L19 Mycobacteria Flashcards
Mycobacteria Characteristics:
Gram Pos/Neg?
Anaerobic/ Aerobic?
Other?
Mycobacteria
Difficulties in identifying
Will NOT show up in traditional gram stain
Acid Fast Bacilli - cannot be decolorized by acid
Fastidious, Slow growing
Aerobic
Lipid-Rich cell wall, more resistant
Epidemiology of Mycobacteria
Epidemiology
1/4 of world infected w/ TB (Most are latent, not active0
2nd most common infective cause of death worldwide
CO-infection w/ HIV played important role in increasing infection
Epidemiology of Mycobacteria
Epidemiology
1/4 of world infected w/ TB (Most are latent, not active0
2nd most common infective cause of death worldwide
CO-infection w/ HIV played important role in increasing infection
Transmission/Detection of TB?
Transmission by respiratory droplets
Bovine TB – drinking unpasteurized milk from infected cow
Sputum positive TB: can detect acid fast bacilli on microscopy
Also known as: OPEN TB, Smear Positive
MUCH more infective than Sputum negative/Closed TB
Occurs when Granuloma erodes though bronchial wall => large number of bacilli exposed to sputum
Patient is highly infectious to others
Pathogenesis of TB
4 possible outcome?
Bacilli inhaled into respiratory tract
=> Engulfed by alveolar macrophages
=> Release of inflammatory mediators (eg IFN-γ) by T-cells
=> Causes activation of macrophages – inhibit replication of bacilli
=>Bacilli walled off by inflammatory response (granuloma)
Bacilli die – anoxia (low oxygen) and acidosis in granuloma
Some may survive in dormant form => LATENT TB may reactivate later
Lesion may become calcified, takes years, apear on chest X Ray
4 possible outcomes
- Clearance of organism
- Latent infection: Most don’t later develop into active Only 5-10% of people infected develop active disease
- Primary disease
- Reactivation disease
Key Virulence factor of TB?
Key virulence factor of TB is its ability to survive in macrophages
Primary TB disease demographics/presentations?
Typically develops in the immunocompromised: especially infants, HIV+
- Pulmonary - replication of bacilli in lung tissue and lymph node involvement (Ghon focus)
- Extra-pulmonary (kidney, brain, spine)
- Disseminated (miliary TB)
Characteristics of Post-Primary- Reactivation TB
Reinfection from a different exposure or infected w/ TB => dormant Foci reactivates
Often when another illness aggravates
Also when immunosuppressants or anti-inflammatories are given
Typically presents as Pulmonary TB, dissemination uncommon
Cavitation and erosion into a bronchiole => Active, OPEN TB and CASEATING NECROSIS
_____________ the most important risk factor for TB
HIV/AIDS are the most important risk factor for TB
Clinical Features of TB
Long time of onset
Fever, night sweats, malaise, fatigue, weight loss
Pulmonary TB
- Cough, sputum, hemoptysis (coughing up blood), pleuritic pain
- Unresolving LRTI, not responding to antimicrobials
Extrapulmonary TB depends on site of infection
- Headache, confusion
- Local swelling, pain
Radiological Diagnosis of TB
What is indicative of active infection?
Primarily looking for Apical Disease (80-90%)
Infiltrates Cavitation (20-40%)
Looking for infiltrates and cavitation
Chest X-RAY normal in up to 5% of cases!!
CT SCAN
Caviation: Idicative of ACTIVE INFECTION
Laborotory Tests for Acid Fast Bacilli (TB)
Specimen types?
Microscopy?
Culture?- Media, Duration
PCR looks for?
Specimen types:
- Sputum (3x) Induced sputum => nebulized saline givne to induce productive cough
- Bronchial washings
- Early morning gastric aspiration (Kids, swallow mucous during night)
- CSF - for TB meningitis suspicion
- Urine - for renal TB suspicion
- Tissue - needs to be stored in a sterile container w/o formaline
Microscopy
- Gram stain does not work for Acid Fast bacilli
- AR Stain more commonly used now then ZN stain
Culture
- Decontamination of non-sterile specimens (eg sputum), No need for specimens from sterile sites (ie. CSF)
- Inoculate enriched media (Lowenstein-Jensen)
- Inhibits growth of other bacilli media
- ‘Rough, tough and buff’ colonies on LJ medium
- Culture for up to 8 weeks=> Test for AFB => If positive, subculture for ID and sensitivity testing
- BACTEC Liquid media - cultures in as little as 7 days
PCR
- XPERT used to identify organisms from culture, also directly on specimens that are AFB positive
- Looks for:
- MTB complex
- Rifampicin resistance (Drug susceptibility)
- Sputum positive highly sensitive, not as sensitive for negative sputum
- XPERT Ultra has higher sensitivity
Tests for Latent TB
Tuberculin Skin testing (Mantoux)
Intradermal injection of purified protein derivative (PPD)
Read at 48-72 hours by measuring induration
Measure the induration, NOT erythema!!!!
TB exposed patients are expected to mount an immune response
CANNOT distinguish between past latent infection or active disease
Can be positive in someone that’s had BCG vaccination
Interferon-γ release assays (IGRAs) QuantiFERON
Not used for diagnosis of active TB, Active TB Diagnosed via microbiological diagnosis (culture)
Add TB antigens to blood sample, see if T cells blood releases TB specific interferon-gamma
Preferred as do not require follow up appointment
IGRAs CANNOT distinguish between latent and active TB
NOT impacted by BCG vaccination status
Treatment of TB?
Monitoring?
Combination drug therapy (to prevent development of resistance)
(RIPE)
_R_ifampicin (Orange coloration, hepatotoxic )
_I_soniazid (hepatic toxicity)
_P_yrazinamide
_E_thambutol (eye, color blindness)
- 4 drugs x 2 months,
- Then 2 drugs x 4 months
- Longer for extra-pulmonary infection (12 months)
Compliance is problematic => promotes development of drug resistance
DOT: Directly observed therapy to ensure compliance
Must monitor hepatic function and have ophthalmologist see patient monthly as well
Prevention of TB?
Isolation
Contact tracing
Vaccination with BCG (bacillus Calmette-Guerin)
Mycobacterium Bovis - given intradermally
Effectiveness:
70-80% effective at preventing miliary TB/ TB Meningitides in children
Less effective at preventing respiratory disease