Sensitivity, specificity, and safety of a novel ESAT6-CFP10 skin test for tuberculosis infection in China: two randomized, self-controlled, parallel-group phase 2b trials.

Abstract

BACKGROUND\nDiagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of the novel ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults.\n\n\nMETHODS\nWe conducted two randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A Bacillus Calmette Guerin (BCG) model was also established to assess the diagnosis of tuberculosis infection using EC skin test.\n\n\nRESULTS\nIn total, 777 healthy participants and 96 tuberculosis patients were allocated to receive the EC skin test at 1.0μg/0.1ml or 0.5μg/0.1ml. The area under the curve was 0.95 (95% CI, 0.91-0.97) from the EC skin test at a dose of 1.0μg/0.1ml at 24-72 hours. Compared to the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI 77.8-97.2 versus 86.5, 95% CI 79.5-93.4) and specificity (98.9, 95% CI 96.0-99.9 versus 96.1, 95% CI 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed.\n\n\nCONCLUSIONS\nThe EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0μg/0.1ml, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination.