Is a chest X-ray needed if the Quantiferon Gold (Interferon-Gamma Release Assay) test is negative and the Purified Protein Derivative (PPD) test is positive?

Management of Discordant TB Test Results: Negative QuantiFERON Gold with Positive PPD

When QuantiFERON Gold (QFT-G) is negative and PPD is positive, a chest X-ray is generally not needed in healthy adults with no risk factors for TB, as the QFT-G result is more specific and likely represents a false-positive PPD due to prior BCG vaccination. 1

Understanding Discordant Results

Discordant results between QFT-G and PPD are common and usually occur due to:

• Higher specificity of QFT-G compared to PPD
• False-positive PPD results from prior BCG vaccination
• False-positive PPD from non-tuberculous mycobacterial exposure

Interpretation Algorithm

1. Evaluate patient risk factors:

   • History of TB exposure
   • Origin from TB-endemic region
   • Immunocompromised status
   • Age <5 years
   • Presence of comorbidities (diabetes, cirrhosis, alcoholism)

2. If no risk factors present:

   • Trust the negative QFT-G result
   • No chest X-ray needed
   • No treatment for latent TB infection (LTBI) required 2, 1

3. If risk factors present:

   • Proceed with chest X-ray to rule out active TB
   • Consider treatment for LTBI based on clinical judgment 2

Special Populations Requiring Chest X-ray Despite Negative QFT-G

A chest X-ray should still be performed in the following high-risk populations despite a negative QFT-G:

• Immunocompromised patients (HIV, organ transplant recipients, patients on TNF-α antagonists) 2, 1
• Children under 5 years of age 2
• Recent close contacts of infectious TB cases 2
• Patients with clinical symptoms suggestive of TB (cough, fever, night sweats, weight loss)
• Patients with recent exposure to TB in high-transmission settings 2

Clinical Approach Based on CDC Guidelines

The CDC guidelines indicate that "the majority of healthy adults who have negative QFT-G results are unlikely to have M. tuberculosis infection and do not require further evaluation." 2

However, the guidelines also note that in certain circumstances, a negative QFT-G should not rule out TB infection:

• Recent contacts to infectious TB cases should have repeat testing 8-10 weeks after exposure ends
• Immunocompromised patients may have false-negative results
• Children under 5 years may need special consideration 2

Pitfalls to Avoid

• Don't automatically order a chest X-ray for every discordant result (QFT-G negative/PPD positive) in low-risk individuals
• Don't ignore a positive PPD in high-risk individuals despite a negative QFT-G
• Don't forget to consider false-negative QFT-G results in immunocompromised patients, as lymphocytopenia and other conditions can affect test performance 3, 4
• Don't overlook the possibility of extrapulmonary TB in patients with symptoms but negative QFT-G 5

Conclusion

For most healthy adults with no risk factors for TB, a negative QFT-G result is reliable even with a positive PPD, and no chest X-ray is needed. The QFT-G has higher specificity and is not affected by prior BCG vaccination 1, 6. However, clinical judgment should be used for patients with risk factors for TB or progression to active disease, in whom chest X-ray and potential LTBI treatment may still be warranted despite a negative QFT-G.