What do I do with a positive Quantiferon (Interferon-Gamma Release Assay) result?

Management of a Positive QuantiFERON-TB Gold Test Result

A positive QuantiFERON-TB Gold (QFT) test indicates latent tuberculosis infection (LTBI) and requires evaluation for active TB disease followed by appropriate LTBI treatment if active disease is ruled out. 1

Initial Assessment After Positive QFT Result

1. Rule out active TB disease:

   • Perform chest radiography
   • Assess for TB symptoms (cough, fever, night sweats, weight loss)
   • Collect sputum samples for bacteriologic studies if symptomatic
   • Consider HIV testing

2. Risk stratification:

   • Determine risk factors for TB exposure:
     • Recent immigration from TB endemic countries
     • Recent stay in TB endemic countries
     • Duration of TB exposure
     • Previous TB disease
     • Immunocompromised status

Interpretation Based on Risk Profile

High-Risk Individuals

For persons with increased risk for LTBI (recent immigrants, injection-drug users, residents/employees of prisons and jails) 2:

• Positive QFT alone is sufficient to recommend LTBI treatment
• Even if subsequent TST is negative, treatment decision should be based on clinical judgment and perceived risk

Low-Risk Individuals

For persons at low risk for LTBI 2:

• Confirmation of positive QFT with TST is recommended before initiating LTBI treatment
• LTBI therapy is not recommended for low-risk persons who are QFT-positive but TST-negative

Treatment Recommendations

• Standard LTBI treatment regimens should be offered to individuals with positive QFT after active TB has been ruled out
• Higher priority for treatment should be given to:
  • Individuals with QFT results ≥10 IU/ml (6.36 times higher risk of developing active TB) 3
  • Persons with abnormal chest radiographs consistent with healed TB 4
  • Those with TST induration ≥15 mm (correlates better with positive QFT in BCG-vaccinated patients) 4

Special Considerations

Immunocompromised Patients

• Severely immunocompromised patients or children <5 years with recent TB exposure should be considered for LTBI treatment regardless of test results 1
• Cancer patients, particularly those with hematologic malignancies, head and neck cancers, and lung cancer have higher risk 1

BCG-Vaccinated Individuals

• QFT has improved specificity compared to TST in BCG-vaccinated individuals 1
• Among BCG-vaccinated adults with positive TST, only 30% have positive QFT results 4
• Strongest predictors of true LTBI (positive QFT) in BCG-vaccinated individuals include:
  • Birth in high-incidence country (8.2 times more likely to have positive QFT)
  • Abnormal chest radiograph consistent with healed TB
  • TST induration ≥16mm 4

Follow-Up After Treatment

• QFT should not be used to monitor treatment effect as most patients (84-87%) remain QFT-positive after completing preventive therapy 5
• Clinical monitoring for TB symptoms is recommended instead of repeat QFT testing

Common Pitfalls to Avoid

1. Misinterpreting indeterminate results: Indeterminate QFT results provide no useful information regarding TB infection and should never be interpreted as absence of infection 1

2. Technical factors: Ensure proper handling of blood specimens (must be incubated with test antigens within 12 hours of collection) 1

3. Delayed evaluation: When TB disease is suspected clinically, do not delay diagnostic evaluations while awaiting QFT results 1

4. Overreliance on test results: Consider clinical and epidemiological factors alongside test results, as QFT has a false positive rate of approximately 2-3% 1