Tubercuosis Flashcards
Who does TB primary affect?
Young adults - 15-59 that are non UK born.
What causes TB?
Microbacterium belonging to Mycobacterium tuberculosis complex.
There at seven closely related species - M tuberculosis, M Bevis, M africanum
What type of bacteria is TB?
Non-motile rod-shaped bacteria
Obligate aerobe
Long-chain fatty (mycolic) acids, complex waxes and glycolipids in cell wall. -Structural rigidity -Staining characteristics -Acid alcohol fast
Relatively slow-growing compared to other bacteria (generation time 15-20hrs)
Can’t gram stain TB -use ZN stain
How does TB spread?
Spread by respiratory droplets -coughing, sneezing..
Droplet nuclei / airborne (<10um particles, suspended in air, reach lower airway macrophage)
Infectious dose 1-10 bacilli
3000 infectious nuclei - cough, talking 5 mins
Air remains infectious for 30mins.
It is contagious but NOT easy to catch. You need prolonged exposure for ya least 8hours / day for up to 6 months.
Decree the pathogenesis of TB
Inhaled aerosols
Engulfed by alveolar macrophages
Local lymph nodes
Primary complex (progression to active disease -5%)
Initial containment of infectio
Latent infection - Heals / self cure or post primary TB
Describe the symptoms of latent TB
Inactive
Asymptomatic
Not infectious
Normal chest X-Ray
Negative sputum add cultures
Not a case of TB
TST or IFN gamma test results usually positive
Describe the symptoms of TB disease
Active -multiplying tubercle bacilli in the body
TST or blood tests usually positive
Chest x-ray usually abnormal
Sputum smears and cultures may be positive
Symptoms such a cough, fever, weight loss
Often infectious before treatment
A case of TB
What is a natural history of a primary TB patient?
Primary TB:
- Ghon focus / complex (small area of granuloma tours tissue - sometimes visible in middle / lower area -subpleural)
- Limited by Cell mediated immune response
- Usually asymptomatic
- Rare allergic reactions include EN
- Occasionally symptomatic -miliary / disseminated
What is post-primary TB?
This is reactivation or exogenous re-infection 5 or more years after the primary infection.
There is a 5-10% risk per lifetime.
They can present with pulmonary or extra-pulmonary symptoms.
What are the risk factors for reactivation of TB?
Infection with HIV
Substance abuse
Prolonged therapy with corticosteroids and other immunosuppressive therapy
TNF-a antagonists
Organ transplant
Haematological malignancy
Severe kidney disease / haemodialysis
Silicosis
Low body weight
Where can Tb cause disease?
Lungs -Most frequent
Extra-pulmonary - found in HIV, immunosuppression or young children Larynx Lymph node Pleura Brain Kidneys Bones and joints
Miliary TB - Rare
Carried to all parts of the body through the bloodstream.
Whats do you see on histology of TB?
Caseating granuloma.
-Langerhans giant cells.
When do you suspect TB?
Non-UK born / recent migrants - recent arrival or travel
HIV
Other immunocompromised states (cancer)
Homeless
Drug users, prison inmates
Close contacts of patients with TB
Specific clinical features: unexplained fever, weight loss, Malaise, Anorexia
What are the symptoms of TB?
Fever Night sweats Weight loss and anorexia Tiredness and malaise Cough Haemoptysis occasionally Breathlessness if pleural effusion
What are the signs on examination of pulmonary TB?
No chest sings despite abnormal CXR
Maybe crackles in affected area
Extensive disease:
- Signs of cavitation
- Fibrosis
Pleural involvement - typically signs of effusion
How do you investigate TB?
Chest X-Ray
Sputum - 3 early morning samples minimum volume 5ml
Induced sputum
Bronchoscopy (dry cough)
What does TB look like on an X-Ray?
Apex involved
Ill defined patchy consolidation
Cavitation usually develops within consolidation
Healing results in fibrosis
What is TB microscopy?
Main way to diagnose Tb worldwide.
Rapid test, cheap
But, it cannot differentiate between NTM (non-infective tiberculosis mycobacterium) and MTB (mycobacterium tuberculosis)
Indicates infectiousness
60-70% of culture positive samples are microscopy positive.
What is a TB culture?
Gold standard for TB diagnoses
One of most sensitive methods for detecting bacteria.
Allows identification of susceptibility testing
What is NAAT?
Numeric acid amplification tests.
This is used for diagnosing positive smears (sputum tests) and also drug resistant mutations.
Describe the histology of TB
Granuloma - Langerhans giant cells.
Caseous necrosis
What is TST?
Tuberculin skin test
Inject tuberlin intradermally to see if patient has already been exposed to TB.
Used to work out who has been exposed to TB (not who is infected).
But, this is oder diagnostic test.
If patient has been infected before, will have redness and swelling.
What are the problems with TST?
Antibody used is shared with other bacteria and BCG vaccine so can get false positives.
Can also get false negatives - immunocompromised e.g. HIV
Subjective interpretation - measuring redness.
What is an IGRAs test?
Detection of antigen-specific IFN-gamma production
No cross reaction with BCG so no false positive.
Cannot diagnose latent TV and active TB.
How do yo diagnose TB?
Radiology
Histolology
Microscopy
How do you diagnose latent TB?
TST
IGRAs
How do you treat TB?
At least four drugs! (RHZE) also vitamin D and maybe surgery to remove lung.
Use second line drugs if patients are intolerant or resistance.
Give combination to ensure it doesn’t become resistance to all drugs.
Early and adequate treatment with anti-TB drugs
Close monitoring of compliance
Describe how drug resistance develops
Natural history - during multiplication small number of naturally drug resistant organisms arise through spontaneous mutations
Improper drug regimens / poor drug compliance leads to selection of these mutants
Single and multi drug resistance occurs
Diagnostic delays - overcrowding and inadequate infection control facilitates transmission of drug resistance.
What is MDR?
Multi-drug distant TB.
This is when it is resistant to rifampicin and isoniazid
What is XDR?
Extremely drug resistant TB
Resistant to rifampicin, isoniazid and fluoroquinolone and at least 1 injectable.
This is rare
What increases risk of drug resistance?
Previous TB treatment
HIV+
Contact of MDR TB
Failure to response to conventional treatment
Over 4 months of positive smear (sputum) or 5 months of positive cultures.
What is military TB?
Bacilli spreading through the bloodstream - widespread infection
Either during primary infection or during reactivation.
The lungs are always involved but fewer respiratory symptoms -fever, very well, dry cough.
Often multiple organs involved so can cause a variety of symptoms depending on what is involves. e.g. headaches (meninges), pericardial effusion, ascites,
Where is extra-pulmonary TB common?
Lymphadenitis -scrofula, cervical LN, abscesses and sinuses
GI - shallowing of tubercles
Peritoneal - ascites or adhesive
Genitourinary - progress to renal disease and lower UT
Bones and joints - Haematogenous spread, spinal TB most common (Pott’s)
TB meningitis - chronic headache, fever, raised proteins and lymphocytes in CSF
How do you prevent TB?
Have to notify public health about TB patients.
-Must start contact tracing and provide surveillance data to detect outbreaks and monitor epidemiological trends.
How do you control TB?
Treat to make sure not infectious
While infectious:
- PPI (special masks)
- Negative pressure rooms
Reduce susceptible contacts
- Address risk factors
- Vaccination
What is BCG?
A vaccine that is 70-80% effective in preventing severe childhood TB.
Given to children who’s parents come from high incidence areas.
What are the four drugs used to treat TB and their side effects?
Rifampicin - raised transaminases and induces CP450, orange secretions.
Isoniazid - peripheral neuropathy, hepatotoxicity
Pyrazinamide - hepatotoxicity
Ethambutol - Visual disturbance
