From the Guidelines
An indeterminate Quantiferon result should be managed by repeating the test with either another Quantiferon or a tuberculin skin test (TST), considering the patient's likelihood of M. tuberculosis infection and immunocompromised status. According to the guidelines for using the Quantiferon-TB Gold test 1, an indeterminate result does not provide useful information regarding the likelihood of M. tuberculosis infection. The optimal follow-up approach has not been determined, but options include repeating the Quantiferon test with a newly obtained blood specimen, administering a TST, or doing neither.
When deciding on the management approach, consider the following factors:
- The patient's likelihood of M. tuberculosis infection: for those with an increased likelihood, administration of a second test, either Quantiferon or TST, might be prudent 1.
- Immunocompromised status: patients with immunosuppressive conditions may have inadequate response to mitogen, leading to indeterminate results 1.
- Technical issues: high background levels of IFN-g in the nil sample or inadequate response to mitogen can cause indeterminate results 1.
In clinical practice, collecting a new blood sample for repeat Quantiferon testing as soon as possible, ideally within 2-4 weeks of the initial test, is a reasonable approach. If the repeat Quantiferon is also indeterminate, proceeding with a TST as an alternative testing method may be necessary. For patients with high-risk TB exposure or symptoms suggestive of TB disease, clinical judgment may warrant empiric treatment or additional diagnostic workup, even with indeterminate Quantiferon results.
From the Research
Management Approach for Indeterminate Quantiferon Results
The management approach for an indeterminate Quantiferon result involves several considerations, including:
- Repeating the test within a certain timeframe, as some studies suggest that indeterminate results may be due to temporary factors 2
- Evaluating the patient's clinical history and risk factors, such as immunocompromised status, elderly age, lymphocytopenia, and hypoalbuminemia, which may increase the likelihood of indeterminate results 2, 3
- Considering alternative diagnostic tests, such as the tuberculin skin test (TST), although it may also have limitations in certain patient populations 2
Predictive Factors for Indeterminate Results
Several predictive factors have been identified as increasing the likelihood of indeterminate Quantiferon results, including:
- Severe lymphopenia 3, 4
- Chronic renal disease 3
- Autoimmune disease 3
- Chronic lung disease 3
- Immunosuppressive treatment 4
- Pancytopenia 4, 5
Interpretation of Indeterminate Results
Indeterminate results should be interpreted with caution, as they may not necessarily indicate a false-negative or false-positive result. In some cases, indeterminate results may be due to high levels of IFN-γ production, even in the presence of lymphocytopenia 5. A thorough clinical evaluation and consideration of alternative diagnostic tests may be necessary to determine the best course of action for patients with indeterminate Quantiferon results.
Test Reproducibility and Weakly Positive Results
The reproducibility of the Quantiferon test and the interpretation of weakly positive results are also important considerations in the management of indeterminate results. Some studies suggest that weakly positive results may be due to temporary factors and that repeated testing may yield negative results 6. However, the clinical significance of weakly positive results and the optimal approach to repeated testing are not yet fully established.