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A Suction Blister Protocol to Study Human T-cell Recall Responses In Vivo
Published on: August 11, 2018
T cell-based diagnosis of childhood tuberculosis infection
Ajit Lalvani1, Kerry A Millington
1Tuberculosis Immunology Group, Department of Respiratory Medicine, National Heart and Lung Institute, Wright-Fleming Institute of Infection & Immunity, Imperial College London, London, UK. a.lalvani@imperial.ac.uk
Insights
T-cell interferon-gamma release assays (TIGRAs) offer improved tuberculosis diagnosis in children compared to the tuberculin skin test (TST). These blood tests, ELISpot and ELISA, show higher specificity and sensitivity, especially ELISpot, aiding pediatric tuberculosis management.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Diagnostic Microbiology
Background:
- Tuberculin skin test (TST) is a traditional method for tuberculosis infection diagnosis.
- Bacille Calmette-Guérin (BCG) vaccination status can affect TST results.
- There is a need for more accurate diagnostic tools for pediatric tuberculosis.
Purpose of the Study:
- To review publications on T-cell interferon-gamma release assays (TIGRAs) in children.
- To evaluate the advantages and limitations of TIGRAs (ELISpot and ELISA) compared to TST.
- To inform pediatricians about the utility of these novel blood tests for tuberculosis diagnosis.
Main Methods:
- Systematic review of studies utilizing TIGRAs in pediatric populations.
- Comparative analysis of ELISpot and ELISA performance against TST.
- Assessment of TIGRA results in relation to tuberculosis infection, exposure, and clinical factors.
Main Results:
- TIGRAs are independent of BCG vaccination, offering higher specificity than TST.
- ELISpot demonstrates higher sensitivity than TST in children with active tuberculosis, unaffected by HIV, age, or malnutrition.
- ELISpot correlates better with tuberculosis exposure than TST; ELISA shows similar correlation.
- Indeterminate results are less frequent with ELISpot than ELISA in young children.
Conclusions:
- TIGRAs, particularly ELISpot, present significant advantages over TST for diagnosing pediatric tuberculosis.
- While further longitudinal studies are needed, current evidence supports the judicious clinical use of TIGRAs.
- National guidelines increasingly recommend TIGRAs for managing childhood tuberculosis.
Purpose Of Review:
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.
Recent Findings:
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.
Summary:
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.
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