The QuantiFERON-TB Gold Test and Other IGRAs: What Occupational Health Teams Need to Know

Reviewed by the carefoundryESC occupational health content team for editorial accuracy. This is a clinical explainer, not medical advice, and is pending review by a licensed clinician before it is used to guide any individual testing or treatment decision — see the disclaimer at the end.

If your TB program still runs on a two-step skin test and an annual PPD for every nurse, the rules changed in 2019. The QuantiFERON-TB Gold test and other IGRA blood tests now sit at the center of how many occupational health teams screen staff — but only at specific moments. That year the CDC and the National Tuberculosis Controllers Association rewrote screening for U.S. health care personnel: screen at baseline (pre-placement) with an individual risk assessment, a symptom evaluation, and a TB test — either an IGRA or a TST — for anyone without prior documented TB disease or latent infection (Sosa et al., MMWR 2019). After that baseline, the same guidance says health care personnel should not undergo routine serial testing at any interval absent a known exposure or evidence of ongoing transmission — while still recommending annual TB education for all staff and annual symptom screening for anyone with untreated latent TB (MMWR 2019).

In practice, the two moments where a test actually gets ordered now are the pre-placement baseline and the post-exposure workup. Both are where a blood-based assay does its most useful work for an occupational health program.

How does the QuantiFERON-TB Gold test work?

An IGRA — interferon-gamma release assay, or "TB blood test" — measures your immune system's response after whole blood is incubated with synthetic peptides representing the M. tuberculosis-specific antigens ESAT-6 and CFP-10 (CDC NHANES Lab Manual). If someone's T-cells have seen TB before, they release interferon-gamma (IFN-γ), and the assay quantifies it.

QuantiFERON-TB Gold Plus (QFT-Plus), the current QIAGEN version, uses four tubes: a Nil control, TB1, TB2, and a Mitogen (positive control) tube. TB1 draws out CD4 T-helper responses; TB2 adds peptides that also engage CD8 cytotoxic T-cells. The tubes incubate at 37°C for 16–24 hours, and IFN-γ is read out by ELISA (CDC NHANES Lab Manual). One blood draw, one visit, a result in about 24 hours (CDC, MMWR 2010).

Two IGRAs are FDA-approved: QFT-Plus (approved by the FDA in 2017 — BioSpace) and T-SPOT.TB (approved 2008 — MDH), an ELISPOT that counts individual IFN-γ-producing cells as spots. The older QuantiFERON-TB Gold In-Tube (the three-tube version, FDA-approved in 2007) has been superseded by QFT-Plus, so build your program around QFT-Plus and T-SPOT.TB.

How do I interpret IGRA results?

QFT-Plus reports one of three results: Positive, Negative, or Indeterminate. The cutoffs below are drawn from the QIAGEN package insert as reproduced in a CDC laboratory manual; because manufacturer inserts are periodically revised, confirm the exact IU/mL thresholds against your lab's current Instructions for Use before you rely on them (CDC NHANES Lab Manual):

The point that matters most in occupational health: a positive IGRA — exactly like a positive skin test — does not distinguish latent TB infection from active TB disease. Any positive has to trigger a medical history, symptom and sign review, and a chest radiograph before you know which you are dealing with (CDC, MMWR 2010). And do not read the number as a severity gauge — the magnitude of the IFN-γ level cannot be correlated to stage of infection, immune responsiveness, or likelihood of progression (CDC NHANES Lab Manual).

Indeterminate results are a separate problem. They often reflect the worker's immune status or technical factors: insufficient tube mixing, storage outside the recommended temperature range before incubation, or more than 16 hours from draw to incubation (CDC NHANES Lab Manual). When you see one, a repeat draw is usually the right call before you read anything into it.

IGRA vs. skin test: when to use the TB blood test

CDC's position is that an IGRA can be used in place of a TST in all situations where TB testing is recommended, and that routine testing with both is not recommended (CDC, MMWR 2010). This is the classic IGRA vs. skin test decision, and the answer is: pick one.

On the whole, IGRAs and TSTs are equally sensitive, but IGRAs are more specific in most situations because they are not thrown off by prior BCG or by most non-tuberculous mycobacteria — and there is no two-step "boosting" effect to manage (CDC, MMWR 2010). For a foreign-trained nurse who received BCG as a child — a group where the skin test drives a stack of false positives every hiring season — the blood test's specificity cuts down on those BCG-driven false positives and the follow-up evaluations they set off. Just remember a negative IGRA never fully rules out infection.

What is a "borderline" QuantiFERON result?

Here is a naming trap worth clearing up. The FDA-approved QuantiFERON result set is only Positive, Negative, or Indeterminate — there is no "borderline" category on QFT-Plus. Borderline is a T-SPOT.TB category (CDC, MMWR 2010). When someone calls a QFT "borderline," they almost always mean a value sitting just above the 0.35 IU/mL cutoff.

That distinction has real consequences in a low-prevalence workforce. For a healthy person at low risk, CDC says a single positive IGRA or TST should not be taken as reliable evidence of infection, and it is reasonable to discount an isolated low-risk positive as a false positive (CDC, MMWR 2010). Before you send a low-risk employee down the LTBI-treatment path off one barely-positive result, confirm it.

Logistics that trip up new IGRA programs

The blood test's biggest weakness is not the science — it is handling. You have to pre-arrange with a CLIA-compliant lab using FDA-approved methods and get the specimen there within the required window (MDH). And live-virus vaccines can interfere: draw the IGRA either the same day as a live-virus vaccine or 4–6 weeks afterward, and wait at least a month after smallpox vaccination (MDH). If your onboarding stacks MMR and a TB blood draw on the same morning, sequence them deliberately.

Tracking all of this — which employees have a baseline on file, whose result came back indeterminate and needs a repeat, and which post-exposure cases are still open — is its own administrative load. It is worth deciding up front where that record lives and how you will prove the timeline later.

FAQ

Can I test with both an IGRA and a TST to be safe? No — CDC does not recommend routine testing with both (CDC, MMWR 2010). Choose one test per person.

Do I still need annual TB testing for all staff? Not routinely. Since 2019, CDC/NTCA advise against serial testing after baseline absent a known exposure, but continue annual TB education and annual symptom screening for anyone with untreated latent TB (MMWR 2019).

A worker's QFT came back indeterminate — now what? Usually repeat it. Indeterminates often stem from specimen handling or immune status rather than true infection (CDC NHANES).

This article is educational and does not replace the judgment of the ordering clinician or the interpreting laboratory. Confirm current cutoffs and package-insert details against the manufacturer's latest Instructions for Use, and follow your facility's medical direction and applicable state health-department requirements.

Building or auditing your TB baseline and post-exposure workflow? See how carefoundryESC tracks screenings, results, indeterminate repeats, and follow-ups in one auditable employee-health record.