Role of QuantiFERON Gold Plus in Diagnosing Latent TB in Patients with Chronic Cough
QuantiFERON Gold Plus (QFT-Plus) is recommended as an appropriate diagnostic test for detecting latent tuberculosis infection (LTBI) in patients with chronic cough and can be used in all circumstances where tuberculin skin testing (TST) would traditionally be employed. 1
Advantages of QFT-Plus Over Traditional TST
QFT-Plus offers several significant advantages over the tuberculin skin test:
- Requires only a single patient visit (versus two visits for TST)
- Results available within 24 hours
- Not affected by prior BCG vaccination
- Less subject to reader bias and error
- Does not boost anamnestic immune responses with repeated testing 1, 2
These advantages make QFT-Plus particularly valuable in evaluating patients with chronic cough who may require TB screening.
Test Mechanism and Interpretation
QFT-Plus is an enzyme-linked immunosorbent assay (ELISA) that:
- Detects interferon-gamma (IFN-γ) release in fresh heparinized whole blood
- Uses synthetic peptides representing two M. tuberculosis proteins: ESAT-6 and CFP-10
- Includes two antigen tubes: TB1 (stimulating CD4+ T cells) and TB2 (stimulating both CD4+ and CD8+ T cells) 1, 3
Interpretation Guidelines:
- Positive Result: Indicates likely M. tuberculosis infection
- Negative Result: Suggests absence of M. tuberculosis infection
- Indeterminate Result: Occurs when mitogen response is inadequate (<1.5 IU/mL), suggesting immunosuppression or technical issues 2
Diagnostic Algorithm for Chronic Cough Patients
Initial Assessment:
- Determine risk factors for TB exposure
- Assess for symptoms suggestive of active TB (fever, night sweats, weight loss)
- Consider chest imaging if active TB is suspected
QFT-Plus Testing:
- Draw blood sample and process within 12 hours
- Ensure proper handling to avoid indeterminate results
Interpretation Based on Results:
- Positive QFT-Plus: Further evaluation needed to rule out active TB before LTBI treatment
- Negative QFT-Plus: TB infection unlikely if immune system functioning normally
- Indeterminate QFT-Plus: Consider repeating test or using alternative diagnostic approaches
Special Considerations
Test Performance in Different Populations
- QFT-Plus shows good sensitivity (83.3%) for active TB in children 4
- In adults, pooled sensitivity for active TB is 94%, with TB2 tube showing slightly higher sensitivity (95%) than TB1 (91%) 5
- Specificity for healthy status is approximately 96% 5
Limitations and Caveats
- Blood Processing Time: Blood must be processed within 12 hours of collection 2
- Immunosuppression: May lead to indeterminate results due to low mitogen response 2
- Extrapulmonary TB: QFT-Plus has lower sensitivity (69%) for extrapulmonary TB compared to pulmonary TB 6
- Cross-reactivity: Possible false positives with certain non-tuberculous mycobacteria (M. kansasii, M. szulgai, and M. marinum) 1
Chronic Cough Evaluation Context
For patients with chronic cough, QFT-Plus should be considered when:
- TB is in the differential diagnosis
- Patient has risk factors for TB exposure
- Other common causes of chronic cough have been ruled out or are being evaluated concurrently
Integration with Other Diagnostic Approaches
While QFT-Plus is valuable for detecting LTBI, it cannot distinguish between active TB and latent infection 1. Therefore:
- Positive QFT-Plus results in patients with chronic cough require additional evaluation (sputum studies, chest imaging)
- Negative QFT-Plus results in highly suspicious cases should not completely rule out TB, especially in immunocompromised patients
By following this evidence-based approach to QFT-Plus testing in patients with chronic cough, clinicians can effectively identify those with LTBI who may benefit from preventive treatment, ultimately reducing morbidity and mortality from TB disease.