Division of Tuberculosis Elimination - Fact Sheets - Diagnosis of Latent TB Infection and TB Disease

The Mantoux tuberculin skin test is used to determine whether a person is infected with Mycobacterium tuberculosis. Tuberculin skin testing is contraindicated only for persons who have had a necrotic or a severe allergic reaction to a previous tuberculin skin test. 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. 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.

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. Institutional guidelines regarding universal precautions for infection control (e.g., the use of gloves) should be followed.

The reaction to the Mantoux tuberculin skin test should be read by a trained health care worker 48 to 72 hours after the injection. The reading should be based on a measurement of induration (swelling), not on erythema, or redness. The diameter of the induration should be measured perpendicularly to the long axis of the forearm. All reactions, even those classified as negative, should be recorded in millimeters.

An induration of 5 or more millimeters is considered positive for

-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 ³ 15 mg/day of prednisone for ³ 1 month)

An induration of 10 or more millimeters is considered positive for

-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*

-Children < 4 years of age, or children and adolescents exposed to adults in high-risk categories.

An induration of 15 or more millimeters is considered positive for persons with no known risk factors for TB. However, targeted skin testing programs should only be conducted among high-risk groups.

* HIV infection, substance abuse (especially drug injection), recent infection with M. tuberculosis (within the past 2 years), previous TB (in a person who received inadequate or no treatment), diabetes mellitus, silicosis, prolonged corticosteroid therapy, other immunosuppressive therapy, cancer of the head and neck, hematologic and reticuloendothelial diseases (e.g., leukemia and Hodgkin's disease), end-stage renal disease, intestinal bypass or gastrectomy, chronic malabsorption syndromes, low body weight (10% or more below the ideal).

Some persons who have positive skin test results may have TB disease. The possibility of TB disease must be ruled out before treatment of latent TB infection is begun.

The Mantoux tuberculin skin test is a valuable tool, but it is not perfect. Some persons may react to the tuberculin skin test even though they are not infected with M. tuberculosis. These false-positive reactions may be caused by infection with mycobacteria other than M. tuberculosis or by immunization with BCG. However, there is no sure way to determine the true cause of the reaction.

Some persons may not react to the tuberculin skin test even though they are truly infected with M. tuberculosis. These false-negative reactions can occur in several circumstances:

In some persons who are infected with M. tuberculosis, the ability to react to tuberculin may wane over time. When given a skin test years after infection, these persons may have a negative reaction. However, this skin test may stimulate the immune system, causing a positive reaction to subsequent tests. This is called the booster phenomenon.

Two-step testing is used to distinguish between the booster phenomenon and new infection. If the reaction to the first test is negative, a second test is given 1 to 3 weeks later. If the reaction to the second test is positive, then it is probably a boosted reaction (usually from infection that occurred years ago) and should not be called a skin-test conversion (i.e., a new infection). Two-step testing can be useful for the initial skin testing of adults who are going to be retested periodically, such as health care workers or nursing home residents.

Some persons may not react to the tuberculin skin test even though they are infected with M. tuberculosis. This may be because of anergy. Anergy is the inability to react to skin tests because of immunosuppression. Anergy is often caused by HIV infection, but it can also be caused by other medical conditions. Anergy is determined by administering two delayed-type hypersensitivity antigens, such as tetanus toxoid, mumps, or Candida, by the Mantoux method. Persons who do not react to any of these antigens, including tuberculin, are probably anergic. The use of anergy testing in conjunction with PPD testing is no longer recommended routinely for screening programs for M. tuberculosis infection conducted among HIV-infected persons in the United States.

In persons vaccinated with BCG, sensitivity to tuberculin is highly variable, depending upon the strain of BCG used and the group vaccinated. The presence or size of a post-vaccination tuberculin skin-test reaction does not predict whether BCG will provide any protection against TB disease. Furthermore, the size of a tuberculin skin-test reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by M. tuberculosis infection or the prior BCG vaccination.

Tuberculin skin testing is not contraindicated for persons who have been vaccinated with BCG, and the skin-test results of such persons are used to support or exclude the diagnosis of M. tuberculosis infection. A diagnosis of M. tuberculosis infection and the use of treatment of latent TB infection should be considered for any BCG-vaccinated person who has a tuberculin skin-test reaction of 10 mm or greater of induration, especially if any of the following circumstances are present:

Treatment of latent TB infection should be considered for BCG-vaccinated persons who are infected with HIV and who are at risk for M. tuberculosis infection if they have a tuberculin skin-test reaction of ³ 5 mm induration.

Pulmonary TB disease should be suspected in persons who have fever; chills; night sweats; fatigue; loss of appetite; weight loss; a productive, prolonged cough (duration of 3 weeks or longer); or hemoptysis. Persons suspected of having TB disease should be evaluated with a medical history, a physical examination, a Mantoux tuberculin skin test, a chest radiograph, and a sputum smear and culture. A positive culture for Mycobacterium tuberculosis confirms the diagnosis of TB. However, a positive culture is not always necessary to begin or continue treatment for TB. In addition, a negative tuberculin skin test does not rule out TB.

Persons with HIV infection and TB may have atypical chest radiographs, and they are more likely to have extrapulmonary TB than are persons without HIV infection. (However, pulmonary TB is the most common form of TB in all persons, including HIV-infected persons). The symptoms of extrapulmonary TB depend on the site affected.

The presence of acid-fast bacilli (AFB) on a sputum smear often indicates TB. Acid-fast microscopy is easy and quick, but it does not confirm a diagnosis of TB because some acid-fast bacilli are not M. tuberculosis. Therefore, a culture is done to confirm the diagnosis. Culture examinations should be done on all specimens, regardless of AFB smear results.

Laboratories should report positive smears and positive cultures within 24 hours by telephone or fax to the primary health care provider.

For all patients, the initial M. tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible in order to ensure appropriate treatment. Drug susceptibility patterns should be repeated for patients who do not respond adequately or who have positive culture results despite 2 months of therapy. Susceptibility results from laboratories should be promptly forwarded to the health department.

To order the following documents, call the CDC’s Voice and Fax Information System (recording) toll free at (888) 232-3228, then press options 2, 5, 1, 2, 2 (Note: You may select these options at any time without listening to the complete message). Request the title or publication number of the document you would like to order. You may also visit the Division of TB Elimination’s Web site at http://www.cdc.gov/nchstp/tb.

Publication # 99-6422. ATS/CDC. Targeted tuberculin testing and treatment of latent TB infection. MMWR 2000;49(No. RR- 6).

Publication # 99-5879. CDC. Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. MMWR 1998;47(No. RR- 20).

Publication # 00-5856. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities, 1994. MMWR 1994;43(No.RR-13).

Publication # 00-6617. Screening for tuberculosis and tuberculous infection in high-risk populations. MMWR 1995;44(RR-11).

Publication # 00-3327. Prevention and control of tuberculosis in facilities providing long-term care to the elderly. MMWR 1990;39(RR-10).

Publication # 99-5791. Recommendations for prevention and control of tuberculosis among foreign-born persons. MMWR 1998;47(RR-16).

Publication # 00-6148. Prevention and control of tuberculosis in U.S. communities with at-risk minority populations and Prevention and control of tuberculosis among homeless persons. MMWR 1992;41(RR-5).

Publication # 00-6223. Prevention and control of tuberculosis in migrant farm workers. MMWR 1992;41(RR-10).