8 Respiratory Tract Infections: Tuberculosis Flashcards
How does TB spread?
Through aerosol transmission
Name the organism that causes the tuberculosis condition
Mycobacterium tuberculosis
Describe the mycobacterium tuberculosis bacteria (in terms of structure and staining)
- 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
Describe the mycobacterium tuberculosis bacteria (in terms of features, transmission etc.)
- 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
Describe the primary pathogenesis of TB (active)
- 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)
Describe the secondary pathogenesis of TB (reactivated)
Secondary (reactivation) TB due to reactivation of a previous primary TB site
Common in:
- Immunocompromised patients
- And patients receiving biological therapy (mAb)
Describe what is is meant by TB disease can be active or latent
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
Describe the clinical course of TB
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
Describe some respiratory clinical findings in TB
- Cough
- Shortness of breath
- Haemoptysis
- Chest pain
Describe some general clinical findings in TB
- Fever
- Drenching night sweats
- Weight loss
Explain how a diagnosis of TB can be made
- 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
List some Pulmonary TB complications
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
Give some active extra-pulmonary complications of TB
- 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)
Some some serious complications of TB
Most serious form is Central Nervous System disease:
- TB meningitis (especially children < 5 and HIV+)
- Space occupying lesions (tuberculomas)
Name two screening techniques done for TB
- Mantoux test
- Interferon Gamma Release Assay Test (IGRA)
Describe the Mantoux test as a screening tool for TB
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
Describe the Interferon Gamma Release Assay (IGRA) test as a screening tool for TB
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
Describe how a chest radiograph may be used in the testing for TB
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
Describe the steps are/management available after a test for latent TB is positive
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)
Describe what investigations can be carried out when testing for TB
- 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)
Describe what antibody sensitivity testing is and how it helps in testing for TB
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
Who gets the BCG vaccine?
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
Describe the epidemiology of TB
- 1.7 billion people estimated to have latent TB in the world
(23% of the world)
