How to manage a patient with a low positive Quantiferon TB (Tuberculosis) Plus test result?

From the Guidelines

Management of a patient with a low positive QuantiFERON-TB Gold Plus test result should start with confirmatory repeat testing on a new specimen, as recommended by the ATS/IDSA/CDC Clinical Practice Guidelines (2017) 1. This approach is crucial because a low positive result may represent a false positive, especially in individuals without risk factors for infection.

• The patient's epidemiologic and medical history, as well as other clinical information, should be considered when interpreting the test results 1.
• A diagnosis of latent tuberculosis infection (LTBI) requires that active tuberculosis be excluded by medical evaluation, which should include taking a medical history and a physical examination to check for suggestive symptoms and signs, a chest radiograph, and, when indicated, testing of sputum or other clinical samples for the presence of M. tuberculosis 1.
• If the patient is at low risk for LTBI, confirmation of a positive QFT result with TST is recommended before initiation of LTBI treatment, as suggested by the guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection (2003) 1.
• Treatment decisions should consider the patient's risk of progression to active TB, which is highest in the first two years after infection and in immunocompromised individuals.
• The preferred treatment regimen for LTBI is isoniazid 300mg daily plus rifapentine 900mg weekly for 3 months (3HP), administered as directly observed therapy, but this should only be considered after careful clinical evaluation and confirmation of the diagnosis.
• Annual follow-up is recommended for patients who do not receive LTBI treatment, to monitor for signs and symptoms of active TB.
• It is essential to weigh the risks and benefits of treatment, considering the potential for hepatotoxicity, especially in patients over 35, those with liver disease, or alcohol users, and to obtain baseline liver function tests and monitor monthly for hepatotoxicity if treatment is initiated.

From the FDA Drug Label

The performance characteristics of the QFT-Plus test has not been evaluated in immune compromised patients, patients taking immunosuppressive drugs, pregnant women, and individuals younger than 18 years of age. Among individuals without risk factors for infection, weak positive values may be false positives in the majority of cases. Per ATS/IDSA/CDC Clinical Practice Guidelines (2017), confirmatory repeat testing on a new specimen is recommended.

The patient with a low positive Quantiferon TB Plus test result should undergo confirmatory repeat testing on a new specimen, as recommended by the ATS/IDSA/CDC Clinical Practice Guidelines (2017) 2. This is because weak positive values may be false positives in the majority of cases, especially among individuals without risk factors for infection.

• Risk assessment should be performed to determine if the patient has any risk factors for tuberculosis infection.
• Clinical evaluation should be done to assess the patient's overall health and medical history.
• Repeat testing should be considered to confirm the diagnosis of latent tuberculosis infection.

It is essential to approach this result with caution and consider the patient's individual circumstances before making any clinical decisions.

From the Research

Management of a Patient with a Low Positive Quantiferon TB Plus Test Result

• The patient's test result is considered a low positive, with a TB1 minus Nil value between 0.35 and 1.1 IU/mL, which may be a false positive in individuals without risk factors for infection 3.
• According to the ATS/IDSA/CDC Clinical Practice Guidelines (2017), confirmatory repeat testing on a new specimen is recommended for low positive results [no reference provided in the evidence, but mentioned in the question].
• The Quantiferon TB Plus test detects interferon gamma responses from individuals infected with M. tuberculosis, M. kansasii, M. szulgai, and M. marinum, but not from BCG-vaccinated individuals without disease or risk for latent TB infections [no reference provided in the evidence, but mentioned in the question].
• The test should not be used as the sole means for diagnosing or excluding active or latent tuberculosis, and caution is warranted when evaluating results from patients with certain clinical conditions, such as diabetes, silicosis, chronic renal failure, and hematological disorders [no reference provided in the evidence, but mentioned in the question].

Considerations for Interpretation of Test Results

• Indeterminate results may warrant careful assessment and re-evaluation, but should not preclude initiation of anti-TNF treatment 3.
• The T-SPOT.TB test may be used as a complementary diagnostic tool for latent tuberculosis infection, particularly in cases of indeterminate QuantiFERON-TB Gold Plus results 4.
• Risk factors for false-negative results with the QuantiFERON-TB Gold In-Tube assay include immunosuppressant diseases and lower platelet, protein, and albumin levels 5.
• The QuantiFERON-TB Gold In-tube assay may not be useful for monitoring the effect of preventive therapy, as most patients remain positive after treatment 6.
• Predictors for a positive QuantiFERON-TB-Gold test in BCG-vaccinated adults with a positive tuberculin skin test include having an abnormal chest radiograph consistent with healed TB, a TST induration of ≥16mm, and birth in a high-incidence country 7.