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. Robert Koch introduced tuberculin in 1890, but the intradermal technique in use today was described in 1912 by a French physician, Charles Mantoux, after whom the test is named.

For the organism and how TB infection produces this immune response, see the Mycobacterium tuberculosis page. This test is one of several used to diagnose TB; the full workup is on the laboratory diagnosis of tuberculosis page.

What the test actually measures

The tuberculin skin test does not detect the bacteria. It detects the immune system's memory of them. If a person's T-cells have met Mycobacterium tuberculosis before (from infection or from BCG), they react to the injected protein and cause a firm, raised swelling (induration) at the site within 2 to 3 days. This is a delayed-type (type IV) hypersensitivity reaction, the same T-cell mechanism the body uses to wall off TB in granulomas.

Two consequences follow, and they explain everything else on this page:

• A positive test means infection or exposure, not active disease. It cannot tell latent TB from active TB, or from past BCG. Anyone positive needs further evaluation.
• Because it measures a T-cell memory response, anything that weakens T-cell immunity (HIV, immunosuppression, overwhelming TB) can make it falsely negative, and anything that primes the same response (BCG, non-tuberculous mycobacteria) can make it falsely positive.

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

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, a person previously exposed to the bacteria mounts an immune response within 48 to 72 hours, leading to the formation of induration (a raised bump in the area of injection) due to the influx and activation of macrophages.

Procedure

1. Allow the patient to sit in a comfortable chair and rest the arm on a table with the inner side of the forearm facing 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 a 27-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 reading of the skin test reaction should be 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 to 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

Interpretation of tuberculin skin tests can be difficult. Factors such as age, immune status, and coexisting illness all influence the result, so it must be interpreted with care. Utmost care is required while interpreting the result and giving an opinion.

According to the Centers for Disease Control and Prevention (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 Test

The cutoff for "positive" is not fixed; it is lower for people more likely to be infected or to progress to disease, and higher for people at low risk. This balances catching true infection against false positives. So the same induration that is positive in an HIV-infected person may not be positive in a healthy low-risk person.

• ≥5 mm (the lowest bar, for the highest-risk): HIV infection, recent contact with an infectious TB case, fibrotic changes on chest X-ray consistent with old TB, organ transplant recipients, and others on significant immunosuppression.

• ≥10 mm (intermediate risk): recent immigrants from high-prevalence countries, injection drug users, mycobacteriology lab staff, residents/employees of high-risk congregate settings, children under 4, and those with high-risk clinical conditions.

• ≥15 mm (for people with no known risk factors).

Limitation

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 non-tuberculous 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 usually means the person has not been infected with M. tuberculosis. But a negative result does not fully exclude infection, because several conditions can cause a false-negative reaction even in an infected person:

   • 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., MMR, varicella)
   • Overwhelming TB disease
   • Some viral illnesses (e.g., measles and chickenpox)
   • Incorrect method of TST administration
   • Incorrect interpretation of reaction

Tuberculin test vs IGRA

The interferon-gamma release assays (IGRAs, such as QuantiFERON-TB Gold and T-SPOT.TB) are blood tests that measure the same T-cell response to M. tuberculosis, but with one key advantage: they use antigens (ESAT-6, CFP-10) that are not present in the BCG vaccine, so prior BCG does not cause a false-positive IGRA. IGRAs also need only one visit (no return to read a result) and avoid reader subjectivity. Like the TST, however, they still cannot distinguish latent from active TB. See the laboratory diagnosis of tuberculosis page for how both fit into the TB workup.

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

How to remember

It reads memory, not the bug. The test does not find M. tuberculosis. It asks whether your T-cells remember meeting it. That is why it is positive in latent TB, active TB, and after BCG, all three have primed the memory, and why it cannot tell them apart.

Induration, not redness. Measure the firm raised bump (induration), never the red area (erythema). Redness is not the immune reaction you are grading; the hard swelling is. Measure across the forearm, not along it.

Lower cutoff for higher risk. The bar for "positive" drops as risk rises: 5 mm for the highest-risk (HIV, TB contact), 10 mm for intermediate, 15 mm for the low-risk general population. More risk, less induration needed to call it positive.

BCG fools the skin test, not the IGRA. Prior BCG can make the tuberculin test falsely positive. IGRA uses antigens not in BCG, so BCG does not affect it. If BCG history is confusing the picture, IGRA is the way around it.

Negative doesn't always mean uninfected. A weakened immune system (HIV, immunosuppression, overwhelming TB, very young age) can give a false negative. A negative test in a sick, immunocompromised patient does not exclude TB.

Where students get confused

Positive means infection, not disease. A positive tuberculin test shows the immune system has met M. tuberculosis, latent infection, active disease, or past BCG. It never diagnoses active TB on its own; anyone positive needs further evaluation.

Measure induration, not erythema. The commonest practical error. Grade the firm, palpable, raised area, not the surrounding redness.

The cutoff is not one number. "Positive" is 5, 10, or 15 mm depending on the person's risk. Applying a single cutoff to everyone is wrong.

BCG causes false positives on the skin test. In BCG-vaccinated populations (like much of South Asia), a positive tuberculin test may reflect the vaccine, not infection. This is a major limitation, and IGRA (unaffected by BCG) helps resolve it.

A false negative can occur in real infection. Anergy from HIV or immunosuppression, very recent infection (within 8 to 10 weeks), or overwhelming TB can all blunt the response. Negative does not always mean uninfected.

References

1. Centers for Disease Control and Prevention. (2000). Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recommendations and Reports, 49(RR-6), 1–51.
2. American Thoracic Society & Centers for Disease Control and Prevention. (2000). Diagnostic standards and classification of tuberculosis in adults and children. American Journal of Respiratory and Critical Care Medicine, 161(4 Pt 1), 1376–1395. https://doi.org/10.1164/ajrccm.161.4.16141
3. Lewinsohn, D. M., Leonard, M. K., LoBue, P. A., et al. (2017). Official ATS/IDSA/CDC clinical practice guidelines: Diagnosis of tuberculosis in adults and children. Clinical Infectious Diseases, 64(2), e1–e33. https://doi.org/10.1093/cid/ciw778
4. Tille, P. M. (2022). Bailey & Scott's Diagnostic Microbiology (15th ed.). Elsevier.
5. Procop, G. W., et al. (2017). Koneman's Color Atlas and Textbook of Diagnostic Microbiology (7th ed.). Wolters Kluwer.
6. World Health Organization. (2020). WHO consolidated guidelines on tuberculosis. Module 1: Prevention – Tuberculosis preventive treatment. World Health Organization.