Uncommon presentations of tuberculosis: the potential value of a novel diagnostic assay based on the Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10

SETTING: Leiden University Medical Center, Leiden, the Netherlands.

OBJECTIVE: To illustrate the potential value of a recently developed diagnostic assay for detection of tuberculosis (TB), based on T cell responses to the early secreted antigenic target 6 kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10). These antigens are Mycobacterium tuberculosis specific because they are expressed by M. tuberculosis but absent from M. bovis bacille Calmette-Guérin (BCG) and most environmental mycobacteria. In recent studies, the assay had a high sensitivity and specificity for detection of active TB.

DESIGN: We describe five patients with uncommon presentations of tuberculosis, in whom the diagnosis was delayed by negative or conflicting results of diagnostic procedures aimed at detection of M. tuberculosis and an uninformative tuberculin skin test. IFN-γ production in response to ESAT-6 and CFP-10 by peripheral blood mononuclear cells from these patients was evaluated before and during anti-tuberculosis treatment.

RESULTS: In all five patients, IFN-γ responses to ESAT-6 and/or CFP-10 were above the cut-off level defined in a previous study. During treatment, IFN-γ responses generally increased.

CONCLUSION: These results indicate that T cell responses to M. tuberculosis-specific antigens have potential diagnostic value when TB is suspected and the results of other diagnostic tests are inconclusive, especially in BCG-vaccinated individuals.