Risk factors for false-negative results of T-SPOT.TB and tuberculin skin test in extrapulmonary tuberculosis

Abstract

Purpose: T-SPOT.TB, a recently developed T cell-based assay, has shown promise in diagnosing extrapulmonary tuberculosis (EPTB). However, a limited number of reports have compared the risk factors for false-negative results of tuberculin skin tests (TSTs) and T-SPOT.TB assays in patients with EPTB. We, thus, conducted a prospective, blinded, observational study to evaluate the risk factors for false-negative T-SPOT.TB and TST results in patients with EPTB.

Methods: Between April 2008 and November 2011, all adult patients with suspected EPTB were prospectively enrolled at Asan Medical Center, Seoul, South Korea (an intermediate TB-burden country). Only patients with confirmed and probable EPTB who underwent TST and T-SPOT.TB were included in the final analysis.

Results: Of the 324 patients who underwent both TST and T-SPOT.TB testing, 128 patients with 96 (75 %) culture- or polymerase chain reaction (PCR)-confirmed and 32 (25 %) probable EPTB were finally analyzed. T-SPOT.TB assays were less likely to yield false-negative results than TSTs [17 % (22/128) vs. 54 % (69/128), p < 0.001]. In a multivariate analysis, miliary TB was associated with false-negative TSTs [odds ratio (OR) = 5.3; 95 % confidence interval (CI) 1.7-16.1], while immunosuppression showed a trend toward false-negative TSTs (OR = 2.5; 95 % CI 0.9-6.8). Conversely, lymph node TB (OR = 0.2; 95 % CI 0.1-0.5) and skeletal TB (OR = 0.2; 95 % CI 0.1-0.5) were associated with true-positive TST results. The only risk factor for false-negative T-SPOT.TB results was TB meningitis (OR = 2.6; 95 % CI 1.0-6.6).

Conclusions: Our findings suggest that T-SPOT.TB has a better sensitivity to diagnose EPTB than TST, especially in patients with immunosuppression or miliary TB.