TB Flashcards
What are the demographics and risk factors of TB?
- Non-UK born/recent migrants especially from South Asia and sub-Saharan Africa
- HIV and other immunocompromised conditions
- Homelessness
- Drug use, prisoners
- Close contacts
- Young adults/elderly
Which organisms cause TB?
- Mycobacterium tuberculosis (primary cause in humans)
- Mycobacterium bovis
- Mycobacterium africanum
Outline the structure of mycobacterium
- Non-motile
- Rod shaped
- Obligate aerobe
- Long-chain fatty (mycolic) acids, complex waxes and glycolipids in cell wall
- Gives structural rigidity, staining characteristics, acid alcohol fast
- Relatively slow-growing compared to other bacteria (generation time 15-20 hours)
How is TB spread?
- Respiratory droplets from coughing, sneezing etc
- Droplet nuclei suspended in air
- Reach lower airway
- Contagious but not easy to acquire infection
- Difficult to acquire TB from casual contact
What is the infectious dose of TB?
- 1-10 bacilli
- Prolonged exposure facilitates transmission (at least 8 hours/ day for up to 6 months)
Outline the pathogenesis of TB
- Inhaled aerosols
- Engulfed by alveolar macrophages
- Local lymph nodes
- Primary complex (Ghon’s focus and draining lymph nodes)
- Only 5% of cases progress to active disease - primary
- Rest of infections are initially contained
- Latent infection
- 95% of latent infections heal/self-cure
- 5% reactivate and cause post primary TB
How does post primary TB occur?
- Reactivation of bacteria can occur at any point
- Multiply, cause infection, and damage host tissues
What are risk factors for reactivation of TB?
- HIV infection
- Substance abuse
- Prolonged therapy with corticosteroids
- Immunosuppressive therapy
- Organ transplant
- Diabetes mellitus
- Severe kidney disease
- Organ transplant
Outline latent TB infection
- Inactive, contained bacilli in body
- TST or IFN gamma test results usually positive
- CXR normal
- Negative sputum smears and cultures
- No symptoms
- Not infectious
- Not a case of TB
Outline TB disease
- Active multiplying bacilli in body
- TST or blood test results usually positive
- CXR 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 the site of pulmonary TB?
- Lungs
- Most TB cases are pulmonary
What are the sites of extrapulmonary TB?
- Larynx
- Lymph nodes
- Pleura
- Brain
- Kidneys
- Bones and joints
Who is more commonly affected by extrapulmonary TB?
- HIV-infected people
- Immunosuppressed people
- Young children
What is miliary TB?
- Carried to all parts of body through bloodstream
- Rare
What pathology can be seen in biopsy of a patient with TB?
- Caseating granulomata
- Central necrosis, fibrin, exudate, dead and dying immune cells
- Surrounded by rich collection of immune cells
What clinical approach should we take when suspecting a patient has TB?
- Index of suspicion
- Detailed history and examination
- Investigate
- Treat
- Prevent onward transmission
When might we suspect someone has TB?
- Non-UK born
- Recent migrants from high risk countries
- HIV
- Immunocompromised states
- Homeless, drug users, prison inmates
- Close contacts of patients with TB
What are the symptoms of TB?
- Fever
- Night sweats
- Weight loss and anorexia
- Tiredness and malaise
- Cough
- Haemoptysis
- Breathlessness
What are the signs of TB on examination?
- Often no chest signs despite CXR abnormality
- Maybe crackles in affected area
- In extensive disease: signs of cavitation and fibrosis
- If pleural involvement: typical signs of effusion
What tests are done to investigate pulmonary TB?
- CXR (mainstay of diagnosis)
- Samples for microbiology: sputum
- Histology i.e. of a lymph node
What sputum samples are taken to investigate TB?
- 3 early morning samples (minimum volume 5ml)
- Induced sputum
- Broncho-alveolar lavage fluid (patients with a dry cough)
What radiological findings are seen in pulmonary TB?
- Apex of lung often involved
- Ill defined patchy consolidation
- Cavitation usually develops within consolidation
- Healing results in fibrosis
- Pleural TB - pleural effusion
Outline TB microscopy
- Mainstay of TB diagnosis worldwide
- 2 staining methods
- Rapid and cheap
- Not very sensitive
- Measures infectiousness - a smear positive case is infectious
- Cannot differentiate MTB from NTM
- Cannot differentiate live and dead organisms
What is the gold standard of TB diagnosis?
- TB culture
- Most sensitive method for detecting mycobacteria
- Different culture methods/media
- Solid and liquid culture systems
- Automated culture technology - improves isolation of TB bacilli
- Allows identification and susceptibility testing
How are nucleic acid detection tests used to diagnose TB?
- Rapid diagnosis
- Drug resistance mutations
- Whole genome sequencing for culture isolates
- Species identification
- Drug susceptibility
How is latent TB diagnosed?
- Tuberculin sensitivity test
- Interferon Gamma Assays
- Interferon Gamma Releasing Assays
How does tuberculin sensitivity testing works?
- Measures cell mediated immune response
- In form of delayed type hypersensitivity to purified protein derivative of M tuberculosis
How is tuberculin skin testing carried out?
- Tuberculin injected intradermally
- Results taken 48-72 hours later
- Subjective interpretation
How accurate is tuberculin skin testing?
- False positives (BCG, Non TB mycobacteria)
- False negatives (immunocompromised i.e. HIV/ drugs/ advanced disease)
What are the pros/cons of tuberculin skin testing?
- Cheap
- Laboratory infrastructure not required
- Evidence to predict progression to active disease
How do interferon gamma assays work?
- In vitro test
- T cell based assay
- Measures interferon gamma
How do interferon gamma releasing assays work?
- Detection of antigen specific IFN-gamma production
- T spot TB assay
- Quantiferon TB gold plus
- No cross-reaction with TB
What are the first line medications for TB?
- Rifampicin
- Isoniazid
- Pyrazinamide
- Ethambutol
What are the second line medications for TB?
- Quinolones (moxifloxacin)
- Injectables (capreomycin, kanamycin, amikacin)
- Ethionamide/Prothionamide
- Cycloserine
What are the principles of TB treatment?
- Early and adequate treatment with anti TB drugs (make patient non-infectious)
- Close monitoring of compliance
- Prevent secondary transmission and cases
Why is TB treated with multi-drug therapy?
- When TB multiply there are mutations
- Long treatment course means mutations are more likely to happen before TB is eradicated
- Using multiple drugs reduces likelihood of resistance
What effects does rifampicin have on the body?
- Raised transaminases
- Induces cytochrome P450
- Orange secretions/urine
What effects does isoniazid have on the body?
- Peripheral neuropathy
- Hepatotoxicity
What effects does pyrazinamide have on the body?
- Hepatotixicity
What effects does ethambutol have on the body?
- Visual disturbance
Other than medication, what is used to treat TB?
- Vitamin D
- Surgery
What is the duration of TB treatment like?
- 3 or 4 drugs for two months
- Then rifampicin and isoniazid for four months
- 18 month treatment if CNS TB
- Cure rate is 90%
- Compliance is a big problem
- Side effects for a long period of time
How do we ensure adherence to TB treatment?
- Directly observed therapy
- Video observed therapy
Outline how drug resistance develops and spreads
- During multiplication, a 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
What makes development and spread of drug resistance more probable?
- Diagnostic delays
- Overcrowding
- Inadequate infection control facilitates transmission of drug resistance
- Previous TB infection
- HIV +
- Known contact of MDR TB
What is multi-drug resistant TB?
- Resistant to rifampicin and isoniazid
What is extremely drug resistant TB?
- Also resistant to fluoroquinolones and at least 1 injectable
- As well as rifampicin and isoniazid
Outline miliary tuberculosis in detail
- Bacilli spreading through bloodstream
- Widespread infection
- Either during primary infection or reactivation
- Lungs always involved
- Often multiple organs involve
Which other organs can be affected by miliary TB?
- Headaches suggest meningeal involvement
- Pericardial, pleural effusions
- Ascites (involvement of peritoneum)
- Retinal involvement
- Lungs are always involved - fever, very unwell, dry cough
What is lymphadenitis?
- Extra-pulmonary TB common in children
- Scrofula
- Cervical lymph nodes most commonly affected
- Abscesses and sinuses
What other areas of the body can be affected by extra-pulmonary TB?
- Gastrointestinal (due to swallowing of tubercles)
- Peritoneal (ascitic or adhesive)
- Genitourinary (slow progression to renal disease and subsequent spread to lower urinary tract)
- Bone and joint via haematogenous spread (spinal TB or Pott’s disease)
What are the symptoms of tuberculous meningitis?
- Chronic headache
- Fevers
- CSF contains markedly raised proteins, lymphocytosis
How is TB prevented?
- TB cases must be notified to public health
- Triggers contact tracing procedures
- Provides surveillance data to detect outbreaks and monitor epidemiological trends
How is TB controlled?
- Infection control to prevent transmission
- PPE
- Negative pressure isolation
- Reduce acquiring TB
- Vaccination
What vaccine is given against TB?
- BCG
- Live attenuated M. bovis strain
- Given to babies in high prevalence communities only
- 70-80% effectiveness in preventing severe childhood TB
- Protection wanes
- Little evidence protecting adults
What are other indications for the BCG vaccine?
- New entrants from high risk areas
- Healthcare workers
- Close contacts of active respiratory TB
