Mycobacterial disease Flashcards
Describe where non-tuberculous mycobacteria can be found, and how it spreads
- Non-tuberculous mycobacteria is environmental and atypical - found in lakes/water and soil
- Ubiquitous in nature
- Varying spectrum of pathogenicity
- No person-to-person transmission
- Commonly resistant to classical anti-TB prescriptions
- May be founf colonizing
- Who is at risk of developing slow-growing Non-tuberculous mycobacteria?
- What are the different types of slow growing NTM and where are they found?
- Immunocompetent and immunocompromised (at risk of disseminated infection)
2.
- Mycobacterium avium intracellulare/ M.avium complex
- M.marinum - swimming pool granuloma
- M.ulcerans - Skin lesions e.g. Bairnsdale ulcer, Buruli ulcer - causing a chronic progressive painless ulcer
- What are the different ‘rapid-growing’ NTM?
- What do they cause?
1.
- M.abscessus
- M.chelonae
- M.fortuitum
2.
- Skin and soft tissue infections
- In hospital settings, isolated BCs - vascular catheters and other devices
Describe the diagnosis of Non-tuberculous mycobacteria from the 2007 American thoracic society guidelines
- 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 Non-tuberculous mycobacteria?
- Susceptibility testing results may not reflect clinical usefulness
- MAI:
- Clarithryomycin/azithromycin
- Rifampicin
- Ethamnutol
- +/- Amikacin/streptomycin
- Rapid-growing NTM
- Based on susceptibility testing, usually macrolide-based
What are the two types of mycobacterium leprae?
- Paucibacillary tuberculoid
- Multibacillary lepromatous
Describe the epidemiology of mycobacterium tuberculosis
- Multi-system disease
- Common worldwide
- 2nd most common cause of death by infectious agent
- 2 million deaths each year
- Increasing prevalence since 1980s
- Most common opportunistic infection in HIV
- Immigration
- 9000 cases reported per annum in UK
What is the transmission of TB?
- Droplet nuclei/airborne
- <10um particles
- Suspended in air
- Reach lower airway macrophages
- Infectious dose 1-10 bacilli
- 3000 infectious nuclei
- cough
- talking for 5 minutes
- Air remains infectious for 30 minutes
How can TB be prevented?
- Detection of cases
- Treatment of TB in a timely manner
- Prevention of transmission
- PPE
- Negative pressure isolation
- Optimisation of susceptible contacts
- Address risk factors
- Vaccination
- Bacille Calmette-Guerin (BCG): Live attenuated M.bovis strain
- Given to babies in high prevalence communities (only since 2005)
- 70-80% effectiveness in preventing severe childhood TB
- Protection wanes
- Little evidence in adults
What is the natural history of pulmonaryTB?
- Primary TB
- Usually asymptomatic
- Ghon focus/complex
- Limited by CMI
- Rare allergic reactions include EN
- Occassionally disseminated/miliary
- Latent TB
- Reactivation
- Describe post-primary TB
- What are the risk factors for reactivation of TB?
- Post-primary TB:
- reactivation or exogenous re-infection
- > 5 years after primary infection
- 5-10% risk per lifetime
- Risk factors for reactivation
- Immunosuppression
- Chronic alcohol excess
- Malnutrition
- Ageing
Clinical presentation - pulmonary or extra-pulmonary
Describe the radilogical features of pulmonary TB
- Caseating granulomata
- Lung parenchyma
- Mediastinal Lymph nodes
- Commonly upper lobe
Describe what can develop in people with Extra-pulmonary TB
- Lymphadenitis
- AKA scrofula
- Cervical lymph nodes most commonly
- Abscesses and sinuses
- Gastrointestinal
- Swallowing of tubercules
- Peritoneal
- Ascitic or adhesive
- Genitiurinary
- Slow progression to renal disease
- Subsequent spreading to lower urinary tract
- Bone and joint
- Haematogenous spread
- Spinal TB most common
- Pott’s disease
- Miliary TB:
- Millet seeds on CXR
- Progressive disseminated haematogenous TB
- Increasing due to HIV
- Tuberculous meningitis
What does this image show?
Millet seeds, a signs of Miliary TB
What is spinal TB known as?
Pott’s disease
Describe the demographics and risk factors for TB
- Non-UK born/recent migrants
- south asia 54.8%
- sub-saharan africa 29.5%
- HIV or other immunocompromise
- Homeless
- Drug users, prison
- Close contacts
- Young adults
What is the presentation of TB?
- Fever
- Weight loss 74%
- Night sweats 55%
- Pulmonary symptoms
- cough 80%
- haemoptysis 6-37%
- Malaise 68%
- Anorexia
What are important questions to ask for someone who you suspect has TB?
- Ethnicity
- Recent arrival or travel
- Contacts with TB
- BCG vaccination
- Non-specific examination findings
What investigations should be performed in suscpected TB?
- CXR and other radiology
- Spuum x3 - induced sputum
- Bronchoscopy
- Biopsies
- EMU
stain for AAFBs ‘smear’
culture
NAAT
Histology
Tuberculin skin test
IGRAs
What does the image show?
Mediastinal lymph node
Describe a smear for TB
- Uses sputum
- 60% sensitivity
- Increases with more samples
- Gastric aspirates in kids
- Other specimens centrifuged
- Rapid
- Operator dependent
Summarise different bacteriological examinations for TB
Describe the use of cultures for diagnosing TB
- Culture is gold standard
- Solid and liquid culture systems
- Takes up to 6 weeks - less with modern automated systems
What do tuberculin skin tests show?
- Tuberculin skin test shows previous exposure to mycobacteria
- 2 units tuberculin
- Delayed type hypersensitivity reaction (type 4)
- Cross-reacts with BCG
- Poor sensitivity
- HIV, age, immunosuppressants
- Overwhelming TB
Describe the use of interferon gamma release assays (IGRAs)
- Detection of antigen-specific IFN-gamma production
- ELISpot
- Quantiferon
- No cross reaction with BCG
- Cannot distinguish latent and active TB
- Similar issues with sensitivity and specificity
What are the first line medications for TB?
- Rifampicin
- Isoniazid
- Pyrazinamide
- Ethambutol
RIPE
What are the second line medications for TB?
- Quinolones (moxifloxacin)
- Injectables - capreomycin, kanamycin, amikacin
- Ethionamide/prothioamide
- Cycloserine
- PAS
- Linezolid
- Clofazamine
The treatment for TB is RIPE, a multi-drug therapy. Describe the side effects of each of the antibiotics
- Rifampicin
- Raised transaminases and induces cytochrome P450
- Orange secretions
- Isoniazid
- Peripheral neuropathy
- Hepatotoxicity
- Pyrazinamide
- Hepatotoxicity
- Ethambutol
- Visual disturbance
Describe the duration of treatment for TB
- 3 or 4 drugs of RIPE for 2/12
- Then Rifampicin and Isonazid 4/12
- 10/12 if CNS TB
- Cure rate 90%
Describe Multidrug resistance TB
- What is it against?
- What has caused it?
- Multidrug resistance TB - resistant to rifampicin and isonazid
- Extremely drug resistant TB
- Also resistant to fluoroquinolones and at least 1 injectable
- Spontaneous mutation + inadequate treatment
- Liklihood increased
- Previous TB prescription
- HIV positive
- Known contact of multi-drug resistant TB
- Failure to respond to conventional Rx
- > 4 months smear +>5 months culture +ve
- 4/5 drug regimen, longer duration
- Quinolones, aminoglycosides, PAS, cycloserine and ethionamide
Describe the following challenges with having TB and HIV when it comes to diagnosis of TB:
- Clinical history
- Chest X ray
- Smear microscopy and culture
- Tuberculin skin test
- Sensitivity of interferon gamma release assays for active tuberculosis
- Clinical history
- Less likely to be classical
- Symptoms and signs are often absent in population with low CD4 count
- Chest X-ray
- More likely extrapulmonary
- X-ray changes variable
- Smear microscopy and culture
* Less sensitive - Tuberculin skin test
* More likely to be negative - Sensitivity of IGRAs for active TB
- Quantiferon - reduced
- T SPOT - reduced
What are the challenges in TB and HIV when it comes to treatment?
- Timing of treatment initiation
- Drug interactions
- Overlapping toxicity
- Duration of treatment - adherence
- Health care resources
Name two novel diagnostic tests
- IGRAs - interferon gamma release assays
- NAATs - Nucleic acid amplification tests
