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Open Access Highly Accessed Research article

Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-Infection

Luigia Elzi1, Ingrid Steffen2, Hansjakob Furrer3, Jan Fehr4, Matthias Cavassini5, Bernard Hirschel6, Matthias Hoffmann7, Enos Bernasconi8, Stefano Bassetti9 and Manuel Battegay1*

Author Affiliations

1 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland

2 Institute of Medical Microbiology, University of Basel, Basel, Switzerland

3 University Clinic for Infectious Diseases, University Hospital Bern and University of Bern, Bern, Switzerland

4 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland

5 Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland

6 Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland

7 Cantonal Hospital, St. Gallen, Switzerland

8 Regional Hospital, Lugano, Switzerland

9 Cantonal Hospital, Olten, Switzerland

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BMC Infectious Diseases 2011, 11:319  doi:10.1186/1471-2334-11-319

Published: 15 November 2011

Abstract

Background

Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection.

Methods

IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study.

Results

64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older).

Conclusions

T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.