In routine clinical practice, a negative blood culture result is almost inevitable for a large proportion of blood cultures because of the submission of an inadequate volume of blood. Even after an educational intervention, nearly one half of blood cultures were inadequate submissions.

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Background: The diagnosis of latent Mycobacterium tuberculosis (MTB) infection with a tuberculin skin test (TST) in children is complicated by the potential influence of prior exposure to Bacille Calmette Geurin (BCG) vaccination or environmental mycobacteria. A whole blood assay has recently been developed to quantitatively measure interferon gamma (IFN-c) production by lymphocytes specific to the MTB antigens ESAT-6 and CFP-10, but its use and assessment in children has been limited. A study was undertaken to compare the performance of the whole blood IFN-c assay with the TST in diagnosing latent tuberculosis (TB) infection or TB disease in children in routine clinical practice. Methods: One hundred and six children with a high risk of latent TB infection or TB disease were enrolled in the study. High risk was defined as contact with TB disease, clinical suspicion of TB disease, or recent arrival from an area of high TB prevalence. The whole blood IFN-c assay was undertaken in 101 children. Results: Seventeen (17%) of the 101 assays yielded inconclusive results due to failure of positive or negative control assays. There was poor correlation between the whole blood IFN-c assay and the TST (kappa statistic 0.3) with 26 (70%) of the 37 children defined as latent TB infection by TST having a negative whole blood IFN-c assay. There were no instances of a positive whole blood IFN-c assay with a negative TST. Mitogen (positive) control IFN-c responses were significantly correlated with age (Spearman's coefficient = 0.53, p,0.001) and, in children with latent TB infection identified by TST, those with a positive IFN-c assay were older (median 12.9 v 6.92 years, respectively, p = 0.007). The whole blood IFN-c assay was positive in all nine children with TB disease. Conclusion: There was poor agreement between the whole blood IFN-c assay and TST for the diagnosis of latent TB. The whole blood IFN-c assay may have lower sensitivity than the TST in diagnosing TB infection in children. A significant proportion of whole blood IFN-c assays fail when used as a screening assay in routine practice.

BackgroundThere are limited data comparing the performance of the two commercially available interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease.Methods and FindingsThe results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, κ = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, κ = 0.50) or T-SPOT.TB (75%, κ = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-γ responses was significantly influenced by TB contact history, but only the TST was influenced by age.ConclusionsAlthough a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.