Tuberculosis Flashcards
Risk factors for TB
- non-UK born/ recent migrants (South Asia 54.8%, Sub-Saharan Africa 29.5%)
- HIV
- immunocompromised
- homeless
- drug users, prison
- close contacts
- young adults
- elderly
Describe the microbiology of TB
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex
7 closely related species
Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium Africanum
Non-motile rod-shaped
Obligate aerobe
Long-chain fatty mycolic acids, complex waxes & glycolipids in cell wall
Structural rigidity, staining characteristics (acid alcohol fast needed)
Relatively slow-growing, generation time 15-20hrs
Latency period
Culture takes 6/12 weeks
Describe the transmission of Tb
Respiratory droplets, droplet nuclei suspended in air for a long time reach lower airway
Infectious dose 1-10 bacilli but prolonged exposure required (8hrs - 6months) e.g. households/ prisons/ schools
Describe the pathogenesis of Tb
Inhaled aerosols -> engulfed by alveolar macrophages -> local LNs -> primary complex/ infection (Ghon’s focus + draining LN) ->
Either:
Immune system failed - Progression to active disease (5%) primary
OR
Initial containment -> latent infection
-> (heals/ self cure (95%) Or reactivation and post primary TB)
What are the two forms of Tb infection? Explain the differences between them
Clinical infection (TB) - active, multiple tubercle bacilli, TST Or blood test usually positive, CXR usually abnormal, sputum smears/ cultures may positive, cough/ fever/ weight loss, often infectious b4 treatment = a case of TB (in the lungs)
Subclinical infection (LTBI) - latent/ inactive, contained tubercle bacilli, TST/ IFN game test usually positive, CXR usually normal, sputum smears/ cultures negative, asymptomatic, uninfectious = not a case of TB
What is primary TB?
Ghon focus/ complex (primary lesion usually subpleural)
Limited by CMI
Usually asymptomatic
Rare allergic reactions include erythema nodosum
Occasionally symptomatic & can disseminate e.g. miliary & extra pulmonary
What is post-primary TB?
Reactivation Or exogenous re-infection
> 5yrs after primary infection
5-10% risk per lifetime
Pulmonary or extra-pulmonary clinical presentation
Risk factors for reactivation of TB
HIV (all TB cases must be tested)
Substance abuse
Prolonged corticosteroids/ immunosuppressive therapy
Tumour necrosis factor- alpha [TNF-a] antagonists
Organ transplant
Haematological malignancy
Severe kidney disease/ haemodialysis
Diabetes mellitus
Silicosis
Low body weight
Sites of Tb disease
Pulmonary TB - lungs (most cases)
Extrapulmonary - larynx, LNs, pleura, Brain, kidneys, bones, joints, anywhere (found more in HIV/ immunosupressed/ young children)
Miliary TB - carried to all parts of body through bloodstream (rare)
Pathology of TB
Caseating granulomata (central necrosis)
- lung parenchyma
- mediastinal LNs
Giant cells (Langhans type granuloma) with epithelioid histiocytes (modified immobile macrophages) and lymphocytes
Slide 22
Symptoms and signs of pulmonary TB
Symptoms: fever, night sweats, weight loss & anorexia, tiredness & malaise, cough (most common), haemoptysis occasionally, breathlessness if pleural effusion
Signs: often no chest signs despite CXR abnormality, maybe crackles, extensive: signs of cavitation/ fibrosis, if pleural involvement typical signs of effusion
Investigations of pulmonary TB
CXR
Sputum - 3 early morning samples min volume 5ml
Induced sputum (inhales nebulised hypertonic saline solution)
Bronchoscopy (patients with dry cough)
Signs on a CXR for pulmonary TB
Apex of the lung often involved,
ill defined patchy consolidation,
Cavitation usually develops within consolidation,
Healing results in fibrosis
Pleural TB - pleural effusion
Slide 27
What are the benefits and negatives of TB microscopy?
Mainstay for TB diagnostics worldwide
auramine stained - Rapid (same day), cheap, high sensitivity, 60-70% culture positive samples are microscopy positive, ZN stained - indicates infectiousness as smear positive cases are more infectious than smear negative
But can’t differentiate between MTB and NTM (nontuberculosis myobacteria) or dead and live organisms
What are the benefits of TB culture?
Remains the gold standard for TB diagnostics
One of the most sensitive methods for mycobacteria
Solid and liquid culture systems
Improved with automated culture technology
Allows identification and susceptibility testing
E.g. Lowenstein Jensen slopes
What is the role of NAAT for primary samples?
Nuclei acid amplification tests
Rapid diagnosis of smear +ve
Shows Drug resistance mutations
Whole genome sequencing
What is the Tuberculin sensitivity test? Negatives and benefits
Oldest diagnostic test - measures CMI (cell mediated immunity), in the form of DTH (delayed type hypersensitivity) to PPD (purified protein derivative) of M tuberculosis
Tuberculin injected intradermally - induration read 48-72hrs later
Subjective interpretation False positives (BCG, non TB) False negatives (immunocompromised)
But cheap and evidence to support ability to predict active disease in those latently infected
What are interferon Gamma Assays? (IFNg assay) when would you do this rather than skin testing? Drawbacks
modern alternative to skin testing
In-vitro test - Quantiferon Gold
T cell based assay (T spot) (causes bacilli to make interferon)
Measures antigen specific interferon gamma (IFNg assay)
✅no cross- reaction with BCG so do if known vaccination
Can’t distinguish between latent and active TB
Similar problems with sensitivity and specificity
First line treatment of TB
First line: RIPE Rifampicin Isoniazid Pyrazinamide Ethambutol
RIPE for 2months and then just RI for 4
(18months if CNS TB) - cure rate 90%
- adherence can do directly observed therapy or video observed
Vitamin D
Surgery
Side effects of TB medications
RIPE ONGO
Rifampicin - orange secretions/ urine (raised transaminases & induces cytochrome P450)
Isoniazid - Neuropathy peripheral (10mg OD) + hepatotoxicity
Pyrazinamide - Gout + hepatotoxicity
Ethambutol - optic neuritis (visual disturbances)
What are multi-drug resistant and extremely drug resistant TB?
Multi resistant (MDR): resistant to rifampicin and isoniazid
Extremely (XDR): resistant to R, I and fluroquinolones and at least one injectable
Risks of developing drug resistant TB? How are they treated?
Inadequate treatment
Previous TB treatment
HIV
Known contact of MDR TB
Failure to respond to conventional treatment
> 4months smear +ve/ >5 months culture +ve
Given 4-5 drug regimen, longer duration - quinolones, aminoglycosides, PAS, cycloserine, ethionamide
What is miliary TB?
Bacilli spreading through the blood stream - widespread infection
Either during primary infection or during reactivation
Lungs are always involved but few respiratory symptoms (fever, v unwell, dry cough)
Often multiple organs involved e.g. headaches- meningeal, pericardial/ pleural effusions small, ascites May, retinal involvement (choroid tubercles seen)
White specks on CXR slide 44
Give examples of extra-pulmonary TB?
Lymphadenitis
Scrofula (glandular swellings)
Cervical most commonly
Abscesses and sinuses
Gastrointestinal
Swallowing of tubercles
Peritoneal ascitic Or adhesive
Genitourinary - slow progression to renal disease, subsequent spreading to LUT
Bone and joint - haematogenous spread, spinal TB most common, Pott’s disease
Tuberculosis meningitis - chronic headache, fevers, CSF markedly raised proteins, lymphocytosis
