to active growing bacilli
Bacteriostatic to very slow growing bacilli
Metabolised in the liver, excreted in the kidneys

Question 18

Side effects of isoniazid

Answer 18

Hypersensitivity, peripheral neuropathy, liver toxicity, increased efficacy of hormonal birth control

Question 19

Define MoA for pyrazinamide

Answer 19

Pro drug
Bactericidal to dormant bacilli
Precise mechanism/action is unclear
Oral

Question 20

Side effects of pyrazinamide

Answer 20

Joint pain, liver damage and hypersensitivity

Question 21

Define MoA of ethambutol

Answer 21

Bacteriostatic against growing bacilli
Increased permeability by affecting synthesis of arabinogalactan in cell wall
Oral
50% excreted unchanged in the urine

Question 22

Side effects of ethambutol

Answer 22

Nerve neuritis and joint pain

Question 23

How is TB prevented ?

Answer 23

Immunisation, BCG vaccine (live attenuated) given to high risk groups such as areas with high incidence, HIV positive, children with parents from a high risk country

Question 24

Why is it difficult to treat TB?

Answer 24

Thick cell wall - antibiotics need to penetrate layer of mycolic acid
Intracellular - antibiotics need to get inside the macrophage
Long periods of treatment - side effects
Slow growing aren’t metabolically active

Question 25

Define MDR-TB

Answer 25

Strains resistant to at least the 1st line drugs Rifampicin and isoniazid

Question 26

Define pre XDR

Answer 26

Strains resistant to more than two 1st line drugs rifampicin and isoniazid aid resistant to any group A fluroquinolones

Question 27

Define XDR-TB

Answer 27

Strains resistant to more than more two 1st line drugs rifampicin and isoniazid and also resistant to any group A fluroquinolones and also at least one additional group A drug

Question 28

What shaped bacteria is TB

Answer 28

Rod shaped bacteria

Question 29

What is the doubling time of TB?

Answer 29

15-24 hours

Question 30

When TB becomes infected in the lungs what is it known as?

Answer 30

Pulmonary TB

Question 31

When TB spreads to other organs what is it known as?

Answer 31

Extrapulmonary

Question 32

What is the TB cell wall rich in?

Answer 32

Lipids, lipoarbinomanan, arabinoglactan , mycolic acid, => thick waxy lipid cell wall

Question 33

What is the TB cell wall resistant to?

Answer 33

It is very hydrophobic
Resistant to drying, weak disinfectants, some antibiotics

Question 34

Describe process of the PCR test for active TB

Answer 34

Someone spits into a cartilage, and it gets led into a machine
Rapid (within 2 hrs)
Sensitive to low levels of bacteria
Can detect rifampicin resistance
Can detect isoniazid resistance