Introduction of Blood Testing for TB: Interferon-Gamma Release Assay

Introduction of Blood Testing for TB: Interferon-Gamma Release Assay

Tuberculosis remains a contemporary disease. Since 1993, the proportion of cases in the United States has increased each year in foreign-born vs. U.S. born individuals. By 2007, the TB rate among immigrants was 9.7 times higher than in U.S.-born citizens and now affects more than one-million immigrants entering the U.S. each year. In 2007 the CDC issued technical instructions to identify latent TB infection (LTBI) in addition to their long-standing strategy of identifying active disease in immigrants and refugees. The screening for LTBI re-introduced the aged tuberculin skin test (TST). If TST positive, the immigrant had further testing (e.g. chest x-ray) to rule out active TB. If active TB is not confirmed, he/she is considered to have LTBI and requires follow-up and treatment.

Many TST-positive immigrants may be falsely diagnosed as having LTBI because of prior BCG vaccination and the cross reactivity between the purified protein derivative in the TST and the Mycobacterium bovis strains used in the BCG vaccine. The most common countries of origin for U.S. immigrants (India, Vietnam, China, Philippines and Mexico) have high vaccination rates (≥ 93%; except Mexico ≈ 80%). A new class of blood tests are now commercially available - Interferon-gamma release assays (IFN-γ) - that greatly improve upon the poor specificity of the TST, and they now are listed as an option in the 2009 CDC technical instructions for TB screening.

IFN-γ release assays are blood tests that determine whether a person has a specific infection. Infected individuals have T-cells in their blood that respond to the antigens of the disease being tested. When a disease antigen is added to blood from such individuals, a rapid re-stimulation of antigen-specific T-cells occurs, with release of the cytokine IFN-γ, which is then measured. In the case of TB, the antigens used are highly specific for TB and absent from the BCG vaccine. Two such TB tests are currently available: an enzyme-linked immunosorbent assay (QuantiFERON-TB Gold In-Tube) and an enzyme-linked immunospot assay (T-SPOT.TB). Both have a large body of supporting clinical evidence (over 400 peer-reviewed & published studies for QuantiFERON and over 80 for T-SPOT). After careful deliberation, we have chosen to perform in house the QuantiFERON-TB Gold In-Tube assay.

A recent meta-analysis (Pai et al. Ann Intern Med 2008;149:177-84) found the QuantiFERON IFN-γ assay to have a specificity ≈96% vs. specificity of 59% for the TST in a BCG vaccinated population. Analyses comparing the sensitivity of the new blood test to the TST reveal inconsistent results (range: new test ≈ 64-93%; TST ≈ 57-100%), but overall are comparable. The blood test does not require a second visit as does the TST for interpretation. While a higher up front charge, the blood test achieves cost effectiveness through reductions in the numbers of chest x-rays, sputum analyses, and resources required to evaluate and treat individuals with false positive TST results. A recent study (Diel et al. Chest 2009;135:1010-18) showed that use of the new test as a replacement for the TST would decrease the number of LTBI suspects to be investigated by 70%.

If there are any questions or concerns about this newer TB testing, please call MuirLab Supervisor of Molecular Diagnostics and Immunology, Cindy Liedstrand (925.692.5681), Medical Director of Molecular Diagnostics and Immunology Nicholas Byrne, M.D. (925.947.5356), or me (925.692.5405). Thank you.