What does a positive QuantiFERON (Quantiferon) Gold Plus test result indicate?

What Does a Positive QuantiFERON Gold Plus Test Mean?

A positive QuantiFERON Gold Plus test indicates Mycobacterium tuberculosis infection, but it cannot distinguish between latent tuberculosis infection (LTBI) and active tuberculosis disease—you must rule out active TB with chest radiography and clinical evaluation before diagnosing LTBI. 1, 2

Immediate Clinical Implications

A positive QFT-Plus result requires the same medical interventions as a positive tuberculin skin test (TST). 1, 2 This means:

• Do not follow a positive QFT-Plus with a TST—it provides no additional value and is not recommended 1, 2
• The test indicates immune sensitization to M. tuberculosis antigens through interferon-gamma release from T cells 1
• The positive result applies regardless of BCG vaccination status, as QFT-Plus has higher specificity than TST and is not affected by BCG 1, 2

Mandatory Evaluation to Rule Out Active TB Disease

Before diagnosing LTBI, you must exclude active tuberculosis disease through: 1, 2

• Chest radiography (minimum requirement—look for infiltrates, cavitation, lymphadenopathy, or pleural effusions) 1, 2
• Detailed symptom assessment (fever, night sweats, weight loss, chronic cough >3 weeks, hemoptysis) 1
• Physical examination (lymphadenopathy, pulmonary findings, signs of extrapulmonary TB) 1
• HIV testing (critical because HIV increases urgency of LTBI treatment and risk of progression to active disease) 1, 2
• Bacteriologic studies if any clinical suspicion exists (sputum AFB smear and culture, nucleic acid amplification tests) 1

Understanding Test Limitations

The predictive value of a positive QFT-Plus depends on the prevalence of M. tuberculosis infection in the tested population. 1 Key considerations:

• In low-risk populations (U.S. healthcare workers with no risk factors), the positivity rate is approximately 3.0%, with some results potentially representing false positives 3
• QFT-Plus has higher specificity than TST, meaning fewer false positives, particularly in BCG-vaccinated individuals 1, 2
• The test shows good agreement with its predecessor QFT-GIT (95.6% agreement, kappa 0.57) 3, 4
• QFT-Plus may detect slightly more LTBI cases than QFT-GIT in patients receiving long-term immunosuppressant therapy 5

Special Populations Requiring Careful Interpretation

In immunocompromised patients, a positive result should be interpreted cautiously but still warrants full evaluation. 1 This includes patients with:

• HIV/AIDS 1
• Treatment with immunosuppressive drugs (high-dose corticosteroids, TNF-alpha antagonists, transplant medications) 1
• Hematologic disorders (leukemias, lymphomas, myeloproliferative disorders) 1
• Specific malignancies (head, neck, or lung cancer) 1
• Diabetes, silicosis, or chronic renal failure 1

Treatment Decisions After Positive Result

Once active TB is excluded, treatment for LTBI should be considered, weighing all epidemiologic, historical, clinical, and diagnostic information. 1, 2 Treatment is particularly important for:

• Recent contacts of infectious TB cases 1, 2
• Immunocompromised individuals (especially HIV-positive or those starting TNF-alpha antagonists) 1, 2
• Children under 5 years old who are close contacts 1

However, the risk of progression from LTBI to active disease in individuals with positive baseline QFT results who are not recently infected is low (0-0.0104/person-year), so treatment may not be recommended unless recent infection is documented. 6

Common Pitfalls to Avoid

• Never assume a positive test alone means active TB disease—always complete the diagnostic workup 1, 2
• Do not reflexively order a TST after a positive QFT-Plus—this adds no clinical value 1, 2
• Do not delay treatment evaluation while waiting for additional testing if clinical suspicion for active TB is high 1
• Remember that discordant results near the cutoff (0.2-0.7 IU/ml) are common and may not be reproducible on repeat testing in low-risk individuals 3