The QuantiFERON-TB Gold Plus (QFT-Plus) test is a modern blood test used to screen for infection with the bacterium Mycobacterium tuberculosis, which causes tuberculosis (TB). This test is a type of Interferon-Gamma Release Assay (IGRA) that does not look for the bacteria itself but measures the body’s immune response to specific TB antigens. When T-cells from a person infected with TB are exposed to these antigens, they release a signaling protein called interferon-gamma (IFN-γ). The test then quantifies the level of this IFN-γ to determine the likelihood of an M. tuberculosis infection.
Defining the Key Result Categories
The QuantiFERON test results are categorized as Positive, Negative, or Indeterminate, based on specific immunological measurements. A Positive result signifies that the level of IFN-γ released by T-cells in response to TB-specific antigens has crossed a predetermined threshold. This indicates a memory immune response to the TB bacteria.
A Negative result means there was no significant IFN-γ production when the blood sample was exposed to the TB antigens, suggesting infection is unlikely. For the result to be validly negative, the positive control tube, which contains the general immune stimulant mitogen, must show an adequate IFN-γ response.
An Indeterminate result is a technical outcome meaning the test could not provide a clear positive or negative determination. This occurs when the control tubes fail, either due to a low response to the mitogen or an excessively high background level of IFN-γ in the negative control tube.
Implications of a Positive Result
A positive QuantiFERON result signifies infection with M. tuberculosis bacteria. This result confirms the presence of infection but cannot distinguish between Latent TB Infection (LTBI) and Active TB Disease. It simply indicates the immune system has encountered the bacteria and developed a memory response.
Following a positive result, a thorough medical evaluation is necessary to determine the clinical status. This evaluation typically includes a physical examination, medical history review, and a chest X-ray to look for signs of active disease. If the chest X-ray is clear and the person has no symptoms, the diagnosis is likely LTBI.
LTBI means the bacteria are dormant, controlled by the immune system, and the person is not contagious. Since the bacteria can become active later, preventive treatment is often recommended to reduce the lifetime risk of developing active disease. If the chest X-ray or physical exam suggests possible disease, further tests, such as sputum samples, are required to confirm Active TB Disease.
Active TB is a serious condition where the bacteria are multiplying and causing illness, making the person potentially contagious if the disease is pulmonary. Active TB treatment is intensive and differs significantly from the preventative regimen used for LTBI. Therefore, the primary goal after a positive test is to quickly rule out active disease before proceeding with treatment for latent infection.
Causes and Actions for Indeterminate Results
An indeterminate result signals that the test was technically unreliable. This outcome relates to the performance of the control tubes within the assay and has two main causes. One cause is a low response to the mitogen control, which is included to ensure the patient’s T-cells are capable of producing IFN-γ.
A low mitogen response often indicates a suppressed immune system, potentially due to conditions like HIV, immunosuppressive medications, or advanced age. If immune cells cannot respond to the general stimulant, they cannot reliably respond to the specific TB antigens, leading to an inconclusive result. Technical issues, such as improper handling or delayed processing, can also cause a low mitogen response.
The second cause is an elevated background level of IFN-γ in the Nil control tube, which measures non-specific, circulating IFN-γ. If this background level is too high, it interferes with the accurate measurement of the TB-specific response. The required action for any indeterminate result is to repeat the QuantiFERON test with a newly collected sample.
If the repeat test is also indeterminate, especially due to a consistently low mitogen response, it suggests a persistent issue with the patient’s immune function. In such cases, the clinical context and risk factors for TB infection become paramount. A healthcare provider may then need to consider alternative testing methods or a clinical decision based on the overall picture.
Interpreting Negative Results and Test Limitations
A negative QuantiFERON result provides reassurance that the individual is not infected with M. tuberculosis. For most healthy adults, a negative result means no further evaluation or action is necessary regarding TB infection. The test’s ability to exclude infection is high, especially in low-risk populations.
However, a negative result is not an absolute guarantee of no infection due to the “window period.” This is the 4 to 8 week time frame between initial exposure and when the immune system develops a detectable IFN-γ response. If a person was tested too soon after recent exposure, the result could be a false negative, necessitating a repeat test 8 to 10 weeks after the exposure ended.
The test has limitations in certain populations, particularly those who are significantly immunocompromised. Since the test measures the immune system’s response, individuals with severely weakened immunity, such as those with advanced HIV or those undergoing intense immunosuppressive therapy, may not mount a detectable reaction even if infected. This can result in a false-negative test, underscoring the need for clinical judgment that incorporates medical history and risk factors alongside the result.