Can a positive QuantiFERON Gold (QFT-G) Tuberculosis (TB) test be a false positive?

False Positive QuantiFERON Gold TB Test Results

Yes, a positive QuantiFERON Gold TB test can be a false positive in certain circumstances, particularly in individuals with exposure to non-tuberculous mycobacteria or those with immune dysregulation.

Causes of False Positive QFT-G Results

The QuantiFERON-TB Gold (QFT-G) test measures interferon-gamma (IFN-γ) release in response to TB-specific antigens. Several factors can lead to false positive results:

1. Cross-reactivity with non-tuberculous mycobacteria:

   • ESAT-6 and CFP-10 (antigens used in QFT-G) are present in certain non-tuberculous mycobacteria including M. kansasii, M. szulgai, and M. marinum 1
   • Sensitization to these organisms can cause IFN-γ release that mimics TB infection

2. Immune dysregulation:

   • Certain malignancies, particularly hematologic malignancies, head and neck cancer, and lung cancer can cause elevated mitogen levels 2
   • Inflammatory conditions may cause immune hyperactivity leading to non-specific responses

3. Technical factors:

   • Improper handling or processing of blood specimens
   • Delays in processing (blood must be incubated with test antigens within 12 hours of collection) 1

Specificity and False Positive Rates

QFT-G was developed specifically to improve upon the specificity issues of the tuberculin skin test (TST):

• QFT-G generally shows fewer positive results than TST in persons without recognized risk factors for TB infection 1
• This improved specificity is due to the use of M. tuberculosis-specific antigens (ESAT-6 and CFP-10) that are absent from BCG vaccine strains and most non-tuberculous mycobacteria 1
• Despite this improved specificity, false positives still occur in approximately 2-3% of cases

Clinical Scenarios with Higher Risk of False Positives

1. Patients with certain malignancies:

   • Hematologic malignancies (highest risk)
   • Head and neck squamous cell carcinoma
   • Lung cancer 2

2. Patients with sarcoidosis:

   • Higher frequency of positive QFT-G results has been observed in culture-negative sarcoidosis patients compared to control groups 3

3. Pediatric patients with chronic medical conditions:

   • A case series found false positive QFT-GIT results in children with chronic medical conditions 4

Interpreting Weakly Positive Results

Weakly positive QFT-G results deserve special consideration:

• Studies have shown that approximately 26% of all positive results fall into a "weakly positive" category 5
• When repeat testing is performed within ten weeks, 69% of weakly positive results revert to negative 5
• Without TB treatment, 48% of positive results revert to negative after one year 5

Management Recommendations

When a positive QFT-G result is obtained:

1. Evaluate for active TB disease:

   • A chest radiograph should be examined for abnormalities consistent with TB disease 1
   • Additional evaluation based on clinical findings, exposure history, and physical examination

2. Consider the pre-test probability:

   • In low-risk individuals with no TB exposure history, consider the possibility of false positive
   • In high-risk individuals or those with known exposure, treat as true positive

3. For weakly positive results in low-risk individuals:

   • Consider repeat testing, especially if the clinical suspicion for TB is low 5

4. For indeterminate results:

   • Options include repeating QFT-G with a new blood specimen, administering a TST, or neither 1
   • For persons with increased likelihood of M. tuberculosis infection, a second test might be prudent

Conclusion

While the QuantiFERON Gold TB test offers improved specificity over the tuberculin skin test, false positive results can still occur. Understanding the potential causes of false positives and interpreting results in the context of clinical and epidemiological factors is essential for appropriate patient management.