Tuberculin is a solution containing a purified protein derivative (PPD) derived from the bacterium that causes tuberculosis, Mycobacterium tuberculosis. Its use is centered around a diagnostic procedure known as the Tuberculin Skin Test (TST), also called the Mantoux test. The purpose of this test is to determine if a person's immune system has been sensitized by a prior exposure to the TB bacteria, which could indicate a latent TB infection (LTBI). A positive result from this test does not mean a person has active, contagious TB disease, but rather that the bacteria is present in their body. Further testing is required to determine the stage of the infection.
How the Tuberculin Skin Test Works
The TST is a procedure that relies on a person's immune system memory. The process is straightforward and typically completed in two healthcare visits:
- Administration: A healthcare professional injects a small amount of the tuberculin PPD solution into the inner surface of the forearm. The injection is administered intradermally, just under the top layer of skin, creating a small, pale bump or wheal. The test site may be marked with a pen to help with locating it later.
- Observation: The individual must return to the clinic for a follow-up visit within 48 to 72 hours. This is a critical timeframe because the test relies on a delayed-type hypersensitivity reaction, which takes time to develop.
- Reading the Result: A trained healthcare worker measures the area of induration, or firm swelling, that has formed at the injection site. Redness is not measured. The size of the induration, measured in millimeters, is used to determine if the result is positive, negative, or inconclusive.
Interpreting TST Results Based on Risk Factors
The size of induration that is considered a positive result varies depending on a person's risk factors for TB infection and progression to disease.
- 5 or more millimeters is considered positive for:
- People living with HIV
- Recent contacts of individuals with infectious TB
- People with suggestive chest x-ray findings
- Organ transplant recipients
- Other immunosuppressed individuals
- 10 or more millimeters is considered positive for:
- People who have immigrated from high-prevalence countries
- Intravenous drug users
- Residents or employees of high-risk congregate settings (e.g., homeless shelters, correctional facilities)
- Certain medical conditions that increase TB risk (e.g., diabetes)
- Children under 5 years of age
- 15 or more millimeters is considered positive for:
- People with no known risk factors for TB exposure
Potential False Results and Limitations
While the TST is a valuable tool, it is not without its limitations, which can lead to false-positive or false-negative results. Understanding these factors is important for accurate diagnosis.
Causes of false-positive TST results:
- Previous vaccination with the Bacillus Calmette-Guérin (BCG) vaccine, which is common in many parts of the world.
- Infection with non-tuberculous mycobacteria.
- Incorrect administration or interpretation of the test.
Causes of false-negative TST results:
- Anergy, an inability to react to the test due to a weakened immune system, often seen in cases of HIV or advanced cancer.
- Recent TB infection, as it can take 8 to 10 weeks for the immune system to react.
- Very young age (under 6 months).
- Recent live-virus vaccination.
- Severe, life-threatening illnesses.
Tuberculin Skin Test vs. TB Blood Tests
Today, the TST is not the only option for detecting TB infection. Interferon-Gamma Release Assays (IGRAs), or TB blood tests, are a modern alternative recommended by the CDC in many cases. These tests measure the release of a specific protein (interferon-gamma) by T-cells in a blood sample when exposed to TB antigens.
| Feature | Tuberculin Skin Test (TST) | TB Blood Test (IGRA) |
|---|---|---|
| Number of Visits | Requires two visits: one for injection, one for reading. | Requires only one visit for a blood draw. |
| Effect of BCG Vaccine | Can produce false-positive results in those with a history of BCG vaccination. | Not affected by previous BCG vaccination. |
| Accuracy | Subject to potential biases and errors in placement and reading, with lower specificity in vaccinated individuals. | Offers objective results and higher specificity, especially in BCG-vaccinated individuals. |
| Timing of Results | Takes 48 to 72 hours for a healthcare provider to read the reaction. | Results are typically available within 24 hours. |
| Cost | Generally less expensive. | Can be more costly. |
| Reading | Interpretation can be subjective, based on manual measurement and reader experience. | Objective, laboratory-based results. |
The Evolution of Tuberculin's Role
Robert Koch's discovery of tuberculin in the late 19th century was met with immense hope, but the disappointment of it not being a cure reshaped its role. Subsequent research, particularly by Clemens von Pirquet, refined its use into the diagnostic tool we know today. Early 20th-century public health campaigns relied heavily on tuberculin screening to control the spread of TB, leading to a deeper understanding of the disease's epidemiology. While modern IGRAs offer certain advantages, particularly in terms of objectivity and avoiding false positives related to BCG vaccination, the TST remains a widely used and reliable diagnostic method in many settings.
Conclusion
Tuberculin is used for one primary purpose: diagnosing a person's prior exposure to the bacteria that cause tuberculosis through a skin test. While it cannot differentiate between latent and active TB disease, a positive tuberculin skin test signals the need for further diagnostic investigation, such as a chest x-ray or sputum test, to guide appropriate treatment. Its long history, coupled with the development of alternative blood tests, underscores the ongoing importance of accurate and accessible diagnostic tools in controlling and treating tuberculosis worldwide.
