Is secretion of IFN-gamma in response to Mycobacterium tuberculosis antigens in youngest children sufficient to play a role in TB diagnostics?

ABSTRACT

OBJECTIVES: To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN-É£) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB antigens) in the QuantiFERON-TB Gold in-Tube test (QFT-GIT), (Cellestis Ltd., Australia). WORKING HYPOTHESIS: Is TB-antigen-induced IFN-É£ response in children ≤5 years sufficient to consider QFT-GIT a possible tool for TB diagnostics? Study design, patient-subject selection, and methods: We recruited children 0-17 years old suspected of TB infection to this cross-sectional study, in whom QFT-GIT and TST were performed. We analyzed the median IFN-É£ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN-É£ level in both tubes and age. RESULTS: A total of 153 children were enrolled, age median was 7.8 (IQR8), 45 (29.4%) aged ≤5 years (median 3.4, IQR1.7), 108 > 5 years (median 10.55, IQR5.93). In the mitogen tubes, the median IFN-É£ level was higher in children >5 years (median 17.87, IQR2.1 vs 16.77, IQR7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR0.21vs 0.06, IQR0.09, P = 0.04). We proved a positive correlation between IFN-É£ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = -0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = -0.39, P = 0.01). CONCLUSIONS: The youngest children release sufficient amount of IFN-É£ in response to TB antigens thus QFT-GIT might be a useful tool for TB diagnostics in this age group.