Management of Indeterminate QuantiFERON-TB Gold Test Results
For patients with an indeterminate QuantiFERON-TB Gold test, the management depends on their risk of TB infection: high-risk patients should receive either a repeat QFT-G test with a new blood specimen or a tuberculin skin test (TST), while low-risk patients require no further testing. 1
Risk-Stratified Approach to Indeterminate Results
High-Risk Patients (Require Additional Testing)
For individuals with increased likelihood of M. tuberculosis infection who have an indeterminate result, administration of a second test—either repeat QFT-G or TST—is prudent. 1
High-risk categories include:
- Close contacts of persons with infectious TB disease 1
- Immunocompromised individuals (HIV-positive, on immunosuppressive therapy) 1
- Healthcare workers or those in congregate settings with TB exposure 1
- Individuals from TB-endemic countries with recent exposure 1
Low-Risk Patients (No Further Testing Needed)
For persons who are unlikely to have M. tuberculosis infection, no further tests are necessary after an indeterminate QFT-G result. 1
If Active TB Disease is Suspected
When TB disease is clinically suspected, additional diagnostic evaluations should be performed immediately and should not be delayed while awaiting repeat QFT-G results. 1
Required evaluations include:
- Chest radiography 1
- Bacteriologic studies (sputum AFB smear and culture) 1
- HIV serology 1
- Additional tests as indicated by clinical presentation 1
Understanding Why Results Are Indeterminate
Laboratories should report the specific reason for the indeterminate result, as this guides clinical interpretation. 1
The two main causes are:
- High background IFN-γ levels in the nil (negative control) sample - more common in Hispanics and foreign-born individuals 2
- Inadequate response to mitogen (positive control failure) - associated with immunosuppressive conditions, young age (<10 years), female sex, Asian ethnicity, and US-born status 1, 2
Repeat Testing Strategy
If repeating the QFT-G test, use a newly obtained blood specimen rather than retesting the same sample. 1
When considering TST as the alternative test:
- Be aware that TST can cause boosting of subsequent test results 1
- Consider the need for two-step testing in settings conducting serial testing 1
- TST may have more false positives in BCG-vaccinated individuals 1
Expected Outcomes of Repeat Testing
Among patients who receive repeat QFT-G testing after an indeterminate result, approximately 64% will have negative results, 4% positive, and 32% will have a second indeterminate result of the same type. 2
The T-SPOT.TB test can resolve 84.8% of indeterminate QFT-G results when performed within 30 days, providing definitive results in most cases. 3
Clinical Factors Associated with Indeterminate Results
Be aware that indeterminate results occur more frequently in patients with:
- Active systemic inflammation (elevated CRP, ESR) 4, 5
- Hypoalbuminemia (albumin <3.5 g/dL) 4
- Systemic corticosteroid use 4
- Advanced age 5
- Anemia 4
These factors should inform your clinical suspicion and threshold for pursuing additional testing or empiric treatment in high-risk scenarios. 4, 5
Critical Pitfall to Avoid
Never follow a positive QFT-G test with a TST, as it provides no added value. 6 This guidance applies to positive results, not indeterminate ones, where TST remains a valid alternative option. 1