Interferon-gamma release assay performance in pulmonary and extrapulmonary tuberculosis

Abstract

Background: The diagnosis of tuberculosis remains difficult. This study aimed to assess performance of interferon-gamma release assay (IGRA) in diagnosis of active tuberculosis (ATB) with pulmonary and extrapulmonary involvements, and to determine the diagnostic role of IGRA (T-SPOT.TB) and tuberculin skin test (TST) in BCG-vaccinated population.

Methods and findings: Two hundred twenty-six ATB suspects were recruited and examined with T-SPOT.TB. Among them, fifty-two and seventy-six subjects were simultaneously tested by TST with 5TU or 1TU of purified protein derivative (PPD). The sensitivity of T-SPOT.TB was 94.7% (71/75), comparable in pulmonary and extrapulmonary disease groups (95.6% vs. 93.3%, P>0.05), while the specificity was 84.10% (90/107) but differed in two groups (69.2% vs. 88.9%, P = 0.02). Compared to T-SPOT.TB, TST with 5TU-PPD showed less sensitivity (92.3% vs. 56.4%) and specificity (84.6% vs. 61.5%) (both P<0.01); the sensitivity of TST with 1TU-PPD was 27.8%, and despite its specificity identical to T-SPOT.TB (both 82.8%) positive predictive value (PPV) was only 33.3%. By combining T-SPOT.TB with TST (1TU), the specificity rose to 95%, but the PPV stayed unchanged.

Conclusions: IGRA could function as a powerful immunodiagnostic test to explore pulmonary and extrapulmonary TB, while TST failed to play a reliable or auxiliary role in identifying TB disease and infection in the BCG-vaccinated population.

Figure 1. Flowchart of the study population.

A total of 226 subjects suspected to have active tuberculosis (ATB) were recruited and 182 were eligible to be included in the final analyses. The analyses were composed of two parts: a study on the diagnostic performance of the T-SPOT.TB on pulmonary and extrapulmonary ATB, and a study comparing the performance between T-SPOT.TB and TST with a dose of 1TU-PPD or 5TU-PPD. ATB, active tuberculosis; no ATB, final diagnosis excluded active tuberculosis.

Figure 2. The deviation features of the T-SPOT.TB, TST in single or combination way.

The deviation from the gold standard test was compared between T-SPOT.TB and TST^{1TU PPD} (A), T-SPOT.TB and TST^{5TU PPD} (B), and between the combination in parallel and serial way for these two comparisons (C, D). The north, south, east and west poles in each panel represented 100%of the true-positive rate, true-negative rate, false-positive rate, and false-negative rate, respectively, and each observed rate located between the top poles of the axes (100%) and the central origin (0%). In A and B, the shape formed by connecting the diagnostic rates of T-SPOT.TB was outlined by the dark lines and the shape of TST were filled with grey color. In C and D, parallel testing was outlined by dashed lines, and serial testing by dotted lines.