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Highly discordant T cell responses in individuals with recent exposure to household tuberculosis
  1. A C Hesseling1,
  2. A M Mandalakas2,
  3. H L Kirchner3,
  4. N N Chegou4,
  5. B J Marais1,
  6. K Stanley4,
  7. X Zhu2,
  8. G Black4,
  9. N Beyers1,
  10. G Walzl4
  1. 1
    Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
  2. 2
    Department of Paediatrics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
  3. 3
    Center for Health Research, Geisinger Health System, Danville, Pennsylvania, USA
  4. 4
    DST/NRF Centre of Excellence in Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
  1. Correspondence to Dr A C Hesseling, Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, 7505, South Africa; annekeh{at}sun.ac.za

Abstract

Background: There are limited data comparing interferon-γ release assays (IGRAs) for the detection of Mycobacterium tuberculosis infection in highly endemic settings.

Methods: A cross-sectional household contact study was conducted to measure the agreement of two IGRAs in relation to the tuberculin skin test (TST) to detect M tuberculosis infection and to assess the influence of M tuberculosis exposure and age.

Results: In 82 individuals in household contact, 93% of children and 42% of adults had a high M tuberculosis contact score. The TST was positive in 78% of adults and 54% of children, the T-SPOT.TB was positive in 89% of children and 66% of adults and the QuantiFERON TB Gold (QTF) was positive in a similar proportion of adults and children (38.1% and 39.6%). In children there was poor agreement between the TST and T-SPOT.TB (κ = −0.15) and the T-SPOT.TB and the QTF (κ = −0.03), but good agreement between the TST and the QTF (κ = 0.78) using 10 mm cut-off. In adults there was fair to moderate agreement between the TST and T-SPOT.TB (κ = 0.38), the TST and QTF (κ = 0.34) and T-SPOT.TB and QTF (κ = −0.50). High levels of exposure to M tuberculosis were associated with at least a sevenfold odds of being T-SPOT.TB positive (95% CI 7.67 to 508.69) and a threefold odds of being QTF positive (95% CI 3.02 to 30.54). There was a significant difference in the magnitude of T-SPOT.TB early secretory antigenic target (ESAT)-6 and culture filtrate protein 10 kD (CFP-10) spot counts between adults and children.

Conclusions: The T-SPOT.TB may be more sensitive than the TST or QTF for detecting recent M tuberculosis infection in children. Differences between assays and the predictive utility of these findings for subsequent disease development should be prospectively assessed.

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Footnotes

  • Funding Supported by the South African National Research Foundation NRF Thuthuka TTK2006051500016 (ACH), NIH IK23-HD40982 (AMM) and the Bill and Melinda Gates Foundation through Grand Challenges in Global Health Grant 37772 (NNC, KS, GB, GW) and the Norwegian Centre or Cooperation in Higher Education (ACH, GW).

  • Competing interests None.

  • Ethics approval Informed consent was obtained for participation and HIV testing. Institutional approval was obtained from Stellenbosch University.