18. Tuberculosis Flashcards
What are the risk factors for TB?
- HIV
- Other immunocompromised conditions
- Homeless
- Drug users, prison
- Close contacts
- Young adults (also higher incidence in elderly)
What bacteria cause TB?
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex 7 closely related species: M tuberculosis M bovis M africanum
WHat type of bacteria is tuberculosis? (4)
Bacilli, acid-alcohol fast, obligate aerobic, non-motile`
What is the cell wall of M tuberculosis made of and what is the result of it?
- Long-chain fatty (mycolic) acids, complex waxes & glycolipids in cell wall
- Structural rigidity - can survive in environment for months to years
- Difficult to stain
- Acid alcohol fast
Why is tuberculosis an acid-fast bacteria? (2)
- resistant to decolourisation by an acid (done in gram stain)
- due to high content of long-chain fatty (mycolic) acid, complex waxes & glycolipids in cell wall
- alcohol and acid needed to stain bacterium
Why is phagocytosis not effective against tuberculosis?
it can survive in macrophages as it interferes with phagocytic killing and can multiply in macrophages
Why is TB difficult to culture in labs?
Relatively slow-growing compared to other bacteria
Generation time 15-20h
How is TB transmitted and what is the infectious dose? (2)
- Airborne respiratory droplets - coughing, sneezing
• Infectious dose 1-10 bacilli
Why is TB hard to acquire? (2)
- requires prolonged exposure
- 8 hrs/day up to 6 months
What is the pathogenesis of TB?
- alveolar macrophages phagocytose MTB
- unable to kill them so TB survives and multiply
- macrophages initiate cell mediated immunity
- leads to activated macrophages -with enhanced ability to kill MTB - takes about 6 weeks
- granulomatous reaction
What is the likely reason why macrophages are unable to kill TB?
Possibly due to the cell wall lipids of MTB blocking the fusion of the phagosomes & lysosomes
What are the characteristics of granuloma associated with TB?
necrotic cheese like core (caseous necrosis) surrounded by epithelioid macrophages, Langerhans giant cells, and lymphocytes
What are the characteristic lesions of TB?
spherical granuloma with central caseation (also known as tubercles)
What is the initial development of TB tubercles called?
Primary focus / Ghon’s focus
- deposition of TB bacilli in the alveoli is followed usually by development of a sub-pleural focus of tubercles. TB bacilli drain from the primary focus into the hilar lymph nodes.
What is the primary complex in TB infection?
Primary (Ghon’s) focus + the draining lymph (hilar) nodes together
How can TB enter the blood stream?
Enter lymph via hilar lymph nodes, and drain into venous blood with lymph
What are the two possible outcomes after primary complex?
- Initial Containment of the infection –> latent infection
- Progression to Active disease (5%) Primary
What is a latent TB infection?
TB bacilli can persist within the human host, without causing disease
- initial containment of the infection by host response
- not infectious
What percent of individuals infected with TB will develop active TB?
10%:
- 5% from primary TB
- 5% from post-primary TB
Describe how latent tuberculosis can occur
- most st primary infections will heal with or without calcification of the primary complex.
- However, in the majority of subjects, before healing occurs, some TB bacilli enter the blood stream and
haematogenous spread occurs resulting in the seeding of tubercle bacilli to other parts of the lung as well as other organs (extra pulmonary sites). - With the development of cell mediated immunity the infection is contained.
- The primary complex heals, but a small number of organisms remain viable in the lungs/other organs.
When are patients susceptible to reactivation of latent tb?
The person remains well but the potential for reactivation at any site is always present. Reactivation usually occurs when the patient’s immune mechanisms wane or fail (e.g. old age, malnutrition, HIV, immunosuppression)
What are the two possible outcomes for latent infection of tb?
- Post Primary TB
- Heals / Self cure(95%)
Summarise features of latent TB infection
- Inactive, contained tubercle bacilli in the body
- TST or IFN gamma test results usually positive
- Chest x-ray usually normal
- Sputum smears and cultures negative
- No symptoms
- Not infectious
- Not a case of TB
Summarise features of TB disease
- Active, multiplying tubercle bacilli in the body
- TST or blood test results usually positive
- Chest x-ray usually abnormal
- Sputum smears and cultures may be positive
- Symptoms such as cough, fever, weight loss
- Often infectious before treatment
- A case of TB
WHat is primary TB?
Occurs when the primary complex does not heal but progresses to cause active TB
- pathological changes similar to reactivation TB
What is the presentation of primary Tb?
– Usually asymptomatic
– Rare allergic reactions include Erythema nodosum
– Occasionally symptomatic & can also disseminate - i.e. miliary & extra pulmonary
What are the risk factors for re-activation of latent TB?
- HIV
- Substance abuse
- prolonged corticosteroid therapy
- Other immunnosuppressive therapy
- Tumor necrosis factoralpha [TNF-α] antagonists
- Organ transplant
- Haematological malignancy
- Severe kidney disease /haemodialysis
- Diabetes mellitus
- Silicosis
- Low body weight
What test must be done in a suspected or confirmed case of TB?
HIV test
What are the different types of TB based on site?
Pulmonary, extra-pulmonary or miliary
Which part of the lung is most commonly affected by pulmonary Tb and why? What is the frequency of pulmonary Tb?
Upper zones (right apex most common) due to the higher pO2. - reactivation commonly occurs in upper zones
- Most TB cases are
pulmonary
Where might extra-pulmonart TB and who is it more likely to occur in?
Larynx, lymph nodes, Pleura, Brain, Kidneys, Bones and joints
- More often in HIV or other immunosuppressed patients
- in young children also
What is miliary TB?
Bacilli spreading through the blood stream - widespread infection
- rare
What is the clinical approach to tb?
• Index of suspicion • Suggestive symptoms – Detailed history • Investigations • Treatment • Preventing onward transmission
Who might you suspect for TB?
- Non-UK born/recent migrants - Recent arrival or travel
- HIV
- Other immunocompromise states (i.e. cancers)
- Homeless
- Drug users, prison inmates
- Close contacts of patients with TB
- Specific clinical features: Unexplained Fever, weight loss, Malaise, Anore
What are the symptoms of pulmonary TB?
Onset is gradual (weeks or months): general manifestations: • Fever • Night sweats • Weight loss and anorexia • Tiredness and malaise lung manifestations: • Cough (most common) • Haemoptysis occasionally • Breathlessness if pleural effusion
What are the clinical signs on examination?
• Often no chest signs despite CXR abnormality
• Maybe crackles in affected area
• In extensive disease:
– signs of cavitation,
– fibrosis
• If pleural involvement: typical signs of effusion
What are the investigations that can be done?
- Chest X Ray
- Sputum – 3 early morning samples - minimum volume 5ml
- Induced Sputum
- Bronchoscopy (patients with a dry cough)
What is seen in a CXR in tb?
- Apex of the lung often involved
- Ill defined patchy consolidation
- Cavitation usually develops within consolidation
- Healing results in fibrosis
What are different diagnostic tests that can be done?
- TB microscopy (sputum smear and stain)
- TB culture (with NAAT)
- Histology
- Tuberculin sensitivity test
- Interferon gamma assay
What stains can be used to visualise TB in microscopy?
- Ziehl-Neelsen stain ( thin red pink)
- Auramine (yellow) - fluorescence dye
What are the advantages and disadvantages of Tb microscopy?
- easy, quick (same day results)
- require large number of bacilli (5x103 AFB/ml of sputum)
- cannot differentiate between MTB and NonTB
- cannot differentiate between live or dead TB
What is a smear positive case and what is this an indication for?
More than 5x103 AFB/ml of sputum
- is infectious, isolate patient
What does smear negative case indicate
less infectious or not infectious - do not need to isolate
What medium can TB be cultured in and how long do they take to grow?
Lowenstein Jensen (LJ) slopes
- depends on change in visual appearance
- can take up to 6 weeks
• One of the most sensitive methods for detecting Mycobacteria
what are additional tests that can be done with tb culture?
Nucleic Acid Amplification Tests (NAAT)
What do we look for in histology of TB?
granuloma
