Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10

Abstract

Tests based on tuberculin purified protein derivative (PPD) cannot distinguish between tuberculosis infection, Mycobacterium bovis BCG vaccination, or exposure to environmental mycobacteria. The present study investigated the diagnostic potential of two Mycobacterium tuberculosis-specific antigens (ESAT-6 and CFP10) in experimental animals as well as during natural infection in humans and cattle. Both antigens were frequently recognized in vivo and in vitro based on the induction of delayed-type hypersensitivity responses and the ability to induce gamma interferon production by lymphocytes, respectively. The combination of ESAT-6 and CFP10 was found to be highly sensitive and specific for both in vivo and in vitro diagnosis. In humans, the combination had a high sensitivity (73%) and a much higher specificity (93%) than PPD (7%).

FIG. 1

Guinea pig DTH responses to specific antigens. Individual DTH responses and mean responses (—) in M. tuberculosis-infected (○), BCG-vaccinated (□), M. avium-sensitized (◊), and naive (▿) guinea pigs to PPD, ESAT-6, or CFP10 are shown. DTH responses were read after 24 h, and the dotted line indicates the limit for positive responses (5 mm).

FIG. 2

Human IFN-γ responses to specific antigens. PBMC from 11 patients with minimal TB, 8 BCG-vaccinated donors, and 6 nonvaccinated donors were stimulated with PPD or ESAT-6–CFP10. IFN-γ in the supernatants was determined after 5 days of culture by ELISA and expressed as the mean picograms per milliliter for triplicate wells. Results are shown as box plots with median values in each group, 25 and 75% quartiles, and 5 and 95% percentile points.