Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: A phase II trial

Abstract

BackgroundThis study aimed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis (TB).Material/MethodsA phase II trial was performed in 158 patients with pulmonary TB (145 initially-treated and 13 re-treated) and 133 healthy subjects. Skin testing was carried out by injecting purified protein derivative (PPD) (on left forearm) or recombinant ESAT-6 protein at a dosage of 2, 5, or 10 μg/mL (on the right forearm) in each subject. Reaction activity and adverse events were monitored at 24, 48, and 72 h following the injection. Receiver operating characteristic curves were plotted to determine the areas under the curves (AUCs) and the cut-off induration diameters for the optimal diagnostic performance.ResultsThe reaction activity was significantly increased upon recombinant ESAT-6 injection in pulmonary TB patients compared with healthy subjects. In pulmonary TB patients, the reaction was dose-dependent, and at 48 h, 10 μg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD. The AUCs for a 10 μg/mL dosage were 0.9823, 0.9552, and 0.9266 for 24 h, 48 h, and 72 h, respectively, and the induration diameters of 4.5–5.5 mm were the optimal trade-off values between true positive rates and false positive rates. No serious adverse events occurred in any subjects.ConclusionsRecombinant ESAT-6 protein is efficacious and safe for diagnosing pulmonary TB. Based on the reaction, performance, safety, and practicability, we recommend that 10 μg/mL at 48 h with an induration cut-off value of 5.0 mm be used.

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

“…C-Tb, a novel M. tuberculosis-specific skin test containing ESAT-6 and CFP-10 antigens, is one such new skin test, developed by Statens Serum Institut, Denmark (43,44). Another product, Diaskintest (Generium Pharmaceutical, Moscow, Russia), is available commercially in Russia, Ukraine, and Kazakhstan (45), and an ESAT-6-based skin test from China is in clinical trials (46). There is currently no policy guidance on these newer skin tests, because the evidence base is weak.…”

Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection

“…This unmet need has now been addressed with the development of C-Tb, a novel M. tuberculosis-specific skin test that contains ESAT-6 and CFP-10 antigens [11][12][13]. Alternative versions have been made in China and Russia [14,15]. The C-Tb skin test can be used by health services to test for M. tuberculosis infection and is applied in exactly the same way as the TST, but without the suboptimal specificity.…”

Diagnostic Value of Convex Probe Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Mediastinal Tuberculous Lymphadenitis: A Systematic Review and Meta-Analysis

“…Although tuberculin skin testing, IFN-γ release assays with M. tuberculosis antigens, and recombinant M. tuberculosis early secreted antigenic target 6-kDa protein (ESAT-6) skin testing can be used to detect the presence of a TB infection [ 43 – 45 ], a definitive TB diagnosis can only be established with a M. tuberculosis- positive culture or smear. Although sputum examination has been useful in diagnosing active pulmonary TB, about half of suspected patients are unable to produce sputum, and even if sputum is produced, acid-fast bacilli (AFB) are often not found by repeated examination of direct smears [ 46 ].…”