Mycobacterial diseases Flashcards
What are the two main types of Mycobacteria?
Non-Tuberculous Mycobacteria (NTM)
M. tuberculosis (MTB)
What are slow growing Mycobacteria?
M. avium complex
- M. avium
- M. intracellulare
MTB complex
- M. bovis BCG
- M. tuberculosis
What are rapid growing Mycobacteria?
M. abscessus complex
- M.abscessus
- M.massiliense
- M.bolletii
Which Mycobacteria spp. is ungrouped?
M. leprae
What is the microbiology of Mycobacteria?
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
- Staining characteristics
Acid alcohol fast
What are tests for acid alcohol fast bacilli (AAFBs)?
Auramine
Ziehl-Neelsen
What is this?
Auramine staining
What is this?
Ziehl-Neelson staining
Where are non-tuberculous mycobacteria found?
Water
Soil
Explain the aetiology/pathophysiology of non-tuberculous mycobacteria.
AKA Environmental or Atypical Mycobacteria
Ubiquitous in nature. Varying spectrum of pathogenicity.
Little risk of person-to-person transmission. Commonly resistant to classical anti-TB Rx. May be found colonizing humans.
What are features of slow-growing non-tuberculous mycobacteria?
Mycobacterium avium complex:
- Immunocompetent
- May invade bronchial tree
- Pre-existing bronchiectasis or cavities
- Immunosuppressed
- Disseminated infection
Mycobacterium chimera: Associated to cardiothoracic procedures
M. marinum: Swimming pool granuloma
M. ulcerans: Skin lesions e.g. Bairnsdale ulcer, Buruli ulcer
Chronic progressive painless ulcer
What are features of fast-growing non-tuberculous mycobacteria?
M. abscessus, M. chelonae, M. fortuitum:
- Skin & soft tissue infections: Tattoo assaociated outbreaks
- In hospital settings, isolated from BCs: Vascular catheters & other devices, Plastic surgery complications
- CF and bronchiectasis
Explain the epidemiology/risk factors of NTM.
Pulmonary is increasing, extrapulmonary is not as common.
Age range: 56-78
Risk factors:
- COPD
- Asthma
- Previous MTB
- Bronchiectasis
- Previous ATB
- CFA
- Lung cancer
- Cystic fibrosis
What is the diagnostic criteria for Mycobacterial diseases?
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 Mycobacterial diseases?
MAC:
- Clarithromycin/azithromycin
- Rifampicin
- Ethambutol
- +/- Amikacin/streptomycin
Rapid-growing NTM:
Based on susceptibility testing, usually macrolide-based
What can Mycobacterium leprae cause?
Leprosy
Systemic disease
Contracted via inhalation of the Bacilli
What are two extremes of Mycobacterium leprae?
Paucibacillary tuberculoid
- Lower number of bacterial cells present
- Milder immune response
- Less destruction of structures such as skin, nerves, bones
Multibacillary Lepromatous
- Characterised by high number of bacterial cells
- Highly disfiguring
- Can eventually kill patient
What is Mycobacterium tuberculosis? Summarise the epidemiology of TB.
Multisystem disease.
Epidemiology:
- Common worldwide
- Most common cause of death by infectious agent – pre COVID-19
- ~2 million deaths each year
- Increasing incidence since 1980s
- Most common opportunistic infection in HIV
A 23 year old male is a close contact of a person with smear positive pulmonary TB. What is his lifetime risk of developing TB?
10% for immunocompetent hosts
What are the TB Disease states?
Once you get TB, it does not mean that you will progress to have clinical manifestation of TB.
Possible outcomes after exposure to TB:
- Nothing
- Mild febrile disease
- Straight progression to clinical TB
Majority of people manage to control first exposure to TB.
They then go into state of latent TB infection, may remain like this for many years until something affects their immune system, causing re-activation.
New evidence is going against this current paradigm.
How is Mycobacterium tuberculosis transmitted?
Droplet nuclei/airborne The particles are so small (<10um) that they can be naturally suspended in air. Reach lower airway macrophages.
Infectious dose 1-10 bacilli.
3000 infectious nuclei:
- Cough
- Talking 5 mins
Air remains infectious for 30 mins
How is TB prevented?
Detection of cases
Treatment of index case
Prevention of transmission:
- PPE
- Negative pressure isolation
Optimisation of susceptible contacts
Address risk factors
Bacille Calmette-Guerin (BCG): live attenuated M. bovis strain.
What is post-primary TB and what is the risk of developing this?
Reactivation or exogenous re-infection: 5-10% risk per lifetime
Risk factors for reactivation:
- Immunosuppression
- Chronic alcohol excess
- Malnutrition
- Ageing
Clinical presentation: Pulmonary or extra-pulmonary
In order of most effective to least effective immune response, what are the outcomes of TB?
Healthy contact (LTBI)
Lymph node
Localised Extrapulmonary
Pulmonary (localized)
Pulmonary (widespread)
Meningeal
Miliary
What is pulmonary TB?
Caseating granulomata
Lung parenchyma
Mediastinal LNs
Commonly upper lobe
What are features of extra-pulmonary TB?
Lymphadenitis:
- AKA scrofula
- Cervical LNs most commonly
- Abscesses & sinuses
Gastrointestinal:
- Swallowing of tubercles
- Peritoneal
- Ascitic or adhesive
Genitourinary:
- Slow progression to renal disease
- Subsequent spreading to lower urinary tract
Bone & 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 are risk factors for TB?
- Non-UK born/recent migrants
- South Asia
- Sub-Saharan Africa
- HIV
- Other immunocompromise
- Homeless
- Drug users, prison
- Close contacts
- Young adults (also higher incidence in elderly)
What is the clinical presentation of TB?
- Fever
- Weight loss 74%
- Night sweats 55%
- Pulmonary symptoms
- Cough 80%
- Haemoptysis 6-37%
- Malaise 68%
- Anorexia
What is this?
Milliary TB
What is this?
Milliary TB
What is this?
Mediastinal lymph nodes
What are the first line treatments of TB?
Rifampicin (R)
Isoniazid (H)
Pyrazinamide (Z)
Ethambutol (E)
What are second line medications for TB?
- Quinolones (Levofloxacin)
- Injectables: Capreomycin, kanamycin, amikacin
- Ethionamide/Prothionamide
- Cycloserine
- PAS
- Linezolid
- Clofazimine
- Beta-lactams
- Bedaquiline
- Delamanid
What are side effects of RHZE?
Rifampicin (R)
- Raised transaminases & induces cytochrome P450
- Orange secretions
Isoniazid (H)
- Peripheral neuropathy (pyridoxine 10mg od)
- Hepatotoxicity
Pyrazinamide (Z)
- Hepatotoxicity
Ethambutol (E)
- Visual disturbance
How long is the duration of therapy for TB? How can compliance be monitored?
Duration:
- 3 or 4 drugs for 2/12
- Then Rifampicin & Isoniazid 4/12
- 12/12 if CNS TB
- Cure rate 90%
Adherence:
- Directly observed therapy (DOT)
- Video observed therapy (VOT)
What is multi-drug resistant TB?
- Resistant to rifampicin & isoniazid
- Extremely drug-resistant TB (XDR)
- Also resistant to fluoroquinolones & at least 1 injectable
Risk factors:
- Previous TB Rx
- HIV+
- Known contact of MDR TB
- Failure to respond to conventional Rx
- >4 months smear +ve/>5 months culture +ve
- 4/5 drug regimen, longer duration
- Quinolones, aminoglycosides, PAS, cycloserine, ethionamide
