SM_182a: TB and Viral Infection Testing

Question 1

What are the benefits of testing for respiratory viruses?

Answer 1

Use if results will influence patient management

When utilized appropriately:

• May direct antiviral therapy
• Reduce unnecessary antibiotic use
• Assist patient cohorting in hospitals

Question 2

What are the benefits/drawbacks of virus culture for the laboratory diagnosis of acute respiratory infections?

Answer 2

Virus culture detects viable viruses but requires longer time for reporting and is technically difficult

Question 3

What are the benefits/drawbacks of antigen detection for the laboratory diagnosis of acute respiratory infections?

Answer 3

Antigen detection (immunofluorescence staining, membrane immunoassays) are relatively fast but less reliable due to lack of sufficient assay sensitivity

Question 4

______ are the preferred method for laboratory diagnosis of acute respiratory infections

Answer 4

Molecular methods (i.e. nucleic acid amplification techniques such as PCR) are the preferred method for laboratory diagnosis of acute respiratory infections

• Provide fast and most accurate laboratory diagnosis for respiratory viral infections

Question 5

______ can be recovered from every organ system of humans

Answer 5

Adenovirus can be recovered from every organ system of humans

(50% of infections are asymptomatic, many serotypes, excretion in stool for up to 18 months without recurrence of symptoms, antibodies may not develop in infants after the onset of infection)

Question 6

What are the benefits of rapid detection of respiratory viruses?

Answer 6

• Reduce utilization of antibiotics
• Reduce/optimize antiviral therapy
• Improve utilization of chest radiographs
• Infection control (patient isolation)
• Reduce length of hospital stays

Question 8

_____ methods are NOT used for clinical diagnosis of viral infection

Answer 8

Serology methods are NOT used for clinical diagnosis of viral infection

Question 9

Describe utility of virus culture for laboratory testing of respiratory viral infection

Answer 9

Virus culture

• Used to be considered gold standard - not anymore
• Not recommended as primary method for respiratory virus diagnostic testing

Question 10

Describe the utility of rapid antigen detection of laboratory diagnosis of respiratory viral infection

Answer 10

Rapid antigen testing

• Fast
• Easy to use
• Reasonable cost
• Lab and point of care
• Less sensitive (limited assay performance)

Question 11

Describe the utility of molecular assays for laboratory diagnosis of respiratory viral infection

Answer 11

Molecular assays

• High speed - rapid results
• High sensitivity
• High specificity
• Automation: full integration, minimum hands on time, no need for batch testing, offers more assays, scalable

Question 12

______ is a type of molecular assay that involves detection of multiple targets in the same reaction

Answer 12

Multiplexing is a type of molecular assay that involves detection of multiple targets in the same reaction

• Useful for diagnosis of infectious syndromes because respiratory infections caused by different viruses can present with similar clinical symptoms
• Helps recover more co-infections

Question 13

What are the limitations of multiplexing?

Answer 13

Multiplexing limitations

• Assay performance: reduced sensitivity for adenoviruses and Bordetella pertussis
• Increased cost: best used for seriously ill / inpatients, less useful for outpatient diagnosis

Question 14

What are the strengths of molecular assays?

Answer 14

Compared to virus culture and antigen based assays, molecular methods have

• Improved performance (sensitivity and specificity)
• Faster result time
• Detection of non-cultureable viruses
• More co-infections
• Automation
• Potential for quantification

Question 15

What are the limitations of molecular assays?

Answer 15

Molecular assay limitations

• Higher cost
• Requires target specific ordering for single target assays
• Cannot provide information about organism variability (not for test of cure assessment)
• Sequence variation: rare false negatives

Question 16

Compare virus culture, antigen detection, and molecular assay

Answer 16

Question 17

____ and ____ are crucial for controlling mycobacterial infections

Answer 17

IFN-gamma and IL-12 signaling are crucial for controlling mycobacterial infections

Question 18

Disseminated mycobacterial infections occur in patients with _____ and ______ deficiency

Answer 18

Disseminated mycobacterial infections occur in patients with IFN-gamma receptor and IL-12 receptor beta-1 deficiency

Question 19

______ loss-of-function mutations lead to defects in the pathway associated with fighting mycobacterial infections

Answer 19

STAT1 loss-of-function mutations lead to defects in the pathway associated with fighting mycobacterial infections

(phosphorylation of STAT1 important for translocation to the membrane)

Question 20

BCG vaccine is effective against _____ and _____ TB but not _____ TB

Answer 20

BCG vaccine is effective against systemic and meningeal TB but not pulmonary TB

Question 21

BCG vaccine is NOT protective against ______

Answer 21

BCG vaccine is NOT protective against pulmonary TB

Question 22

What are the advantages and disadvantages of the PPD-TB skin test (TST)?

Answer 22

PPD-TB skin test (TST)

• Advantages: pretty simple
• Disadvantages: false positive in BCG vaccinees, false positive due to repeat PPD testing, return visit to physician’s office required within 48-72 hours, inaccuracies in placement and interpretation of the test are common

Question 23

What are the advantages and disadvantages of IFN-gamma release assays?

Answer 23

IFN-gamma release assays

• Advantages: unaffected by previous BCG vaccination and most other environmental mycobacteria, requires only one patient visit, is a controlled lab test, does not boost subsequent test results, provides objective and reproducible result unaffected by subjective interpretation, results available within 24 hours
• Disadvantages: fluctuations in IFN-gamma response in serially tested individuals, performance data lacking in kids < 5 yo, laege number of indeterminate results, need at least 2-4 mL of blood from infants, repeat testing requires re-draw

Question 24

In which people is IGRA preferred but TST acceptable?

Answer 24

IGRA preferred but TST acceptable

• BCG vaccinees
• Cohorts with poor return-visit statistics

Question 25

Neither TST or IGRA can distinguish between ______ and ______

Answer 25

Neither TST or IGRA can distinguish between latent TB infection and active TB disease

(this distinction is based on microbiological + clinical + radiological + histopathological evidence of active disease)

Question 26

Emerging diagnostic tests to try to distinguish latent TB from active TB include _____ and _____

Answer 26

Emerging diagnostic tests to try to distinguish latent TB from active TB include interferon-inducible neutrophil-driven blood transcriptional signatures and urine glycans