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Interferon-gamma assays in TB diagnosis
P13 Interferon-gamma release assay (IGRA) conversion, reversion and implications for the diagnosis of latent tuberculosis infection using a multimodality approach: a retrospective, observational study within a central London TB centre
  1. M H Almond1,
  2. M O'Donoghue1,
  3. N Drey2,
  4. S Seneviratne3,
  5. A Lalvani4,
  6. M Wickremasinghe1,
  7. O M Kon1
  1. 1Chest and Allergy Department, St. Mary's Hospital, Imperial College NHS Trust, London, UK
  2. 2School of Community and Health Sciences, City University, London, UK
  3. 3Department of Clinical Immunology, St. Mary's Hospital, Imperial College NHS Trust, London, UK
  4. 4Tuberculosis Research Unit, St. Mary's Hospital, Imperial College NHS Trust, London, UK

Abstract

Introduction and Objectives Accurate diagnosis & management of latent tuberculosis infection (LTBI) among TB contacts is critical for both the health of infected individuals and prevention of disease transmission. Interferon gamma release assays (IGRAs) measure T cell release of interferon-gamma following stimulation by antigens not confounded by the BCG vaccination. The current NICE guidelines recommend their use following a positive TST. In addition some centres have moved to a single step IGRA test for LTBI. Our institution adopts a triple investigation approach comprising a chest radiograph (CXR), TST and IGRA on presentation followed by a rescreen if the TST & IGRA are discordant or if pulmonary contacts are screened prior to 6 weeks. The aim of our study was to evaluate the prevalence of IGRA conversion and reversion in rescreened asymptomatic TB contacts that attended our centre.

Methods This was a retrospective, observational study carried out at a central London teaching hospital. The study population comprised 593 consecutive, adult TB contacts screened between 1 January 2008 and 31 December 2010. Data were collected through retrospective review of chest radiographs, TST & IGRA tests.

Results Of 498 asymptomatic TB contacts screened, 460 had both an initial TST and IGRA performed (Abstract P13 figure 1). 81 (17.7%) contacts had discordant TST & IGRA results. 52 (64%) of these discordant cases had a positive TST & Negative IGRA; these patients would have been discharged under NICE guidelines however, our rescreen revealed 9 (17%) positive 2nd IGRAs that is, conversion. Three of these patients were under 35 and would therefore by eligible for chemoprophylaxis. Twenty-nine (36%) of the discordant cases had a negative TST and positive IGRA however, 8 (28%) of these IGRAs reverted to negative. It is important to note that if following a single-step IGRA screening protocol (ie, without a rescreen) these cases may have been commenced on chemoprophylaxis unnecessarily (four of these reversion cases were under the age of 35).

Abstract P13 Figure 1

LTBI Diagnostic Flow showing that an IGRA rescreen can both identify LTBI and reduce the number of false positives.

Conclusions Our results show that adoption of either a sequential TST + ve/IGRA approach or single IGRA approach can result in a significant number of false negative LTBI diagnoses due to IGRA conversion. Conversely, we have also shown that an IGRA rescreen because of discordant TST/IGRA tests can improve LTBI diagnostic specificity and therefore reduce unnecessary chemoprophylaxis due to the effect of reversion.

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