Tuberculosis (TB) is a serious bacterial infection caused by Mycobacterium tuberculosis, which most often targets the lungs but can affect other organs. The purpose of TB screening is to detect infection before it progresses to active disease, known as latent TB infection (LTBI). Receiving a “borderline” result on a TB test can be confusing, as it creates uncertainty regarding whether an infection is present. This ambiguous finding is not uncommon and necessitates a deeper understanding of how these tests work and the biological factors that influence their outcome.
Understanding TB Screening Methods
Two primary methods are used to screen for TB infection: the Tuberculin Skin Test (TST), also called the PPD test, and Interferon Gamma Release Assays (IGRAs), which are blood tests. The TST involves injecting purified protein derivative (PPD) under the skin. A healthcare worker measures the diameter of the resulting hard swelling, or induration, 48 to 72 hours later to interpret the result.
IGRAs, such as the QuantiFERON-TB Gold Plus and T-SPOT.TB, measure the immune system’s response to specific TB antigens in a blood sample. They quantify the release of interferon-gamma, a signaling protein produced by T-cells that have encountered the TB bacteria. The IGRA provides a result from a single patient visit, unlike the TST, which requires two visits.
Defining the Borderline Result
A borderline result signifies a zone of uncertainty in the measurement of the immune response, meaning the result is neither clearly negative nor clearly positive. For the TST, a positive result is defined by the size of the induration, but the required size threshold varies depending on the patient’s risk factors. For example, a reaction of 5 millimeters may be considered positive for a high-risk individual, while 15 millimeters is required for a person with no known risk factors. A borderline TST result often falls near the specific threshold for a patient’s risk group, creating clinical ambiguity.
For IGRAs, which provide a quantitative value like the level of interferon-gamma in the blood, “borderline” refers to a measurement close to the positive cutoff. For instance, the cutoff for a positive result in a QuantiFERON test is typically 0.35 IU/mL, but a result slightly above or below this may be placed in a “gray zone” or borderline category by the lab. The T-SPOT.TB assay explicitly includes a borderline result category when the immune cell spots fall within a specific uncertain range. This ambiguous result indicates that the immune system’s reaction was too weak to be definitively positive but too strong to be definitively negative.
Common Causes of Test Ambiguity
Prior vaccination with the Bacillus Calmette-Guérin (BCG) vaccine is a frequent cause of a borderline or false-positive TST result. The BCG vaccine uses a weakened strain of Mycobacterium bovis, which shares antigens with M. tuberculosis. The PPD solution used in the skin test contains these shared antigens, causing a cross-reaction that can lead to a positive or borderline reading even without a true TB infection.
The degree of TST cross-reactivity from BCG depends heavily on the patient’s age at vaccination and the time elapsed since they received the shot. BCG vaccination in infancy has a minimal effect on the TST result ten years later, but vaccination after the first birthday produces more frequent and persistent false-positive results. Exposure to environmental non-tuberculous mycobacteria (NTM), which are common in soil and water, can also cause a cross-reaction in the TST. Unlike the TST, IGRAs use more specific antigens that are largely absent from the BCG strain and most NTM, making them less susceptible to false-positive readings.
The immune status of the individual is another factor contributing to ambiguous results in both test types. A weakened immune system, often due to conditions like HIV or immunosuppressive medications, may not produce a robust immune response. This can lead to a false-negative or borderline result, particularly in the IGRA, because immune cells fail to release sufficient interferon-gamma. Technical variability, such as improper handling of the blood sample or delays in lab processing, can also push a result into the borderline zone.
Necessary Follow-Up and Clinical Evaluation
A borderline TB test result is not a final diagnosis but a trigger for further clinical action, as it means the initial test did not provide definitive information. The healthcare provider will first conduct a thorough clinical evaluation, reviewing the patient’s medical history, including any potential exposure to active TB and travel to high-prevalence countries. This risk assessment is critical for interpreting the ambiguous test result in the proper context.
The most common next step is repeat testing, either by using the same test after a short period, typically four to six weeks, or by switching to the alternative test method. For example, if the initial TST was borderline, an IGRA may be ordered to overcome the TST’s limitations regarding BCG vaccination. If the repeat test remains borderline or becomes positive, a chest X-ray is usually ordered to rule out active TB disease, which is a contagious and more serious condition. The final decision—whether to diagnose the patient with latent TB infection or no infection—is based on combining the test results with the full clinical picture and risk factors.