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U.S. Department of Health and Human Services

  

Core Curriculum on Tuberculosis, 2000

Chapter 4
Testing for TB Disease and Infection

Tuberculin Skin Testing

Administration of the Tuberculin Test

The Mantoux tuberculin skin test is the standard method of identifying persons infected with M. tuberculosis. Multiple puncture tests (MPTs) should not be used to determine whether a person is infected. MPTs are not reliable because the amount of tuberculin injected intradermally cannot be precisely controlled. Tuberculin skin testing is both safe and reliable throughout the course of pregnancy.

The Mantoux tuberculin test is performed by placing an intradermal injection of 0.1 ml of purified protein derivative (PPD) tuberculin containing 5 tuberculin units (TU) into the inner surface of the forearm. The injection should be made with a disposable tuberculin syringe, just beneath the surface of the skin, with the needle bevel facing upward. This should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter.

To prevent needle stick injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, or otherwise manipulated by hand. After they are used, disposable needles and syringes should be placed in puncture-resistant containers for disposal. Institutional guidelines regarding universal precautions for infection control (e.g., the use of gloves) should be followed.

The reaction to the Mantoux test should be read by a trained health care worker 48 to 72 hours after the injection. Patients should never be allowed to read their own tuberculin skin test results. If a patient fails to show up for the scheduled reading, a positive reaction may still be measurable up to 1 week after testing. However, if a patient who fails to return within 72 hours has a negative test, tuberculin testing should be repeated.

The area of induration (palpable raised hardened area) around the site of injection is the reaction to tuberculin. The diameter of the indurated area should be measured across the forearm (perpendicular to the long axis). Erythema (redness) should not be measured. All reactions should be recorded in millimeters, even those classified as negative. If no induration is found, "0 mm" should be recorded. A tuberculin skin test conversion is defined as an increase of ³10 mm of induration within a 2-year period regardless of age.

Classification of the Tuberculin Reaction

A tuberculin reaction of ³5 mm of induration is classified as positive in the following groups:

  • HIV-positive persons
  • Recent contacts of TB case
  • Persons with fibrotic changes on chest radiograph consistent with old healed TB
  •  Patients with organ transplants and other immunosuppressed patients (receiving the equivalent of ³15 mg/day of prednisone for ³1 month)

A tuberculin reaction of ³10 mm of induration is classified as positive in persons who do not meet the preceding criteria but who have other risk factors for TB. These include:

  • Recent arrivals (< 5 years) from high-prevalence countries
  • Injection drug users
  • Residents and employees of high-risk congregate settings: prisons and jails, nursing homes and other long-term facilities for the elderly, hospitals and other health-care facilities, residential facilities for AIDS patients, and homeless shelters
  • Mycobacteriology laboratory personnel
  • Persons with clinical conditions that place them at high risk (see Transmission and Pathogenesis)
  • Children < 4 years of age, or children and adolescents exposed to adults in high-risk categories.

A tuberculin reaction of ³15 mm of induration is classified as positive in persons with no known risk factors for TB. However, targeted skin testing programs should only be conducted among high-risk groups.

In general, these guidelines for interpreting skin test reactions should also be applied to persons who may have occupational exposure to TB (e.g., health care workers or staff of nursing homes, drug  treatment centers, or correctional facilities). Thus, the appropriate cutoff for defining a positive reaction depends on the employee's individual risk factors for TB, including recent TB exposure, and the prevalence of TB in the facility. In facilities where the risk of exposure is very low, ³15 mm may be an appropriate cutoff for employees with no other risk factors. In facilities where TB patients receive care, ³10 mm may be an appropriate cutoff for employees with no other risk factors.

The tuberculin skin test is a valuable tool, but it is not perfect. Several factors can affect the skin test reaction (see Table 1). Infection with mycobacteria other than M. tuberculosis (nontuberculous mycobacteria) and vaccination with bacille Calmette-Guérin (BCG) can lead to false-positive reactions (a positive skin test reaction in a person not infected with M. tuberculosis). See BCG Vaccination for further information on interpreting tuberculin reactions in persons with a history of BCG vaccination.

Vaccination with live viruses may also interfere with tuberculin skin test reactivity and cause false-negative reactions (a negative skin test reaction in a person infected with M. tuberculosis). The Advisory Committee on Immunization Practices recommends that tuberculin skin testing be done on either the same day as vaccination with live-virus measles vaccine or 4-6 weeks after measles vaccination. 1 Other factors, such as anergy and overwhelming TB disease, can also lead to false-negative reactions.

Table 1. Factors that may cause false-positive ad false-negative reactions to the tuberculin skin test.

Type of reaction Possible Cause
False-positive Nontuberculous mycobacteria
BCG vaccination
False-negative Anergy
Recent TB infection
Very young age (< 6 months old)
Live-virus vaccination
Overwhelming TB disease

Anergy Testing

The absence of a reaction to the tuberculin skin test does not rule out the diagnosis of TB disease or infection. In immunosuppressed persons, delayed-type hypersensitivity responses such as tuberculin reactions may decrease or disappear. This condition, known as anergy, may be caused by many factors, such as HIV infection, severe or febrile illness, measles or other viral infections, Hodgkin’s disease, sarcoidosis, live-virus vaccination, or the administration of corticosteroids or immunosuppressive drugs. On average, 10% to 25% of patients with TB disease have negative reactions when tested with a tuberculin skin test at diagnosis before treatment. 2,3

Anergy is detected by administering at least two other delayed-type hypersensitivity antigens by the Mantoux method of intradermal injection. The lack of standardization and outcome data limit the evaluation of the effectiveness of anergy testing. The use of anergy testing in conjunction with tuberculin skin testing is no longer routinely recommended for testing programs for M. tuberculosis infection conducted among HIV-positive persons in the United States.

 

Two-Step Testing

In some people who are infected with M. tuberculosis, delayed-type hypersensitivity to tuberculin may wane over the years. When these people are skin tested many years after infection, they may have a negative reaction. However, this skin test may stimulate (boost) their ability to react to tuberculin, causing a positive reaction to subsequent tests. This boosted reaction may be misinterpreted as a new infection. The booster phenomenon may occur at any age; its frequency increases with age and is highest among older persons. Boosted reactions may occur in persons infected with nontuberculous mycobacteria or in persons who have had a prior BCG vaccination.

Two-step testing is used to reduce the likelihood that a boosted reaction will be misinterpreted as a recent infection. If the reaction to the first test is classified as negative, a second test should be done 1 to 3 weeks later. A positive reaction to the second test probably represents a boosted reaction (past infection or prior BCG vaccination). On the basis of this second test result, the person should be classified as previously infected and cared for accordingly. This would not be considered a skin test conversion. If the second test result is also negative, the person should be classified as uninfected. In these persons, a positive reaction to any subsequent test is likely to represent new infection with M. tuberculosis (skin test conversion). Two-step testing should be used for the initial skin testing of adults who will be retested periodically, such as health care workers.

Because of cross-reactions with other mycobacteria, the specificity of the tuberculin test is less when serial skin testing is performed than when a single test is administered. Thus, serial skin-testing programs tend to overestimate the incidence of new TB infection in the tested population. Because of this potential for overestimation of new infections, serial skin-testing programs should be targeted to populations at high risk for continued exposure to infectious persons.

 


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination - http://www.cdc.gov/tb

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