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There is no reliable means of detecting latent M. tuberculosis infection, and even in patients with active tuberculosis, infection is often unconfirmed. We hypothesized that M. tuberculosis antigen-specific T cells might reliably indicate infection. We enumerated peripheral blood-derived interferon gamma (IFN-gamma)-secreting T cells responding to epitopes from ESAT-6, an antigen that is highly specific for M. tuberculosis complex but absent from BCG, in four groups of individuals. Forty-five of 47 patients with bacteriologically confirmed tuberculosis had ESAT-6-specific IFN-gamma-secreting T cells, compared with four of 47 patients with nontuberculous illnesses, indicating that these T cells are an accurate marker of M. tuberculosis infection. This assay thus has a sensitivity of 96% (95% confidence interval [CI] 92-100) for detecting M. tuberculosis infection in this patient population. By comparison, of the 26 patients with tuberculosis who had a diagnostic tuberculin skin test (TST), only 18 (69%) were positive (p = 0.003). In addition, 22 of 26 (85%) TST-positive exposed household contacts had ESAT-6-specific T cells, whereas zero of 26 unexposed BCG-vaccinated subjects responded. This approach enables rapid detection of M. tuberculosis infection in patients with active tuberculosis and in exposed asymptomatic individuals at high risk of latent infection; it also successfully distinguishes between M. tuberculosis infection and BCG vaccination. This capability may facilitate tuberculosis control in nonendemic regions.

Original publication

DOI

10.1164/ajrccm.163.4.2009100

Type

Journal article

Journal

Am J Respir Crit Care Med

Publication Date

03/2001

Volume

163

Pages

824 - 828

Keywords

Adolescent, Adult, Aged, Antigens, Bacterial, CD4 Antigens, CD4 Lymphocyte Count, Enzyme-Linked Immunosorbent Assay, Epitopes, T-Lymphocyte, Female, Humans, Male, Middle Aged, Mycobacterium tuberculosis, Prospective Studies, Reference Values, Sensitivity and Specificity, Tuberculin Test, Tuberculosis