Tuberculosis (TB) is a serious bacterial infection primarily affecting the lungs, caused by the bacterium Mycobacterium tuberculosis. Screening tests are widely used to identify infected individuals, allowing for timely treatment to prevent progression to active disease. These methods detect the body’s immune response to the bacteria, but they are not perfect diagnostic tools. A TB screening test can yield a positive result even when a true infection with M. tuberculosis is absent, which is known as a false positive.
Types of Tuberculosis Screening Tests
Two primary methods are used for initial screening: the Tuberculin Skin Test (TST), also known as the PPD test, and the Interferon-Gamma Release Assay (IGRA). The TST involves an intradermal injection of a purified protein derivative (PPD) derived from the TB bacteria. A healthcare professional observes the injection site 48 to 72 hours later to measure the size of the resulting raised, hardened area (induration), which indicates an immune reaction.
The IGRA is a blood test. It measures the release of a specific signaling molecule, interferon-gamma (IFN-γ), from white blood cells when the sample is exposed to antigens that mimic those found in M. tuberculosis. This test offers a quantitative measurement of the immune response, unlike the visual assessment required for the TST.
Factors Leading to False Positive Results
False positive results are largely influenced by the type of screening test used. This occurs when the test detects an immune response not caused by a true M. tuberculosis infection. The Bacille Calmette-Guérin (BCG) vaccine, a vaccine for TB used in many countries outside the United States, is the most common cause of TST false positives.
The BCG vaccine contains a weakened strain of Mycobacterium bovis, which shares antigens with M. tuberculosis. When a person who received the BCG vaccine is given a TST, their immune system recognizes the PPD antigens, leading to a positive skin reaction even without genuine infection. The duration and intensity of this false positive reaction are generally greater if the vaccination was administered later than infancy or if multiple doses were received.
Another source of false-positive results, particularly with the TST, is exposure to nontuberculous mycobacteria (NTM). These are common mycobacteria found naturally in the environment, such as in soil and water. Exposure to these organisms can sensitize the immune system, leading to a cross-reaction when the PPD is introduced.
IGRA tests are significantly less susceptible to false positives from both the BCG vaccine and NTM exposure. This is because IGRA assays use antigens highly specific to M. tuberculosis that are not present in the BCG strain or most NTM. Therefore, for individuals who have received the BCG vaccine, an IGRA is often the preferred screening method.
Interpreting a True Positive Result
When factors leading to a false positive have been ruled out, a positive TB screening test signifies that the person has been infected with M. tuberculosis bacteria. However, a positive screen alone cannot distinguish between the two states of infection: latent TB infection (LTBI) and active TB disease. This distinction requires further medical evaluation.
Latent TB infection means the bacteria are present but remain dormant and inactive. In this state, the person is asymptomatic, not sick, and cannot spread the bacteria to others. The immune system has successfully contained the bacteria, which can remain alive for many years.
Active TB disease occurs when the bacteria overcome the body’s immune defenses and multiply rapidly. This condition causes the person to become ill, often presenting with symptoms like a persistent cough, fever, night sweats, and unexplained weight loss. Individuals with active disease can transmit the infection to others through the air.
A positive screening test indicates the presence of the bacteria, but it is the clinical evaluation that determines the disease state. A diagnosis of LTBI is made only after a medical assessment, including imaging and laboratory work, has confirmed that active disease is not present. Treatment for LTBI is then offered to prevent the potential progression to the active, contagious form of the disease.
Confirmatory Testing and Diagnosis
After an initial positive screening test, a comprehensive medical evaluation is required to determine the status of the infection. This evaluation begins with a detailed medical history, a physical examination, and a chest radiograph. The chest X-ray looks for physical evidence of active disease, such as infiltrates or cavities in the lungs.
If the chest radiograph is normal and the person shows no symptoms, a diagnosis of Latent TB Infection is typically made. If the X-ray is abnormal or if the patient is experiencing symptoms suggestive of TB, definitive laboratory testing is necessary to confirm active disease and check for drug resistance.
Confirming active TB disease involves collecting respiratory samples, such as sputum, for bacteriologic examination. These samples are tested using acid-fast bacilli (AFB) smears and are cultured to allow the bacteria to grow, which provides a definitive identification of M. tuberculosis. Nucleic acid amplification tests (NAATs) can also be used to rapidly detect the genetic material of the bacteria in the sample.