Tuberculosis screening

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Screening for tuberculosis is generally done with using a mantoux tuberculin skin test, also known as a tuberculin skin test or a PPD. The test involves injecting a small amount of a purified protein derivative of the tuberculosis bacterium intradermally, and watching for a reaction in the following days.

Screening

Mantoux Tuberculin Skin Test

The Mantoux tuberculin skin test (TST) is the standard method of determining whether a person is infected with Mycobacterium tuberculosis. Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice. The TST 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. The TST is an intradermal injection. When placed correctly, the injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter.

The skin test reaction should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will need to be rescheduled for another skin test.

The reaction 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).

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

In some persons who are infected with M. tuberculosis, the ability to react to tuberculin may wane over time. When given a TST years after infection, these persons may have a false-negative reaction. However, the TST may stimulate the immune system, causing a positive, or boosted reaction to subsequent tests. Giving a second TST after an initial negative TST reaction is called two-step testing.

Two-step testing is useful for the initial skin testing of adults who are going to be retested periodically, such as health care workers or nursing home residents. This two-step approach can reduce the likelihood that a boosted reaction to a subsequent TST will be misinterpreted as a recent infection.

Classification of Tuberculin Reaction

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.

Image from Public Health Image Library (PHIL) Image from Public Health Image Library (PHIL)

Tuberculin Reaction	Considered a Positive Result in:
≥ 5 mm	HIV-positive person Recent contacts of TB case Persons with nodular or fibrotic changes on CXR consistent with old healed TB Patients with organ transplants and other immunosuppressed patients
≥ 10 mm	Recent arrivals (less than 5 years) from high-prevalent countries Injection drug users Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters) Mycobacteriology lab personnel Persons with clinical conditions that place them at high risk (e.g., diabetes, prolonged corticosteroid therapy, leukemia, end-stage renal disease, chronic malabsorption syndromes, low body weight) Children less than 4 years of age, or children and adolescents exposed to adults in high-risk categories
≥ 15 mm	Persons with no known risk factors for TB
Table adapted from CDC

False-Positive Reactions	False-Negative Reactions
Some persons may react to the TST 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: Infection with nontuberculosis mycobacteria Previous BCG vaccination Incorrect method of TST administration Incorrect interpretation of reaction Incorrect bottle of antigen used	Some persons may not react to the TST even though they are 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 6 months old) Recent live-virus vaccination (e.g., measles and smallpox) Overwhelming TB disease Some viral illnesses (e.g., measles and chicken pox) Incorrect method of TST administration Incorrect interpretation of reaction
Table adapted from CDC

Heaf Test

The Heaf test is a diagnostic skin test performed in order to determine whether or not a child has been exposed to tuberculosis. Patients who exhibit a negative reaction to the test may be offered BCG vaccination. The test is named after F. R. G. Heaf.

Until 2005, the test was used in the United Kingdom to determine if the BCG vaccine was needed; the Mantoux test is now used instead. The Heaf test was preferred in the UK, because it was felt that the Heaf test was easier to interpret, with less inter-observer variability, and that less training was required to administer and to read the test. The test was withdrawn because manufacturers could not be found for tuberculin or for Heaf guns.

The Heaf test may be informally referred to as the six pricks, as it gives six individual injections.

Procedure

A Heaf gun is used to inject multiple samples of testing serum under the skin at once. A Heaf gun with disposable single-use heads is recommended.

The gun injects purified protein derivative equivalent to 100,000 units per mL to the skin over the flexor surface of the left forearm in a circular pattern of six. The test is read between 2 and 7 days later. The injection must not be into sites containing superficial veins.

The reading of the Heaf test is defined by a scale:

• Negative - No induration, maybe 6 minute puncture scars
• Grade 1 - 4-6 papules (also considered negative)
• Grade 2 - Confluent papules form indurated ring (positive)
• Grade 3 - Central filling to form disc (positive)
• Grade 4 - Disc >10 mm with or without blistering (strongly positive)

Grades 1 and 2 may be the result of previous BCG or avian tuberculosis.

Children who have a grade 3 or 4 reaction require X-ray and follow-up.

The equivalent Mantoux test positive levels done with 10 TU (0.1 mL 100 TU/mL, 1:1000) are:

• 0-4 mm induration (Heaf 0-1)
• 5-14 mm induration (Heaf 2)
• >15 mm induration (Heaf 3-4)

The Mantoux test is preferred in the United States for the diagnosis of tuberculosis; multiple puncture tests, such as the Heaf test and Tine test, are not recommended.