Session 9: Tuberculosis Flashcards
What is TB caused by?
Mycobacterium tuberculosis
Virulence factors of Mycobacterium tuberculosis.
Non-motile rod-shaped bacteria
Obligate aerobe
Long-chain fatty acids
Glycolipids in cell wall
This offers structural rigidity, staining characteristics, and acid alcohol fast.
Generation time of TB (Division)
15-20 hrs
Transmission of TB
Person to person via infected droplets
(Cough, sneeze)
Risk factors of TB.
Non-UK born/recent migrants
HIV
Immunocompromised patients
Homeless
Drug users
Close contact
Young adults
TB is contagious but not easily acquired. How is transmission risk increased?
By prolonged exposure (8 hours a day for up to 6 months)
Incubation time for TB.
Can take up to 6 weeks.
Explain the pathogenesis of TB.
Inhaled aerosols reach the Ghon’s focus (close to a fissure). Here macrophages phagocytose the bacterium. However the macrophages are unable to digest and kill the bacterium.
The bacterium can also reach lymphatics and reach lymph nodes. This is what happens in primary infection.
After the initial contact and the primary infection there are two outcomes.
What are the outcome of the primary infection?
Latent infection (95%)
Progression to active disease (5%)
What is the outcome of latent infection?
95% heals/self cure
5% get reactivation of their latent infection.
What is the Ghon’s focus and associated lymph node infection collectively called?
Ghon’s complex or more recently primary complex.
What happens to the macrophages as they engulf the Mycobacterium tuberculosis?
There is a granulamatous reaction and a granuloma is formed.
Explain the characteristics of a granuloma due to tuberculosis.
Spherical with a caseating core (caseous necrosis)
Also Langerhans giant cells can be found
Epithelioid macrophages
Lymphocytes
What is extrapulmonary TB?
Reactivation of TB in other sites than the lungs.
Give locations of extrapulmonary TB.
Larynx
Lymph nodes
Pleura
Brain
Kidneys
Bones and joints
In which patients might you see extrapulmonary TB?
More often found in HIV-infected
Immunocompromised
Young children
What is the most common cause of TB?
Reactivation of latent TB.
This occurs most commonly in the lungs.
What is post-primary TB?
Reactivation of a latent primary TB infection
Where is post-primary pulmonary TB most commonly found?
In the upper lung zones.
Give complications of post-primary TB.
Cavity formation
Haemorrhage
Spread to involve rest of the lung
Pleural effusion
Miliary TB
Explain cavity formation in post-primary TB.
Softening and liquefaction of caseous material leads to cavity formation.
Fibrous tissue forms around the periphery of the lesions (cavity formation)
Explain why haemorrhage might occur in post-primary TB.
Extension of the caseous process into vessels in the cavity wall.
This leads to haemoptysis.
Explain how post-primary TB can spread to rest of the lung.
Through the bronchial tree to other lung sites.
Explain how post-primary TB can cause pleural effusion.
Seeding of TB bacilli in pleura or hypersensitivity.
What is miliary TB?
Formation of multiple miliary (small seed-like) tuberculous foci in the entire body.
How can post-primary TB cause miliary TB?
By rupture of a caseous pulmonary focus into a blood vessel and then dissemination into systemic circulation.
Explain the differences of latent TB and active TB.
Latent TB has an inactive tubercle bacilli in the body.
Active TB has an active multiplying tubercle.
No symptoms in latent. Symptoms in active.
Latent is not infections. Active is infectious.
Clinical features of pulmonary TB.
Gradual onset over several weeks or even months.
Malaise, tiredness, weight loss, fever, sweats and cough.
Cough may be productive or not.
Haemoptysis may occur.
Also pleural effusion can occur.
Typical CXR finding on pulmonary TB.
Shadowing due to patchy solid lesions/cavitated solid lesions/streaky fibrosis/flecks of calcification.
Most commonly found in the upper lobe usually in the apex.
How is active TB diagnosed?
By identification of the tubercle bacillus.
Culture (bodily fluid) (5000 or more organisms)
Direct smear
CXR
NAAT
Treatment of TB.
A combination of antibiotics over several months.
Also Vitamin B6
What combination of antibodies are used to treat TB?
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Why is vitamin B6 given in TB treatment?
It’s needed to be given along side with isoniazid to prevent peripheral nerve damage.
Why is a combination of 4 antibiotics used?
The mycobacterium tuberculosis strain contain a small number of drug resistant organisms that will arise spontaneously by mutations.
If there is only one antibiotic used the resistant strain might emerge.
The likelihood of the bacilli to be resistant to all 4 given drugs is very unlikely.
This prevents emergence of resistant strains.
What is used to test for a latent infection of TB.
Interferon gamma release assay (IGRA) aka QuantiFERON test.
Tuberculin skin test.
Explain IGRA.
Test the ability of mycobacterium tuberculosis antigens to stimulate a host production of interferon gamma.
Lymphocytes from the patient’s blood are cultured with these antigens. If patient has been exposed to TB before then T cells will produce interferon gamma in response.
Can IGRA differentiate between latent TB and active TB?
No
Can IGRA differentiate between latent TB and other atypical mycobacterium or previous BCG vaccination?
Yes
How does IGRA differentiate between atypical mycobacterium/BCG and latent TB?
The antigen that is used in the IGRA test is not present in Non-TB mycobacteria or the bacilli used in BCG.
Explain the tuberculin skin test.
A protein derived from the mycobacteria is injected intra-dermally. There is a skin reaction 48-72 hours if there has been previous exposure to TB. This is due to type IV hypersensitivity reaction from the protein.
