Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country

JAMA. 2005 Jun 8;293(22):2756-61. doi: 10.1001/jama.293.22.2756.


Context: A recently developed whole-blood interferon gamma (IFN-gamma) assay based on stimulation with the Mycobacterium tuberculosis-specific antigens early secreted antigenic target 6 and culture filtrate protein 10 shows promise for the diagnosis of latent tuberculosis (TB) infection.

Objective: To compare the tuberculin skin test (TST) and the whole-blood IFN-gamma assay in the diagnosis of latent TB infection according to the intensity of exposure.

Design and setting: A prospective comparison between the whole-blood IFN-gamma assay and the TST using a 2-TU dose of purified protein derivative RT23 in a population with intermediate TB burden was conducted sequentially between February 1, 2004, and February 28, 2005, in a Korean tertiary referral hospital.

Participants: Of 273 participants, 220 (95.7%) had received BCG vaccine. Participants were grouped according to their risk of infection: group 1, no identifiable risk of M tuberculosis infection (n = 99); group 2, recent casual contacts (n = 72); group 3, recent close contacts (n = 48); group 4, bacteriologically or pathologically confirmed TB patients (n = 54).

Main outcome measures: Levels of agreement between the TST and the IFN-gamma assay and the likelihood of infection in the various groups.

Results: For the TST with a 10-mm induration cutoff, the positive response rate in group 1 was 51%; group 2, 60%; group 3, 71%, and group 4, 78%. For the IFN-gamma assay, the positive response rate in group 1 was 4%; group 2, 10%; group 3, 44%; and group 4, 81%. The overall agreement between the TST and the IFN-gamma assay in healthy volunteers was kappa = 0.16. The odds of a positive test result per unit increase in exposure across the 4 groups increased by a factor of 5.31 (95% confidence interval [CI], 3.62-7.79) for the IFN-gamma assay and by a factor of 1.52 (95% CI, 1.20-1.91) for the TST (P<.001). Using a 15-mm induration cutoff for the TST did not make a substantial difference to the test results.

Conclusion: The IFN-gamma assay is a better indicator of the risk of M tuberculosis infection than TST in a BCG-vaccinated population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Bacterial / immunology
  • BCG Vaccine
  • Bacterial Proteins / immunology
  • Female
  • Humans
  • Interferon-gamma / immunology*
  • Korea
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / isolation & purification*
  • Mycobacterium tuberculosis / physiology
  • Risk
  • Tuberculin Test*
  • Tuberculosis, Pulmonary / diagnosis*
  • Tuberculosis, Pulmonary / immunology
  • Virus Latency


  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Interferon-gamma