8 Respiratory Tract Infections: Tuberculosis

Question 1

How does TB spread?

Answer 1

Through aerosol transmission

Question 2

Name the organism that causes the tuberculosis condition

Answer 2

Mycobacterium tuberculosis

Question 3

Describe the mycobacterium tuberculosis bacteria (in terms of structure and staining)

Answer 3

• It has a modified peptidoglycan layer (outmost) - primarily consisted of proteins
• Covalently attached to arabinogalactan polymer
• Mycolic acid waxy coat - lips rich
• Poor gram stain (high lipid content = less permeable to gram staining)
• Acid fast (Ziehl-Neelsen stain) - needed for staining

Question 4

Describe the mycobacterium tuberculosis bacteria (in terms of features, transmission etc.)

Answer 4

• Obligate aerobes (need oxygen - obligated for oxygen - TB pass into the lung via air)
• TB causes more deaths worldwide than any other single infectious agent
• Facultative intracellular bacteria (can be fine outside host) - usually invading macrophages, dendritic cells
• Slow growing (generation time of 12 to 18 hours; 20-30 mins for E. coli)
• Disease course has insidious nature

Question 5

Describe the primary pathogenesis of TB (active)

Answer 5

• Generally, affects upper lobes (lower upper or upper lower lobes) of lung
• Ghon focus (caseous necrosis)
• Ghon complex (caseous necrosis) in hilar lymph nodes

Usually resolved but can produce a calcified granuloma or area of scar tissue AND may be a nidus for a secondary TB (reactivated TB)

Question 6

Describe the secondary pathogenesis of TB (reactivated)

Answer 6

Secondary (reactivation) TB due to reactivation of a previous primary TB site

Common in:

• Immunocompromised patients
• And patients receiving biological therapy (mAb)

Question 7

Describe what is is meant by TB disease can be active or latent

Answer 7

Latent disease is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens, with no evidence of clinically active TB:
- i.e. person is asymptomatic + not infectious

There is a 5–10% risk of progression to active (symptomatic) disease:
- e.g. if the patient is immunocompromised or has intercurrent illness

Multiple longitudinal epidemiological studies indicate that majority of TB disease occurs soon after initial infections, with disease rarely occurring more than 2 years after infection

Question 8

Describe the clinical course of TB

Answer 8

TB is an example of Type 4 HSR

• In most individuals, cell-mediated immunity (CMI) develops 2-8 weeks after infection (associate with the development of a positive tuberculin skin test)
• Activated T cells and macrophages form granulomas that limit further replication and spread
• Bacterial cells remain in centre of necrotic ‘caveating’ granulomas
• Most individuals are symptomatic (latent infection) and never develop active disease (unless a subsequent in CMI occurs) = +ve skin prick test

Question 9

Describe some respiratory clinical findings in TB

Answer 9

• Cough
• Shortness of breath
• Haemoptysis
• Chest pain

Question 10

Describe some general clinical findings in TB

Answer 10

• Fever
• Drenching night sweats
• Weight loss

Question 11

Explain how a diagnosis of TB can be made

Answer 11

• Early stages of disease can be difficult to detect, leading to diagnostic delays/misdiagnosis
• Suspect active TB in any person who:
  > is at high risk of developing TB
  AND
  > has general symptoms of weight loss, fever, night sweats, anorexia or malaise

Consider pulmonary involvement if the person has a persistent productive cough, which may be associated with breathlessness and haemoptysis - but exclude other causes also

• Extra-pulmonary involvement - involves target organ - and gives relevant symptoms

Question 12

List some Pulmonary TB complications

Answer 12

Post-TB bronchiectasis, COPD and aspergillosis
- (fungus ball in lung - TB made space in which they exist in - residual lung cavities)

Post-TB corpulmonale (R-sided heart failure - pulmonary hypertension - fibrosis of lung) OR
Respiratory failure (low O2 and low CO2)

DEATH
- in 2006, 5.5% people notified in England were reported to have died at the last recorded outcome, and TB is known to have contributed to 35.2% of deaths

Question 13

Give some active extra-pulmonary complications of TB

Answer 13

• Miliary spread in lungs - invasion into:
  > (Bronchus) > (lymphatics)
• Miliary spread to extra-pulmonary sites (spread via pulmonary veins):
  > Lymph nodes are a common site (firm, discrete, painless lymph nodes) - kidney
  > Adrenal improvement may result in Addison disease
  > Granulomatous hepatitis
  > Spread to vertebra (Pott Disease)

Question 14

Some some serious complications of TB

Answer 14

Most serious form is Central Nervous System disease:

• TB meningitis (especially children < 5 and HIV+)
• Space occupying lesions (tuberculomas)

Question 15

Name two screening techniques done for TB

Answer 15

• Mantoux test

- Interferon Gamma Release Assay Test (IGRA)

Question 16

Describe the Mantoux test as a screening tool for TB

Answer 16

Mantoux test

• Tuberculin (cell envelope protein) is injected intradermally
• Gives a firm red bump (local skin reaction)
• Test considered positive at induration of 5mm or more

Question 17

Describe the Interferon Gamma Release Assay (IGRA) test as a screening tool for TB

Answer 17

IGRA test

• Blood test based on detecting the response of white blood cells to TB antigens
• Less likely to give a false positive result compared to Mantoux test
• Rapid result

Question 18

Describe how a chest radiograph may be used in the testing for TB

Answer 18

The chest radiograph can be suggestive of TB, but not diagnostic:

Active: consolidation = opaque (most likely upper of mid zone)
> cavitating lesions, with or without calcifications
> Latent: nodules and fibrotic changes

Question 19

Describe the steps are/management available after a test for latent TB is positive

Answer 19

If a test for latent TB infection is positive:

• The person should be assessed for active TB,
• and if there is no evidence of active infection on the basis of symptoms and chest X-ray,
• the person should be treated for latent infection by the local MDT TB specialist team to prevent progression to active disease

Drug regimens are usually either:

• 3 months of isoniazid (with pyridoxine) and rifampicin
  OR
• 6 months of isoniazid (with pyridoxine)

Question 20

Describe what investigations can be carried out when testing for TB

Answer 20

• Bronchoalveolar lavage best for staining and culture (tissue can be cultured, urine, CSF)
• Sputum cultures (cat 3 pathogen must be handled in cat 3 lab)
• Culture is slow growing (2-8 weeks)

Question 21

Describe what antibody sensitivity testing is and how it helps in testing for TB

Answer 21

Performed in reference lab

Agents include (class = antimycobacterial)

• Rifampicin (other indications)
• Isoniazid (just TB - on cell wall and inhibition of synthesis of mycelia acids)
• Pyrazinamide (Just TB, mechanism N/A)
• Ethambutamol (just TB, works on cell wall)

Important to detect resistance - especially multi-drug resistant (MDR TB)
- resistance to rifampicin and isoniazid

Question 22

Who gets the BCG vaccine?

Answer 22

Bacillus Calmette-Guerin (BCG) -
- live attenuated M. Bovis strain

• Anyone who works or lives in an area with a high rate of TB (40/100,000 or more)
• A baby under 12 months OR previously unvaccinated should under 5
• Any child under 16 with specific risk factors for TB
• Anyone who works in close contact with TB bacteria
• Previously unvaccinated people going to live or work (in countries with high rate of TB)

Also:
- Co-morbid conditions
> HIV, diabetes M, history or organ transplant
- Immunosuppressive drugs
- Under-serves groups - more deprived etc
- History of excessive alcohol, injecting drug users and smokers

Question 23

Describe the epidemiology of TB

Answer 23

• 1.7 billion people estimated to have latent TB in the world
  (23% of the world)