title: Trajectories of tuberculosis-specific interferon-gamma release assay responses among medical and nursing students in rural India.
abstract: BACKGROUND
  Interferon gamma release assays (IGRAs) have been shown to be highly dynamic tests when used in serial testing for TB infection. However, there is little information demonstrating a clear association between TB exposure and IGRA responses over time, particularly in high TB incidence settings.
  
  
  OBJECTIVE
  To assess whether QuantiFERON-TB Gold In-Tube (QFT) responses are associated with occupational TB exposures in a cohort of young health care trainees in India.
  
  
  METHODS
  All medical and nursing students at Mahatma Gandhi Institute of Medical Sciences were approached. Participants were followed up for 18 months; QFT was performed 4 times, once every 6 months. Various modeling approaches were used to define IFN-gamma trajectories and correlations with TB exposure.
  
  
  RESULTS
  Among 270 medical and nursing trainees, high rates of conversions (6.3-20.9%) and reversions (20.0-26.2%) were found depending on the definitions used. Stable converters were more likely to have had TB exposure in hospital pre-study. Recent occupational exposures were not consistently associated with QFT responses over time.
  
  
  CONCLUSIONS
  IFN-gamma responses and rates of change could not be explained by occupational exposure investigated. High conversion and subsequent reversion rates suggest many health care workers (HCWs) would revert in the absence of treatment, either by clearing the infection naturally or due to fluctuations in the underlying immunological response and/or poor assay reproducibility. QFT may not be an ideal diagnostic test for repeated screening of HCWs in a high TB incidence setting.
authors.affiliation: Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada.
authors.forename: Alice
authors.initials: A
authors.lastname: Zwerling
authors.forename: Rajnish
authors.initials: R
authors.lastname: Joshi
authors.forename: S P
authors.initials: SP
authors.lastname: Kalantri
authors.forename: Gajalakshmi
authors.initials: G
authors.lastname: Dakshinamoorthy
authors.forename: Maryada Venkatarama
authors.initials: MV
authors.lastname: Reddy
authors.forename: Andrea
authors.initials: A
authors.lastname: Benedetti
authors.forename: Kevin
authors.initials: K
authors.lastname: Schwartzman
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
mesh_terms: D000293:Adolescent; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D059425:Interferon-gamma Release Tests; D008297:Male; D016273:Occupational Exposure; D013337:Students, Medical; D013338:Students, Nursing; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology; D055815:Young Adult
keywords: Health care workers; LTBI; Serial testing; TB screening