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This study compared the enzyme linked immunospot assay (ELISPOT) with tuberculin skin testing (TST) for the diagnosis of latent tuberculosis infection (LTBI) in low prevalence settings. The ELISPOT assay measures interferon gamma secretion by blood mononuclear cells to ESAT-6, an antigen present in Mycobacterium tuberculosis but not in M bovis or environmental mycobacteria. 535 students were tested in a large tuberculosis outbreak in a UK school. Although agreement between the tests was high (89%), ELISPOT correlated significantly more closely with M tuberculosis exposure than did TST based on duration of exposure (p=0.007) and measures of proximity to the single index case (p=0.002). TST was significantly more likely to be positive in BCG vaccinated than in non-vaccinated students. The authors conclude that ELISPOT offers a more accurate approach than TST for the identification of patients with LTBI, and is more precise at targeting preventative treatment.
Interpretation of studies in this area is difficult because of the lack of a gold standard for diagnosing LTBI. There are no comparative studies between ELISPOT and QuantiFERON, an existing assay which measures the interferon response to PPD in whole blood. Although the TST requires a return visit for interpretation, it does not require phlebotomy, analysis within a few hours, laboratory expertise, or expensive equipment like an ELISPOT reader. Studies are required to assess the cost/benefit ratio of ELISPOT and its positive predictive value for the subsequent development of tuberculosis.
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