MICRO: Mycobacterial diseases (TB) Flashcards
What % of world’s population is infected with TB?
33%
What is the difference between NTM and MTB?
NTM - non-tuberculous mycobacteria (usually environmental)
MTB - mycobacterium tuberculosis
What is “slow growing” mycobacteria?
<7 days = rapid-growing e.g. M abscessus complex (affect CF patients)
>7 days = slow growing e.g. MTB complex (e.g. MTB and M bovis BCG) and M.avium complex (M avium and M intracellulare)
What are the microbiological features 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
How common is transmission in NTM?
Uncommon but may colonise humans
What are the features of myobacterium avium complex?
Slow growing
Immunocompetent
- May invade bronchial tree
- Pre-existing bronchiectasis or cavities
Immunosuppressed
- Disseminated infection
Who is affected by mycobacterium chimera, marinum and ulcerans?
(NB: also all slow growing)
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 the rapid growing NTMs?
- M. abscessus,
- M. chelonae,
- M. fortuitum
What type of infections are caused by rapid growing NTMs?
- Skin & soft tissue infections
- Tattoo associated outbreaks
- In hospital settings, isolated from BCs
- Vascular catheters & other devices
- Plastic surgery complications
- CF and bronchiectasis
Which are the slow growing NTMs?
- Mycobacterium avium complex
- Mycobacterium chimera
- M. marinum
- M. ulcerans
How do you diagnose NTM infections?
BTS 2017 guidelines/ IDSA guidelines 2020
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
(make sure to send MC&S)
What is the treatment of NTM infections?
Susceptibility testing results may not reflect clinical usefulness
MAC
- Clarithromycin/azithromycin
- Rifampicin
- Ethambutol
- +/- Amikacin/streptomycin
Rapid-growing NTM
- Based on susceptibility testing, usually macrolide-based
What is leprosy caused by? How does it present (2)?
Mycobacterium leprae
What are the risk factors for NTM?
How has COVID affected TB?
TB was the biggest killer perviously then COVID took over in 2020
Fewest cases diagnosed in for years when COVID became prevalent
How is TB transmitted?
- Droplet nuclei/airborne
- <10µm particles
- Suspended in air
- Reach lower airway macrophages
- Infectious dose 1-10 bacilli
- 3000 infectious nuclei
- Cough
- Talking 5 mins
- Air remains infectious 30 mins
How effective is BCG and what is it not effective againts?
70-80% but protection wanes
Only given to high prevalence communities
Protects against CNS tuberculousis but not pulmonary TB
What are the 3 forms of TB infections?
Primary TB
- Usually asymptomatic
- Ghon focus/complex
- Limited by CMI
- Rare allergic reactions include EN
- Occasionally disseminated/miliary
Latent TB
Reactivation
What are the risk factors for post-primary TB/reactivation?
5-10% lifetime risk
Risk factors for reactivation
- Immunosuppression
- Chronic alcohol excess
- Malnutrition
- Ageing
List how a less effective immune response leads to more severe forms of TB.
What is seen in pulmonary TB? Where is it usually found?
- Commonly in upper lobe
- Caseating granulomata of lung parenchyma and mediastinal LN
What is lymphadenitis TB (extra-pulmonary) also known as?
Scrofula and cervical lymph nodes are most commonly affected
What are the risk factors/demographics 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 are the signs/symptoms of TB?
- Fever
- Weight loss 74%
- Night sweats 55%
- Pulmonary symptoms
- Cough 80%
- Haemoptysis 6-37%
- Malaise 68%
- Anorexia
But depends on site affected
List some sites that can be affected by TB (extrapulmonary).
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
How many sputum samples are needed to diagnose TB?
x3
What is a “smear” for TB testing for?
Acid fast bacilli
What is this?
Granuloma
What is the use of NAAT in TB diagnosis?
nucleic acid amplification test = NAAT
- rapid diagnosis of smear +ve TB
- drug resistance mutations detected
- along with chromatography, it is used for speciation
What is the sensitivity of sputum for TB diagnosis?
60% sensitivity which increases by 10% with 2nd and 3rd samples of sputum
What is the turnaround time for culture of TB?
6 weeks
What is the treatment for TB including supportive?
Multi-drug therapy (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
Vitamin D
Nutrition
Surgery
What is the duration of treatment for TB?
Duration
- 3 or 4 drugs for 2/12
- Then Rifampicin & Isoniazid 4/12
- 12/12 if CNS TB
- Cure rate 90%
How do you ensure adherence to TB therapy?
DOT - directly observed therapy
VOT - video observed therapy
How has prevalence of MDR TB changed?
Increasing and most common in Russia
What is MDR TB resistant to?
Rifampicin and isoniazid
What is extremely drug resistant TB resistant to? (XDR)
Resistant to fluoroquinolones and at least 1 injectible
What are the risk factors for MDR TB?
- Spontaneous mutation
- Inadequate treatment
- Previous TB Rx
- HIV+
- Known contact of MDR TB
- Failure to respond to conventional Rx
- >4 months smear +ve/>5 months culture +ve
What is the treatment of latent TB?
rifampicin and isoniazid for 3 months - effective for penetrating the granuloma
What is the treatment for MDR TB?
4 or 5 drug regimen, with a longer duration
- Quinolones,
- aminoglycosides,
- PAS,
- cycloserine,
- ethionamide,
How does HIV affect the tuberculin skin test?
More likely to be negative
How sensitive are IGRAs for active tuberculosis diagnosis?
70-90%
T-SPOT better than Quantiferon Gold
What are the main challenges in TB and HIV treatement?
- Timing of treatment initiation
- Drug interactions
- Overlapping toxicity
- Duration of treatment – adherence
- Health care resources
What is a problem ith IGRAs? What do they detect?
- Detect antigen specific IFN-gamma production
- They cannot distinguish between latent and active TB
- Problems with sensitivity and specificity
How does the tuberculin skin test work? What are the main problems with it?
- Detects previous exposure to mycobacteria
- 2 units of tuberculin injected
- Detection of delayed type hhypersensitivity reaction
BUT
- cross-reacts with BCG
- poor sensitivity - HIV, age, immunosuppressants, overwhelming TB.
A 23 year old male is a close contact of a person with smear positive pulmonary TB, What is his lifetime risk of developing active TB?
- 1.0.1%
- 2.1%
- 3.10%
- 4.Don’t worry, be happy!
10%
