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MBBS IV - Supplementary Courses > Tuberculosis - Classification and Laboratory Diagnosis (I) > Flashcards

Tuberculosis - Classification and Laboratory Diagnosis (I) Flashcards

1
Q

Mycobacterium

Family
Gram stain
Aerobic requirement

A

Mycobacteriaceae

Gram positive bacilli

Obligate aerobe

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2
Q

3 reasons why mycobacterium takes long time to diagnose and is difficult to treat

A

1) Long generation time, slow growing&raquo_space; need long incubation culture
2) High lipid content in cell wall&raquo_space; Poor penetration by antibiotics
3) Unique antibiotic susceptibility patterns&raquo_space; Limited anti-mycobacterial agents

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3
Q

3 classes and subclasses of mycobacteria ***

A

1) Mycobacterium tuberculosis COMPLEX
2) Mycobacterium leprae
3) Other: Non-tuberculosis mycobacteria (NTM), MOTT, Atypical mycobacteria

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4
Q

3 dominant species in Mycobacterium tuberculosis COMPLEX

A

M. tuberculosis (human, captive animals)

M. bovis (Cattle, human, captive animals)

M. bovis BCG (Human, for vaccination)

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5
Q

2 methods to classify NTM

A

Runyon classification (growth rate and pigmentation)

Molecular techniques

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6
Q

4 classes of NTM based on Runyon classification

Growth rate?

A 
I = Photochromogens 
II = Scotochromogens 
III = Non-chromogens 
IV = Rapid growers

All slow growth except Runyon group IV

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7
Q

Give examples of 4 classes of Runyon classification

A 
I = Photochromogens = M. kansasii, M. marinum 
II = Scotochromogens = M. gordonae 
III = Non-chromogens  = M. avium complex
IV = Rapid growers  = M. fortuitum complex, M. abscessus
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8
Q

Compare latent and active TB

  • Bacteriological Dx result
  • Clinical symptoms and signs?
  • Diagnostic methods
  • Drug treatment
A

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

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9
Q

3 immunological tests for Latent TB Dx/ adjunctive tests

Can they differentiate active and latent TB

A

Tuberculin skin test (TST)
Interferon gamma release assay (IGRA)
Adenosine deaminase (ADA)

Cannot differentiate active and latent TB, evidence of post-infection

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10
Q

Non-tuberculous mycobacteria.

Types of infections? (5)

A
  • 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

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11
Q

5 approaches to TB Dx?

A 
Clinical 
Radiological 
Microscopy 
Culture 
Nucleic acid amplification test (NAAT) - PCR
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12
Q

Course of action after positive M. tuberculosis culture?

A

Act asap on treatment

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13
Q

Difference in action after positive culture of NTM from normally sterile sites vs superficial sites

A

NTM +ve at normally sterile sites (e.g. immunocompromised with IV line infection)&raquo_space; Act asap on treatment after excluding contamination

NTM +ve at superficial site (e.g. sputum, wound swabs)&raquo_space; Check clinical symptoms and radiological changes, contamination

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14
Q

List 3 techniques to identify mycobacterium species.

Is culture still necessary?

A
  • PCR +/- Sequencing ***
  • MALDI-TOF Mass spectrometry
  • Physiological and biochemical tests

Culture still gold standard: most sensitive, can identify species, Can test antimicrobial resistance

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15
Q

Define MDR-TB

A

M. tuberculosis

Resistant to at least isoniazid and rifampin

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16
Q

Define XDR - TB

A

Resistant to at least isoniazid and rifampin
+ any fluoroquinolone
+ at least 1 of Amikacin, Kanamycin, Capreomycin

17
Q

Define TDR -TB

A

Total drug resistant

XDR TB plus more

18
Q

antimicrobial susceptibility testing for each class of mycobacterium?

A

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

19
Q

What contexts must be accounted for to build clinical suspicion for TB?

A
  • 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
20
Q

CSF characteristics for TB infection

Look, pressure, WBC, Protein, glucose, culture rate

A 
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)
21
Q

List 4 specimens for Bacteriological, pathological or molecular Dx of TB

A 
Sputum 
Urine (first void)

Blood

Others: CSF

22
Q

List 2 specimen for immunological adjunctive Dx of TB

A

Blood for Interferon gamma release assay

Skin - Tuberculin skin test

23
Q

What determines the yield of lab Dx tests for TB? (3)

A

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
24
Q

Indication for bronchoscopy to Dx Pulmonary TB. (5)

A

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

25
Q

3 advantages and 4 disadvantages of microscopic Dx of TB

Next step if microscopy is negative?

A

Adv:

  • Simple
  • Cheap
  • Rapid

Disadv:

  • Low sensitivity
  • Operator dependent
  • Cannot differentiate M. tuberculosis from NTM; live from dead bacteria
  • Low positive rate (<50% active pulmonary TB have +ve result)

Next step: PCR

26
Q

Limitations to AFB culture, PCR tests, IGRA assays, Histopathology for TB Dx.

A

AFB:
Takes 6-8 weeks for positive

PCR:

  • Negative PCR does not rule out TB, esp. Pulmonary TB
  • Sensitivity rate varies too much between brands

IGRA:
- Cannot tell latent vs active TB

Histopathology:
- Site of biopsy might miss location of TB

27
Q

Is Adenosine Deaminase test useful for TB? Why is it used?

A

No

Derived from host lymphocytes and monocytes
Not specific for M. tuberculosis or TB at all

Only specific to show Pleuritis, Peritonitis, Pericarditis, Meningitis

28
Q

4 Advantages and 5 disadvantages of NAAT test to Dx TB

A

Adv:

  • Highly Specific
  • Fast
  • Can identify species
  • Rapid detect resistance genes (e.g. rifampicin)

Disadv:

  • Expensive
  • Varied sensitivity depends on specimen
  • Inhibitors in specimen
  • No definitive information on drug susceptibility
  • Can’t easily tell living or dead
29
Q

Specificity and sensitivity of NAAT tests to Dx TB?

A

Varied sensitivity: Low in extrapulmonary, CSF, blood, pleural fluid; High in respiratory specimen

Highly specific

30
Q

2 Advantages and 2 disadvantages of Histopathology and Cytology in Dx of TB ?

A

Adv:

  • Useful when bacilli are few
  • Can show typical pathology (caseous necrosis, Langhans giant cells)

Disadv:

  • Cannot tell species, only AFB
  • Cannot tell drug resistance
31
Q

Skin biopsy features of TB lesions?

A

Panniculitis (fat cell inflammation)

Granuloma with epithelial giant cells

Miescher’s granuloma

Lympho-histiocystic infiltration

Fibrinoid necrosis of arterioles

32
Q

Describe Tuberculin skin test

  • What’s injected?
  • Response time?
  • Interpret positive result?
A

Purified protein derivative&raquo_space; intradermal injection

Delayed type (IV) Hypersensitivity reaction: 48-72 hours

+ve: Cut-off of 5mm, 10mm and 15mm induration

  • Does not mean protective immunity against M. tuberculosis
  • BCG vaccine given
  • Past TB infection or NTM infection
33
Q

Standardized methods to record TST result for TB testing?

A

Induration measured in diameter - transversely to long axis of forearm, at widest diameter

Palpate or Sokal’s ballpoint method to find boundaries

34
Q

Causes of false positive TST for latent TB testing

False negative?

A
  • False positive:
    BCG vaccine (but >20mm is not due to BCG)
    NTM exposure/ infection
  • False negative:
    Technical: injected too deep
    Biological: Immune response variation
35
Q

Describe IGRA for TB testing

  • 2 examples
  • Mechanism
  • Limitations (2)
A

QuantiFERON-TB; T-SPOT TB

Release of interferon gamma in response to MTB-specific antigens

Affected by underlying immunity
Cannot tell latent vs active TB

36
Q

2 complications from BCG vaccination

Absolute contraindication?

A

Severe suppurative adenopathy
Inoculation site abscess

Never give to immunocompromised baby&raquo_space; disseminated TB

MBBS IV - Supplementary Courses (54 decks)

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