Specific Detection of Tuberculosis Infection

TLDR

The tuberculin skin test is limited by BCG vaccination and exposure to nontuberculous mycobacteria, but M. tuberculosis–specific antigens absent from BCG have been identified. This study evaluated the CFP‑10 and ESAT‑6 antigens in a whole‑blood IFN‑γ assay as a diagnostic test for tuberculosis in BCG‑vaccinated individuals. Specificity was estimated using 216 BCG‑vaccinated Japanese adults with no exposure risk, and sensitivity was assessed in 118 culture‑confirmed patients who had received less than one week of treatment.

Abstract

The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis–specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-γ assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-γ assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-γ assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status.