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Open Access Highly Accessed Research article

Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection

Adithya Cattamanchi12*, Isaac Ssewenyana3, J Lucian Davis12, Laurence Huang14, William Worodria6, Saskia den Boon7, Samuel Yoo7, Alfred Andama7, Philip C Hopewell12 and Huyen Cao5

Author Affiliations

1 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, USA

2 Francis J. Curry National Tuberculosis Center, University of California, San Francisco, San Francisco, USA

3 Joint Clinical Research Centre, Kampala, Uganda

4 HIV/AIDS Division, University of California, San Francisco, San Francisco, USA

5 California Department of Public Health, Richmond, USA

6 Faculty of Medicine, Makerere University, Kampala, Uganda

7 Makerere University-University of California San Francisco Research Collaboration, Kampala, Uganda

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BMC Infectious Diseases 2010, 10:75  doi:10.1186/1471-2334-10-75

Published: 20 March 2010

Abstract

Background

T-cell interferon-gamma release assays (IGRAs) may have a role in the diagnosis of active tuberculosis when evaluating patients for whom standard microbiology has limited sensitivity. Our objective was to examine the accuracy of a commercial IGRA for diagnosis of active tuberculosis in HIV-infected persons.

Methods

We enrolled HIV-infected patients admitted to Mulago Hospital in Kampala, Uganda with cough ≥ 2 weeks. All patients underwent standard medical evaluation. We collected peripheral blood specimens at enrollment and performed a commercial, ELISPOT-based IGRA according to the manufacturer's recommendations. IGRA sensitivity and specificity were determined using mycobacterial culture results as the reference standard.

Results

Overall, 236 patients were enrolled. The median CD4+ T-lymphocyte count was 49 cells/μl and 126 (53%) patients were diagnosed with active pulmonary tuberculosis. IGRAs were not performed in 24 (10%) patients due to insufficient mononuclear cell counts. In the remaining 212 patients, results were indeterminate in 54 (25%). IGRAs were positive in 95 of 158 (60%) patients with interpretable results. The proportion of positive test results was similar across CD4+ count strata. IGRA sensitivity was 73% and specificity 54%. IGRA results did not meaningfully alter the probability of active tuberculosis in patients with negative sputum smears.

Conclusions

An ELISPOT-based IGRA detected a high prevalence of latent tuberculosis infection in a hospitalized population of tuberculosis suspects with advanced HIV/AIDS but had limited utility for diagnosis of active tuberculosis in a high prevalence setting. Further research is needed to identify stronger and more specific immune responses in patients with active tuberculosis.