The Quantiferon-TB Gold Plus (QFT-Plus) is a modern blood test used worldwide for screening for Mycobacterium tuberculosis infection, the bacteria that causes tuberculosis (TB). This test is an improvement over older screening methods, offering a laboratory-based assessment of the body’s immune response. A negative result generally means the person has not been infected, but understanding the science behind the test is important for accurate interpretation.
Understanding the Quantiferon-TB Gold Plus Test
The Quantiferon-TB Gold Plus is an Interferon-Gamma Release Assay (IGRA) that detects immune memory to the TB bacteria. The test mixes a patient’s blood sample with specific synthetic proteins that mimic antigens found only on M. tuberculosis. If the patient has been infected, specialized white blood cells (T-cells) recognize these antigens and release interferon-gamma (IFN-γ).
This release of IFN-γ is the measured response that determines a positive result. The QFT-Plus uses antigens like ESAT-6 and CFP-10, which are not shared by the BCG vaccine or most environmental mycobacteria. This specificity significantly reduces the chance of a false-positive result compared to the older Tuberculin Skin Test (TST).
A key advancement of the QFT-Plus is its use of two antigen tubes (TB1 and TB2) optimized to stimulate both CD4 and CD8 T-cells. The inclusion of the CD8 T-cell response provides a more comprehensive view of the patient’s cell-mediated immune response to the infection. Furthermore, the QFT-Plus requires only a single blood draw visit, unlike the TST, which requires a follow-up visit several days later.
Interpreting a Negative Result
A negative QFT-Plus result is the most common outcome and signifies that M. tuberculosis infection is unlikely. This means the patient’s T-cells did not recognize the TB antigens and did not release a measurable amount of interferon-gamma. For the average person undergoing routine screening, a negative result indicates that no further testing or treatment for TB infection is needed.
The result is determined by comparing the IFN-γ levels in the antigen tubes against a negative control tube, which measures background IFN-γ production. If the IFN-γ level released in response to the TB antigens is below a specific cutoff value, the test is interpreted as negative. This objective, laboratory-based reading contrasts with the TST, which relies on a healthcare provider visually measuring a skin induration.
A negative result means the immune system has not developed a memory response to the TB bacteria. However, it does not completely rule out infection, especially following very recent exposure or if the person has a compromised immune system. Clinical interpretation must always consider the individual’s medical history and risk factors.
Distinguishing Latent Infection from Active Disease
The primary purpose of the QFT-Plus is to detect Latent TB Infection (LTBI), which differs fundamentally from Active TB Disease. In LTBI, M. tuberculosis bacteria are present but kept dormant and inactive by the immune system. People with LTBI are asymptomatic, feel healthy, and cannot spread the bacteria to others.
Active TB Disease occurs when the bacteria multiply and overwhelm the immune defenses, causing noticeable illness. Individuals with active disease typically experience symptoms such as a prolonged cough, unexplained weight loss, night sweats, and fever. This form of the disease is infectious, transmitted through the air when the person coughs or sneezes.
Without treatment, about five to ten percent of people with LTBI will develop active TB disease, with the highest risk occurring within the first two years after infection. The QFT-Plus confirms the presence of the immune response to the bacteria, but it cannot differentiate between the asymptomatic latent state and the symptomatic active disease.
Reliability and Clinical Follow-Up
The QFT-Plus is reliable, but a negative result must be interpreted considering exposure and immune status. One limitation is the “window period,” the time between initial infection and the development of a detectable immune response. If a person was recently exposed, their T-cells may not have had enough time to become sensitized, potentially leading to a false-negative result.
A false-negative result can also occur due to an impaired or weakened immune system (immunosuppression). Patients taking certain medications or those with conditions like HIV may not mount a sufficient IFN-γ response, even if infected. In these cases, the predictive value of a negative QFT-Plus result is uncertain.
A negative result following a known, recent, high-risk exposure may warrant repeat testing. Clinicians often recommend a second QFT-Plus test eight to ten weeks after the last exposure to ensure the window period has passed. The final assessment of TB infection status rests with a healthcare professional who considers the test result alongside all epidemiological, historical, and clinical findings.