The PPD test, also known as the Mantoux tuberculin skin test, is a screening tool used to determine if a person has been infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). The test works by injecting a small amount of PPD solution, which contains specific proteins from the bacteria, just beneath the skin of the forearm. If a person has previously been exposed to TB, their sensitized immune cells recognize these proteins, triggering a localized, delayed-type hypersensitivity reaction. This reaction indicates the presence of a latent TB infection, not necessarily active disease, and requires a follow-up assessment by a medical professional.
The Critical Reading Window
The accuracy of the PPD test relies entirely on reading the reaction within a very specific timeframe after the injection. The test must be read between 48 and 72 hours (two to three days) following the initial administration. This window captures the peak of the immune response, which is a delayed-type hypersensitivity reaction.
If the test is evaluated before the 48-hour mark, the immune response may not have fully developed, potentially leading to a false-negative result. Conversely, if the reading is performed after 72 hours, the reaction often begins to subside, which can cause the size of the reaction to be underestimated. If the result is not assessed within the 48- to 72-hour period, the PPD test is considered invalid and must be repeated.
How to Measure the Reaction Site
Reading the PPD test involves measuring the diameter of the hardened swelling. This measurement must focus exclusively on the induration, which is the raised, firm, palpable area of swelling, and ignore any surrounding redness or bruising, known as erythema. The erythema is not used in the interpretation of the result because it does not indicate a specific immune response to the TB proteins.
To accurately find the edges of the induration, the healthcare provider should lightly feel the area of the forearm with their fingers, a process called palpation. Gently stroking a ballpoint pen toward the center of the reaction from two opposite directions is a useful technique. The tip of the pen will catch or stop at the distinct, raised edge of the induration.
The diameter of this indurated area is then measured in millimeters using a flexible ruler. The measurement must be taken transversely, or perpendicular, to the long axis of the forearm. This ensures a consistent and standardized measurement, regardless of the shape of the reaction. If there is no palpable induration, the result is recorded as 0 millimeters.
Defining a Positive Result
The reading in millimeters does not automatically determine if the test is positive; instead, the interpretation is tiered and depends on the patient’s individual risk factors for TB exposure or disease progression. The size of the induration that is considered positive is lower for high-risk individuals, reflecting a greater concern for infection in these groups. A positive result suggests that the person has been infected with TB bacteria, though further diagnostic tests are necessary to rule out active disease.
The smallest positive cutoff is an induration of 5 millimeters or more, which applies to the highest-risk groups. These individuals are at the greatest risk for developing active TB disease if infected. High-risk groups include:
- Individuals with HIV.
- Recent close contacts of a person with infectious TB.
- Organ transplant recipients.
- People who are significantly immunosuppressed (e.g., those on long-term corticosteroid therapy).
A larger induration of 10 millimeters or more is considered positive for a moderate-risk group. This category includes individuals with clinical risk factors or those exposed to high-risk environments:
- Recent immigrants from countries where TB is common.
- Individuals who inject drugs.
- Residents or employees of high-risk congregate settings (e.g., prisons or hospitals).
- Children under the age of four.
- People with certain chronic medical conditions (e.g., diabetes or severe kidney disease).
Finally, the largest cutoff is an induration of 15 millimeters or more, which is considered positive only for people with no known risk factors for TB. This tiered system highlights that a measurement of, for example, 12 millimeters, would be a positive result for a recent immigrant but a negative result for an otherwise healthy person with no known exposure. The interpretation must always be made by a healthcare provider who can accurately assess the patient’s clinical history and risk profile.
Situations That Influence Interpretation
Certain factors can complicate the interpretation of the PPD test result. One common issue is a prior vaccination with the Bacille Calmette-Guérin (BCG) vaccine, which is given in many parts of the world but not routinely in the United States. The BCG vaccine is made from a weakened strain of Mycobacterium bovis and can cause a cross-reaction, resulting in a false-positive PPD test.
This false positivity often fades over time, particularly seven years after vaccination, and a strongly positive reaction of greater than 14 millimeters is unlikely to be solely due to the BCG vaccine. Because the effect of the vaccine is variable, and because a positive result may still indicate a true latent infection, the history of BCG vaccination is disregarded during interpretation, and a positive result is followed up with additional testing.
Another factor is a weakened immune system, or immunosuppression, which can cause a false-negative result, even if the person is infected with TB. When the immune system is significantly compromised due to conditions like HIV or certain medications, the body cannot mount the necessary delayed hypersensitivity response to the PPD injection. This inadequate reaction means the test result will show no or minimal induration, incorrectly suggesting the absence of TB infection. In such cases, alternative testing methods, such as a blood test called an Interferon-Gamma Release Assay (IGRA), may be preferred for a more reliable diagnosis.