Paediatrics (RCH) - Research Publications

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    Performance of a whole blood interferon gamma assay for detecting latent infection with Mycobacterium tuberculosis in children
    Connell, TG ; Curtis, N ; Ranganathan, SC ; Buttery, JP (BMJ PUBLISHING GROUP, 2006-07)
    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-gamma) 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-gamma 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-gamma 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-gamma 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-gamma assay. There were no instances of a positive whole blood IFN-gamma assay with a negative TST. Mitogen (positive) control IFN-gamma 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-gamma assay were older (median 12.9 v 6.92 years, respectively, p = 0.007). The whole blood IFN-gamma assay was positive in all nine children with TB disease. CONCLUSION: There was poor agreement between the whole blood IFN-gamma assay and TST for the diagnosis of latent TB. The whole blood IFN-gamma assay may have lower sensitivity than the TST in diagnosing TB infection in children. A significant proportion of whole blood IFN-gamma assays fail when used as a screening assay in routine practice.
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    Early detection of perinatal tuberculosis using a whole blood interferon-γ release assay
    Connell, T ; Bar-Zeev, N ; Curtis, N (OXFORD UNIV PRESS INC, 2006-06-01)
    BACKGROUND: The diagnosis of perinatal tuberculosis (TB) is problematic because of its nonspecific presentation, the difficulty of obtaining microbiological confirmation, and the unreliability of the tuberculin skin test. Immunodiagnosis of TB has received new attention with the discovery of Mycobacterium tuberculosis-specific immunodominant antigens (early secreted antigenic target 6 [ESAT-6] and culture filtrate protein 10 [CFP-10]) that are encoded by the RD1 region of the pathogen. A whole blood assay has recently been developed to quantitatively measure interferon- gamma production by lymphocytes specific to these antigens, but its evaluation in the diagnosis of TB in infants and children has been limited to date. METHODS: In addition to routine diagnostic evaluation (tuberculin skin tests, culture of early-morning gastric aspirate samples, and chest radiographs), 2 infants with suspected perinatal TB were investigated with a whole blood interferon-gamma release assay. RESULTS: The results of the tuberculin skin tests were negative for both patients. The findings of the chest radiographs were abnormal with features suggestive of miliary TB. A whole blood interferon- gamma release assay was performed and yielded positive results within 48 h after admission to the hospital for both patients, prompting early antituberculous treatment. M. tuberculosis was cultured after 6 weeks from gastric aspirate samples collected on admission to the hospital from both infants. At 6 months of age, both infants were thriving and had acheived normal developmental milestones. CONCLUSIONS: The advent of interferon- gamma release assays may prove to be useful in the evaluation of infants with suspected perinatal TB.