Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection

JAMA. 2001 Oct 10;286(14):1740-7. doi: 10.1001/jama.286.14.1740.


Context: Identifying persons with latent tuberculosis infection (LTBI) is crucial to the goal of TB elimination. A whole-blood interferon gamma (IFN-gamma) assay, the QuantiFERON-TB test, is a promising in vitro diagnostic test for LTBI that has potential advantages over the tuberculin skin test (TST).

Objectives: To compare the IFN-gamma assay with the TST and to identify factors associated with discordance between the tests.

Design and setting: Prospective comparison study conducted at 5 university-affiliated sites in the United States between March 1, 1998 and June 30, 1999.

Participants: A total of 1226 adults (mean age, 39 years) with varying risks of Mycobacterium tuberculosis infection or documented or suspected active TB, all of whom underwent both the IFN-gamma assay and the TST.

Main outcome measure: Level of agreement between the IFN-gamma assay and the TST.

Results: Three hundred ninety participants (31.8%) had a positive TST result and 349 (28.5%) had a positive IFN-gamma assay result. Overall agreement between the IFN-gamma assay and the TST was 83.1% (kappa = 0.60). Multivariate analysis revealed that the odds of having a positive TST result but negative IFN-gamma assay result were 7 times higher for BCG-vaccinated persons compared with unvaccinated persons. The IFN-gamma assay provided evidence that among unvaccinated persons with a positive TST result but negative IFN-gamma assay result, 21.2% were responding to mycobacteria other than M tuberculosis.

Conclusions: For all study participants, as well as for those being screened for LTBI, the IFN-gamma assay was comparable with the TST in its ability to detect LTBI, was less affected by BCG vaccination, discriminated responses due to nontuberculous mycobacteria, and avoided variability and subjectivity associated with placing and reading the TST.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BCG Vaccine
  • Female
  • Humans
  • Immunologic Tests*
  • Interferon-gamma / blood*
  • Lymphocyte Activation
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycobacterium tuberculosis / isolation & purification*
  • Prospective Studies
  • Tuberculin
  • Tuberculin Test*
  • Tuberculosis / diagnosis*


  • BCG Vaccine
  • Tuberculin
  • Interferon-gamma