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Pulm by Minnie: AH Update > 182a - TB and Viral Infection Testing > Flashcards

182a - TB and Viral Infection Testing Flashcards

1
Q

Which of the following is not used for clinical diagnosis?

  1. Virus culture
  2. Serology
  3. Rapid antigen detection
  4. Molecular methods
A

b. Serology

Molecular methods (PCR) are preferred

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2
Q

What are the strengths of molecular assays (PCR) over other diagnostic methods?

A
  • Better performance
    • Sensitivity and specificity
  • Faster result time
  • Detection of non-culturable viruses
  • Detection of more coinfections
  • Automation
  • Potential for quantification
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3
Q

What are the limitations of the PPD skin test for tuberculosis?

A
  • False positives
    • BCG vaccinees
    • Repeat PPD testing
    • Other mycobacterial infection
  • Return visit to physician’s office required within 48-72h
  • Innacuracies in the placement and interpretation of the test
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4
Q

What are the US recommendations for the BCG vaccine?

A

Administer to…

  • TST-negative individuals residing in areas with annual TB incidence of > 1%
  • TST-negative children exposed to individuals with active TB and MDR-TB and unable to take oral isoniazid

The vaccine is protective against systemic and meningeal TB, but not pulmonary TB

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5
Q

____ and ______ signaling are crucial for controlling mycobacterial infections (keeping them in a latent form)

A

IFN-gamma** and **IL-12 signaling are crucial for controlling mycobacterial infections (keeping them in a latent form)

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6
Q

How does the IGRA overcome the problem of false-positives due to BCG vaccination?

A

The IGRA uses antigens that are not present in the BCG sub-strains of M. bovis.

(ESAT-6, CFP-10, TB-7.7)

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7
Q

Why is multiplexing so useful for the diagnosis of infectious syndromes?

A

Similar respiratory syndromes can be caused by many different viruses or bacteria

Multiplexing allows us to detect the presence of several different viruses with one test

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8
Q

If a patient has a LOF mutation in their STAT1 IFN-gamma receptor, which infections are they more susceptible to?

Why?

A

Mycobacterial infections

The IFN-gamma signalling pathway is important for the control of these infections.

A LOF mutation in the STAT1 IFN-gamma receptor prevents this pathway from working

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9
Q

Which respiratory virus is most likely to present year-round?

  1. RSV
  2. Influenza
  3. Adenovirus
A

c. Adenovirus

RSV and influenza present more seasonally

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10
Q

Which pathogens have reduced sensitivity in multiplex testing?

A

Adenovirus

Bordetella pertussis

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11
Q

Is viral culture used clinically for diagnosis?

Why or why not?

A

Used to be the gold standard, but is not longer recommended as a primary method for respiratory virus diagnostic testing

It takes too long to inform clinical management

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12
Q

Lateral flow immunoassay and DFA are examples of what kind of diagnostic method?

A

Rapid antigen detection

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13
Q

What is the threshold for a positive PPD-skin test (TST) in the United States?

A

Depends on pre-test probability

The following induration diameters qualify as positive:

  • ≥ 5 mm
    • If the patient has HIV and is immunosuppressed
    • If the patient has had close contact with a known TB patient
  • ≥ 10 mm
    • If TB exposure is suspected
    • If the patient is a resident of a TB-endemic area
  • ≥ 15 mm
    • If the patient has no known risk factors
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14
Q

What are the recommendations for latent TB testing?

A
  • IGRA is preferred but TST is acceptable
    • Except for immigration screening: TST is no longer used
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15
Q

What are the limitations of molecular assays (PCR)?

A
  • Higher cost
  • Require specific target ordering
    • For single target assays
  • Cannot provide info about organism viability
    • => Cannot test to see if the patient is cured
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16
Q

What are the limitations of multiplex detection?

A
  • Assay performance
    • Reduced sensitivity for adenovirus and B**ordetella pertussis
  • High cost
17
Q

Increased phosphorlyation of the STAT1 IFN-gamma receptor may indicate the presence of which infection?

A

Mycobacterium tuberculosis

IFN-gamma signalling works to control the bacteria inside of granulomas

Phosphorylation of the STAT1 IFN-gamma receptor is part of this pathway

18
Q

What is the difference between ELISA and ELISPOT testing for TB?

A

ELISA = QunterFERON assay (IGRA)

ELISPOT = T-Spot (the technically challenging, difficult to interpret one)

19
Q

Deficiency of which signaling pathway enhances a patient’s susceptibility to mycobacterial infections?

A

The IL-12 / IFN-gamma signaling axis

This axis regulates the CD4 Th1 T cell respose that helps us control mycobacterial infections

20
Q

What is the threshold for a positive result on the ELISPOT assay?

A
  • Positive result: ≥ 8 spots
  • Negative result: ≤ 4 spots
  • Inconclusive: 5-7 spots
21
Q

Describe the signaling pathway that controls mycobacterial infections (ex: keeps them in a latent form)

A
  • Dendritic cells and macrophages produce IL-12
  • IL-12 activates naive CD4 T cells
  • Activated CD4 T cells differentiate into Th1 CD4 T cells
  • Th1 CD4 T cells release IFN-gamma
  • IFN-gamma causes…
    • Signaling to continue IL-12 secretion
    • Increased transcription of IFN-stimulated genes via the STAT1 IFN-gamma receptor
  • Expression of these genes causes granulomas to form around the TB infection to control it
22
Q

What are the advantages and disadvantages of rapid antigen detection for viruses?

A
  • Advantages
    • Fast
    • Easy to use
    • Low cost
  • Disadvantage
    • Limited sensitivity (10-90%)

Less commonly used, PCR is preferred

23
Q

How is latent vs active TB distinguished?

A

TST and IGRA cannot tell

Use microbiological, clinical, radiological, histopathological evidence

24
Q

In a TST, which diameter of the induration should you measure?

A

Transverse

(False positive more likely with longitudinal)

25
Q

What are the important glycoproteins of influenza?

A
  • Hemaglutinin (HA)
    • Involved in the attachemtn fo virus to cells and initiation of infection
  • Neuraminidase (NA)
    • Facilitates the release of new virions from infected cells
26
Q

What are the advantages of the QuantiFERON-TB assay over the TST?

A
  • Unaffected by previous BCG vaccination
  • Does not with environemental mycobacteria
    • But will react with some other mycobacteria
  • Requires only 1 visit
  • Multiple tests do not cause false positive results
  • Results available in 24h
27
Q

When should specimens be tested to test for viruses?

A

ASAP

  • <5 days after symptom onset
    • Within 48h is preferred
    • No later than 7 days after symptom onset
28
Q

Who are the best candidates for multiplex testing?

A
  • Serious infections
  • Immunocompromised patients
  • Patients with cancer
  • Inpatients

Shouldn’t be used for everyone - high cost

29
Q

The BCG vaccine protects against _____________ TB, but not _______________ TB

A

The BCG vaccine protects against systemic and meningeal** TB, but not **pulmonary TB

30
Q

Which method of diagnostic testing for viruses can be automated?

A

Molecular testing (PCR)

(GeneXpert, BD MAX)

31
Q

What is the current reference method for diagnosing viral infections?

A

Molecular assay (PCR)

32
Q

What kind of cells produce IL-12?

A

Dendritic cells and macrophages

33
Q

What are the 4 tubes used in the QuantiFERON Gold assay?

A
  • Positive control
  • Negative control
  • CD4 T cell response
  • CD8 T cell response
34
Q

What are the advantages of molecular assays (PCR) for diagnosing viral infections?

A

Fast

High sensitivity

High specificity

Pulm by Minnie: AH Update (34 decks)

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