From the Guidelines
An indeterminate result from the TB QuantiFERON Gold test means the test was unable to provide a clear positive or negative result for tuberculosis infection, and the test should be repeated as soon as possible, considering the patient's individual clinical situation and risk factors. This is based on the most recent and highest quality study available, which emphasizes the importance of considering the patient's overall clinical context when interpreting test results 1.
Understanding Indeterminate Results
Indeterminate results can occur due to various factors, including technical issues with the sample, low immune response in the patient, or improper handling of the blood specimen. It's also important to note that certain conditions, such as immunosuppressive medications, HIV infection, extremes of age, and laboratory processing errors, can increase the likelihood of an indeterminate result 1.
Next Steps
If the repeat test is also indeterminate, alternative testing methods, such as a tuberculin skin test (TST), should be considered. For immunocompromised patients who consistently have indeterminate results, clinical evaluation becomes more important, including assessment of TB risk factors, symptoms, and chest imaging. The indeterminate result itself does not indicate TB infection or disease; it simply means the test could not provide reliable information.
Clinical Considerations
It's crucial to discuss the result with a healthcare provider to determine the appropriate next steps based on the individual's clinical situation and risk factors. The provider should consider the patient's medical history, epidemiologic context, and other clinical information to make an informed decision about further testing or treatment. As emphasized in the guidelines, diagnoses of M. tuberculosis infection and decisions about medical or public health management should not be based solely on IGRA or TST results but should include a comprehensive evaluation of the patient's condition 1.
Prioritizing Patient Care
Ultimately, the management of an indeterminate TB QuantiFERON Gold test result should prioritize the patient's morbidity, mortality, and quality of life. This involves a careful consideration of the potential risks and benefits of further testing or treatment, taking into account the patient's unique circumstances and the latest clinical guidelines. By doing so, healthcare providers can ensure that patients receive the most appropriate care, minimizing unnecessary interventions while maximizing the detection and treatment of tuberculosis infection when present.
From the Research
Significance of Indeterminate Results
The significance of an indeterminate result for the Tuberculin (TB) QuantiFERON Gold (Interferon-Gamma Release Assay, IGRA) test can be understood by considering the following points:
- Indeterminate results may decrease the clinical usefulness of the QuantiFERON-TB Gold In-Tube (QFT-G IT) test 2
- Predictive factors for indeterminate results include severe lymphopenia, chronic renal disease, autoimmune disease, and chronic lung disease 2
- Indeterminate or negative results from the QFT-GIT may indicate lower sensitivity of the method, especially in patients with active TB 3
- Age, race/ethnicity, and sex may be associated with indeterminate QFT-G results 4
- High levels of IFN-γ production can lead to indeterminate QuantiFERON results, even in immunocompromised individuals or patients with miliary tuberculosis 5
- In HIV-infected patients, the CD4 T-cell count, lymphocyte count, and lymphocyte percentage are influential factors for indeterminate QFT-IT results 6
Factors Influencing Indeterminate Results
Some key factors that influence indeterminate results include:
- Severe lymphopenia (odds ratio [OR] = 8.839; p < 0.001) 2
- Chronic renal disease (OR = 2.838; p = 0.007) 2
- Autoimmune disease (OR = 2.527; p = 0.017) 2
- Chronic lung disease (OR = 3.169; p = 0.007) 2
- Age (1.030,1.005-1.056,0.02) 3
- CRP levels (odd ratio, 1.069; 95% CI, 1.013-1.127; P = 0.014) 3
- Lymphocyte count and lymphocyte percentage 6
- CD4 T-cell count 6
Clinical Implications
The clinical implications of indeterminate results are:
- Careful attention to pre-analytical conditions may minimize the proportion of indeterminate results 2
- QFT-GIT results should be interpreted carefully and correlated with additional tests for TB, especially when levels of markers of inflammation are high or the patient is older 3
- Indeterminate results should be interpreted with caution, as IFN-γ production in patients with miliary tuberculosis can vary significantly, even with sustained lymphocytopenia 5
- The QFT-IT could be a potential, simple, and feasible method for diagnosing and screening TB in HIV-infected patients, considering the influential factors of indeterminate results 6