title: Risk Assessment of Tuberculosis in Contacts by IFN-γ Release Assays. A Tuberculosis Network European Trials Group Study.
abstract: BACKGROUND
  Latent infection with Mycobacterium tuberculosis is defined by a positive IFN-γ release assay (IGRA) result in the absence of active tuberculosis. Only few, mostly monocentric studies have evaluated the role of IGRAs to predict the development of tuberculosis in recent contacts in low-incidence countries of tuberculosis.
  
  
  OBJECTIVE
  To analyze IGRA results and the effect of preventive chemotherapy on tuberculosis progression rates among recent contacts.
  
  
  METHODS
  Results from contact investigations at 26 centers in 10 European countries including testing for latent infection with M. tuberculosis by the QuantiFERON-TB Gold In-Tube (QFT) test or the T-SPOT.TB (TSPOT) were prospectively collected and analyzed.
  
  
  RESULTS
  Among 5,020 contacts of 1,023 index cases, 25 prevalent secondary cases were identified at screening. Twenty-four incident cases occurred among 4,513 contacts during 12,326 years of cumulative follow-up. In those with a positive IGRA result, tuberculosis incidence was 0.2 (QFT) and 0 (TSPOT) per 100 patient-years when contacts received preventive chemotherapy versus 1.2 (QFT) and 0.8 (TSPOT) per 100 patient-years in those not treated (38 and 37 patients needed to be treated to prevent one case, respectively). Positive and negative predictive values were 1.9% (95% confidence interval [CI], 1.1-3.0) and 99.9% (95% CI, 99.7-100) for the QFT and 0.7% (95% CI, 0.1-2.6) and 99.7% (95% CI, 99.1-99.9) for the TSPOT.
  
  
  CONCLUSIONS
  Tuberculosis rarely developed among contacts, and preventive chemotherapy effectively reduced the tuberculosis risk among IGRA-positive contacts. Although the negative predictive value of IGRAs is high, the risk for the development of tuberculosis is poorly predicted by these assays.
authors.affiliation: 1 Swiss Lung Association, Berne, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zellweger
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Michael
authors.initials: M
authors.lastname: Block
authors.forename: Simone
authors.initials: S
authors.lastname: Dore
authors.forename: Neus
authors.initials: N
authors.lastname: Altet
authors.forename: Rebecca
authors.initials: R
authors.lastname: Blunschi
authors.forename: Matthias
authors.initials: M
authors.lastname: Bogyi
authors.forename: Graham
authors.initials: G
authors.lastname: Bothamley
authors.forename: Christina
authors.initials: C
authors.lastname: Bothe
authors.forename: Luigi
authors.initials: L
authors.lastname: Codecasa
authors.forename: Patrizia
authors.initials: P
authors.lastname: Costa
authors.forename: Jose
authors.initials: J
authors.lastname: Dominguez
authors.forename: Raquel
authors.initials: R
authors.lastname: Duarte
authors.forename: Andreas
authors.initials: A
authors.lastname: Fløe
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fresard
authors.forename: José-María
authors.initials: JM
authors.lastname: García-García
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
authors.forename: Petra
authors.initials: P
authors.lastname: Halm
authors.forename: Doris
authors.initials: D
authors.lastname: Hellwig
authors.forename: Eveline
authors.initials: E
authors.lastname: Henninger
authors.forename: Helga
authors.initials: H
authors.lastname: Heykes-Uden
authors.forename: Liane
authors.initials: L
authors.lastname: Horn
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kruczak
authors.forename: Irene
authors.initials: I
authors.lastname: Latorre
authors.forename: Geneviève
authors.initials: G
authors.lastname: Pache
authors.forename: Heidrun
authors.initials: H
authors.lastname: Rath
authors.forename: Felix C
authors.initials: FC
authors.lastname: Ringshausen
authors.forename: Asunción Seminario
authors.initials: AS
authors.lastname: Ruiz
authors.forename: Ivan
authors.initials: I
authors.lastname: Solovic
authors.forename: Maria-Luiza de
authors.initials: ML
authors.lastname: Souza-Galvão
authors.forename: Ursula
authors.initials: U
authors.lastname: Widmer
authors.forename: Peter
authors.initials: P
authors.lastname: Witte
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage*; D018890:Chemoprevention; D002648:Child; D002675:Child, Preschool; D016358:Contact Tracing; D018450:Disease Progression; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D018570:Risk Assessment / Q000379:methods; D014374:Tuberculin Test / Q000379:methods; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: IFN-γ release assay; LTBI; QuantiFERON; T-SPOT.TB; tuberculosis