Performance of Tuberculin Skin Tests and Interferon-γ Release Assays in Children Younger Than 5 Years

Abstract

Background: Available data to assess the optimal diagnostic approach in infants and preschool children at risk of tuberculosis (TB) are limited.

Methods: We conducted a prospective observational study in children younger than 5 years undergoing assessment with both tuberculin skin tests (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays at 2 tertiary TB units in Barcelona, Spain.

Results: A total of 383 children were included. One of 304 participants considered uninfected developed active TB during follow-up {median [interquartile range (IQR)]: 47 [30; 48] months}, compared with none of 40 participants with latent TB infection [follow-up since completion of anti-TB treatment: 42 (32; 45) months]. Overall test agreement between TST and QFT-GIT was moderate (κ = 0.551), but very good in children screened after TB contact (κ = 0.801) and in Bacillus Calmette-Guérin (BCG)-unvaccinated children (κ = 0.816). Discordant results (16.8%, all TST+/QFT-GIT-) were mainly observed in new-entrant screening and in BCG-vaccinated children. Children with indeterminate QFT-GIT results were on average younger than those with determinate results (median age: 12 vs. 30 months; P < 0.001). The sensitivity of TSTs and QFT-GIT assays in children with confirmed active TB was 100% (95% confidence interval: 79.4%-100%) and 93.7% (95% confidence interval: 69.8%-99.8%), respectively. In patients with latent TB infection or active TB, there was no correlation between age and antigen-stimulated interferon-γ responses (r = -0.044; P = 0.714).

Conclusions: In young BCG-unvaccinated children with recent TB contact, a dual testing strategy using TST and QFT-GIT in parallel may not be necessary. However, TST+/QFT-GIT- discordance is common, and it remains uncertain if this constellation indicates TB infection or not. In active TB, QFT-GIT assays do not perform better than TSTs.