Risk assessment of tuberculosis in immunocompromised patients. A TBNET study

Am J Respir Crit Care Med. 2014 Nov 15;190(10):1168-76. doi: 10.1164/rccm.201405-0967OC.


Rationale: 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.

Objectives: 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.

Measurements and main 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).

Trial registration: ClinicalTrials.gov NCT00707317.

Keywords: TBNET; immunocompromised; interferon-γ release assays; tuberculin-skin test; tuberculosis.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • HIV Infections / immunology
  • Humans
  • Immunocompromised Host*
  • Interferon-gamma Release Tests*
  • Kidney Failure, Chronic / immunology
  • Latent Tuberculosis / diagnosis*
  • Male
  • Middle Aged
  • Organ Transplantation
  • Risk Assessment
  • Stem Cell Transplantation
  • Tuberculin Test*

Associated data

  • ClinicalTrials.gov/NCT00707317