Comparison of interferon-γ release assays and tuberculin skin test in predicting active tuberculosis (TB) in children in the UK: a paediatric TB network study
- Alasdair R J Bamford1,
- Angela M Crook2,
- Julia E Clark3,
- Zohreh Nademi3,
- Garth Dixon4,
- James Y Paton5,
- Anna Riddell6,
- Francis Drobniewski7,
- Andrew Riordan8,
- Suzanne T Anderson9,
- Amanda Williams10,
- Sam Walters11,
- Beate Kampmann1
- 1Academic Department of Paediatrics, Imperial College London, London, UK
- 2MRC Clinical Trials Unit, London, UK
- 3Department of Paediatrics, Newcastle General Hospital, Newcastle, UK
- 4Department of Microbiology, Great Ormond Street Hospital, London, UK
- 5Division of Developmental Medicine, University of Glasgow, Glasgow, UK
- 6The Royal London Hospital, London, UK
- 7HPA Mycobacterium Reference Unit, London, UK
- 8Alder Hey Children's NHS Foundation Trust, Liverpool, UK
- 9Brighton and Sussex Medical School, Brighton, UK
- 10Northwick Park Hospital, London, UK
- 11Imperial College NHS Trust, London, UK
- Correspondence to Dr Beate Kampmann, Academic Department of Paediatrics, Imperial College London, Norfolk Place, London W2 1PG, UK;
Contributors BK was PI and initiated the study concept and collaborative work. She is the guarantor of the study. AB and AMC analysed the collaborative data. AB and BK drafted the manuscript. JC, ZN, GD, JYP, AR, FD, AR, STBA, AW, SW and BK conducted the clinical studies at their local hospitals, compiled the data for the joint analysis and reviewed the manuscript. All authors made significant contributions to the interpretation of the data, the writing of the manuscript and its final version. All authors have approved the final version of the manuscript. We would like to acknowledge all the laboratory personnel who performed the IGRA assays, particularly V Nikolayevskyy and A Gordon.
- Accepted 14 September 2009
- Published Online First 8 October 2009
Background The value of interferon-γ release assays (IGRA) to diagnose active tuberculosis (TB) in children is not established, but these assays are being widely used for this purpose. The authors examined the sensitivity of commercially available IGRA to diagnose active TB in children in the UK compared with the tuberculin skin test (TST).
Methods The authors established a paediatric tuberculosis network and conducted a retrospective analysis of data from children investigated for active TB at six large UK paediatric centres. All centres had used TST and at least one of the commercially available IGRA (T-Spot.TB or Quantiferon-Gold in Tube) in the diagnostic work-up for active TB. Data were available from 333 children aged 2 months to 16 years. The authors measured the sensitivity of TST and IGRA in definite (culture confirmed) and probable TB in children, agreement between TST and either IGRA, and their combined sensitivity.
Results Of 333 children, 49 fulfilled the criteria of definite TB, and 146 had probable TB. Within the definite cohort, TST had a sensitivity of 82%, Quantiferon-Gold in tube (QFT-IT) had a sensitivity of 78% and T-Spot.TB of 66%. Neither IGRA performed significantly better than a TST with a cut-off of 15 mm. Combining the results of TST and IGRA increased the sensitivity to 96% for TST plus T-Spot.TB and 91% for TST plus QFG-IT in the definite TB cohort.
Conclusions A negative IGRA does not exclude active TB disease, but a combination of TST and IGRA increases the sensitivity for identifying children with active TB.
Funding Consumable grants from the PEEL Foundation (The Peel Medical Research Trust, Sceptre Court, 40 Tower Hill, London EC3N 4DX, UK), the European Society for Paediatric Infectious Diseases (c/o Kenes International, Rue de Chantepoulet 1–3, PO Box 1726, CH-1211 Geneva 1, Switzerland) and the HPA Mycobacterium Reference Unit (Clinical Sciences Research Centre, Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and the London Queen Mary's School of Medicine and Dentistry, 2 Newark Street, London E1 2AT, UK) contributed to this work. BK is funded by the Wellcome Trust. She is supported by the Biomedical Research Centre and is a coinvestigator at the Centre for Respiratory Infection (CRI) at Imperial College London. STA is supported by a European Union grant (European Commission, EuropeAid Co-operation Office, B 1049 Brussels, Belgium): aid for poverty-related diseases in developing countries (EuropeAid/121404/C/G/Multi). AB is funded by the NIHR (National Institute of Health Research, Room 132, Richmond House, 79 Whitehall, London SW1A2NL, UK) as a Training Fellow. None of the funding sources had a role in the design of the study, data collection, analysis, data interpretation or writing of the paper.
Competing interests None.
Ethical approval Study approval was obtained from the ethics committees of Imperial College Healthcare NHS Trusts, North West London Hospitals Trust and Newcastle NHS Trust.
Provenance and peer review Not commissioned; not externally peer reviewed.
Patient consent Obtained from the parents.