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.

Background: 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.TB for etiological diagnosis of classic FUO in adult patients in a high TB endemic area.

Methods: 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.TB. Clinical assessment and T-SPOT.TB were performed. Test results were compared with the final confirmed clinical diagnosis.

Results: 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.TB 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.TB, sensitivity was 91.7%) and 56 cases were clinically diagnosed (37 cases with positive T-SPOT.TB, sensitivity was 66.1%); 14 cases were pulmonary TB (13 cases with positive T-SPOT.TB, sensitivity was 92.9%) and 54 cases were extrapulmonary TB (35 cases with positive T-SPOT.TB, sensitivity was 64.8%).

Conclusions: For patients presenting with classic FUO in this TB endemic setting, T-SPOT.TB appears valuable for excluding active TB, with a high negative predictive value.