TB + Viral Testing

Question 1

Of the following tests, which ones are most sensitive?

1. culture
2. rapid antigen
3. PCR

Answer 1

culture and PCR

Question 2

Of the following, which ones are specific?

1. culture
2. rapid antigen
3. PCR

Answer 2

all of them

Question 3

Of the following, which ones are the fastest?

1. culture
2. rapid antigen
3. PCR

Answer 3

rapid antigen

Question 4

What are pros of PCR virus testing?

Answer 4

sensitive and specific
fast
multiplex

con: expensive

Question 5

What are the benefits for testing respiratory viruses?

Answer 5

It is recommended that such testing should be performed if the result will influence patient management. When utilized appropriately, testing may help directing antiviral therapy, reducing unnecessary antibiotic use, and assisting patient cohorting in hospital setting.

Question 6

What are the preferred methods for laboratory diagnosis of acute respiratory infections?

Answer 6

Virus culture detects viable viruses but requires much longer time for reporting and is technically demanding; antigen detections that include either immunofluorescence staining and membrane immunoassays are relatively fast but are less reliable due to the lack of sufficient assay sensitivity. Therefore, molecular methods, i.e., nucleic acid amplification techniques such as PCR, provide most accurate and fast laboratory diagnosis for respiratory viral infections.

Question 7

What is important from a public health perspective about administering BCG?

Answer 7

cold chain storage must be preserved

Question 8

What are possible complications of BCG vaccination?

Answer 8

(a) Accelerated reaction suggests prior exposure to Mtb hence a TST is recommended prior to receiving a BCG shot.
(b) Local lymphadenitis
(c) Keloid scarring
(d) Disseminated infection in immunosuppressed individuals.

Question 9

Who should get the BCG vaccine?

Answer 9

individuals living in areas where annual TB incidence is > 1% or TST negative children exposed to active TB

Question 10

What is the cut off for a positive PPD in individuals residing in TB endemic areas?

Answer 10

> 10 mm

Question 11

What is the cut off for a positive PPD in immunosuppressed individuals or those with chronic active TB or close contact to active TB?

Answer 11

> 5 mm

Question 12

What is the cut off for a positive PPD in individuals with no know TB risk factors or southern US residents with MAC exposure

Answer 12

> 15 mm

Question 13

What is the PPD cross reactive with?

Answer 13

BCG vaccination and environmental mycobacteria (i.e. MAC)

Question 14

Which CD4 TH1 regulator plays an important part in mycobacterial defense?

Answer 14

the IL-12 IFNgamma axis

Question 15

Although antigens in IGRA are not cross reactive with the BCG, what are they still cross reactive against?

Answer 15

parental m bovis

m africanum, szulgai, marinum and kansasii

Question 16

Since IGRA still has cross reactivity to some mycobacteria, what is necessary following a positive IGRA?

Answer 16

confirmation via sputum or BAL culture for Mtb, molecular testing, radiology and clinical evidence of TB

Question 17

What is the main drawback of ALL forms of TB testing?

Answer 17

they don’t differentiate between active and latent TB

Question 18

What form of testing may eventually allow us to differentiate between latent and active TB? what cell type does it use?

Answer 18

interferon producing molecular signature testing, eventually should turn into rapid flow cytometry of proteins specific to active TB infection
neutrophils

Question 19

What is the difference between an ELISA and an ELISPOT?

Answer 19

ELISA is a sandwich assay with fluorescence (GOLD quantiferon)
ELISPOT uses whole cells then T spot is evaluated on the agar plate that binds antibody

Question 20

How do the IGRA overcome the problem of false-positive reactions observed with the PPD-skin test in BCG- vaccinated individuals?

Answer 20

The main advantage the IGRA offer over the TST is the lack of a false-positive reaction due to prior BCG vaccination. This is achieved by utilizing antigens (ESAT-6, CFP-10, TB-7.7) that are lacking in the BCG sub-strains of M. bovis. These antigens are however expressed by the parental M.bovis strain as well as other mycobacteria such as, M. africanum, M. szulgai, M. marinum, M. kansasii.

Hence prior exposure to these mycobacteria will give a positive response with the IGRA. As a result, any positive IGRA result has to be confirmed by sputum and/or bronchoalveolar lavage culture for Mtb, molecular tests, radiological and clinical evidence of TB.

Question 21

What is the major drawback of the TB skin test (TST) as well as both the Quantiferon TB GoldPlus and T- Spot assays:

Answer 21

None of these tests differentiate between latent TB

infection and active TB disease.

Question 22

Deficiency of which set of molecules enhances an individual’s susceptibility to mycobacterial infections?

Answer 22

The IL12-IFNγ signaling axis (which regulates the CD4-Th1 response) plays a critical role in promoting host defense against mycobacterial infections. Consequently, patients with molecular defects affecting this signaling pathway display enhanced susceptibility to mycobacterial infections