QuantiFERON-TB Gold In-Tube test performance in a paediatric population

Key words: Tuberculosis, QuantiFERON-TB GOLD In-Tube, Bacille Calmette-Guérin vaccine, Tuberculin skin test

Background - The performance of QuantiFERON-TBGold In-Tube (QTF-IT) in children is under debate, especially under 5 years of age and for the interpretation of discordant results between QFT-IT and Tuberculin-Skin-Test (TST).
Materials and Methods - Children consecutively referred to our Unit between 2010-2017 for suspected tuberculosis infection (TB) were enrolled. All children underwent clinical evaluation, TST and QFT-IT. Finally, the sensitivity of QFT-IT and TST in active TB cases and the risk factors associated with discordant TST+/QFT-IT- results were assessed.
Results - In this study 4,631 children (477 under two years of age, 1,318 between 2-4 years and 2,836 between 5-18 years) were enrolled. Overall, 205 active TB cases were reported (83 microbiologically confirmed, among them 63 with positive QFT-IT and 60 with positive TST). Considering microbiologically confirmed active TB children, a high sensitivity of QFT-IT was observed (95.0%; 95% CI: 85.4-100; n = 19) among children between 2-4 years of age and in those between 5-18 years (89.1%; 95% CI: 79.2-99.2; n = 33) while sensitivity was suboptimal in children younger than 2 years (84.6%; 95% CI: 65.0-100; n = 11). Independent risk factors associated with discordant TST+/QFT-IT- results, in LTBI children investigated with both tests, were: previous BCG vaccination (aOR: 2.18; 95% CI: 1.33-3.58; p = 0.002), age < 2 years vs 5-18 years (aOR: 7.54; 95% CI: 2.52-22.59; p < 0.0001), and age 2-4 years vs 5-18 years (aOR: 4.63; 95% CI: 2.66-8.06; p < 0.0001) and investigation for screening rather than for contact with a suspected or confirmed case (aOR: 3.58; 95% CI: 2.30-5.59; p < 0.0001).
Conclusions - The data suggest that QFT-IT might be used as unique assay in children over 2 years of age investigated for recent immigration/adoption screening and in case of recent low risk TB contact. This approach could considerably reduce the number of children undergoing pharmacological treatment. Conversely, both tests are recommended in case of strong clinical suspicious or high risk TB contact in children less than 5 years of age, in order to avoid misdiagnosis.