Tuberculosis (TB) is an infectious disease primarily affecting the lungs, caused by the bacterium Mycobacterium tuberculosis. It spreads through the air when a person with active TB disease coughs, speaks, or sneezes, releasing tiny airborne droplets containing the bacteria. Exposure occurs when an individual inhales these droplets, but this does not immediately mean they are infected or will become sick. The global health burden of this bacterium is significant, as an estimated one-fourth of the world’s population has been infected with TB bacteria. The goal of testing after exposure is to determine if the immune system has successfully mounted a response, indicating that the bacteria have taken hold.
The Different TB Tests and What They Detect
Screening for TB infection relies on detecting the body’s immune memory of the bacteria rather than the bacteria itself. The two main tests for this initial screening are the Tuberculin Skin Test (TST) and the Interferon Gamma Release Assay (IGRA). Both tests are designed to identify an infection, not to distinguish between a contained infection and an active, multiplying disease.
The TST, often called the Mantoux test, involves injecting a small amount of purified protein derivative (PPD) under the skin of the forearm. If a person has been infected, their T-cells will recognize the PPD, causing a localized, delayed-type hypersensitivity reaction that is measured 48 to 72 hours later. A drawback of the TST is that it can produce a false-positive result in individuals who have received the Bacille Calmette-Guérin (BCG) vaccine.
The IGRA is a blood test that offers an alternative to the skin test and is generally preferred in BCG-vaccinated individuals. This test detects a cellular immune response by mixing a blood sample with specific TB antigens. If the person has been infected, their T-cells will release the signaling molecule interferon-gamma (IFN-γ), which is then measured by the laboratory. Unlike the TST, the IGRA is not affected by prior BCG vaccination, providing a more specific result.
The Testing Window: When Immunity Registers
The timing of a positive test result depends on the speed at which the body’s immune system recognizes and responds to the bacteria. Testing immediately after exposure is ineffective because the immune system has not had sufficient time to build up a detectable response. This period between initial infection and the development of a measurable immune reaction is called the window period.
The immune response needed for a positive test result typically takes between two and eight weeks to develop. Therefore, an initial test within the first few weeks of exposure may be negative even if a person has become infected. The initial test serves as a baseline to ensure the person was not already infected before the known exposure event.
If an initial test is negative following a known exposure, a repeat test is necessary to rule out infection. Health guidelines recommend re-testing approximately 8 to 10 weeks after the last date of exposure. This waiting period allows virtually all individuals who have become infected to develop the T-cell memory required for a positive result. If the second test remains negative, the person likely did not become infected.
Distinguishing Between Infection and Active Disease
A positive result from either the TST or the IGRA indicates that the individual is infected with M. tuberculosis bacteria. The positive test does not specify whether the person has Latent TB Infection (LTBI) or Active TB Disease. This distinction is important because the two conditions require different medical approaches.
Latent TB Infection (LTBI)
Latent TB Infection means the bacteria are present but inactive, with the immune system successfully containing them. Individuals with LTBI are asymptomatic, do not feel sick, and cannot spread the bacteria to others. Without treatment, the contained infection can progress to active disease, particularly if the immune system becomes weakened.
Active TB Disease
Active TB Disease occurs when the bacteria overcome the immune system and begin multiplying. Individuals with active disease usually feel sick, often presenting with symptoms such as a prolonged cough, fever, night sweats, and unexplained weight loss. Active disease is contagious and requires a more intense, multi-drug treatment regimen.
Following a positive screening test, the next step is a thorough symptom evaluation and usually a chest X-ray to check for signs of active disease in the lungs. If the chest X-ray is abnormal or if the person has symptoms, further diagnostic tests are performed, such as collecting sputum samples for culture or a Nucleic Acid Amplification Test (NAAT). These additional steps are necessary to confirm if the infection is active and to guide appropriate treatment.