Management of Positive QuantiFERON-TB Gold Plus in Asymptomatic Low-Risk Individual
In an asymptomatic person with low likelihood of M. tuberculosis infection and a single positive QuantiFERON-TB Gold Plus result, repeat testing with either QFT or tuberculin skin test should be considered on a case-by-case basis, as a single positive result is not reliable evidence of true infection in this population. 1
Immediate Next Steps
Rule Out Active TB Disease First
- Obtain a chest radiograph to exclude active tuberculosis disease before any further decisions are made 1
- Perform a detailed history focusing on TB exposure, symptoms (cough, fever, night sweats, weight loss), travel to TB-endemic areas, and immunosuppressive conditions 1
- Conduct a physical examination looking specifically for signs of active TB disease 1
- Order HIV testing, as HIV-positive status increases both risk and urgency for treatment 1
Consider Repeat Testing Strategy
- For low-risk individuals with weakly positive results (interferon-γ response near the cutoff), repeat testing with a new blood specimen often yields negative results—69% revert to negative within 10 weeks 2
- If repeating QFT-Plus, use a newly obtained blood specimen rather than retesting the same sample 3
- Alternatively, tuberculin skin test (TST) can be used, though two-step testing should be considered due to potential boosting 3
- Research in low-risk healthcare workers showed that 90.9% of discordant positive QFT-Plus results were negative on follow-up QFT testing 4
Understanding the Context of This Result
Why Low-Risk Positives Are Unreliable
- In 626 healthcare workers with no identifiable risk factors, the positivity rate was only 2.1-3.0%, and many of these were non-reproducible 4
- Weakly positive results (26% of all positives in one study) showed 69% reversion to negative on repeat testing within 10 weeks 2
- Among individuals followed for an average of 4.7 years with positive baseline QFT, none developed active TB, with a probability of clinical breakdown of 0-0.0104/person-year 5
Critical Pitfalls to Avoid
- Never follow a positive QFT-Plus with a TST—it provides no added value 3, 1
- Do not initiate latent TB infection treatment without first ruling out active disease with at minimum chest radiography 1
- Recognize that results falling in the 0.2-0.7 IU/ml range are particularly prone to being non-reproducible in low-risk populations 4
If Active TB Is Ruled Out and Repeat Testing Remains Positive
- Treatment decisions should incorporate all epidemiologic, historical, and clinical information, with particular attention to actual TB exposure risk 1
- A positive QFT-Plus requires the same medical interventions as a positive TST once active disease is excluded 1
- Consider that recent infection carries higher risk than remote infection when deciding on latent TB infection treatment 5