T cell-based diagnosis of childhood tuberculosis infection

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Abstract
T-cell interferon-gamma release assays (TIGRAs), available as enzyme-linked immunospot (ELISpot) and enzyme-linked immunoassay (ELISA), potentially significantly advance on the tuberculin skin test (TST) for diagnosis of tuberculosis infection. We review all publications using TIGRAs in children to appraise paediatricians of the advantages and limitations of these new blood tests. Unlike TST, both tests are independent of Bacille Calmette-Guérin vaccination status, providing higher diagnostic specificity. In children with active tuberculosis ELISpot is more sensitive than TST and is unaffected by HIV infection, age under 3 years or malnutrition; ELISA data are currently limited. In the absence of a gold-standard test for latent tuberculosis infection, tuberculosis exposure was used as a surrogate marker; ELISpot generally correlates better with tuberculosis exposure than TST, while ELISA correlates broadly similarly. Indeterminate test results in young children are rare with ELISpot and are more common with ELISA. Although longitudinal studies quantifying risk of progression to tuberculosis in tuberculosis-exposed children with positive TIGRA results are required urgently, the small but rapidly expanding evidence-base since the first application of TIGRAs to childhood tuberculosis in 2003 combined with recent national guidelines makes a strong case for judicious use of TIGRAs in clinical management of paediatric tuberculosis.