Mycobacterial diseases Flashcards
What species causes the most TB cases?
M. tuberculosis (MTB)
List 5 Mycobacteria that can cause TB
M. tuberculosis
M. bovis
M. africanum
M. microti
M. canetti
Name 4 non-TB Mycobacteria and which populations are most susceptible
M. avium complex: untreated HIV
M chelonae: Salmon farmers
M abscessus: CF
M chimaera: vascular bypass device
How is TB transmitted?
Aerosol
Infectious expulsion on: coughing, sneezing, speaking, singing
Droplet nuclei suspended in air for up to 30min
Inhalation of droplet nuclei, reach lower airway macrophages
What percentage of the world’s population have latent TB infection? How many go on to develop active TB?
¼ to ⅓
~10% lifetime risk of progression to active TB
~30-50% if HIV +ve
What can be used to diagnose latent TB infection?
Mantoux with PPD
Gamma Interferon Release Assays (IGRA)
What is the normal incubation period of active TB? What may have happened if active TB occurs later?
3-9m
Almost always <2y
Most are endogenously reinfected with TB (not TB activation)
What drugs are used in treatment of TB?
Rifampicin: 6m
Isoniazid: 6m
Pyrazinamide: 2m
Ethambutol: 2m
Directly observed therapy (DOTs)
Name the side effects of each TB drug
Rifampicin: orange secretions, raised transaminases, induces CYP450
Isoniazid: peripheral neuropathy, hepatoxicity
Pyrazinamide: hepatotoxic
Ethambutol: optic neuritis
What drug can be given to prevent the peripheral neuropathy caused by Isoniazid?
Pyridoxine
What is the natural clinical course of TB?
Infection usually asymptomatic, controlled by cell mediated immunity: becomes latent in Gohn focus/ caeseating granuloma
Upon reactivation (e.g. immunosuppression) becomes symptomatic
Which baseline investigations must be made before commencing anti-TB treatment?
FBC, LFT, U+Es, CRP
CXR
What is the duration of treatment for TB meningitis?
12m
What is the microbiology of Mycobacteria?
Non-motile rod-shaped bacteria
Relatively slow-growing cf. other bacteria
Long-chain fatty (mycolic) acids, complex waxes + glycolipids in cell wall giving structural rigidity
Acid alcohol fast
What are tests for acid alcohol fast bacilli (AAFBs)? What is the turn around time? Which is more sensitive?
Auramine 20-30m (more sensitive)
Ziehl-Neelsen 30m
What is this?
Auramine staining
What is this?
Ziehl-Neelson staining
Name 3 slow growing non tuberculous mycobacterium
Mycobacterium avium-intracellulare complex (MAC)
Mycobacterium marinarum
Mycobacterium ulcerans
Describe the pathology of mycobacterium avium intracellulare complex
RF: pre-existing lung disease, heavy smoking/ drinking, HIV
Immunocompetent: invades bronchial tree
Immunocompromised: disseminated infection
Describe the pathology of mycobacterium marinarum
“Fish tank/ Swimming pool granuloma”
Swimmers/ Aquarium owners
Plaques/ papules- granulomatous ulcers
Describe the pathology of mycobacterium ulcerans
aka. Buruli ulcer
Tropical: S America, Australia, Africa
Painless nodule/ induration/ swelling progressing to ulceration, scarring + contractures
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.
List 3 fast-growing non-tuberculous mycobacteria
M. abscessus
M. chelonae
M. fortuitum
What are fast-growing non-tuberculous mycobacteria outbreaks associated with?
Skin + soft tissue infections
Tattoo assaociated outbreaks
In hospital settings from BCs: Vascular catheters, Plastic surgery
Give 2 broad risk factors for NTM.
Age
Underlying lung disease: COPD, Asthma, Bronchiectasis, CF, cancer
What is the diagnostic criteria for Mycobacterial diseases?
Clinical: Pulmonary Sx, nodular/cavitary opacities, multifocal bronchiectasis with multiple small nodules.
Exclusion of other dx.
Microbiologic:
- +ve culture >1 sputum samples
- OR +ve BAL
- OR +ve biopsy with granulomata
What is the treatment of MAC/ slow growing non tuberculous Mycobacterial diseases?
Rifampicin
Clarithromycin/ azithromycin
Ethambutol
+/- Amikacin/streptomycin
“RiCES”
What is the treatment for fast growing non tuberculous mycobacterial diseases?
Based on susceptibility testing, usually macrolide-based
What is Leprosy? What is it caused by?
aka Hansen disease
Chronic infectious disease caused by prolonged exposure to Mycobacterium Leprae
Give 3 cardinal clinical manifestations of Leprosy
Hypopigmented skin lesions
Nerve thickening
Peripheral nerve palsies +/- repeated injury due to sensory loss
Compare the two types of Mycobacterium leprae
Paucibacillary/ Tuberculoid
- Few bacilli
- Strong Th1 response
- Less destruction of structures- skin, nerves, bones
Multibacillary/ Lepromatous
- Abundance of bacilli
- Th2 response
- Multiple skin lesions + joint infiltration
What is Mycobacterium tuberculosis? Summarise the epidemiology of TB.
Multisystem disease.
Obligate aerobe
- Common worldwide
- Most common cause of death by infectious agent, pre COVID: ~2 million deaths each year
- Increasing incidence since 80s
- Most common opportunistic infection in HIV
What vaccination is given to protect against TB?
BCG
Attenuated strain of M. bovis
Given to infants + high risk
CI in immunosuppressed (live vaccine)
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 3 possible outcomes after exposure to TB?
- Nothing
- Mild febrile disease
- Straight progression to clinical TB
Majority control 1st exposure, 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.
List 5 clinical investigations for TB
CXR: predilection to apices, mediastinal LNs, miliary TB
Sputum x 3
EBUS TBNA (endobronchial US transbronchial needle aspiration)
Bronchoscopy
Early morning urine
What tests are performed on broncho-alveolar lavage for TB?
Check for acid fast bacilli on smear
Culture on Lowenstein-Jenson medium, stain with auramine/ Ziehl-Neelson
How is an endobronchial ultrasound transbronchila needle aspiration utilised in diagnosis of TB?
Histology- caseating granuloma
What is the tuberculin skin test?
aka. Mantoux
Intradermal tuberculin purified protein derivative (PPD)
Examine induration 48-72h later
Indicates previous exposure- BCG, active, latent
List 3 disadvantages of the tuberculin skin test
No differentiation of vaccination, latent or active
Poor sensitivity (HIV, age, immunosuppression, overwhelming TB)
Risk of delayed type hypersensitivity reaction from PPD
What is an IGRA test?
Interferon gamma release assay
e.g. Elispot, Quantiferon
Detects antigen-specific IFNg production
No cross reaction with BCG
Give 2 disadvantages of IGRAs
Can’t distinguish latent + active TB
Issues with sensitivity + specificity
How is TB prevented?
Detection + Tx of index case
Prevention of transmission:
- PPE
- -ve pressure isolation
Optimisation of susceptible contacts
Address RFs
Bacille Calmette-Guerin (BCG): live attenuated M. bovis strain.
What is post-primary TB and how does this present?
Reactivation or exogenous re-infection: 10% risk per lifetime
Clinical presentation: Pulmonary or extra-pulmonary depending on host immune response
List 4 risk factors for reactivation of latent TB
Immunosuppression
Chronic alcohol excess
Malnutrition
Ageing
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 in lung parenchyma + mediastinal LNs
Commonly upper lobe
Give 5 systems affected by extra-pulmonary TB. What are the features of involvement in each?
Lymphadenitis: aka scrofula
Cervical LNs most commonly
Abscesses + sinuses
GI: May present like IBD, due to swallowing of tubercles
Peritoneal: Ascitic or adhesive
GU: slow progression to renal disease
Subsequent spreading to lower urinary tract
Bone + joint: Haematogenous spread
Spine (Pott’s disease)
What is miliary TB?
Disseminated haematogenous spread
Millet seeds on CXR
Increasing due to HIV
Give 4 features of presentation of tuberculosis meningitis. How is it diagnosed?
Headaches
Personality change
Meningism
Confusion
Ix: LP- turbid
What are 8 risk factors for TB?
Non-UK born/recent migrants
South Asia
SS Africa
HIV/ Other immunocompromise
Homeless
IVDU, prison
Close contacts
YA (also higher in elderly)
List 8 signs/ symptoms of TB
Cough 80%
Weight loss 74%
Night sweats 55%
Fever
Pulmonary Sx
Haemoptysis 6-37%
Malaise 68%
Anorexia
What is this?
Milliary TB
What is this?
Milliary TB
What is this?
Mediastinal lymph nodes
List 7 second line medications for drug resistant TB
- Quinolones (Levofloxacin)
- Bedaquiline
- Linezolid
- Clofazimine
- Injectables: kanamycin, amikacin
- Ethionamide/ Prothionamide
List 4 risk factors for drug resistant TB
Previous TB Rx
HIV+
Known contact of MDR TB
Failure to respond to conventional
What test can be used to determine TB drug sensitivity?
Molecular line-probe assays
Whole genome sequencing on culture
Next gen sequencing
What are the forms of resistant TB?
Multidrug resistant (MDR): resistant to Rifampicin + Isoniazid
Extremely drug resistant (XDR): resistant to rifampicin, isoniazid, fluoroquinolones + at least 1 injectable
What is drug resistant TB though to be due to?
Spontaneous mutation
Inadequate tx
What is the treatment for drug resistant TB?
>,4 drugs for 9-12m
Levofloxacin/ Moxifloxacin
Bedaquiline
Linezolid
Clofazimine
Pretomanid
List 5 diagnostic challenges of HIV and TB coinfection
- Clinical presentation less likely to be classical, Sx + signs absent if low CD4
- CXR may be normal (more likely extra pulmonary manifestations)
- Smear microscopy + culture less sensitive
- Tuberculin skin test more likely to be -ve
- Low sensitivity of IGRAs
List 5 treatment challenges of HIV and TB coinfection
Timing of tx initiation
Drug interactions
Overalapping toxicity
Duration of tx ?adherence
Healthcare resources
What is the MTB complex? List 3 important members
Genetically related group of mycobacterium that can cause TB
Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium africanum
