QuantiFERON Test Sensitivity
The QuantiFERON-TB Gold Plus (QFT-Plus) demonstrates a pooled sensitivity of approximately 81-83% for detecting culture-confirmed active tuberculosis in adults, with specificity of 96-99%, though sensitivity may be reduced to 73% in immunocompromised patients and performance in elderly populations remains variable. 1
Overall Sensitivity in Active Tuberculosis
Pooled sensitivity across multiple studies for QFT-GIT (the predecessor to QFT-Plus) was 81% when calculated from patients with culture-confirmed active tuberculosis, meaning approximately 19% of true TB cases will test negative. 1
When comparing QFT-GIT directly to tuberculin skin test (TST) in culture-confirmed cases, pooled sensitivity was 83% for QFT-GIT versus 89% for TST, showing TST maintains slightly higher sensitivity. 1
The newer QFT-Plus demonstrates sensitivity of 94-99% in recent high-quality studies from Japan, representing a potential improvement over QFT-GIT, though this requires validation in broader populations. 2, 3
A systematic review and meta-analysis found QFT-Plus overall sensitivity of 94% (95% CI 89-97%) with specificity of 96% (95% CI 94-98%), though these figures include both active TB and latent TB infection populations. 3
Sensitivity in Immunocompromised Patients
In immunocompromised patients with active tuberculosis, sensitivity drops substantially to approximately 73%, with indeterminate results occurring in up to 21% of hospitalized immunocompromised patients. 1, 4
The test's sensitivity and indeterminate rate in immunocompromised populations has not been adequately established, representing a critical limitation when interpreting negative results in HIV-positive patients, those on TNF-alpha antagonists, organ transplant recipients, or patients with hematologic malignancies. 1, 5
One study specifically found QFT-Plus sensitivity of 72.7% in immunocompromised active TB patients compared to 86.4% in non-immunocompromised patients, with immunosuppression also increasing indeterminate results. 4
A negative QFT result cannot exclude M. tuberculosis infection in immunocompromised individuals, and clinical judgment incorporating epidemiologic exposure, symptoms, chest radiography, and bacteriologic studies must guide management. 6, 5
Sensitivity in Elderly Populations
QFT-Plus demonstrated 93.6% sensitivity in elderly patients with active pulmonary tuberculosis (median age 84 years), significantly outperforming T-SPOT.TB which showed only 68.1% sensitivity in this population. 7
Among elderly active TB patients with CD4 T-cell counts <200/μL (39 of whom were ≥80 years), QFT-Plus maintained 83.7% sensitivity compared to 74.4% for QFT-GIT and 58.1% for T-SPOT. 7
A meta-analysis found QFT-Plus demonstrated higher sensitivity than QFT-GIT specifically in older adults, suggesting the addition of the TB2 antigen tube (which stimulates CD8 T-cells) may improve detection in this population. 3
Critical Clinical Caveats
QFT-Plus cannot differentiate active tuberculosis from latent TB infection, and therefore must never be used as a sole diagnostic test for active disease—chest radiography, sputum AFB smear, and mycobacterial culture remain mandatory for diagnosing active TB. 8, 5
The 81-83% sensitivity means that 6-26% of true active TB cases will be missed if relying on QFT testing alone, making negative results insufficient to rule out disease when clinical suspicion exists. 1, 8
Indeterminate results occur due to inadequate mitogen response (IFN-γ ≤0.5 IU/mL in positive control) or high background IFN-γ (>8 IU/mL in nil control), requiring repeat testing with a new specimen or TST in high-risk patients. 6
Severe diabetes mellitus may produce false-negative results on all IGRAs, as demonstrated by cases showing negative results across QFT-Plus, QFT-GIT, and T-SPOT in patients with uncontrolled diabetes. 2
Comparison to Other Tests
T-SPOT.TB demonstrates pooled sensitivity of 90-91% in culture-confirmed active tuberculosis, performing slightly better than QFT-GIT (81-83%) but with similar performance to TST (89%). 1
In the largest head-to-head comparison involving 270+ patients with culture-confirmed TB, T-SPOT and TST showed similar sensitivity (94% and 95% respectively), both significantly higher than QFT-GIT (83%, p<0.01). 1
QFT-Plus and QFT-GIT show substantial agreement (89.9-96.0%, kappa 0.80-0.91) in high-risk populations, with sensitivity differences ranging only -4.0% to +2.0% across studies. 9