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Indirect test for Mycobacterium tuberculosis complex infection (latent tuberculosis infection and active disease)
Latent tuberculosis infection (LTBI) is a noncommunicable, asymptomatic condition that persists for many years in individuals and may progress to tuberculosis disease. The main purpose of diagnosing LTBI is to consider medical treatment for preventing active tuberculosis disease. Until recently, the tuberculin skin test (TST) was the only method available for diagnosing LTBI. Unfortunately, the TST is a subjective test that can be falsely positive for individuals who have been vaccinated with bacille Calmett-Guerin (BCG), are infected with other mycobacteria than Mycobacterium tuberculosis complex, or due to other factors such as a digital palpitation error when reading the test.
The QuantiFERON-TB Gold In-Tube test is a measure of cell-mediated immune response to antigens simulating the mycobacterial proteins ESAT-6, CFP-10, and TB7.7. Individuals infected with Mycobacterium tuberculosis complex organisms including Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti, and Mycobacterium canetti usually have lymphocytes in their blood that recognize these specific antigens. The recognition process involves the generation and secretion of the cytokine, interferon-gamma (IFN-gamma). The detection and quantification of IFN-gamma by enzyme-linked immunosorbent assay (ELISA) is used to identify in vitro responses to TB antigens that are associated with Mycobacterium tuberculosis complex infection. The ESAT-6, CFP-10, and TB7.7 antigens are absent from the Mycobacterium bovis BCG strains and from most nontuberculous mycobacteria with the exception of Mycobacterium kanasii, Mycobacterium szulgai, and Mycobacterium marinum. Numerous studies have demonstrated that ESAT-6, CFP-10, and TB7.7 stimulate IFN-gamma responses in T cells from individuals infected with Mycobacterium tuberculosis but usually not from uninfected or BCG-vaccinated persons without disease or risk for LTBI.
A positive result indicates that Mycobacterium tuberculosis infection is likely. However, positive reactivity to proteins present in other mycobacteria such as Mycobacterium kansasii, Mycobacterium szulgai, and Mycobacterium marinum may cause false-positive results.
A positive QuantiFERON-TB Gold result should be followed by further medical and diagnostic evaluation for tuberculosis disease (eg, acid-fast bacilli smear and culture, chest x-ray).
QuantiFERON-TB Gold is usually negative in individuals vaccinated with Mycobacterium bovis bacille Calmett-Guerin.
A positive QuantiFERON-TB Gold result may not indicate infection with Mycobacterium tuberculosis; false positives do occur.
A negative QuantiFERON-TB Gold result does not preclude the possibility of Mycobacterium tuberculosis infection or tuberculosis disease. Falsely-negative results can be due to the stage of infection (eg, specimen drawn prior to the development of cellular immune response), comorbid conditions that affect immune functions, or other individual immunological factors.
A false-negative QuantiFERON-TB Gold result can be caused by incorrect blood specimen drawn or improper handling of the specimen affecting lymphocyte function. Blood must be incubated with stimulation antigens within 16 hours of draw. Delay in incubation may cause false-negative or indeterminate results.
The effect of lymphocyte count on reliability is unknown. Lymphocyte counts may vary from person to person. The minimum number required for a reliable result has not been established.
QuantiFERON-TB Gold has been evaluated with specimens from patients with culture-confirmed active tuberculosis and from apparently healthy adults with and without identified risk factors for Mycobacterium tuberculosis infection.
The performance of QuantiFERON-TB Gold has not been evaluated in specimens from:
-Individuals with impaired or altered immune functions (HIV infections, transplant patients, those receiving immunosuppressive drugs such as corticosteroids) and those with other clinical conditions (eg, diabetes, hematological disorders)
-Individuals younger than 17 years old
The most recent Centers for Disease Control and Prevention recommendations for diagnosis of Mycobacterium tuberculosis infections (including disease) and selecting persons for testing can be found at http://www.cdc.gov/nchstp/tb.
1. Mori T, Sakatani M, Yamagishi F, et al: Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 2004:170;59-64
2. Kang YA, Lee HW, Yoon HI, et al: Discrepancy between the tuberculin skin test and the whole blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis burden country. JAMA 2005:293;2756-2761
3. Ferrara G, Losi M, Meacci M, et al: Routine hospital use of a commercial whole blood interferon-gamma assay for tuberculosis infection. Am J Respir Crit Care Med 2005 Sep 1;172(5):631-635