The QuantiFERON-TB Gold test is a blood-based diagnostic tool used to identify individuals infected with Mycobacterium tuberculosis, the bacteria responsible for tuberculosis (TB). A false positive result indicates the test suggests an infection when none exists. This article explores the reasons why a QuantiFERON-TB Gold test might yield such a misleading outcome.
The QuantiFERON-TB Gold Test Explained
The QuantiFERON-TB Gold test is an Interferon-Gamma Release Assay (IGRA) designed to detect latent TB infection. This test measures the immune system’s specific response to Mycobacterium tuberculosis antigens. When blood from an infected individual is exposed to these antigens in a test tube, their T-cells, a type of white blood cell, release interferon-gamma (IFN-γ).
The test involves collecting a blood sample into specialized tubes containing specific TB antigens (ESAT-6, CFP-10, and TB7.7), along with positive and negative controls. These antigens are specific to Mycobacterium tuberculosis and are absent from most non-tuberculous mycobacteria and all BCG vaccine strains. After incubation, the amount of IFN-γ produced is measured.
This method offers advantages over older screening tools like the tuberculin skin test (TST), as its results are not influenced by prior Bacille Calmette-Guérin (BCG) vaccination. The QuantiFERON-TB Gold test is widely used for screening large populations, including healthcare workers and individuals in contact tracing, due to its high specificity and sensitivity. However, a positive result does not distinguish between active TB disease and latent TB infection.
Factors Leading to False Positive Results
Despite its high specificity, the QuantiFERON-TB Gold test can sometimes produce a false positive result. The false positive rate is generally low, estimated to be around 2-3%. Several factors can contribute to these outcomes.
Laboratory or technical issues are a common source of errors. These include improper blood collection, such as filling specialized tubes with too much or too little blood. Delays in processing samples, incorrect incubation temperatures, or contamination of samples or reagents during handling can also lead to erroneous results. Manufacturing defects in antigen vials from a specific lot have also been identified as a cause for elevated false positive rates.
Biological variability in an individual’s immune response can also contribute. While the test is highly specific, certain medical conditions like autoimmune diseases, chronic inflammatory disorders, or other infections can cause a temporary, non-specific activation of the immune system. This generalized immune activation might interfere with the test’s accuracy, leading to a false positive.
Cross-reactivity, though less common with QuantiFERON-TB Gold compared to the tuberculin skin test, can still occur with certain non-tuberculous mycobacteria. Some species, such as Mycobacterium kansasii, Mycobacterium szulgai, or Mycobacterium marinum, possess antigens that can trigger an immune response similar to that caused by Mycobacterium tuberculosis. Although the QuantiFERON-TB Gold test is engineered to minimize this, it remains a consideration in specific cases.
Next Steps After a False Positive Result
When a QuantiFERON-TB Gold test yields a positive result, a comprehensive clinical evaluation becomes necessary. A healthcare provider will thoroughly review the patient’s medical history, assess any symptoms, and consider their individual risk factors for TB exposure. This initial assessment helps determine the likelihood of a true infection versus a false positive.
To confirm or rule out an actual TB infection, further diagnostic testing is performed. This may involve repeating the QuantiFERON-TB Gold test with a new blood sample to check for consistency. Other common confirmatory tests include a chest X-ray to look for signs of active TB disease in the lungs, and if active disease is suspected, sputum tests may be ordered. These additional tests help differentiate between active TB disease, latent TB infection, or no infection at all.
In ambiguous or complex cases, consultation with an infectious disease specialist may be recommended. These specialists have expertise in diagnosing and managing TB and can provide guidance on further testing or management strategies. A single positive QuantiFERON-TB Gold test result, especially without clinical symptoms or known risk factors, does not automatically confirm TB infection. Further investigation is always needed to ensure an accurate diagnosis and appropriate course of action.