Management of Indeterminate QuantiFERON-TB Gold Results
For high-risk patients (close TB contacts, immunocompromised individuals, healthcare workers, or those from TB-endemic countries), repeat the QuantiFERON test with a new blood specimen or perform a tuberculin skin test (TST); for low-risk patients, no further testing is needed. 1
Risk-Stratified Management Algorithm
High-Risk Patients Requiring Further Testing 1
Repeat testing is mandatory for:
- Close contacts of persons with infectious TB disease 1
- Immunocompromised individuals (including those on TNF-α antagonists, HIV-positive, or receiving other immunosuppressive therapy) 1, 2
- Healthcare workers 1
- Individuals from TB-endemic countries 1
Low-Risk Patients
- No further testing is required after an indeterminate result 1
When Active TB Disease is Suspected
Immediately proceed with comprehensive diagnostic workup regardless of the indeterminate result, including: 1
- Chest radiography 1
- Bacteriologic studies (sputum acid-fast bacilli smear and culture) 1
- HIV serology 1
This is critical because indeterminate results do not rule out active TB disease, and delays in diagnosis can be fatal. 3
Repeat Testing Strategy
If Repeating QuantiFERON 1
- Use a newly obtained blood specimen, not the same sample 1
- Minimize incubation delay to less than 6 hours between blood draw and incubation, as delays significantly increase indeterminate rates (from 2.7% to 11.4%) 4
If Using TST as Alternative 1
- Consider two-step testing due to potential boosting of subsequent results 1
- Never follow a positive QuantiFERON with a TST, as this provides no added value 1
Understanding Why Results Are Indeterminate
Request the laboratory report the specific reason for the indeterminate result (positive control failure versus negative control failure), as this guides interpretation: 1
Common causes of indeterminate results include: 5, 6
- Severe lymphocytopenia (strongest predictor, OR = 8.839) 6
- Hypoalbuminemia 5
- Chronic renal disease (OR = 2.838) 6
- Autoimmune disease (OR = 2.527) 6
- Chronic lung disease (OR = 3.169) 6
- Elderly age 5
Critical Pitfalls to Avoid
- Do not repeat QuantiFERON testing after completing TB treatment, as the test often remains positive and does not indicate treatment failure 2
- Weakly positive results (26% of all positives) show 69% reversion to negative when retested within 10 weeks, suggesting caution in interpretation 7
- In immunocompromised patients with miliary TB, indeterminate results can occur from either very low OR paradoxically very high IFN-γ production, making clinical correlation essential 3
- Indeterminate results in elderly and immunocompromised patients may remain indeterminate even with repeat testing (only 16.7% convert to determinate results) 5