Management of Two Indeterminate QuantiFERON-TB Gold Results
Do not start latent tuberculosis treatment based on two indeterminate QuantiFERON-TB Gold results, as indeterminate results provide no useful information about the presence of Mycobacterium tuberculosis infection and cannot justify treatment. 1
Understanding Indeterminate Results
An indeterminate QFT-G result conveys zero diagnostic information about TB infection status—it is neither positive nor negative. 1 These results arise from either:
- High background interferon-γ in the nil control (non-specific immune activation), or 1
- Inadequate mitogen response (impaired T-cell function, often from immunosuppression) 1
The specific control failure should guide your next steps, so confirm which type of indeterminate result occurred. 1
Risk-Stratified Management Algorithm
For High-Risk Patients
If your patient falls into high-risk categories—close TB contacts, immunocompromised individuals, healthcare workers, or persons from TB-endemic countries—you have two options: 1
- Repeat QFT-G with a newly drawn blood specimen (not the same sample), or 1
- Perform a tuberculin skin test (TST) as an alternative 1
Critical timing consideration: If choosing TST after indeterminate QFT-G, implement a two-step testing protocol, as TST can boost subsequent test results. 1
Research supports that repeating testing within 30 days of the initial indeterminate result yields the highest resolution rate (84.8% definitive results). 2
For Low-Risk Patients
No further testing is required after indeterminate QFT-G results in persons unlikely to have TB infection. 1
When Active TB Disease Is Suspected
If clinical suspicion for active TB exists, immediately initiate diagnostic evaluation without waiting for repeat QFT-G results. 1 Required evaluations include:
- Chest radiography 1
- Sputum acid-fast bacilli smear and culture 1
- HIV serology 1
- Additional tests based on clinical presentation 1
Never delay these investigations based on indeterminate QFT-G results. 1
Treatment Decision After Repeat Testing
Treatment for latent TB infection should only be initiated after a positive test result (either repeat QFT-G or TST) and after active TB disease has been excluded with chest radiography at minimum. 3
If Repeat Testing Remains Indeterminate
Research from immunosuppressed populations demonstrates that patients with persistently indeterminate results who require immunosuppressive therapy (including anti-TNF agents) can proceed with treatment after careful clinical assessment, provided active TB has been excluded. 4 However, this requires:
- Normal chest radiograph 4
- No TB symptoms on detailed history 5
- Regular clinical monitoring for TB disease 4
Risk factors for indeterminate results include immunosuppressive drug use, lymphopenia, hypoalbuminemia, and decreased kidney function—these patients warrant particularly careful evaluation. 6
Critical Pitfalls to Avoid
- Never interpret indeterminate as negative—it provides no information about infection status 1
- Never start single-drug LTBI treatment until active TB is definitively excluded 5
- Never follow a positive QFT-G with TST—it adds no value 3
- Do not delay evaluation for active TB while awaiting repeat test results 1
Clinical Impact of Indeterminate Results
Be aware that indeterminate results are associated with delayed treatment initiation (23% greater probability of delay beyond 30 days) and increased hospitalization risk (12% greater probability within 60 days) in IBD patients requiring anti-TNF therapy. 7 This underscores the importance of efficient repeat testing protocols in high-risk patients who genuinely need immunosuppressive therapy.