Tuberculin Skin Test (Mantoux test): Principle, Procedure, Results

The Mantoux tuberculin skin test is the standard method of determining whether a person is infected with Mycobacterium tuberculosis or has exposure to tubercle bacilli. Koch developed it in 1890, but the intradermal technique currently in use was described in 1912 by a French physician, Charles Mantoux, after whom the test is named.

Mantoux tuberculin skin test
Mantoux tuberculin skin test

Administration of the test

Tuberculin skin test (TST) is an intradermal injection. It is performed by injecting 0.1 ml of tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The injection should be made with a tuberculin syringe, with the needle bevel facing upward. When placed correctly, the injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter.

Principle of Mantoux tuberculin skin test

The tuberculin skin test is the classic clinical demonstration of the function of the delayed-type hypersensitivity response. When purified protein derivative (PPD) of tubercle bacilli is injected intradermally into an individual. A person exposed to the bacteria is expected to mount an immune response within 48-72 hrs leading to the formation of induration (a raised bump in the area of injection) due to the influx and activation of macrophages.

Test Procedure

  1. Allow the person to be tested to sit in a comfortable chair and place his hands on a table-turning the inner side of the forearm up.
  2. Clean the test area and allow it to air dry.
  3. Inject a standard dose of five tuberculin units (TU) (0.1ml) intradermally (into the skin) using 28 or 26-gauge needle or tuberculin syringe from which 0.1 ml can be delivered accurately. The fluid makes a little bump (wheal) under the skin. A circle may be drawn around the test area with a pen.
  4. Read the results within 48 to 72 hours.

Reading the results:

The skin test reaction should be read 48 to 72 hours after administration. The response should be measured in millimeters of the induration (palpable, raised, hardened area, or swelling). The reader should not measure erythema (redness). The diameter of the indurated area should be measured across the forearm (perpendicular to the long axis)

If a person does not return within 48-72 hours for a tuberculin skin test reading, a second test can be placed as soon as possible. There is no contraindication to repeating the TST, unless a previous TST was associated with a severe reaction.

Interpretation of Tuberculin skin test results

Interpretation of tuberculin skin tests always remain difficult and controversial. Various factors like age, immunological status coexisting illness, etc. influence its outcome. Utmost care is required while interpreting the result and giving an opinion.

According to the Center for Disease Control (CDC), skin test interpretation depends on two factors:

  • Measurement in millimeters of the induration
  • Person’s risk of being infected with TB and of progression to disease if infected

Positive Tuberculin skin test reactions:

  • An induration of 5 or more millimeters is considered positive in
    1. HIV-infected persons
    2. A recent contact with a person with TB disease
    3. Persons with fibrotic changes on chest radiograph consistent with prior TB
    4. Patients with organ transplants
    5. Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for one month or longer, taking TNF-a antagonists)
  • An induration of 10 or more millimeters is considered positive in
    1. Recent immigrants (< 5 years) from high-prevalence countries
    2. Injection drug users
    3. Residents and employees of high-risk congregate settings
    4. Mycobacteriology laboratory personnel
    5. Persons with clinical conditions that place them at high risk
    6. Children < 4 years of age
    7. Infants, children, and adolescents exposed to adults in high-risk categories
  • An induration of 15 or more millimeters is considered positive in
    • any person, including persons with no known risk factors for TB. However, targeted skin testing programs should only be conducted among high-risk groups.

Limitations of the test:

Although widely used, the test has several limitations

  1. A positive reaction may be observed in both latent and active TB infection. Therefore, it is unreliable in differentiating whether the person is currently having TB or had been infected in the past or at the carrier stage. Confirmatory tests such as chest X-ray, sputum culture, or both are usually done to rule out an active TB infection.
  2. False-Positive Reactions
    Some persons may react to the tuberculin skin test even though they are not infected with M. tuberculosis. The causes of these false-positive reactions may include, but are not limited to, the following:  
    1. Infection with nontuberculosis mycobacteria
    2. Previous BCG vaccination
    3. Incorrect method of TST administration
    4. Incorrect interpretation of reaction
    5. Wrong bottle of antigen used
  3. False-Negative Reactions

    A negative Mantoux test result usually signifies that the individual has never been exposed to M. tuberculosis. However, some factors may cause a false-negative result or diminished ability to respond to tuberculin even if the person is infected with M. tuberculosis. The reasons for these false-negative reactions may include, but are not limited to, the following:
    • Cutaneous anergy (anergy is the inability to react to skin tests because of a weakened immune system)
    • Recent TB infection (within 8-10 weeks of exposure)
    • Very old TB infection (many years)
    • Very young age (less than six months old)
    • Recent live-virus vaccination (e.g., measles and smallpox)
    • Overwhelming TB disease
    • Some viral illnesses (e.g., measles and chickenpox)
    • Incorrect method of TST administration
    • Incorrect interpretation of reaction

Who Can Receive a tuberculin skin test?

Most persons can receive a TST. TST is contraindicated only for persons with a severe reaction (e.g., necrosis, blistering, anaphylactic shock, or ulcerations) to a previous TST. It is not contraindicated for other persons, including infants, children, pregnant women, HIV-infected persons, or persons vaccinated with BCG.

Vaccination with live viruses may interfere with TST reactions. For persons scheduled to receive a TST, testing should be done as follows:

  • Either on the same day as vaccination with a live-virus vaccine or 4-6 weeks after the administration of the live-virus vaccine
  • At least one month after the smallpox vaccination

Additional Information

Nisha Rijal

I am working as Microbiologist in National Public Health Laboratory (NPHL), government national reference laboratory under the Department of health services (DoHS), Nepal. Key areas of my work lies in Bacteriology, especially in Antimicrobial resistance.

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