Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells.

Journal article

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.

Authors: Lalvani, A; Pathan, A; Mcshane, H; Wilkinson, R; Latif, M

• Publication status: Published
• Journal: American journal of respiratory and critical care medicine
• Volume: 163
• Issue: 4
• Pages: 824-828
• Publication date: 2001-03-01
• DOI: 10.1164/ajrccm.163.4.2009100
• EISSN: 1535-4970
• ISSN: 1073-449X
• Language: English
• Keywords: Humans; CD4 Lymphocyte Count; Reference Values; Adolescent; Tuberculin Test; Antigens, CD4; Mycobacterium tuberculosis; Sensitivity and Specificity; Aged; Prospective Studies; Female; Male; Tuberculosis; Enzyme-Linked Immunosorbent Assay; Adult; Middle Aged; Antigens, Bacterial; Epitopes, T-Lymphocyte