Differential positive TSPOT assay responses to ESAT-6 and CFP-10 in health care workers

Tuberculosis (Edinb). 2016 Dec:101S:S83-S91. doi: 10.1016/j.tube.2016.09.012. Epub 2016 Sep 28.

Abstract

Background: The TSPOT.TB (TSPOT) diagnostic test for latent tuberculosis infection is based on a cell-mediated response to the Mycobacteria tuberculosis antigens, ESAT-6 and/or CFP-10, producing an "interferon-gamma footprint". We investigated the within-sample and within-subject variability of positive TSPOT assays due to the individual assay antigens' reactivity.

Methods: Positive TSPOT assay frequencies due to ESAT-6 or CFP-10 among health care workers (HCWs) at 6-month intervals for 18 months were compared. Differences in result interpretation (positive or negative) for ESAT-6 and CFP10 and potential prognostic factors were investigated.

Results: There were 576 positive results in 8805 TSPOT assays representing 2418 participants. A significant difference was detected in positive TSPOT results due to a positive response to either ESAT-6, CFP-10 or both antigens at baseline through 12 M (p < 0.001), but not for the 18 M follow-up. Gender, ethnicity, occupation, previous positive tuberculin skin test (TST) and study site were significantly associated with specific antigen positivity.

Conclusions: Among our HCW samples with positive TSPOT assays, CFP-10 induced a larger proportion of positive TSPOT results than ESAT-6. Potential causes for this finding include: BCG vaccinated subpopulations, certain jobs, history of positive TST, U.S. birth, and study site. A high proportion of single-positive specimens may reflect false-positives results.

Keywords: CFP-10; ESAT-6; IGRA; TSPOT; Tuberculosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / immunology*
  • Cross-Sectional Studies
  • Enzyme-Linked Immunospot Assay*
  • False Positive Reactions
  • Female
  • Health Personnel*
  • Humans
  • Interferon-gamma / blood*
  • Interferon-gamma / immunology
  • Interferon-gamma Release Tests*
  • Latent Tuberculosis / blood
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / immunology
  • Latent Tuberculosis / microbiology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Time Factors
  • Tuberculin Test
  • United States
  • Young Adult

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • IFNG protein, human
  • Interferon-gamma