QFT-TB Plus (QuantiFERON-TB Gold Plus) Test Interpretation
A positive QFT-TB Plus result indicates immune sensitization to Mycobacterium tuberculosis antigens, signifying either latent tuberculosis infection (LTBI) or active tuberculosis disease, and requires immediate evaluation to exclude active TB before diagnosing LTBI. 1
What the Test Measures
The QFT-TB Plus is an interferon-gamma release assay (IGRA) that measures cell-mediated immune response to M. tuberculosis-specific antigens through blood testing. 1 Unlike the older QFT versions, QFT-Plus includes two antigen tubes (TB1 and TB2) designed to elicit responses from both CD4+ and CD8+ T lymphocytes, potentially improving sensitivity for detecting recent infection. 2, 3
Immediate Actions Required for Positive Results
When you receive a positive QFT-TB Plus result, you must evaluate for active tuberculosis disease before diagnosing LTBI. 1 This evaluation includes:
- Chest radiograph to identify abnormalities consistent with TB disease 1
- Clinical history focusing on TB exposure, symptoms (cough, fever, night sweats, weight loss), and duration of symptoms 1
- Physical examination for signs of active disease 1
- HIV testing is strongly recommended, as HIV infection increases both the likelihood of TB and urgency of treatment 1
- Bacteriologic studies (sputum cultures, molecular testing) if active TB is suspected based on symptoms or radiographic findings 1
Do not perform a tuberculin skin test (TST) to confirm a positive QFT-Plus result—there is no reason to follow a positive QFT result with TST. 1 The positive QFT-Plus should prompt the same interventions as a positive TST. 1
Risk-Stratified Interpretation
The clinical significance of a positive result depends on the patient's risk profile:
High-Risk Populations (Increased Risk for LTBI)
For recent immigrants from high-prevalence countries, injection drug users, prison residents/employees, and healthcare workers with known TB exposure, a positive result strongly indicates M. tuberculosis infection requiring treatment consideration. 1
Low-Risk Populations
In populations with minimal TB exposure risk (military personnel, healthcare workers without prior exposure, college students), positive results may warrant confirmation given the lower pre-test probability, though the CDC guidelines from 2003 suggest different interpretation thresholds based on risk. 1
Special Considerations
Recent TB contacts with negative results require repeat testing 8-10 weeks after exposure ends, following the same timing recommendations as TST to account for the window period of immune response development. 1
For contacts aged <5 years or severely immunocompromised persons exposed to highly contagious TB, window period prophylaxis (presumptive LTBI treatment) should be initiated even with negative testing, with repeat testing at 8-10 weeks. 1 A full treatment course should be considered even with negative results if transmission rates among other contacts were high or false-negative results are suspected due to medical conditions. 1
Indeterminate Results
An indeterminate QFT-Plus result provides no useful information about M. tuberculosis infection status. 1 Options include:
- Repeat QFT-Plus with a new blood specimen 1
- Administer TST 1
- No further testing if the patient is unlikely to have infection 1
For patients with increased likelihood of infection and indeterminate results, performing a second test (either QFT-Plus or TST) is prudent. 1 Indeterminate results due to inadequate mitogen response are associated with immunosuppressive conditions and lower lymphocyte counts. 1, 4
Test Performance Nuances
Recent studies show QFT-Plus has high agreement with its predecessor QFT-GIT (κ = 0.859 in immunocompromised patients, κ = 0.8 in TB contacts). 5, 4, 2 The TB2 antigen tube, which stimulates CD8+ T cells, may detect additional LTBI cases, particularly in patients receiving long-term immunosuppressant therapy. 4 The difference between TB2 and TB1 responses (TB2-TB1 >0.6 IU/mL) correlates with increased M. tuberculosis exposure and may identify individuals with recent infection. 2
Common Pitfalls to Avoid
- Never delay diagnostic evaluation for active TB while awaiting QFT-Plus results—if TB disease is suspected clinically, proceed with chest radiography and bacteriologic studies immediately. 1
- Blood must be processed within 12 hours of collection for valid results, limiting the test's practical utility in some settings. 1
- Negative results do not absolutely exclude M. tuberculosis infection, particularly in immunocompromised patients, those on immunosuppressive therapy, or individuals with recent exposure. 1, 4
- The T-SPOT.TB test can resolve 84.8% of indeterminate QFT-Plus results when performed within 30 days, providing a useful complementary diagnostic approach. 6