Does a positive Quantiferon (Interferon-Gamma Release Assay) -TB Gold Plus test result in a patient who received the BCG (Bacillus Calmette-Guérin) vaccine indicate active tuberculosis (TB) or is it due to the vaccine?

From the Guidelines

A positive QuantiFERON-TB Gold Plus test in a patient who has received the BCG vaccine likely indicates true TB infection rather than a false positive from the vaccine. Unlike the tuberculin skin test (TST), the QuantiFERON-TB Gold Plus is an interferon-gamma release assay (IGRA) that is specifically designed to not cross-react with BCG vaccination, as it measures the immune response to specific TB proteins such as early secretory antigenic target-6 (ESAT-6) and culture filtrate protein 10 (CFP-10) that are absent from the BCG vaccine strain, making it more specific for detecting actual TB infection 1.

Key Considerations

• The patient should be evaluated further to determine if they have latent TB infection or active TB disease, which typically includes a thorough medical history, physical examination, chest X-ray, and possibly sputum tests if active TB is suspected 1.
• If active TB is ruled out, the patient likely has latent TB infection and may be a candidate for preventive therapy, typically isoniazid for 6-9 months or a shorter rifampin-based regimen.
• The decision to treat latent TB depends on factors such as age, overall health, and risk factors for progression to active disease, including those with HIV infection, infants and children aged <5 years, and persons receiving immunosuppressive therapy 1.

Evaluation and Treatment

• A chest radiograph should be examined for abnormalities consistent with TB disease, and additional medical evaluation would depend on clinical judgment on the basis of findings from history, physical examination, and chest radiography 1.
• HIV counseling, testing, and referral is recommended because HIV infection increases the suspicion for TB and the urgency of treating LTBI 1.
• After TB has been excluded, treatment of LTBI should be considered, taking into account the patient's individual risk factors and medical history 1.

From the Research

Interpretation of Quantiferon-TB Gold Plus Test Results

• A positive Quantiferon-TB Gold Plus test result in a patient who received the BCG vaccine does not necessarily indicate active tuberculosis (TB) 2, 3, 4, 5.
• The test measures the release of interferon-gamma in response to TB antigens, which can be triggered by both active TB and latent TB infection (LTBI) 6, 4.
• BCG vaccination can cause a false-positive result in the tuberculin skin test (TST), but the Quantiferon-TB Gold Plus test is more specific for TB infection and less likely to be affected by BCG vaccination 2, 3, 4, 5.

Factors Influencing Test Results

• The likelihood of a positive Quantiferon-TB Gold Plus test result is higher in individuals from high-incidence countries and those with abnormal chest radiographs consistent with healed TB 3.
• The test result can also be influenced by the patient's immune status, with immunocompromised individuals more likely to have indeterminate results 6.
• The use of anti-tumor necrosis factor-alpha (TNF-α) agents can increase the risk of active TB, and screening with the Quantiferon-TB Gold Plus test can help identify patients at risk 5.

Clinical Implications

• The Quantiferon-TB Gold Plus test can be used to screen for latent TB in patients who have received BCG vaccination, particularly in countries with high BCG vaccination rates 5.
• A positive test result should be interpreted in the context of the patient's clinical history, radiographic findings, and risk factors for TB 3, 4.
• The test can help reduce the number of false-positive diagnoses and unnecessary treatment for latent TB, particularly in low-risk individuals 2, 5.