QuantiFERON-TB Gold Plus is an interferon-gamma release assay (IGRA) for tuberculosis infection. It measures the immune response to TB-specific antigens against background and positive controls, and a fixed decision algorithm turns those numbers into a positive, negative, or indeterminate call.
How it works
The classification depends on two corrected values:
TB-Nil = TB antigen IFN-γ - Nil IFN-γ
Mitogen-Nil = Mitogen IFN-γ - Nil IFN-γ
The QIAGEN algorithm is then applied in order:
Nil > 8.0 -> Indeterminate
TB-Nil >= 0.35 and TB-Nil >= 25% of Nil -> Positive
else if Mitogen-Nil >= 0.5 -> Negative
else -> Indeterminate
The Positive test fires regardless of the mitogen, because a clear antigen response is meaningful on its own. The Negative test requires a competent mitogen control, otherwise the result is indeterminate.
Worked examples
Example 1 — Clear positive:
- Nil: 0.10 IU/mL, TB antigen: 2.50 IU/mL, Mitogen: 8.00 IU/mL
- TB-Nil = 2.40 IU/mL (≥ 0.35 and ≥ 25% of 0.10) → Positive
Example 2 — Clear negative:
- Nil: 0.05 IU/mL, TB antigen: 0.08 IU/mL, Mitogen: 6.00 IU/mL
- TB-Nil = 0.03 IU/mL (< 0.35) → check Mitogen: 5.95 IU/mL (≥ 0.5) → Negative
Example 3 — Borderline positive:
- Nil: 0.12 IU/mL, TB antigen: 0.47 IU/mL, Mitogen: 5.00 IU/mL
- TB-Nil = 0.35 IU/mL — just at the cutoff threshold
- Formally Positive, but sits in the borderline zone (0.20–0.70 IU/mL); the tool flags this for consideration of retesting
Example 4 — Indeterminate (failed mitogen):
- Nil: 0.15 IU/mL, TB antigen: 0.10 IU/mL, Mitogen: 0.40 IU/mL
- TB-Nil = −0.05 IU/mL (< 0.35), Mitogen-Nil = 0.25 IU/mL (< 0.5) → Indeterminate
Interpretation and clinical context
A positive IGRA indicates immune sensitisation to TB antigens but does not distinguish latent infection from active disease. A chest X-ray and clinical assessment are needed to determine whether treatment for latent TB infection (LTBI) is appropriate or whether active TB workup is required.
An indeterminate result should prompt a repeat test after addressing potential causes — high background immunostimulation, immunosuppression, or a technical issue with specimen handling. A second indeterminate result may indicate a true immunological problem rather than a test failure.
The borderline zone (approximately 0.20 to 0.70 IU/mL for TB-Nil) is less reproducible: repeat testing of samples in this range sometimes flips the result. Clinicians managing patients at high risk for TB where a borderline result would change management may choose to repeat or to use a TST (tuberculin skin test) as a second test.
This calculator reproduces the published QIAGEN decision logic for education and cross-checking. The validated software in the analyser and the issuing laboratory remain the authoritative source.
IGRA versus tuberculin skin test (TST)
IGRAs and the tuberculin skin test (TST/Mantoux) both detect immune sensitisation to TB, but they differ in several practically important ways:
| Feature | IGRA (QFT) | TST (Mantoux) |
|---|---|---|
| Visits required | One (blood draw only) | Two (read 48–72 h later) |
| BCG vaccine interference | None — antigens used are not in BCG | Yes — BCG causes false positives |
| Prior TB sensitisation | May boost a subsequent TST | Can boost a repeat TST |
| Indeterminate rate | Low in immunocompetent individuals | Not applicable (visual read) |
For populations that received BCG vaccination in childhood — including people born in many South Asian, African, and Eastern European countries — IGRA is strongly preferred because BCG does not cause a false-positive IGRA result. TST remains useful in some resource-limited settings and for children under 5 years, where IGRA data are more limited.