Utility of T-Cell Interferon-γ Release Assays for Etiological Diagnosis of Classic Fever of Unknown Origin in a High Tuberculosis Endemic Area — a pilot prospective cohort

<div><p>Background</p><p>Tuberculosis (TB), especially extrapulmonary TB is still the leading cause of fever of unknown origin (FUO) in China. However, diagnosis of TB still remains a challenge. The aim of this study was to evaluate the diagnostic value of T-SPOT.<i>TB</i> for etiological diagnosis of classic FUO in adult patients in a high TB endemic area.</p><p>Methods</p><p>We prospectively enrolled patients presenting with classic FUO in a tertiary referral hospital in Beijing, China, to investigate the diagnostic sensitivity, specificity, predictive values and likelihood ratio of T-SPOT.<i>TB</i>. Clinical assessment and T-SPOT.<i>TB</i> were performed. Test results were compared with the final confirmed clinical diagnosis.</p><p>Results</p><p>387 hospitalized patients (male n = 194, female n = 193; median age 46 (range 29–59) yrs) with classic FUO were prospectively enrolled into this study. These FUOs were caused by infection (n = 158, 40.8%), connective tissue disease (n = 82, 21.2%), malignancy (n = 41, 10.6%) and miscellaneous other causes (n = 31, 8.0%), and no cause was determined in 75 (19.4%) patients. 68 cases were diagnosed as active TB eventually. The sensitivity of T-SPOT.<i>TB</i> for the diagnosis of active TB was 70.6% (95%CI 58.9–80.1%), while specificity was 84.4% (95%CI 79.4–88.4%), positive predictive value was 55.8% (95%CI 45.3–65.8%), negative predictive value was 91.2% (95%CI 86.7–94.2%). Among these 68 active TB patients, 12 cases were culture or histology confirmed (11 cases with positive T-SPOT.<i>TB</i>, sensitivity was 91.7%) and 56 cases were clinically diagnosed (37 cases with positive T-SPOT.<i>TB</i>, sensitivity was 66.1%); 14 cases were pulmonary TB (13 cases with positive T-SPOT.<i>TB</i>, sensitivity was 92.9%) and 54 cases were extrapulmonary TB (35 cases with positive T-SPOT.<i>TB</i>, sensitivity was 64.8%).</p><p>Conclusions</p><p>For patients presenting with classic FUO in this TB endemic setting, T-SPOT.<i>TB</i> appears valuable for excluding active TB, with a high negative predictive value.</p></div

Diagnostic Value of Interferon-γ Release Assays on Pericardial Effusion for Diagnosis of Tuberculous Pericarditis

<div><p>Diagnosis of tuberculous pericarditis remains a challenge. We aimed in this study to evaluate the diagnostic value of T-SPOT.<i>TB</i> on pericardial effusion for diagnosis of tuberculous pericarditis. Patients with suspected tuberculous pericarditis were enrolled consecutively between August 2011 and December 2015. T-SPOT.<i>TB</i> was performed on both pericardial effusion mononuclear cells (PEMCs)and peripheral blood mononuclear cells (PBMCs). Sensitivity, specificity, predictive value (PV), and likelihood ratio (LR) of T-SPOT.<i>TB</i> on PEMCs and PBMCs were analyzed. Among the 75 patients enrolled, 24 patients (32%) were diagnosed with tuberculous pericarditis, 38 patients (51%) with nontuberculous pericarditis, and 13 patients (17%) were clinically indeterminate and were excluded from the final analysis. The sensitivity, specificity, positive PV (PPV), negative PV (NPV), positive LR (LR+), and negative LR (LR-) of T-SPOT.<i>TB</i> on PEMCs was 92%,92%,88%,95%,11.61, and 0.09, respectively, compared to 83%, 95%, 91%, 90%,15.83, and 0.18, respectively of T-SPOT.<i>TB</i> on PBMCs. In patients with tuberculous pericarditis, the median frequencies of spot-forming cells (SFCs) of T-SPOT.<i>TB</i> on PEMCs and PBMCs was 172SFCs/10⁶MCs (IQR 39~486), and 66 SFCs/10⁶MCs (IQR 24~526), respectively, but the difference was not statistically significant (P = 0.183). T-SPOT.<i>TB</i> on PEMCs appeared to be a valuable and rapid diagnostic method for diagnosis of tuberculous pericarditis with high sensitivity and specificity.</p></div

Diagnostic category of tuberculous pericarditis.

<p>Diagnostic category of tuberculous pericarditis.</p

Baseline clinical characteristics and laboratory tests in 75 patients with suspected tuberculous pericarditis.

<p>Baseline clinical characteristics and laboratory tests in 75 patients with suspected tuberculous pericarditis.</p

Frequencies of T-SPOT.TB on PEMCs and PBMCs in patients with tuberculous pericarditis.

<p>Frequencies of T-SPOT.TB on PEMCs and PBMCs in patients with tuberculous pericarditis.</p

Flowchart of enrolling patients.

<p>Flowchart of enrolling patients.</p

Sensitivity, specificity, PPV, NPV, LR+, LR-, and area under the receiver operating characteristic curve (AUC) of T-SPOT.TB on PEMCs and PBMCs of patients with tuberculous pericarditis.

<p>Sensitivity, specificity, PPV, NPV, LR+, LR-, and area under the receiver operating characteristic curve (AUC) of T-SPOT.TB on PEMCs and PBMCs of patients with tuberculous pericarditis.</p

CSFMC: PBMC ratio in TBM or Non-TBM cases with positive T-SPOT.TB results.

<p>CSFMC: PBMC ratio in TBM or Non-TBM cases with positive T-SPOT.TB results.</p

Demographic and clinical characteristics of the patients.

<p>Duration: the course of the disease before definitive diagnosis was made</p><p>Pre-existing conditions: diseases could damage the function of immune system.</p><p>Demographic and clinical characteristics of the patients.</p

Single and combined diagnostic parameters of T-SPOT.TB on CSFMC and PBMC.

<p>Single and combined diagnostic parameters of T-SPOT.TB on CSFMC and PBMC.</p