The Magnitude of Interferon Gamma Release Assay Responses in Children With Household Tuberculosis Contact Is Associated With Tuberculosis Exposure and Disease Status

Background: The clinical utility of the magnitude of interferon gamma (IFN gamma) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFN gamma response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children. Methods: We completed cross-sectional analysis of children (<= 15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa. IFN gamma values were reported as concentrations and spot forming units for the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, respectively. Random-effects linear regression was used to investigate the relation between the M. tuberculosis contact score, clinical phenotype (TB diseased, infected, uninfected) and IFN gamma square response as outcome, adjusted for relevant covariates. Results: We analyzed data from 669 children (median age, 63 months; inter-quartile range, 33-108 months). A 1-unit increase in M. tuberculosis contact score was associated with an increase of IFN gamma 0.60 international unit/mL (95% confidence interval [CI], 0.44-0.76 international unit/mL), and IFN gamma spot forming unit 2 counts (95% CI, 1-3). IFN gamma response was significantly lower among children with M. tuberculosis infection compared with children with TB disease (beta = -1.42; 95% CI, -2.80 to -0.03) for the QFT-GIT, but not for the T-SPOT.TB. This association was strongest among children 2-5 years (beta = -2.35 years; 95% CI, -4.28 to -0.42 years) and absent if <2 years. Conclusions: The magnitude of IFN gamma response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFN gamma values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children. Discussion: The magnitude of IFN gamma response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFN gamma values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.