Mycobacterial Diseases (TB) Flashcards
What two terms are important for TB
Non-tuberculosis mycobacteria (NTM)
M. tuberculosis (MTB) - pathological form
What is the microbiology of tuberculosis (4)
Non-motile rod-shaped bacteria
Relatively slow-growing compared to other bacteria
Long-chain fatty (mycolic) acids, complex waxes & glycolipids in (cell wall, Structural rigidity, Complete Freund’s adjuvant, Staining characteristics_
Acid alcohol fast
What are the two stains used for acid alcohol fast bacilli detection (2)
Auramine
Ziehl Neelsen
What are the features fo NTM (6)
AKA (Environmental, Atypical) Ubiquitous in nature Varying spectrum of pathogenicity No person-to-person transmission Commonly resistant to classical anti-TB Rx May be found colonising
What are some examples of slow growing NTM (3)
Mycobacterium avium intracellulare (MAI)
M. marinum
M. ulcerans
What are the pathologies of m. avium intracellulare (2)
Immunocompetent: may invade bronchial tree, pre-existing bronchectasis or cavities.
Immunosuppressed: Disseminated infection
Where does m. marinum cause
Swimming pool granuloma
What does m ulcerans cause (2)
Skin lesions (bairnsdale ulcer, buruli ulcer) Chronic progressive painless ulcer
What are some fast growing NTM (3)
M abscessus
M chelonae
M fortuitum
What do fast growing NTMs cause
Skin and soft tissue infections
What are the typical sources of fast growing NTMs
Hospital settings - vascular catheters and other devices
What are some risk factors for NTM infection (4)
COPD
Asthma
Previous MTB
Bronchiectasis
What is in the diagnostic criteria for NTM (3)
Lung disease: Clinical: pulmonary symptoms, nodular/cavitary opacities, multifocal bronchiectasis with multiple small nodules
Exclusion of other diagnoses
Microbiologic: Positive culture >1 sputum samples, OR +ve BAL, OR +ve biopsy with granulomata
What is the treatment of NTM
MAI: clarithromycin/asithromycin, rifampicin, ethambutol, +/- amikacin/stretpomycin
Rapid-growing NTM: based on susceptibility testing, usually macrolide based.
What are the subtypes of m. leprae (2)
Paucibacillary tuberculoid
Multibacillary lepromatous
What are the features of MTB
Multisystem disease
Common worldwide
2nd most common cause of death by infectious agent (after HIV)
~2 million deaths each year
Increasing incidence since 1980s: Most common opportunistic infection in HIV, Immigration
9000 cases reported p.a. in UK
What are the disease states for MTB (5)
Exposed individual can develop: Uninfected - insufficiency dose Cleared - innate response/resistance Contained - localised immune response Active TB Latent TB
How is MTB transmitted
Droplet nuclei/airborne
<10microm particles
Suspended in air
Reach lower airway macrophages
What dose is required for MTB infection
1-10 bacilli
3000 infectious nuclei - cough, talking for 5 mins
Air remains infectious for 30mins
How is TB prevented (4)
Detection of cases
Treatment of index cases
Prevention of transmission (PPE, negative pressure isolation)
Optimisation of susceptible contacts (address risk factors, BCG)
What type of vaccine is the BCG
Live attenuated M bovis strain
What is the natural history of TB (3)
Primary TB - usually asymptomatic, ghon focus/complex, limited by CMI, rare allergic reactions, occasionally disseminated/milliary.
Latent TB
Reactivation
What is post-primary TB
Reactivation or exogenous re-infection
When does post-primary TB occur
> 5 years after primary infection
What is the lifetime risk of post-primary TB
5-10% per lifetime
What are the risk factors for TB reactivation (4)
Immunosuppression
Chronic alcohol excess
Malnutrition
Ageing
What is the clinical presentation of post-primary TB
Pulmonary or extra-pulmonary
How does the immune system affect the clinical outcome of TB
From more effective to less effective immune response:
Healthy contact (LTBI)
Lymph node
Localised extrapulmonary
Pulmonary (localised)
Pulmonary (widespread)
Meningeal
Miliary
What is the typical presentation of pulmonary TB (2)
Caeseating granulomatoma (lung parenchyma, mediastinal lymph nodes) Commonly in the upper lobe
What are the extra-pulmonary manifestations of TB (6)
Lymphadenitis (AKA scrofula, cervical lymph nodes most commonly, abscesses and sinuses)
GI (swallowing or tubercles)
Peritoneal (ascitic or adhesive)
GU (slow progression to renal disease, subsequent spreading to lower urinary tract)
Bone and joints (haematogenous spread, spinal TB most common, Pott’s disease)
Miliary TB (millet seeds on CXR, progressive disseminated haematogenous TB, increasing due to HIV)
Tuberculosis meningitis
What is the most common form of spinal TB
Pott’s disease
What is a risk factor for milliary TB
HIV
What are the steps involved in the clinical approach to suspected TB (5)
Index of suspicion Suggestive of symptoms? (detailed history) Investigations Treatment Preventing onward transmission
What are the geographical demographics of TB (2)
Non-UK born/recent migrants.
South Asia, Sub-Saharan Africa
What are the risk factors for TB (6)
Non-UK born/recent migrants HIV Other immunocompromise Homeless Drug users, prison Close contacts Young adults (also higher incidence in elderly)
How does TB present (6)
Fever Weight loss Night sweats Pulmonary symptoms (cough, haemoptyisis) Malaise Anorexia
What are important questions in a TB history (5)
Ethnicity Recent arrival or travel Contacts with TB BCG vaccine Non-specific examination findings
What systems must be considered when assessing TB (6)
Pulmonary (most common) Extra-pulmonary LN GI Spine Meningitis GU
What are the important investigations for TB (5)
CXR and other radiology Sputum x 3 (induced sputum) Bronchoscopy Biopsies EMU
What are some analyses that can be done on samples in a patient suspected of TB (6)
Stain for AAFBs (smear) Culture NAAT Histology Tuberculin skin test IGRAs
What is needed for a diagnosis of TB (5)
Microbiology
Radiology
Histology
Epidemiology
What are the key features of a smear for TB (5)
Sputum (60% sensitive, increased 10% and 2% with 2nd and 3rd sputa) Gastric aspirates in kids Other specimens centrifuged Rapid Operator dependent
What is the gold standard to diagnose TB
Culture
What are the key features of TB culture (4)
Gold standard for diagnosis
Solid and liquid culture systems
Up to 6 weeks (1-3 weeks with modern automated systems)
Further testing of cultured isolates
Histology features of TB (6)
Granulomatous Epithelious macrophages Langerhans giant cells Lymphocytes Plasma cells Caeseous necrosis in teh centre
How does TB appear with Ziehl Neelsen stain
Thin red rods
How is species determined in TB infection (2)
NAAT
Chromatography
What is the role of NAAT for primary samples of TB (2)
Rapid diagnosis of smear positive
Drug resistance mutations
What are the key features of tuberculin skin tests (5)
Identifies previous exposure to mycobacteria
Uses 2 units of tuberculin
Delayed type hypersensitivity reaction
Cross-reacts with BCG
Poor sensitivity (HIV, age, immunosuppressants, overwhelming TB)
What is IGRAs for TB detection (6)
Detection of antigen specific IFNgamma production
ELISpot
Quantiferon
No cross-reaction with BCG
Cannot distinguish latent and active TB
Similar problems with sensitivity and specificity
What is the first-line treatment for TB (4)
Rifampicin and isoniazid and pyrazinamide and ethambutol
What are the second line drugs for TB (7)
Quinolones (moxifloxacin), injectables (capreomycin, kanamycin, amikacin), ethionamide/prothionamide, cycloserine, PAS, linezolid, clofazamine
How is TB treated (4)
Multi-drug therapy (rifampicin, isoniazid, pyrazinamide, ethambutol)
Vitamin D
Nutrition
Surgery
What is the MOA of rifampicin
Raised transaminiases and induced cytochrome p450
What is a side effect of rifampicin
Orange secretions
Side effects of isoniazid (2)
Hepatotoxicity Peripheral neuropathy (pyridoxine 10mg OD)
Side effects of pyrazinamide
Hepatotoxicity
Side effect of ethambutol
Visual disturbance
What are the treatment regimens for TB (3)
3 or 4 drugs for 2 months
Then rifampicin and isoniazid for 4 months.
Treatment for 10 months if CNS TB
What is the cure rate for TB
90%
How is adherence monitored for TB (2)
Directly observed therapy (DOT)
Video observed therapy (DOT)
What are the main features of MRD TB (2)
Resistant to rifampicin and isoniazid
What is extremely drug resistant TB resistant to (4)
Rifampicin
Isoniazid
Fluoroquinolones
And at least 1 injectable
What increases the risk of MDR and XDR TB (5)
Previous TB Rx HIV Known contact with MDR TB Failure to respond to conventional Rx >4 months smear +ve/>5 months culture +ve
How is MDR TB treated (5)
4/5 drug regimen for a longer duration
Quinolones, aminoglycosides, PAS, cycloserine, ethionamide
What are the WHO recommendations for MDR TB shorter duration treatment
7 drugs and a treatment duration of 9-12 months.
What is the exclusion criteria for shorter MDR-TB treatment (3)
2nd line drug resistance
Extrapulmonary TB
Pregnancy
What are the challenges in TB diagnosis in HIV+ve patients (5)
Clinical history (less likely to be classical, symptoms and signs often absent in populations with low CD4 count)
CXR (more likely extrapulmonary, X-ray changes variable)
Smear microscopy and culture less sensitive
Tuberculin skin test more likely to be negative
IGRA sensitivity reduced
What are the challenges in TB treatment in HIV+ve patients (5)
Timing of treatment initiation Drug interactions Overlapping toxicity Duration of treatment - adherence Health care resources
