The Tuberculin Skin Test (TST), also known as the Mantoux test, is a common method used to determine if an individual has been infected with Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB). A “false positive” result means the test indicates a condition is present when it is not actually there. Understanding the reasons behind a false-positive TST result is important for accurate diagnosis and management.
Understanding the TST and Its Mechanism
The TST involves injecting a small amount of tuberculin purified protein derivative (PPD) into the inner surface of the forearm, creating a pale, raised area on the skin, known as a wheal. After 48 to 72 hours, a healthcare professional measures the reaction, specifically looking for induration, which is a firm, raised, hardened area. Redness around the site is not measured.
A positive TST result indicates that the person’s immune system has developed a response to tuberculosis proteins. This response suggests past exposure to Mycobacterium tuberculosis or similar substances, but it does not necessarily mean the individual has active TB disease. The test measures a delayed-type hypersensitivity reaction, an immune response where specialized white blood cells react to the injected proteins.
Primary Causes of False-Positive Results
Several factors can lead to a false-positive TST result, indicating a positive reaction even when there is no true Mycobacterium tuberculosis infection. These include prior vaccination, exposure to other types of bacteria, and issues with the test procedure itself.
The Bacille Calmette-Guérin (BCG) vaccine, used in many parts of the world to prevent tuberculosis, is a common cause of false-positive TST results. This vaccine contains a weakened strain of Mycobacterium bovis, closely related to Mycobacterium tuberculosis. Individuals who have received the BCG vaccine can develop an immune response that cross-reacts with the tuberculin in the TST. The effect of BCG on TST reactivity can diminish over time, particularly more than 10 years after vaccination, but it can still influence results.
Infection with nontuberculous mycobacteria (NTM) can also cause a false-positive TST. NTM are environmental bacteria found in soil and water that are related to Mycobacterium tuberculosis but typically do not cause tuberculosis disease. Exposure to these common bacteria can trigger an immune response that cross-reacts with the tuberculin antigens used in the TST, leading to a positive result without actual TB infection.
Technical errors during the administration or interpretation of the TST can also contribute to false positives. Incorrect injection technique, such as injecting the tuberculin too deeply or using the wrong amount of solution, can affect the test’s accuracy. Errors in measuring the induration, for example, measuring redness instead of just the raised, hardened area, can also lead to misinterpretation of the result.
Confirming a False-Positive Result
When a false-positive TST result is suspected, further testing is often recommended to clarify the individual’s true infection status. Interferon Gamma Release Assays (IGRAs) are blood tests that help differentiate between a true Mycobacterium tuberculosis infection and a false positive caused by BCG vaccination or most NTM infections. Common IGRA tests include the QuantiFERON-TB Gold (QFT) test and the T-SPOT.TB test. These tests measure the immune response by detecting interferon-gamma released by T-cells when exposed to specific Mycobacterium tuberculosis antigens.
These specific antigens, such as ESAT-6 and CFP-10, are present in Mycobacterium tuberculosis but are generally absent from all currently used BCG vaccine strains and most NTM. This specificity means that IGRAs are less affected by prior BCG vaccination or exposure to NTM, making them a more reliable follow-up test. A positive IGRA suggests a true Mycobacterium tuberculosis infection, while a negative IGRA in someone with a positive TST often indicates the TST was a false positive.