title: Potential role for IL-2 ELISpot in differentiating recent and remote infection in tuberculosis contact tracing.
abstract: Interferon (IFN)-gamma release assays (IGRA) have improved tuberculosis contact tracing, but discrimination of recent from remote Mycobacterium tuberculosis contacts is not possible by IGRA alone. We present results of a tuberculosis contact investigation with a new early-secretory-antigenic-target (ESAT)-6 and culture-filtrate-protein (CFP)-10 specific interleukin (IL)-2 ELISpot in addition to ESAT-6 and CFP-10 specific IFN-gamma ELISpot and tuberculin skin testing (TST). Results of the TST, IFN-gamma ELISpot and IL-2 ELISpot were positive in 6/172 (3.4%), 7/167 (4.2%) and 6/196 (3.1%) of contacts, respectively. Close contact (> or =100 hours) to the index case increased the risk of positive results in the IFN-gamma ELISpot, TST, and IL-2 ELISpot by 40.8, 19.3, and 2.5 times, respectively. Individuals with a positive IFN-gamma ELISpot/negative IL-2 ELISpot result had a median (IQR) duration of index case exposure of 568 hours (133_1000) compared to individuals with a positive IFN-gamma ELISpot/positive IL-2 ELISpot result (median = 24 hours; 20_130; p-value = 0.047). Combination of a M. tuberculosis specific IFN-gamma ELISpot with a M. tuberculosis specific IL-2 ELISpot significantly improved the identification of individuals with the highest risk of recent M. tuberculosis infection and is a promising method that should be explored to target tuberculosis preventive chemotherapy.
authors.affiliation: Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krummel
authors.forename: Alan
authors.initials: A
authors.lastname: Strassburg
authors.forename: Martin
authors.initials: M
authors.lastname: Ernst
authors.forename: Norbert
authors.initials: N
authors.lastname: Reiling
authors.forename: Barbara
authors.initials: B
authors.lastname: Eker
authors.forename: Heidrun
authors.initials: H
authors.lastname: Rath
authors.forename: Robert
authors.initials: R
authors.lastname: Hoerster
authors.forename: Waltraud
authors.initials: W
authors.lastname: Wappler
authors.forename: Andrea
authors.initials: A
authors.lastname: Glaewe
authors.forename: Volker
authors.initials: V
authors.lastname: Schoellhorn
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002648:Child; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D012882:Skin Tests; D014373:Tuberculin / Q000378:metabolism; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D014373:Tuberculin; D007371:Interferon-gamma