Publications

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 > or = 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/microl 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.

Studies of the initiation and maintenance of asthma and allergic inflammation implicate dysregulated interactions between mucosal epithelia and innate immune cells as the underlying cause of these disorders. The similarities of these responses with mucosal responses to parasitic intestinal worms may reveal pathways relevant to the perplexing rise of these chronic inflammatory disorders.