uh oh, someone ordered a QuantiFERON—what the heck is a mitogen & who's nil? what do ➕, ➖, & indeterminate results mean? a pragmatic #meded 🧵 re: the definition, indication(s), & interpretation of the #QuantiFERON (QFT) test👇 #TBSky #IDSky 1/10 - ThreadSky

tbrnaughttb.bsky.social • 92 days ago

uh oh, someone ordered a QuantiFERON—what the heck is a mitogen & who's nil? what do ➕, ➖, & indeterminate results mean?

a pragmatic #meded 🧵 re: the definition, indication(s), & interpretation of the #QuantiFERON (QFT) test👇

#TBSky #IDSky

1/10

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atrophywife.bsky.social•92 days ago

Great thread, thank you.

tbrnaughttb.bsky.social•92 days ago

QFT is an "interferon-gamma release assay" (IGRA), a test that quantifies an individual's release of the cytokine interferon-gamma (IFN-γ) when exposed to tuberculosis (TB)-related antigens (ags)

so the test [Quanti]fies inter[FERON]-γ release: how is this helpful?

2/10

tbrnaughttb.bsky.social•92 days ago

the test operates on the principle that T lymphs that have been exposed to (ie, have "seen") TB ags before will produce IFN-γ in response to re-exposure to these ags

IFN-γ prdxn = "hey, I have seen these antigens before!"

so what is IFN-γ?

3/10

tbrnaughttb.bsky.social•92 days ago

IFN-γ is crucial for macrophage (Mφ) & T cell activation & immune control of intracellular pathogens

MTB inhalation ➡️ phagocytosis by alveolar Mφ ➡️ IFN-γ prdxn ➡️ T cell recruitment/activation ➡️ ↑ IFN-γ prdxn ➡️ immune cell recruitment ➡️ granuloma formation

to QFT!

4/10

tbrnaughttb.bsky.social•92 days ago

when is a QFT indicated?

QFT is a screen for prior MTB exposure; its strongest indication is as a screening test for (latent) TB infection (infxn) in epidemiologically high-risk populations, especially when a ➕ test may lead to treatment to ↓ risk of active disease (dz)

5/10

tbrnaughttb.bsky.social•92 days ago

- a ➖ test does not r/o prior exposure OR current infxn/dz
- a ➕ test cannot distinguish bw (latent) TB infxn & (active) TB dz

all test results = probability titrations!

sensitivity & specificity vary widely by tested population (eg, US vs India); here are some ranges:

tbrnaughttb.bsky.social•92 days ago

QFT interpretation:

4 values: mitogen, nil, TB1, & TB2 (pic)

@ bottom, mitogen is a nonspecific (not TB) stimulator of T cell proliferation (➕ control): it should be >2 IU/mL, but ↑er = better!

↑ mito = this pt's T cells can proliferate & release IFN-γ *in general*

7/10

quiltbunny.bsky.social•91 days ago

Great explanation!

dr-lungs.bsky.social•92 days ago

Good thread.
Additional key point often misunderstood by non specialists: a +ve QFT usually STAYS +ve after effective treatment/recovery.
So meaningless test in context of prior TB or LTBI.
Just because you recovered doesn't mean T cells forget the antigens (that is kind of the point of immunity!)

tbrnaughttb.bsky.social•92 days ago

absolutely! i always emphasize to learners that IGRAs are tests of T cell memory, not tests of mycobacterial presence or mycobacterial infection

gardeninglisa.bsky.social•91 days ago

Considering IGRA is more expensive than tuberculin skin tests, which have similar problems with interpretation (can’t distinguish latent from active), what are the benefits of IGRA?

dr-lungs.bsky.social•91 days ago

1. Unlike skin test (TST) IGRA not affected by prior BCG or by (most) non tuberculosis mycobacteria (so more specific)
2. Not subject to inter observer variability (20mm vs 2mm easy, 9mm vs 10mm...?)
3. Only needs one visit
4. Doesn't need specially trained nurses HCW to see patients to do test

ydnew.bsky.social•91 days ago

Another (admittedly niche!) benefit is that the TST, administered regularly over time (eg through monitoring programs for researchers), can eventually cause false positives.

gardeninglisa.bsky.social•91 days ago

yes! I know several people in healthcare that decline this test as they know all the previous ones will cause a false positive (again). I work with people with HIV and the sensitivity of TST and IGRA for them is decreased, making the tests less useful.

spudbeach.bsky.social•92 days ago

As a medical courier, I'm getting a kick out of this! I regularly deliver 2 or 3 a day -- now I know that when I start getting 20 or 30, TB is back!

sc345.bsky.social•92 days ago

Great thread! To follow up the useful learning you can ask some trivia - in what species/setting was the TB interferon gamma release assays first applied?

sc345.bsky.social•92 days ago

Cows in the in Australian bovine brucellosis and tuberculosis eradication campaign (1970s - 1997)!

The IGRA was first used in 1992 (https://pubmed.ncbi.nlm.nih.gov/1554334/) in predominately NT herds. It was then marketed as human test from 1995ish, and is now up to it's 4th gen.

sc345.bsky.social•92 days ago

also #clinmicro

katiehitchings.bsky.social•92 days ago

📌

kswilliamsrx.medsky.social•86 days ago

📌

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