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

Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, USA.
BMC Infectious Diseases (Impact Factor: 2.56). 03/2010; 10:75. DOI: 10.1186/1471-2334-10-75
Source: PubMed

ABSTRACT 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.
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.
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.
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.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objectiveIn low and middle-income countries where HIV infection is prevalent, identifying patients at high risk of dying from lower respiratory tract infections is challenging and validated prognostic models are lacking. Serum procalcitonin may be a useful prognostic tool in these settings. We sought to determine if elevated serum procalcitonin is associated with increased in-hospital mortality and to combine serum procalcitonin with available clinical characteristics to create a clinically useful prognostic model. Methods We conducted a prospective, nested case-control study of 241 HIV-infected adults admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks in duration. We collected demographic and clinical information, baseline serum for procalcitonin analysis, and followed patients to determine in-hospital mortality. ResultsSerum procalcitonin was a strong and independent predictor of inpatient mortality (aOR = 7.69, p = 0.01, sensitivity = 93%, negative predictive value = 97%). Best subset multivariate analysis identified 3 variables that were combined into a prognostic model to risk stratify patients; these variables included respiratory rate ≥30 breaths/minute (aOR = 2.07, p = 0.11), oxygen saturation 0.5 ng/ml (aOR = 7.69, p = 0.01). The predicted probability of inpatient mortality ranged from 1% when no variables were present, to 42% when all variables were present. Conclusions Elevated serum procalcitonin >0.5 ng/ml is an independent predictor of in-hospital mortality. Elevated serum procalcitonin, tachypnea, and hypoxemia may be combined into a prognostic model to identify patients at high risk of dying in the hospital. This model may be used to estimate the probability of death and to guide triage and treatment decisions.
    Respirology 02/2014; DOI:10.1111/resp.12237 · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the diagnostic value of interferon-γ (IFN-γ) release assays for active tuberculosis (TB) is limited, the characteristic of non-TB-specific IFN-γ responses among TB suspects deserves further evaluation. We enrolled clinically suspected pulmonary TB (PTB) patients, and QuantiFERON-TB Gold In-Tube (QFT-GIT) was performed. The characteristics of IFN-γ responses were analyzed. Among 392 patients, active PTB patients had stronger IFN-γ responses to TB antigen (TBAg-Nil, P < 0.001) and lower responses to mitogen (Mitogen-Nil, P < 0.001). Lower body mass index (P = 0.001), without bacille Calmette-Guerin vaccination (P = 0.026), and active PTB (P = 0.011) were independent factors associated with lower non-TB-specific IFN-γ responses. Among TB suspects with higher TBAg-Nil (>1.02 U/mL) and lower Mitogen-Nil (<5.5 U/mL), 84.3% were active PTB cases. Among TB suspects with lower TBAg-Nil and higher Mitogen-Nil, only 4.7% were active PTB. The present study suggested that the possibilities of active PTB should be carefully excluded in TB suspects with stronger TB-specific and lower non-TB-specific IFN-γ responses in QFT-GIT.
    Diagnostic microbiology and infectious disease 07/2013; DOI:10.1016/j.diagmicrobio.2013.05.020 · 2.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For years, the ability to study immune responses in patients with active visceral leishmaniasis (VL) has been hampered by the absence of detectable antigen-specific Th1 responses using cells from peripheral blood mononuclear cells (PBMCs). Employing whole blood assay (WBA), we recently reported that whole blood cells of active VL patients maintain the capacity to secrete significant levels of antigen driven IFN-γ and IL-10. Furthermore, WBA that uses soluble leishmania antigen (SLA) have advantages over the leishmanin skin test (LST), in terms of higher specificity and better correlation with surrogate markers of exposures to L. donovani. These findings open the door to a series of immunological and epidemiological studies not previously possible for VL. In the present review, we discuss current status, future perspectives as well as obstacles in the research on WBA. Research in this area is essential for development of potential immunological and epidemiological tools for VL.
    Immunobiology 04/2014; DOI:10.1016/j.imbio.2014.01.005 · 3.18 Impact Factor

Full-text (3 Sources)

Available from
May 29, 2014