TB

Question 1

MDR-TB

Answer 1

multi drug resistant TB

Question 2

bacteria that causes TB

Answer 2

mycobacterium tuberculosis

Question 3

What type of bacteria is mycobacterium tuberculosis?

Answer 3

• aerobic (needs O2)
• G+ve
• acid fast (stain not removed by acid)
• bacilli

Question 4

What does intracellular mean (about mycobacterium tuberculosis)?

Answer 4

able to survive inside macrophages

Question 5

structure of mycobacterium tuberculosis

Answer 5

• layer of mycolic acid surrounds the cell
• gives it a waxy, waterproof coating
• difficult to penetrate by ABX - resistance

Question 6

How is TB transmitted?

Answer 6

aerolised droplets from infected patient

inhaled into alveoli of new host

Question 7

outcomes TB can have

Answer 7

– Primary Tuberculosis (first infection)
– Complete clearance
– Post-primary Tuberculosis (re-infection)
– Active Tuberculosis
– Latent Tuberculosis

Question 8

first infection of TB

Answer 8

• Mostly affects lungs
• Usually clinically silent in immunocompetent
• Results in an area of granulomatous inflammation, shadow on an x-ray, called Ghon focus.
• 90% will never develop active disease due to good immune response

Question 9

latent TB

Answer 9

• bacillus can stay trapped inside the granuloma in some patients
• skin prick test to ID latent TB
• can reactivate any time, from abnormalities in cell mediated immunity
• long ABX regimens used to get rid of latent TB

Question 10

What test to detect latent TB?

Answer 10

skin prick test - tuberculin test

Question 11

active/post primary active TB

Answer 11

• small no. develop at 1st aquisiton
• more commonly reactivation of latent TB infection
• can occur if become immunocompromised (HIV, cs, chemo)
• aggressive immune system reaction
• large granulomas with ‘cheesy’ contents called caseation
• coughed up (incl live bacteria) leaving large lesions, seen on x-ray
• lesions become pus filled, can exudate
• ideal breeding ground for bacillus and large nos. released
• active = contagious

Question 12

What is extrapulmonary TB?

Answer 12

• can cause disease at any site of body
• usually from reactivation of latent infection

common sites:
- lymph nodes
- GIT
- bone
- CNS

• eg. Miliary TB

Question 13

What is disseminated disease? (Miliary tuberculosis)

Answer 13

• bacilli transported in blood or lymphatic system
• can develop as primary infection or post primary reactivation
• can affect many organs
• can cause diagnostic delay, esp if lungs not infected
• more common in children and immunocompromised
• CXR look like small seeds

Question 14

presentation of active TB

Answer 14

initial Sx vague/non-specific
cough - persistent, productive
weight loss
fever
night sweats
fatigue
dyspnoea
chest pain
haemoptysis

(depends on site of infection, 60% respiratory)

Question 15

people who are at inc risk of TB

Answer 15

• born in high prevalence area
• immunocompromised
• contact with active TB
• previous TB Tx
• alcohol/drug misusers
• settled migrants in UK

Question 16

diagnosis of TB

Answer 16

respiratory
- CXR
- acid fast bacilli test
- sputum cultures
- NAAT (nucleic acid amplification test), often PCR
non respiratory
- biopsy/needle aspiration (culture)
- MRI/CT/ultrasouns
- CXR (confirm/exclude respiratory disease)

Question 17

diagnosis of TB

Answer 17

respiratory
- CXR
- acid fast bacilli test
- sputum cultures
- NAAT (nucleic acid amplification test), often PCR

non respiratory
- biopsy/needle aspiration (culture)
- MRI/CT/ultrasouns
- CXR (confirm/exclude respiratory disease)

Question 18

INITIAL management of pulmonary TB

Answer 18

• TB specialist
  hospital
• isolated
• PPE
• -ve pressure room if MDR-TB

community
- advise highly contagious when active
- no work/school/crowded places
- face mask in public during first 2 weeks of Tx

Question 19

phases of TB Tx

Answer 19

1. intensive/initial phase Tx
2. continuation phase

Question 20

intensive/initial phase Tx

Answer 20

lasts 2 months

with 4 drugs

Question 21

continuation phase Tx

Answer 21

4-7 months

with 2 drugs

Question 22

drugs in initial Tx

Answer 22

rifampicin
isoniazid (with pyridoxine)
pyrazinamide
ethambutol

-> for 2 months

Question 23

drugs in continuation Tx

Answer 23

rifampicin
isoniazid (with pyridoxine)

-> for further 4 months

Question 24

Why is combination of drugs used?

Answer 24

to reduce risk of resistance

Question 25

MOA of rifampicin

Answer 25

- bactericidal - blocks RNA polymerase and prevents protein formation

Question 26

rifampicin and food

Answer 26

- absorbed in the GIT - reduced if taken with food - take on empty stomach

Question 27

s/e of rifampicin

Answer 27

- red/orange disconoration of body fluid (stains contact lenses) - liver damage (inc liver enzymes, 4x ULN STOP Tx) - enzyme inducer

Question 27

s/e of rifampicin

Answer 27

red/orange disconoration of body fluid - stains contact lenses liver damage - inc liver enzymes - 4x ULN then STOP Tx

Question 28

isoniazid MOA

Answer 28

- inhibits synthesis of mycolic acids required for cell wall - bactericidal - acts rapidly to reduce initaial bacterial load

Question 29

metabolism of isoniazid

Answer 29

by liver acetylation - some people fast metabolisers, some slow - affects t1/2

Question 30

Who is more likely to have adverse effects with isoniazid?

Answer 30

slow acetylates advanced HIV

Question 31

of isoniazid

Answer 31

- hepatotoxicity - N&V - hypersensitivity rxn - peripheral neuropathy

Question 32

How to avoid PN with isoniazid?

Answer 32

supplement with vitamin B6 -> pyridoxine

Question 33

Why does pyrazinamide no longer become effective later in therapy?

Answer 33

- pyrazinamide only works in acidic pH, inside the macrophages in the tubercle (nodules of dead cells filled with TB bacteria) - no. of these decrease later in therapy - it no longer becomes effective

Question 34

Is pyrazinamide bacteriostatic or bacteriocidal?

Answer 34

bacteriostatic

Question 35

adverse effects of pyrazinamide

Answer 35

hepatotixicity rashes urticaria gout

Question 36

pyrazinamide and hepatotoxicity

Answer 36

- elevation of LFTs - regular LFTs Sx of liver disease - N&V - malaise - jaundice