title: Risk assessment of tuberculosis in immunocompromised patients. A TBNET study.
abstract: BACKGROUND
  In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency.
  
  
  OBJECTIVE
  This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.
  
  
  METHODS
  Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.
  
  
  RESULTS
  Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.
  
  
  CONCLUSIONS
  Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).
authors.affiliation: 1 Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sester
authors.forename: Frank
authors.initials: F
authors.lastname: van Leth
authors.forename: Judith
authors.initials: J
authors.lastname: Bruchfeld
authors.forename: Dragos
authors.initials: D
authors.lastname: Bumbacea
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Cirillo
authors.forename: Asli Gorek
authors.initials: AG
authors.lastname: Dilektasli
authors.forename: José
authors.initials: J
authors.lastname: Domínguez
authors.forename: Raquel
authors.initials: R
authors.lastname: Duarte
authors.forename: Martin
authors.initials: M
authors.lastname: Ernst
authors.forename: Fusun Oner
authors.initials: FO
authors.lastname: Eyuboglu
authors.forename: Irini
authors.initials: I
authors.lastname: Gerogianni
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Janssens
authors.forename: Inger
authors.initials: I
authors.lastname: Julander
authors.forename: Berit
authors.initials: B
authors.lastname: Lange
authors.forename: Irene
authors.initials: I
authors.lastname: Latorre
authors.forename: Monica
authors.initials: M
authors.lastname: Losi
authors.forename: Roumiana
authors.initials: R
authors.lastname: Markova
authors.forename: Alberto
authors.initials: A
authors.lastname: Matteelli
authors.forename: Heather
authors.initials: H
authors.lastname: Milburn
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
authors.forename: Theresia
authors.initials: T
authors.lastname: Scholman
authors.forename: Paola M
authors.initials: PM
authors.lastname: Soccal
authors.forename: Marina
authors.initials: M
authors.lastname: Straub
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagner
authors.forename: Timo
authors.initials: T
authors.lastname: Wolf
authors.forename: Aslihan
authors.initials: A
authors.lastname: Yalcin
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D059425:Interferon-gamma Release Tests; D007676:Kidney Failure, Chronic / Q000276:immunology; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D018570:Risk Assessment; D033581:Stem Cell Transplantation; D014374:Tuberculin Test
keywords: TBNET; immunocompromised; interferon-γ release assays; tuberculin-skin test; tuberculosis