Identifying predictors of interferon-gamma release assay results in pediatric latent tuberculosis: a protective role of BCG?

Abstract

Rationale: Interferon-gamma release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. Objectives: To investigate factors influencing results of interferon gamma release assays in children using a large European dataset. Methods: The Pediatric Tuberculosis Network European Trials group pooled and analysed data from five sites across Europe comprising 1128 children who were all investigated for latent tuberculosis infection by using TST and at least one interferon-gamma release assay. Multi-variate analyses examined age, Bacille Calmette-Guérin (BCG) vaccination status, and gender as predictor variables of results. Subgroup analyses included children who were household contacts. Measurements and results:1,093 children had a Quantiferon Gold In-Tube and 382 had a T-SPOT.TB interferon gamma release assay. Age was positively correlated with a positive blood result (Quantiferon Gold In-Tube: OR=1.08 per year increasing age, p<0.0001; T-SPOT.TB: OR=1.14 per year increasing age, p<0.001). 5.5% of children with a tuberculin skin test result <5mm, 14.8% if <10mm, and 23.9% if <15mm, had a positive Quantiferon Gold In-Tube result. Prior BCG vaccination was associated with a negative interferon gamma release assay result (Quantiferon Gold In-Tube: OR=0.41, p<0.001; T-SPOT.TB: OR=0.41, p<0.001). Young age was a predictor of indeterminate IGRA, but indeterminate rates were low (3.6% in <5years, 1% in >5 years). Conclusions: Our data show BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of interferon-gamma release assays to children with positive skin tests risks underestimating latent infection