Detection and Prediction of Active Tuberculosis Disease by a Whole-Blood Interferon-γ Release Assay in HIV-1–Infected Individuals

Department of Dermatology, Division of Immunology, Allergy, and Infectious Diseases, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Clinical Infectious Diseases (Impact Factor: 8.89). 03/2009; 48(7):954-62. DOI: 10.1086/597351
Source: PubMed


The sensitivity of whole-blood interferon-gamma release assays to detect or predict active tuberculosis in individuals infected with human immunodeficiency virus type 1 (HIV-1) has as yet not been determined. Methods. In this prospective, longitudinal, single-center study, 830 HIV-1-infected patients underwent testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. Clinical screening for active tuberculosis was performed at least every 3 months for a median follow-up time of 19 months.
At baseline, the QFT-GIT assay yielded positive or indeterminate results in 44 (5.3%) and 47 (5.7%) of the 830 patients, respectively. A positive QFT-GIT assay result occurred at significantly higher frequencies among black individuals than among white individuals (odds ratio, 4.84; 95% confidence interval, 2.25-9.97; P< .001), among patients from Africa than among patients from Austria (odds ratio, 6.57; 95% confidence interval, 2.99-14.25; P< .001), and among patients from high-prevalence countries than among patients from low-prevalence countries (odds ratio, 5.86; 95% confidence interval, 2.41-13.44; P< .001). In patients with indeterminate QFT-GIT assay results, both median actual and nadir CD4(+) T cell counts were significantly lower than in patients with interpretable QFT-GIT assay results (P< .001). At the time of baseline QFT-GIT screening, active tuberculosis was found in 7 (15.9%) of 44 individuals with a positive result and in 1 (0.1%) of 739 patients with a negative result. During the follow-up period, however, progression to active tuberculosis occurred exclusively in patients with a positive QFT-GIT assay result, at a rate of 8.1% (3 of 37 patients; P< .001). Collectively, the sensitivity of the QFT-GIT assay for active tuberculosis was 90.9% (95% confidence interval, 62.3%-98.4%).
Our results suggest that the QFT-GIT assay may be a sensitive tool for the detection and prediction of active tuberculosis in HIV-1-infected individuals.

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    • "More importantly, QFT-GIT alone was more effective to detect LTBI than TST, assuming that any test is a marker of LTBI. This is important because despite absence of substantial evidence of the benefit of isoniazid preventive therapy in QFT-GIT positive patients, recent studies have shown a high risk of active TB in these patients [2, 7, 29–31] and thus treatment of PLWHA with discordant tests has been recommended [15, 16] considering the high efficacy of isoniazid preventive therapy [3, 5, 32] to prevent disease and death among these patients. "
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    ABSTRACT: Objective: To evaluate the added value of QuantiFERON TB-Gold in-Tube (QTF-GIT) over the tuberculin skin testing (TST) for detecting latent tuberculosis (TB) infection (LTBI) among patients with AIDS in a city with a low TB incidence rate (11.1/100,000 inhabitants) and universal BCG coverage. Methods: Three hundred consecutive patients with AIDS in eight outpatient sexually transmitted disease public clinics in Brasilia were submitted to QFT-IT and TST between May 2011 and March 2013. A positive result of either test was considered to be LTBI. Results: Median CD4-cell count was 477.5 cells/mm(3); 295 (98.3%) were using antiretroviral therapy. Eighteen patients (6%, 95% CI: 3.6%-9.3%) had LTBI, of whom 4 (1.3%, 95% CI: 0.04%-2.63%) had only a positive TST, 8 (2.7%, 95% CI: 0.8%-4.5%) had only a QFT-GIT positive test, and 6 (2%, 95% CI: 0.4%-3.6%) had positive results for both tests. This represents an 81.8% relative increase in LTBI detection when QFT-GIT is added to TST. The concordance between both tests was 96% (k = 0.48). Conclusions: The QFT-GIT alone was more effective to detect LTBI than TST alone and had an 81% added value as an add-on sequential test in this population with mild immunosuppression. The cost-effectiveness of these strategies remains to be evaluated.
    BioMed Research International 05/2014; 2014:294963. DOI:10.1155/2014/294963 · 1.58 Impact Factor
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    • "Kang, et al.17 and Aichelburg, et al.18 reported that the sensitivity of IGRA is not different between immunocompetent patients and immunocompromised patients. These results are compatible to the results of our study, which suggested that IGRA results are also not affected by immune status. "
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    ABSTRACT: We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate. We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.
    Yonsei medical journal 05/2014; 55(3):725-31. DOI:10.3349/ymj.2014.55.3.725 · 1.29 Impact Factor
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    • "These one-visit, ex vivo blood tests have high specificity and avoid sensitization, boosting of immune response, and cross-reactivity following Bacillus Calmette-Guérin vaccination and exposure to most non-tuberculous mycobacteria [17,18]. Several recent studies have demonstrated their superiority over the TST in elderly populations and their improved ability to predict progression to active TB in populations at risk like recent TB contacts, HIV-infected individuals, and silicotic subjects [10,11,16,19-21]. Accordingly, the national guidelines on the screening of TB contacts recommend the primary use of an IGRA among adults in Germany [22]. "
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    ABSTRACT: Miners are at particular risk for tuberculosis (TB) infection due to exposure to silica dust and silicosis. The objectives of the present observational cohort study were to determine the prevalence of latent TB infection (LTBI) among aged German underground hard coal miners with silicosis or chronic obstructive pulmonary disease (COPD) using two commercial interferon-gamma release assays (IGRAs) and to compare their performance with respect to predictors of test positivity. Between October 2008 and June 2010, miners were consecutively recruited when routinely attending pneumoconiosis clinics for an expert opinion. Both IGRAs, the QuantiFERON®-TB Gold In-Tube (QFT) and the T-SPOT®.TB (T-SPOT), were performed at baseline. A standardized clinical interview was conducted at baseline and at follow-up. The cohort was prospectively followed regarding the development of active TB for at least two years after inclusion of the last study subject. Independent predictors of IGRA positivity were calculated using logistic regression. Among 118 subjects (mean age 75 years), none reported recent exposure to TB. Overall, the QFT and the T-SPOT yielded similarly high rates of positive results (QFT: 46.6%; 95% confidence interval 37.6-55.6%; T-SPOT: 61.0%; 95% confidence interval 52.2-69.8%). Positive results were independently predicted by age ≥80 years and foreign country of birth for both IGRAs. In addition, radiological evidence of prior healed TB increased the chance of a positive QFT result fivefold. While 28 subjects were lost to follow-up, no cases of active TB occurred among 90 subjects during an average follow-up of >2 years. Considering the high prevalence of LTBI, the absence of recent TB exposure, and the currently low TB incidence in Germany, our study provides evidence for the persistence of specific interferon-gamma responses even decades after putative exposure. However, the clinical value of current IGRAs among our study population, although probably limited, remains uncertain.
    PLoS ONE 12/2013; 8(12):e82005. DOI:10.1371/journal.pone.0082005 · 3.23 Impact Factor
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