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

Adithya Cattamanchi,J Lucian Davis,Philip C Hopewell,William Worodria,Huyen Cao,Samuel Yoo,Alfred Andama,Saskia Den Boon,Laurence Huang,Isaac Ssewenyana

doi:10.1186/1471-2334-10-75

Abstract

BackgroundT-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.MethodsWe 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.ResultsOverall, 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.ConclusionsAn 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.

Highlights

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
Though IGRAs are highly accurate for diagnosis of latent tuberculosis infection (LTBI) [1], their use as a diagnostic tool for active tuberculosis (TB) poses several challenges
We considered IGRA results to be positive if: 1) the negative control had < 5 spots and wells stimulated with test Panel A or Panel B had 6 or more spots or 2) the negative control had 5-10 spots and wells stimulated with test Panel A or Panel B had at least twice the number of spots in the negative control

Summary

Introduction

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. T-cell interferon-gamma release assays (IGRAs) measure interferon-gamma release by sensitized T-lymphocytes stimulated with Mycobacterium tuberculosis Standard microbiologic tests (smear microscopy, nucleic acid amplification tests, and mycobacterial culture) have well known limitations, in patients co-infected with HIV [3,4]. Such patients more commonly present with atypical clinical and radiographic findings and pauci-bacillary disease [5]. The consequences of missing a diagnosis are greater, as the disease is more likely to progress rapidly [6]

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