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U.S. Department of Health and Human Services

  

TB Facts for Health Care Workers
2006

Identification of Persons with Latent TB Infection
and
TB Disease

Identifying Latent TB Infection (LTBI)

A person exposed to an individual with infectious TB or who has other risk factors for TB as noted above should be given a Mantoux tuberculin skin test (TST) or the QuantiFERON®-TB Gold test (QFT-G).

The Mantoux Tuberculin Skin Test

The Mantoux tuberculin skin test is the intradermal injection of purified protein derivative (PPD) of killed tubercle bacilli, usually on the inner forearm. The site is examined by a trained health care worker 48 to 72 hours after injection for induration (palpable swelling). The diameter of induration is measured and recorded; erythema or bruising is disregarded.

The criteria endorsed by the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC) for a positive tuberculin skin-test result (Table 1) are intended to increase the likelihood that persons at high risk for TB will be candidates for treatment of LTBI and that persons having tuberculin reactions not caused by M. tuberculosis will not receive unnecessary diagnostic evaluation or treatment.

For each of the risk groups listed in Table 1, reactions below the cutoff point are considered negative. A negative TST result does not absolutely rule out LTBI, especially in persons with TB-like symptoms, HIV infection, or AIDS. Also, it takes up to 8 weeks from the time of exposure for a person to react to tuberculin; thus, the initial TST result of an infected contact may be falsely negative. Therefore, a repeat TST 8–10 weeks postexposure is warranted.

Some persons with both HIV and latent TB infections may have false-negative TST reactions (anergy). Anergy refers to the inability to react to a skin-test antigen even though the person is infected with the organism being tested. Several delayed-type hypersensitivity (DTH) antigens (such as tetanus toxoid, mumps, or Candida) administered by the Mantoux technique have been used in an attempt to determine anergy status. Recent CDC recommendations, however, note several factors that limit the usefulness of anergy skin testing. These include problems with standardization and reproducibility, the low risk for TB associated with a diagnosis of anergy, and the lack of apparent benefit of LTBI treatment for groups of anergic HIV-infected persons. Therefore, the use of anergy testing in conjunction with PPD testing is no longer routinely recommended for TB testing programs in the United States.

Persons with LTBI should be evaluated for HIV risk behaviors and offered counseling and HIV-antibody testing especially if such risk behaviors are present.

Table 1: Summary of interpretation of tuberculin skin-test (TST) results

An induration of >5 mm is classified as positive in the following groups:

  • Persons who have HIV infection;
  • Persons who have had recent close contact with persons who have TB;
  • Patients who have had organ transplants, and other immunosuppressed patients (receiving the equivalent of >15 mg/day of prednisone for >1 month);
  • Persons with fibrotic changes on chest radiograph consistent with old TB;
  • Persons receiving specialized treatment for rheumatoid arthritis or Crohn’s disease.

An induration of >10 mm is classified as positive in all persons who do not meet any of the above criteria, but belong to one or more of the following groups having high risk for TB:

  • Foreign-born persons recently arrived (e.g., within the last 5 years) from areas having a high prevalence or incidence of TB;
  • Persons who inject illicit drugs;
  • Residents and employees of high-risk congregate settings: prisons and jails, nursing homes and other long-term facilities for the elderly, health-care facilities (including some residential mental health facilities), and homeless shelters;
  • Mycobacteriology laboratory personnel;
  • Persons who have other medical conditions that have been reported to increase the risk for progressing from LTBI to TB -- these medical conditions include diabetes mellitus, silicosis, prolonged corticosteroid therapy and other immunosuppressive therapy, cancer of the head and neck, hematologic and reticuloendothelial diseases, end-stage renal disease, intestinal bypass or gastrectomy, chronic malabsorption syndromes, or  weight loss of >10% below ideal body weight;
  • Children <4 years of age, or children and adolescents exposed to adults in high-risk categories.

An induration of >15 mm is classified as positive in persons who do not meet any of the above criteria.

Quantiferon®-TB Gold Test (QFT)

The Quantiferon®-TB Gold test (QFT-G) is a blood test that measures a person’s immune reactivity to M. tuberculosis. Blood specimens are mixed with antigens and incubated for 16–24 hours. In a person with LTBI, the blood cells recognize the tuberculin antigen and release interferon-gamma (IFN-γ); results are based on the proportion of IFN-γ released. The first generation QFT (Quantiferon®-TB test) was approved by the U.S. Food and Drug Administration (FDA) in 2001. The second generation test (Quantiferon®-TB Gold test) was approved by the FDA in 2005.

QFT-G advantages:

  • Requires a single patient visit
  • Does not cause booster phenomenon
  • Less subject to reader bias than TST

QFT-G disadvantages:

  • Blood sample must be processed in 12 hours

QFT-G is recommended for

  • Initial and serial testing for those at increased risk for LTBI

CDC discourages use of diagnostic tests for LTBI among populations at low risk for infection with M. tuberculosis. However, initial testing is occasionally performed among certain population groups for surveillance purposes or where cases of infectious TB disease might result in extensive transmission to highly susceptible populations, including the following:

  • Initial and serial testing of persons who are at low risk for LTBI, but whose future activity places them at increased risk of exposure;
  • Testing of those who are not considered to have an increased possibility of infection, such as persons meeting entrance requirements for certain schools and workplaces.

There are limited data regarding the use of QFT-G for

  • Screening of pregnant women, children under the age of 17, or persons with clinical conditions that increase the risk of progression to disease

QFT-G is not currently recommended for

  • Confirmation of TST results
  • Diagnosis of M. avium-complex disease

Please refer to the CDC website for the most current information on the use of QFT-G: www.cdc.gov/tb.

The Bacille Calmette-Guérin (BCG) Vaccine

The Bacille Calmette-Guérin (BCG) vaccine is a live vaccine derived from a strain of Mycobacterium bovis that was attenuated by Calmette and Guérin at the Pasteur Institute in Lille, France. An early version of BCG was first administered to humans in 1921. Since that time, many different strains have been derived and are used today throughout the world. BCG vaccination is not generally recommended in the United States because of the low risk of infection with M. tuberculosis, the variable effectiveness of the BCG vaccine against adult pulmonary TB, and the vaccine’s interference with the ability to interpret tuberculin reactivity.

Many foreign countries still use BCG as an appropriate part of their TB control programs for infants. In persons vaccinated with BCG, sensitivity to tuberculin is highly variable, depending upon the strain of BCG used, the group vaccinated, and age at vaccination.


Neither the TST nor QFT-G is contraindicated for persons who have been vaccinated with BCG. The presence or size of a postvaccination TST reaction does not predict whether BCG will provide any protection against TB disease. The size of a TST reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by M. tuberculosis infection or by the prior BCG vaccination.

The TST results are used to support or exclude the diagnosis of LTBI. TST results in persons vaccinated with BCG should be interpreted using the same criteria for those not BCG vaccinated. Such persons should be evaluated for isoniazid to treat LTBI after disease has been ruled out.

Identifying TB Disease

If the skin-test result or QFT-G is positive, or if symptoms suggestive of TB are present (e.g., productive and prolonged cough, fever, chills, loss of appetite, weight loss, fatigue, or night sweats), a chest radiograph should be obtained to determine if active pulmonary TB is present. The chest radiograph may also be used to detect the presence of fibrotic lesions suggestive of old, healed TB or silicosis.

Acid-fast bacilli (AFB) smears and cultures should be performed on sputum specimens of all persons who have symptoms of TB or whose chest radiograph suggests TB. A positive AFB smear is an indication for beginning treatment for TB. However, a positive AFB smear may also indicate the presence of nontuberculous mycobacteria. A positive culture for M. tuberculosis is the only definitive proof of TB disease.

Health care providers of HIV-infected persons should be aware of atypical patterns of TB disease in these persons. Extrapulmonary TB is more common among HIV-infected persons. Also, pulmonary TB may present in an unusual manner (e.g., in the lymph nodes or in the lower part of the lungs).

All persons with LTBI or TB disease should routinely be offered HIV counseling, testing, and referral because medical management may be altered in the presence of HIV infection.

Maintain a high index of suspicion for TB in persons with undiagnosed pulmonary disease, especially in persons who are HIV seropositive.

 


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

Please send comments/suggestions/requests to: hsttbwebteam@cdc.gov, or to
CDC/Division of Tuberculosis Elimination
Communications, Education, and Behavioral Studies Branch
1600 Clifton Rd., NE - Mailstop E-10, Atlanta, GA 30333