Tuberculosis - Classification and Laboratory Diagnosis (I) Flashcards
Mycobacterium
Family
Gram stain
Aerobic requirement
Mycobacteriaceae
Gram positive bacilli
Obligate aerobe
3 reasons why mycobacterium takes long time to diagnose and is difficult to treat
1) Long generation time, slow growing»_space; need long incubation culture
2) High lipid content in cell wall»_space; Poor penetration by antibiotics
3) Unique antibiotic susceptibility patterns»_space; Limited anti-mycobacterial agents
3 classes and subclasses of mycobacteria ***
1) Mycobacterium tuberculosis COMPLEX
2) Mycobacterium leprae
3) Other: Non-tuberculosis mycobacteria (NTM), MOTT, Atypical mycobacteria
3 dominant species in Mycobacterium tuberculosis COMPLEX
M. tuberculosis (human, captive animals)
M. bovis (Cattle, human, captive animals)
M. bovis BCG (Human, for vaccination)
2 methods to classify NTM
Runyon classification (growth rate and pigmentation)
Molecular techniques
4 classes of NTM based on Runyon classification
Growth rate?
I = Photochromogens II = Scotochromogens III = Non-chromogens IV = Rapid growers
All slow growth except Runyon group IV
Give examples of 4 classes of Runyon classification
I = Photochromogens = M. kansasii, M. marinum II = Scotochromogens = M. gordonae III = Non-chromogens = M. avium complex IV = Rapid growers = M. fortuitum complex, M. abscessus
Compare latent and active TB
- Bacteriological Dx result
- Clinical symptoms and signs?
- Diagnostic methods
- Drug treatment
Active TB = likely +ve bacteriological Dx, Clinical symptoms present
Latent TB Dx by immunological test or past history of TB
Immunological tests cannot tell active vs latent TB
Latent TB Tx: 1 or 2 drug regimen
Active TB Tx: 4 drugs
3 immunological tests for Latent TB Dx/ adjunctive tests
Can they differentiate active and latent TB
Tuberculin skin test (TST)
Interferon gamma release assay (IGRA)
Adenosine deaminase (ADA)
Cannot differentiate active and latent TB, evidence of post-infection
Non-tuberculous mycobacteria.
Types of infections? (5)
- Pulmonary infection (superimposed with existing disease) - M. avium complex, M. kansasii
- Lymphadenitis - M. abscessus
- Skin and soft tissue infections - M. abscessus, M. marinum
- Catheter-related, Nosocomial infections - Rapid growers
- Disseminated infection in immunocompromised - M. haemophilum
Usually all environmental, contamination
5 approaches to TB Dx?
Clinical Radiological Microscopy Culture Nucleic acid amplification test (NAAT) - PCR
Course of action after positive M. tuberculosis culture?
Act asap on treatment
Difference in action after positive culture of NTM from normally sterile sites vs superficial sites
NTM +ve at normally sterile sites (e.g. immunocompromised with IV line infection)»_space; Act asap on treatment after excluding contamination
NTM +ve at superficial site (e.g. sputum, wound swabs)»_space; Check clinical symptoms and radiological changes, contamination
List 3 techniques to identify mycobacterium species.
Is culture still necessary?
- PCR +/- Sequencing ***
- MALDI-TOF Mass spectrometry
- Physiological and biochemical tests
Culture still gold standard: most sensitive, can identify species, Can test antimicrobial resistance
Define MDR-TB
M. tuberculosis
Resistant to at least isoniazid and rifampin
Define XDR - TB
Resistant to at least isoniazid and rifampin
+ any fluoroquinolone
+ at least 1 of Amikacin, Kanamycin, Capreomycin
Define TDR -TB
Total drug resistant
XDR TB plus more
antimicrobial susceptibility testing for each class of mycobacterium?
For M. tuberculosis:
- Phenotypic method = standard
- Genotypic method = Fast, may miss some resistance
For M. leprae:
- Can’t culture, routine testing impossible
For NTM:
- No standardized testing method for most species
What contexts must be accounted for to build clinical suspicion for TB?
- Clinical presentation
- Epidemiology: age group, close contacts
- Host predisposition: Immunocompromised (HIV, Diabetics, Malnutrition), Smoking, Drugs, Cancers…etc
- Radiological: Not only in apical lung, can be basal; cannot tell TB from NTM infection
CSF characteristics for TB infection
Look, pressure, WBC, Protein, glucose, culture rate
Appearance: cloudy, fibrin webs Opening pressure: high White cell count: 10-350, slightly elevated, polymorphs and lymphocytes Protein: High Glucose: Low (<50%) Culture: (35% positive)
List 4 specimens for Bacteriological, pathological or molecular Dx of TB
Sputum Urine (first void)
Blood
Others: CSF
List 2 specimen for immunological adjunctive Dx of TB
Blood for Interferon gamma release assay
Skin - Tuberculin skin test
What determines the yield of lab Dx tests for TB? (3)
Quality and Quantity of specimen at site of infection
- Quality: e.g. BAL, Transbronchial/ transthoracic biopsy for good sputum instead of saliva sample
- Quantity: e.g. volume of CSF, fluids
- Tissue biopsy at exact site of infection
Indication for bronchoscopy to Dx Pulmonary TB. (5)
BAL +/- Transbronchial/ transthoracic biopsy
Always >2 sputum samples
1) Lack of respiratory symptoms
2) No sputum production
3) CRAPPY sample (saliva)
4) Exclusion of concurrent infection/ non-infectious pathologies
5) Certain location of TB e.g. Endobronchial TB
