Mycobacterial diseases Flashcards
What are mycobacterium?
Non motile rod shaped bacteria which are slow growing
What do mycobacteria have in their cell wall?
Long chain fatty (mycolic) acids, complex waves and glycolipids in cell wall
THEREFORE they are acid alcohol fast
What stain do you use for TB/ AFB?
Ziehl Neelson - Red on blue
Auramine - Yellow
How do you get non TB mycobacteria?
Environmental
Water
Soil
Atypical
What is non TB mycobacterium from?
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 the slow growing NTM?
Mycobacterium avium intracellulare
M marinum
M ulcerans
What is MAI?
Mycobacterium avium intracellulare (MAI) AKA M. avium complex (MAC) Immunocompetent May invade bronchial tree Pre-existing bronchiectasis or cavities Immunosuppressed Disseminated infection
What is rapid growing NTM?
M. abscessus, M. chelonae, M. fortuitum
Skin & soft tissue infections
In hospital settings, isolated from BCs
Vascular catheters & other devices
What is the epidemiology of MTB?
Getting better
Endemic to asia and africa
What are the RFs of MTB?
COPD
Asthma
Previous MTB
Lung cancer
How do you diagnose lung MTB?
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
How do you treat MTB?
Rifampicin (6 months)
Isoniazid (6 months)
Pyrazinamide (2 months)
Ethambutol (2 months)
How do you treat MAI?
Clarithromycin/azithromycin
Rifampicin
Ethambutol
+/- Amikacin/streptomycin
How do you treat rapid growing NTM?
Based on susceptibility testing, usually macrolide-based
What is mycobacterium leprae?
Paucibacillary tuberculoid
Multibacillary Lepromatous
Mostly in S America, Africa and Asia
What is the in depth epidemiology 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 kind of aerobe is MTB?
An obligate aerobe, generation time 15-20h
How is MTB transmitted?
Droplet/ 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 do you prevent MTB?
Detection of cases- treat index case
Prevent transmission- PPE, negative pressure isolation
Optimisation of susceptible contacts- Address RFs, Vaccinations
What are the MTB vaccines?
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 TB?
Primary TB Usually asymptomatic Ghon focus/complex Limited by CMI Rare allergic reactions include EN Occasionally disseminated/miliary
Latent TB
Reactivation
What is 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
What is the most to least effective immune response to TB?
Healthy contact (LTBI) Lymph node (Scrofula TB) Localised Extrapulmonary
Pulmonary (localized)
Pulmonary (widespread)
Meningeal
Miliary
What are the X-ray findings of MTB?
Caseating granulomata
Lung parenchyma
Mediastinal LNs
Commonly upper lobe
What are some common 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
What is bone/joint and TB meningitis and miliary TB?
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 is the clinical approach to MTB?
Index of suspicion
Suggestive symptoms
Detailed history
Investigations
Treatment
Preventing onward transmission
What are RFs for TB?
Non-UK born/recent migrants
South Asia 54.8%
Sub-Saharan Africa 29.5%
HIV
Other immunocompromise
Homeless
Drug users, prison
Close contacts
Young adults (also higher incidence in elderly)
What is presentation of MTB?
FLAWS: Fever Lethargy/ Malaise 68% Appetite loss/ Anorexia Weight loss 74% Sweats (Night) 55%
Pulmonary symptoms:
Cough 80%
Haemoptysis 6-37%
What would you find on history and exam of MTB?
Other localising symptoms Pulmonary 54.1% Extra-pulmonary LN 20.4% GI 4.1% Spine 4.1% Meningitis 2% GU 1.3%
Ethnicity
Recent arrival or travel
Contacts with TB
BCG vaccination
Non-specific examination findings
What investigations do you do for TB?
CXR & other radiology
Sputum x3 Induced sputum Bronchoscopy Biopsies EMU
Stain for AAFBs (“smear”)
Culture
NAAT- Gene Xpert
Histology
Tuberculin skin test
IGRAs- e.g. T Spot
What do you see on a sputum of TB?
Sputum
60% sensitivity
Increased 10% & 2% with 2nd & 3rd sputa
Gastric aspirates in kids
Other specimens centrifuged
Rapid
Operator dependent
How do you do a TB culture?
Gold standard
Solid & liquid culture systems
Up to 6 weeks
1-3 weeks with modern automated systems
Further testing of cultured isolates
What additional tests can you do for TB?
Speciation
NAAT
Chromatography
Drug sensitivity
Role of NAAT for primary samples?
Rapid diagnosis of smear +ve
Drug resistance mutations
How good is the tuberculin skin test?
Previous exposure to Mycobacteria
2 units tuberculin
Delayed type hypersensitivity reaction
Cross-reacts with BCG
Poor sensitivity
HIV, age, immunosuppressants
Overwhelming TB
What is an IGRA?
Detection of antigen-specific IFN-γ production
ELISpot
Quantiferon
No cross-reaction with BCG
Cannot distinguish latent & active TB
Similar problems with sensitivity & specificity
What are anti TB drugs?
RHZE (RIPE)
+
Second line Quinolones (Moxifloxacin) Injectables Capreomycin, kanamycin, amikacin Ethionamide/Prothionamide Cycloserine PAS Linezolid Clofazamine
What are the side affects 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
Vitamin D
Nutrition
Surgery
How long do you give TB treatment?
Duration 3 or 4 drugs for 2/12 Then Rifampicin & Isoniazid 4/12 10/12 if CNS TB Cure rate 90%
Adherence
Directly observed therapy (DOT)
Video observed therapy (VOT)
What is MDR TB?
Multi-drug resistant TB (MDR)
Resistant to rifampicin & isoniazid
Extremely drug-resistant TB (XDR)
Also resistant to fluoroquinolones & at least 1 injectable
Spontaneous mutation + inadequate treatment
Likelihood increased
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
What are the challenges in a TB history?
Clinical history
Less likely to be classical
Symptoms and signs often absent in population with low CD4 count (data from a number of cohorts starting HAART in Africa)
Chest X-ray
More likely extrapulmonary
X-ray changes variable
Smear microscopy & culture
Less sensitive
Tuberculin skin test
More likely to be negative
Sensitivity of IGRAs for active tuberculosis (Goletti et al PloS One 2008) Quantiferon Gold 78.1% (95% CI 70.7, 84.3) T SPOT 85.1% (95% CI 79.2, 89.9)
How many people have TB?
33%
The laboratory calls you saying they have found Acid Fast Bacilli in a clinical sample. Which answer is most appropriate?
Recommend TB therapy
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?
10%
HIV +ve, risk = 10% per year
Which drug is the most important?
Rifampicin is the most important drug
