title: Differential positive TSPOT assay responses to ESAT-6 and CFP-10 in health care workers.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Houston Methodist Hospital Institute, 6670 Bertner Ave, Houston, TX, 77030, USA; University of Texas School of Public Health, Center for Infectious Diseases, 1200 Pressler St, Houston, TX, 77030, USA. Electronic address: vagarwal@houstonmethodist.org.
authors.forename: Saroochi
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Houston Methodist Hospital Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. Electronic address: dtnguyen6@houstonmethodist.org.
authors.forename: Duc T
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Houston Methodist Hospital Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. Electronic address: jdlew@houstonmethodist.org.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lew
authors.affiliation: Houston Methodist Hospital Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. Electronic address: larry.teeter@dshs.state.tx.us.
authors.forename: Larry D
authors.initials: LD
authors.lastname: Teeter
authors.affiliation: University of Texas School of Public Health, Center for Infectious Diseases, 1200 Pressler St, Houston, TX, 77030, USA. Electronic address: jose-miguel.yamal@uth.tmc.edu.
authors.forename: Jose-Miguel
authors.initials: JM
authors.lastname: Yamal
authors.affiliation: University of Texas School of Public Health, Center for Infectious Diseases, 1200 Pressler St, Houston, TX, 77030, USA. Electronic address: blanca.i.restrepo@uth.tmc.edu.
authors.forename: Blanca I
authors.initials: BI
authors.lastname: Restrepo
authors.affiliation: University of Texas School of Public Health, Center for Infectious Diseases, 1200 Pressler St, Houston, TX, 77030, USA. Electronic address: eric.l.brown@uth.tmc.edu.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Brown
authors.affiliation: Johns Hopkins Medicine, 733 North Broadway, Baltimore, MD, 21205, USA. Electronic address: dsusan1@jhmi.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
authors.affiliation: Houston Methodist Hospital Institute, 6670 Bertner Ave, Houston, TX, 77030, USA. Electronic address: eagraviss@houstonmethodist.org.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003430:Cross-Sectional Studies; D058501:Enzyme-Linked Immunospot Assay; D005189:False Positive Reactions; D005260:Female; D006282:Health Personnel; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000276:immunology; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013997:Time Factors; D014374:Tuberculin Test; D014481:United States; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: CFP-10; ESAT-6; IGRA; TSPOT; Tuberculosis